WorldWideScience

Sample records for e3 m3 transition

  1. On M3-transition rates in selected odd-mass nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Lombard, R.J. E-mail: lombard@ipno.in2p3.fr; Vdovin, A.I.; Shirikova, N.Yu.; Sushkov, A.V

    2003-06-02

    The reduced probabilities of M3 transitions are studied in five deformed and three spherical or near-spherical odd-mass nuclei. In deformed nuclei, the states linked by M3 transitions are predominantly of single-quasiparticle nature and the calculations are performed taking into account the single-quasiparticle as well as core-polarization terms in the M3-operator. Whereas in {sup 159}Ho, {sup 175}Yb, and {sup 179}Hf the ratio between theoretical and experimental B(M3) values range from 0.5 to 1.4, the situation is much worse in neutron deficient nuclides {sup 179}W and {sup 183}Pt where the theory used can not explain a very sharp drop of the B(M3) values. In the soft nuclei {sup 121}Cs and {sup 207}Po the states connected by M3 transitions are treated as 'quasiparticle x phonon' states. In {sup 113}Sn, the small 'quasiparticle x phonon' components are not sufficient to compensate vanishing contribution of the dominant quasiparticle component, which shares {delta}l forbidden transitions. Thus, on the whole theoretical description of B(M3) with the present simple models seems to be unsatisfactory. It constitutes a challenging problem both at the level of the nuclear structure and the transition operator.

  2. Odd tensor E3 transitions and the generalized seniority in Sn-isotopes

    CERN Document Server

    Maheshwari, Bhoomika

    2016-01-01

    In our recent paper [Phys. Lett. B 753, (2016) 122], we have shown that both the odd and even tensor electric transition probabilities exhibit similar behavior within the generalized seniority scheme in a multi-j environment. This microscopic approach was used to show for the first time the occurrence of seniority isomers in the $ {13}^-$ isomers of Sn-isotopes, which decay by odd tensor $E1$ transition to the same seniority ($\\Delta v = 0$) state. In this letter, we extend our studies to odd tensor $E3$ transitions connecting different seniority states ($\\Delta v = 2$), and show for the first time that the generalized seniority scheme explains reasonably well the systematics of the $B(E3)$ values for the $(0^+ \\rightarrow 3_1^-)$ transitions in the Sn-isotopes. Additionally, we support these results by seniority guided Large Scale Shell Model (LSSM) calculations. The generalized seniority results are able to single out the most crucial valence space required in the LSSM calculations.

  3. {ital E}3 transition probabilities in the platinum, mercury, and lead isotopes

    Energy Technology Data Exchange (ETDEWEB)

    Egido, J.L.; Martin, V.; Robledo, L.M.; Sun, Y. [Departamento de Fisica Teorica C-XI, Universidad Autonoma de Madrid, E-28049 Madrid (Spain)]|[Analisis Numerico, Facultad de Informatica, Universidad Politecnica de Madrid, E-28660 Madrid (Spain)]|[Department of Physics and Atmospheric Science, Drexel University, Philadelphia, Pennsylvania 19104 (United States)]|[Joint Institute for Heavy Ion Research, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831 (United States)

    1996-06-01

    Spectroscopical properties of the platinum, mercury, and lead isotopes are studied within the Hartree-Fock plus BCS framework with the finite range density-dependent Gogny force. These properties are also studied beyond mean-field theory by combining the use of generator-coordinate-method-like wave functions with the angular momentum projection technique as to generate many-body correlated wave functions that are at the same time eigenstates of the angular momentum operator. We apply this formalism to the calculation of reduced transition probabilities {ital B}({ital E}3) from the lowest-lying octupole collective state to the ground state of several isotopes of the platinum, mercury, and lead nuclei whose experimental {ital B}({ital E}3) values present a peculiar behavior. The projected calculations show a large improvement over the unprojected ones when compared with the experimental data. The unprojected calculations are unable to predict any structure in the {ital B}({ital E}3). {copyright} {ital 1996 The American Physical Society.}

  4. Disorder-driven topological phase transition in B i2S e3 films

    Science.gov (United States)

    Brahlek, Matthew; Koirala, Nikesh; Salehi, Maryam; Moon, Jisoo; Zhang, Wenhan; Li, Haoxiang; Zhou, Xiaoqing; Han, Myung-Geun; Wu, Liang; Emge, Thomas; Lee, Hang-Dong; Xu, Can; Rhee, Seuk Joo; Gustafsson, Torgny; Armitage, N. Peter; Zhu, Yimei; Dessau, Daniel S.; Wu, Weida; Oh, Seongshik

    2016-10-01

    Topological insulators (TI) are a phase of matter that host unusual metallic surface states. Unlike the states that exist on the surface of conventional materials, these so-called topological surfaces states (TSS) are protected against disorder-related localization effects by time reversal symmetry through strong spin-orbit coupling. By combining transport measurements, angle-resolved photoemission spectroscopy, and scanning tunneling microscopy, we show that there exists a critical level of disorder beyond which the TI B i2S e3 loses its ability to protect the metallic TSS and transitions to a fully insulating state. The absence of the metallic surface channels dictates that there is a change in the material's topological character, implying that disorder can lead to a topological phase transition even without breaking the time reversal symmetry. This observation challenges the conventional notion of topologically protected surface states and should prompt new studies as to the fundamental nature of topological phase of matter in the presence of disorder.

  5. Structural and electronic properties of reduced transition metal oxide clusters, M3O8 and M3O8- (M = Cr, W), from photoelectron spectroscopy and quantum chemical calculations.

    Science.gov (United States)

    Li, Shenggang; Zhai, Hua-Jin; Wang, Lai-Sheng; Dixon, David A

    2009-10-22

    We report a comparative study of reduced transition metal oxide clusters, M(3)O(8)(-) (M = Cr, W) anions and their neutrals, via anion photoelectron spectroscopy (PES) and density functional theory (DFT) and molecular orbital theory (CCSD(T)) calculations. Well-resolved PES spectra are obtained for M(3)O(8)(-) (M = Cr, W) at 193 and 157 nm photon energies. Different PES spectra are observed for M = Cr versus M = W. Extensive DFT and CCSD(T) calculations are performed to locate the ground and low-lying excited states for the neutrals and anions. The ground states of Cr(3)O(8) and Cr(3)O(8)(-) are predicted to be the (3)B(2) and (4)B(2) states of a C(2v) structure, respectively, revealing ferromagnetic spin coupling for Cr 3d electrons. In contrast, the ground states of W(3)O(8) and W(3)O(8)(-) are predicted to be the (1)A' state (C(s) symmetry) and the (2)A(1) state (C(2v) symmetry), respectively, showing metal-metal d-d bonding in the anion. The current cluster geometries are in qualitative agreement with prior DFT studies at the PBE level for M = Cr and the B3LYP level for M = W. The BP86 and PW91 functionals significantly outperform the B3LYP functional for the Cr species, in terms of relative energies, electron detachment energies, and electronic excitation energies, whereas the B3LYP functional is better for the W species. Accurate heats of formation for the ground states of M(3)O(8) are calculated from the clustering energies and the heats of formation of MO(2) and MO(3). The energetics have been used to predict redox reaction thermochemistry.

  6. Variation with mass of $\\boldmath{B(E3; 0_1^+ \\to 3_1^-)}$ transition rates in $A=124-134$ even-mass xenon nuclei

    CERN Document Server

    Müller, W F; Church, J A; Dinca, D C; Gade, A; Glasmacher, T; Henderson, D T; Hu, Z; Janssens, R V F; Lisetskiy, A F; Lister, C J; Moore, E F; Pennington, T O; Perry, B C; Wiedenhöver, I; Yurkewicz, K L; Zelevinsky, V G; Zwahlen, H

    2006-01-01

    $B(E3; 0_1^+ \\to 3_1^-)$ transition matrix elements have been measured for even-mass $^{124-134}$Xe nuclei using sub-barrier Coulomb excitation in inverse kinematics. The trends in energy $E(3^-)$ and $B(E3; 0_1^+ \\to 3_1^-)$ excitation strengths are well reproduced using phenomenological models based on a strong coupling picture with a soft quadrupole mode and an increasing occupation of the intruder $h_{11/2}$ orbital.

  7. Realization of stable ferromagnetic order in a topological insulator: Codoping-enhanced magnetism in 4 f transition metal doped B i2S e3

    Science.gov (United States)

    Deng, Bei; Zhang, Yiou; Zhang, S. B.; Wang, Yayu; He, Ke; Zhu, Junyi

    2016-08-01

    The quantum anomalous Hall effect (QAHE) originates from a combination of the spin-orbital coupling and the breaking of time-reversal symmetry due to intrinsic ferromagnetic ordering and was recently observed in Cr and V doped magnetic topological insulators (TIs). However, it was only observed at extremely low temperatures due to the low ferromagnetic Curie temperature and the tiny magnetically induced gap. To fully understand the mechanism of the ferromagnetic ordering, thereby improving the ferromagnetism, we investigated 4 f transition metal doped B i2S e3 , using density functional theory approaches. We predict that Eu and Sm can introduce stable long-range ferromagnetic states in B i2S e3 , with large magnetic moments and low impurity disorders. Additionally, codoping is proposed to tune the Fermi level into the gap, which simultaneously improves the magnetic moment and the incorporation of magnetic ions. Our findings, thus, offer a step in facilitating the realization of QAHE in TI systems.

  8. Spectroscopy of f -f transitions, crystal-field calculations, and magnetic and quadrupole helix chirality in DyF e3(BO3) 4

    Science.gov (United States)

    Popova, M. N.; Chukalina, E. P.; Boldyrev, K. N.; Stanislavchuk, T. N.; Malkin, B. Z.; Gudim, I. A.

    2017-03-01

    We present the results of temperature- and polarization-dependent high-resolution optical spectroscopy studies of DyF e3(BO3) 4 performed in spectral ranges 40 -300 c m-1 and 3000 -23 000 c m-1 . The crystal-field (CF) parameters for the D y3 + ions in the P 3121 (P 3221 ) phase of DyF e3(BO3) 4 are obtained from calculations based on the analysis of the measured f-f transitions. Recently, quadrupole helix chirality and its domain structure was observed in resonant x-ray diffraction experiments on DyF e3(BO3) 4 using circularly polarized x rays [T. Usui, Y. Tanaka, H. Nakajima, M. Taguchi, A. Chainani, M. Oura, S. Shin, N. Katayama, H. Sawa, Y. Wakabayashi, and T. Kimura, Nat. Mater. 13, 611 (2014), 10.1038/nmat3942]. Using the obtained set of the CF parameters, we calculate temperature dependencies of the electronic quadrupole moments of the D y3 + ions induced by the low-symmetry (C2) CF component and show that the quadrupole helix chirality can be explained quantitatively. We also consider the temperature dependencies of the bulk magnetic dc-susceptibility and the helix chirality of the single-site magnetic susceptibility tensors of the D y3 + ions in the paramagnetic P 3121 (P 3221 ) phase and suggest the neutron and resonant x-ray diffraction experiments in a magnetic field to reveal the helix chirality of field-induced magnetic moments.

  9. TEM Method for Identification of Domains in Materials which Undergo a Pm3m3->R3c or R3c Phase Transition

    DEFF Research Database (Denmark)

    Bilde-Sørensen, Jørgen

    1979-01-01

    The c-axis of the domains formed by a Pm3m→R3c or R3¯c phase transition may lie along any of the four 〈111〉 C directions of the cubic phase. It is shown that the orientation of the c-axis can be determined by TEM by examining whether two suitable 1/3{113}C superlattice reflections are allowed...... or forbidden in the trigonal phase. As an example, the method is used to examine domains in LaAlO3...

  10. CDK1-dependent inhibition of the E3 ubiquitin ligase CRL4CDT2 ensures robust transition from S Phase to Mitosis.

    Science.gov (United States)

    Rizzardi, Lindsay F; Coleman, Kate E; Varma, Dileep; Matson, Jacob P; Oh, Seeun; Cook, Jeanette Gowen

    2015-01-02

    Replication-coupled destruction of a cohort of cell cycle proteins ensures efficient and precise genome duplication. Three proteins destroyed during replication via the CRL4(CDT2) ubiquitin E3 ligase, CDT1, p21, and SET8 (PR-SET7), are also essential or important during mitosis, making their reaccumulation after S phase a critical cell cycle event. During early and mid-S phase and during DNA repair, proliferating cell nuclear antigen (PCNA) loading onto DNA (PCNA(DNA)) triggers the interaction between CRL4(CDT2) and its substrates, resulting in their degradation. We have discovered that, beginning in late S phase, PCNA(DNA) is no longer sufficient to trigger CRL4(CDT2)-mediated degradation. A CDK1-dependent mechanism that blocks CRL4(CDT2) activity by interfering with CDT2 recruitment to chromatin actively protects CRL4(CDT2) substrates. We postulate that deliberate override of replication-coupled destruction allows anticipatory accumulation in late S phase. We further show that (as for CDT1) de novo SET8 reaccumulation is important for normal mitotic progression. In this manner, CDK1-dependent CRL4(CDT2) inactivation contributes to efficient transition from S phase to mitosis.

  11. E3 Staff Database

    Data.gov (United States)

    US Agency for International Development — E3 Staff database is maintained by E3 PDMS (Professional Development & Management Services) office. The database is Mysql. It is manually updated by E3 staff as...

  12. Wave-vector-dependent electron-phonon coupling and the charge-density-wave transition in TbT e3

    Science.gov (United States)

    Maschek, M.; Rosenkranz, S.; Heid, R.; Said, A. H.; Giraldo-Gallo, P.; Fisher, I. R.; Weber, F.

    2015-06-01

    We present a high-energy-resolution inelastic x-ray scattering investigation of the soft phonon mode in the charge-density-wave (CDW) system TbT e3 . We analyze our data based on lattice dynamical calculations using density-functional-perturbation theory and find clear evidence that strongly momentum-dependent electron-phonon coupling defines the periodicity of the CDW superstructure: Our experiment reveals strong phonon softening and increased phonon linewidths over a large part in reciprocal space adjacent to the CDW ordering vector qCDW=(0 ,0 ,0.3 ) . Further, qCDW is clearly offset from the wave vector of (weak) Fermi surface nesting qFS=(0 ,0 ,0.25 ) , and our detailed analysis indicates that electron-phonon coupling is responsible for this shift. Hence, we can add TbT e3 , which was previously considered as a canonical CDW compound following the Peierls scenario, to the list of distinct charge-density-wave materials characterized by momentum-dependent electron-phonon coupling.

  13. Absolute E3 and M2 transition probabilities for the electromagnetic decay of the ensuremath I^{π=K^{π}=8-} isomeric state in 132Ce

    Science.gov (United States)

    Perkowski, J.; Andrzejewski, J.; Srebrny, J.; Bruce, A. M.; Droste, Ch.; Grodner, E.; Kisieliński, M.; Korman, A.; Kowalczyk, M.; Kownacki, J.; Król, A.; Marganiec, J.; Mierzejewski, J.; Morek, T.; Sobczak, K.; Trzaska, W. H.; Zielińska, M.

    2009-12-01

    The decay of the ensuremath I^{π}=K^{π}=8- isomeric state at 2340keV in 132Ce has been investigated in the 120Sn(16O, 4n)132Ce reaction. The measurements were carried out in e - γ and γ - γ coincidence modes using an electron spectrometer coupled to the OSIRIS II gamma-ray array at the Heavy Ion Laboratory of the University of Warsaw. Experimentally obtained internal conversion coefficients for the ensuremath 8- rightarrow 6+ and ensuremath 8- rightarrow 5+ transitions allowed the multipolarities, mixing ratios, reduced transition probabilities and hindrance factors to be determined.

  14. High-pressure/high-temperature synthesis and characterization of the first palladium or platinum containing lithium transition-metal sulfides Li2M3S4 (M=Pd, Pt)

    Science.gov (United States)

    Heymann, Gunter; Niehaus, Oliver; Krüger, Hannes; Selter, Philipp; Brunklaus, Gunther; Pöttgen, Rainer

    2016-10-01

    The new lithium transition-metal sulfides Li2M3S4 (M=Pd, Pt) were obtained via multianvil high-pressure/high-temperature syntheses at 8 GPa and 1150 °C starting from a stoichiometric mixture of lithium nitride, sulfur, and palladium or platinum. Single crystal structure analyses indicated the space group P21/c (no. 14) with the following lattice parameters and refinement results: a=492.9(1), b=1005.9(2), c=614.9(2) pm, β=110.9 (1)°, R1=0.0165, wR2=0.0308 (all data) for Li2Pd3S4 and a=498.2(1), b=1005.5(2), c=613.0(2) pm, β=110.8(1)°, R1=0.0215, wR2=0.0450 (all data) for Li2Pt3S4. The crystal structures are built up from two distinct Pd/Pt sites, one of which is a special position (0,0,0), two sulfur sites, and one lithium site. The atoms Pd2/Pt2 form isolated square planar PdS4/PtS4 units, whereas the Pd1/Pt1 atoms form pairs of square planar PdS4/PtS4 units, which are connected via a common edge. These two structural motives built up a three-dimensional network structure by linking through common corners. The lithium atoms are positioned inside of the so formed channels. Li2M3S4 (M=Pd, Pt) are isostructural to the minerals jaguéite, Cu2Pd3Se4 and chrisstanleyite, Ag2Pd3Se4, which are up to now the only representatives of this structure type. Both compounds were studied with respect to their magnetic properties and can be classified as Pauli paramagnetic or diamagnetic. Regarding the possibility of lithium mobility inside the channels, of the structure, solid state 7Li NMR and high-temperature single crystal investigations revealed localization of the lithium atoms on their crystallographic sites.

  15. RING E3 ligases

    DEFF Research Database (Denmark)

    Cho, Seok Keun; Ryu, Moon Young; Kim, Jong Hum

    2017-01-01

    response pathways of plants through various molecular and genetic studies. In particular, it was recently discovered that ubiquitin proteasome system (UPS), a regulatory mechanism for protein turn over, is greatly involved in the stress responsive pathways. In the UPS, many E3 ligases play key roles...... in recognizing and tethering poly-ubiquitins on target proteins for subsequent degradation by the 26S proteasome. Here we discuss the roles of RING ligases that have been defined in related to abiotic stress responses in plants....

  16. E3 Portfolio Review Database

    Data.gov (United States)

    US Agency for International Development — The E3 Portfolio Review Database houses operational and performance data for all activities that the Bureau funds and/or manages. Activity-level data is collected by...

  17. E3 Sustainable Manufacturing Curriculum

    Science.gov (United States)

    A short E3 course containing three modules on Environmental Sustainability; Lean Manufacturing and Pollution Prevention; and Energy and Carbon. Each module includes slides, a facilitator's guide with handouts, activities, quizzes, and facilitator's notes.

  18. Significance of M2 and E3 transitions for $4p^54d^{N+1}$ and $4p^64d^{N-1}4f$ configuration metastable level lifetimes

    CERN Document Server

    Karpuškienė, R; Kisielius, R

    2015-01-01

    Magnetic quadrupole and electric octupole transitions from the configurations $4p^54d^{N+1}$ and $4p^64d^{N-1}4f$ were calculated along with magnetic dipole, electric dipole and electric quadrupole radiative transitions in quasirelativistic Hartree-Fock approximation. Their significance in determining the metastable level radiative lifetimes was investigated along several isoelectronic sequences for the ions from $Z=50$ to $Z=92$. Strontium-like ions, zirconium-like ions, molybdenum-like ions and rhodium-like ions were studied comprehensively. Remaining isoelectronic sequences with the ground configuration $4d^{N}$ ($N=1,3,5,7,8,10$) were also reviewed albeit in less detail. A systematic trends of determined total radiative lifetimes were studied. The importance of magnetic quadrupole and electric octupole transitions from metastable levels of ions from these isoelectronic sequences was investigated and discussed. Inclusion of such transitions of higher multipole order can change theoretical radiative lifetim...

  19. The Luminosity Function of M3

    CERN Document Server

    Rood, R T; Paltrinieri, B; Ferraro, F R; Pecci, F F; Dorman, B; Chieffi, A; Straniero, O; Buonanno, R

    1999-01-01

    We present a high precision, large sample luminosity function (LF) for the Galactic globular cluster M3. With a combination of ground based and Hubble Space Telescope data we cover the entire radial extent of the cluster. The observed LF is well fit by canonical standard stellar models from the red giant branch (RGB) tip to below the main sequence turnoff point. Specifically, neither the RGB LF-bump nor subgiant branch LF indicate any breakdown in the standard models. On the main sequence we find evidence for a flat initial mass function and for mass segregation due to the dynamical evolution of the cluster.

  20. Transport Coefficients of Black M3-Branes

    CERN Document Server

    Dhuria, Mansi

    2014-01-01

    The local uplift via local SYZ mirror symmetry of (M)N (fractional)D3-branes, and wrapped N_f flavor D7-branes in the presence of a black-hole resulting in a non-Kaehler resolved warped deformed conifold (NKRWDC) in [1], was carried out in [2] and resulted in black M3-branes; the deviation from the ISD condition of G_3 proportional to the square of the resolution parameter, in the limits of [1] and MQGP limit of [2], imposed on (g_s,M,N), can be ignored [3]. The uplift, if valid globally, asymptotes to M5-branes wrapping a two-cycle (homologously an (large) integer sum of two-spheres) in AdS_5xM_6. Interestingly, in the limits of [1]/ [2], assuming the deformation > resolution, by estimating the five SU(3) structure torsion (\\tau) classes W_{1,2,3,4,5} we show that \\tau\\in W_5 in the large-r limit, implying the NKRWDC reduces to a warped Kaehler deformed conifold. Further, the local T^3 of [2] in the large-r limit and the limits of [1] and the `MQGP' limit of [2], satisfies the same conditions as the maximal ...

  1. Formando planetas habitables en estrellas M3

    Science.gov (United States)

    Dugaro, A.; de Elía, G. C.; Brunini, A.

    2016-08-01

    Studies of stellar evolution allow us to infer that the low-mass stars are the most abundant in the galaxy. In the present investigation, we analyze the formation of planetary systems without gas giants around M3-type stars, which have a mass of 0.29 M. In particular, we are interested in studying the terrestrial-like planet formation processes and water delivery in the Habitable Zone (HZ) of those systems. To develop this investigation, we assume massive protoplanetary disks for such stars, which have 5 of the mass of the central star. Once defined the working disk, we use a semi-analytical model, which is able to determine the distribution of planetary embryos and planetesimals at the end of the gaseous phase. Then, these distributions are used as initial conditions for running -body simulations. Due to the stochastic nature of the accretion process, we carry out ten -body simulations in order to analyze the evolution of the planetary systems after the gas dissipation. Our results suggest the efficient formation of terrestrial-like planets in the HZ with a wide range of masses and water contents. The planets formed in the HZ of the system have masses between 0.07 M and 0.15 M and final water contents between 5.4 and 29 by mass. The physical properties of the terrestrial-like planets formed in the HZ of our simulations suggest that they should be able to retain a permanent and substantial atmosphere.

  2. New BMW M3 sports coupe; Neues Sportcoupe M3 von BMW

    Energy Technology Data Exchange (ETDEWEB)

    Biermann, A.; Friedmann, S.; Gehrig, H.; Huebner, W.; Weidhase, U. [Bayerische Motoren Werke AG (BMW), Muenchen (Germany); Koplenig, W. [BMW, Muenchen (Germany). Fachbereich Karosserie

    2000-10-01

    Since 1972 Motorsport (which has been known as BMW M since 1994) has been manufacturing automobiles of exceptionally sporting character on the basis of suitable series-production cars. With its new M3, BMW M continues this tradition. It is a sports coupe based on the latest BMW 3 Series model line. Its sports design embodies the essentials of BMW M's performance philosophy. Both visible and invisible 'highlights' such as the new high-speed driveline rating elevate its longitudinal and lateral driving dynamics to the level of a racing car. We have also succeeded in maintaining the basic car's unlimited suitability for everyday use. The new M3 is therefore a fully-fledged sports car without the typical disadvantages of this type of vehicle. (orig.) [German] Bereits seit 1972 entstehen bei BMW Motorsport (seit 1994 BMW M) auf der Basis von Serienfahrzeugen Automobile mit aussergewoehnlichen sportlichen Eigenschaften. Mit dem neuen M3, abgeleitet von der aktuellen BMW Dreier-Reihe, setzt BMW M diese Tradition fort. Das Sportcoupe erschliesst ueber die weiterentwickelte Hochdrehzahlauslegung eine Fahrdynamik in Laengs- und Querrichtung auf dem Niveau eines Rennsportwagens. Gleichzeitig ist es gelungen, die uneingeschraenkte Alltagstauglichkeit des Basis-Fahrzeugs zu erhalten. Der neue M3 ist somit ein vollwertiger Sportwagen, vermeidet aber dessen typische Nachteile. (orig.)

  3. On Generalized Euler Spirals in E^3

    OpenAIRE

    Saracoglu, Semra

    2012-01-01

    The Cornu spirals on plane are the curves whose curvatures are linear. Generalized planar cornu spirals and Euler spirals in E^3, the curves whose curvatures are linear are defined in [1,5]. In this study, these curves are presented as the ratio of two rational linear functions. Also here, generalized Euler spirals in E^3 has been defined and given their some various characterizations. The approach I used in this paper is useful in understanding the role of Euler spirals in E^3 in differentia...

  4. E3: Extreme Energy Event monitoring

    CERN Document Server

    CERN. Geneva

    2015-01-01

    World peace through CERN technology: Use of explosives especially in urban areas is the defining phenomenon of the last and current century. E3 aims to reduce such excesses of violence by collecting scientific hard evidence.

  5. Freezing E3-brane instantons with fluxes

    Energy Technology Data Exchange (ETDEWEB)

    Bianchi, M.; Martucci, L. [Dipartimento di Fisica, Universita di Roma Tor Vergata (Italy); I.N.F.N., Sezione di Roma Tor Vergata (Italy); Collinucci, A. [Theory Group, Physics Department, CERN, Geneva (Switzerland); Physique Theorique et Mathematique Universite Libre de Bruxelles (Belgium)

    2012-07-15

    E3-instantons that generate non-perturbative superpotentials in IIB N = 1 compactifications have a much more frequent occurrence than currently believed. Worldvolume fluxes will typically lift the E3-brane geometric moduli and their fermionic superpartners, leaving only the two required universal fermionic zero-modes. We consistently incorporate SL(2,Z) monodromies and world-volume fluxes in the effective theory of the E3-brane fermions and study the resulting zero modes spectrum, highlighting the relation between F-theory and perturbative IIB results. This leads us to a IIB derivation of the index for generation of superpotential terms, which reproduces and generalizes available results. Furthermore, we show how E3 worldvolume fluxes can be explicitly constructed in a one-modulus compactification, such that the instanton has exactly two fermonic zero-modes. This construction is readily applicable to numerous scenarios. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  6. E3 Travel & Mission Support System

    Data.gov (United States)

    US Agency for International Development — ETRAMS is a travel data collection system developed by the CKM team in E3 that collects information on both the basic details of an employee's trips (destination,...

  7. E3: Economy, Energy and Environment

    Science.gov (United States)

    E3 is a technical assistance framework helping communities, manufacturers, and manufacturing supply chains adapt and thrive in today's green economy. Find information on pollution prevention, sustainable business practices, and energy efficiency.

  8. HECT E3s and human disease

    Directory of Open Access Journals (Sweden)

    Staub Olivier

    2007-11-01

    Full Text Available Abstract In a simplified view, members of the HECT E3 family have a modular structure consisting of the C-terminal HECT domain, which is catalytically involved in the attachment of ubiquitin to substrate proteins, and N-terminal extensions of variable length and sequence that mediate the substrate specificity of the respective HECT E3. Although the physiologically relevant substrates of most HECT E3s have remained elusive, it is becoming increasingly clear that HECT E3s play an important role in sporadic and hereditary human diseases including cancer, cardiovascular (Liddle's syndrome and neurological (Angelman syndrome disorders, and/or in disease-relevant processes including bone homeostasis, immune response and retroviral budding. Thus, molecular approaches to target the activity of distinct HECT E3s, regulators thereof, and/or of HECT E3 substrates could prove valuable in the treatment of the respective diseases. Publication history: Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com.

  9. Genomic standards consortium workshop: metagenomics, metadata and metaanalysis (M3).

    Science.gov (United States)

    Sterk, Peter; Hirschman, Lynette; Field, Dawn; Wooley, John

    2010-01-01

    The M3 workshop has, as its primary focus, the rapidly growing area of metagenomics, including the metadata standards and the meta-analysis approaches needed to organize, process and interpret metagenomics data. The PSB Workshop builds on the first M3 meeting, a Special Interest Group (SIG) meeting at ISMB 2009, organized by the Genomics Standards Consortium.

  10. Scaling laws in (e,3e) processes

    Energy Technology Data Exchange (ETDEWEB)

    Gasaneo, G; Rodriguez, K V [Departamento de Fisica - Universidad Nacional del Sur and CONICET, 8000 BahIa Blanca, Buenos Aires (Argentina); Ancarani, L U; Cappello, C Dal [Laboratoire de Physique Moleculaire et des Collisions, Universite Paul Verlaine - Metz, 57078 Metz (France); Charpentier, I [Laboratoire de Physique et Mecanique des Materiaux, UMR CNRS 7554, Ile du Saulcy, 57045 Metz (France)

    2009-11-01

    We study the double ionization of helium-like ions by impact of electrons with high incident energy. Within the isoelectronic sequence, an approximate scaling law for (e,3e) differential cross sections is proposed and confirmed by calculations. The latter are performed using 14-parameters Hylleraas-like wave functions to represent the bound electrons in the initial channel, plane waves for the fast incoming and scattered electrons, and a continuum distorted wave approach for the two ejected electrons in the final channel.

  11. M3: Matrix Multiplication on MapReduce

    DEFF Research Database (Denmark)

    Silvestri, Francesco; Ceccarello, Matteo

    2015-01-01

    M3 is an Hadoop library for performing dense and sparse matrix multiplication in MapReduce. The library is based on multi-round algorithms exploiting the 3D decomposition of the problem.......M3 is an Hadoop library for performing dense and sparse matrix multiplication in MapReduce. The library is based on multi-round algorithms exploiting the 3D decomposition of the problem....

  12. M3D project for simulation studies of plasmas

    Energy Technology Data Exchange (ETDEWEB)

    Park, W.; Belova, E.V.; Fu, G.Y. [Princeton Univ., NJ (United States). Plasma Physics Lab.; Strauss, H.R. [New York Univ., NY (United States); Sugiyama, L.E. [Massachusetts Inst. of Tech., Cambridge, MA (United States)

    1998-12-31

    The M3D (Multi-level 3D) project carries out simulation studies of plasmas of various regimes using multi-levels of physics, geometry, and mesh schemes in one code package. This paper and papers by Strauss, Sugiyama, and Belova in this workshop describe the project, and present examples of current applications. The currently available physics models of the M3D project are MHD, two-fluids, gyrokinetic hot particle/MHD hybrid, and gyrokinetic particle ion/two-fluid hybrid models. The code can be run with both structured and unstructured meshes.

  13. Assembly language programming ARM Cortex-M3

    CERN Document Server

    Mahout, Vincent

    2013-01-01

    ARM designs the cores of microcontrollers which equip most "embedded systems" based on 32-bit processors. Cortex M3 is one of these designs, recently developed by ARM with microcontroller applications in mind. To conceive a particularly optimized piece of software (as is often the case in the world of embedded systems) it is often necessary to know how to program in an assembly language.This book explains the basics of programming in an assembly language, while being based on the architecture of Cortex M3 in detail and developing many examples.It is written for people who have never pr

  14. Optimizing Concurrent M3-Transactions: A Fuzzy Constraint Satisfaction Approach

    Directory of Open Access Journals (Sweden)

    Peng LI

    2004-10-01

    Full Text Available Due to the high connectivity and great convenience, many E-commerce application systems have a high transaction volume. Consequently, the system state changes rapidly and it is likely that customers issue transactions based on out-of-date state information. Thus, the potential of transaction abortion increases greatly. To address this problem, we proposed an M3-transaction model. An M3-transaction is a generalized transaction where users can issue their preferences in a request by specifying multiple criteria and optional data resources simultaneously within one transaction. In this paper, we introduce the transaction grouping and group evaluation techniques. We consider evaluating a group of M3-transactions arrived to the system within a short duration together. The system makes optimal decisions in allocating data to transactions to achieve better customer satisfaction and lower transaction failure rate. We apply the fuzzy constraint satisfaction approach for decision-making. We also conduct experimental studies to evaluate the performance of our approach. The results show that the M3-transaction with group evaluation is more resilient to failure and yields much better performance than the traditional transaction model.

  15. Optimizing Concurrent M3-Transactions: A Fuzzy Constraint Satisfaction Approach

    Directory of Open Access Journals (Sweden)

    Peng LI

    2004-10-01

    Full Text Available Due to the high connectivity and great convenience, many E-commerce application systems have a high transaction volume. Consequently, the system state changes rapidly and it is likely that customers issue transactions based on out-of-date state information. Thus, the potential of transaction abortion increases greatly. To address this problem, we proposed an M3-transaction model. An M3-transaction is a generalized transaction where users can issue their preferences in a request by specifying multiple criteria and optional data resources simultaneously within one transaction. In this paper, we introduce the transaction grouping and group evaluation techniques. We consider evaluating a group of M3-transactions arrived to the system within a short duration together. The system makes optimal decisions in allocating data to transactions to achieve better customer satisfaction and lower transaction failure rate. We apply the fuzzy constraint satisfaction approach for decision-making. We also conduct experimental studies to evaluate the performance of our approach. The results show that the M3-transaction with group evaluation is more resilient to failure and yields much better performance than the traditional transaction model.

  16. M3: An Open Model for Measuring Code Artifacts

    NARCIS (Netherlands)

    Izmaylova, A.; Klint, P.; Shahi, A.; Vinju, J.J.

    2013-01-01

    In the context of the EU FP7 project ``OSSMETER'' we are developing an infra-structure for measuring source code. The goal of OSSMETER is to obtain insight in the quality of open-source projects from all possible perspectives, including product, process and community. This is a "white paper" on M3,

  17. Low-lying electronic states of M(3)O(9)(-) and M(3)O(9)(2-) (M = Mo, W).

    Science.gov (United States)

    Li, Shenggang; Dixon, David A

    2007-11-01

    Multiple low-lying electronic states of M(3)O(9)(-) and M(3)O(9)(2-) (M = Mo, W) arise from the occupation of the near-degenerate low-lying virtual orbitals in the neutral clusters. We used density functional theory (DFT) and coupled cluster theory (CCSD(T)) with correlation consistent basis sets to study the structures and energetics of the electronic states of these anions. The adiabatic and vertical electron detachment energies (ADEs and VDEs) of the anionic clusters were calculated with 27 exchange-correlation functionals including one local spin density approximation functional, 13 generalized gradient approximation (GGA) functionals, and 13 hybrid GGA functionals, as well as the CCSD(T) method. For M(3)O(9)(-), CCSD(T) and nearly all of the DFT exchange-correlation functionals studied predict the (2)A(1) state arising from the Jahn-Teller distortion due to singly occupying the degenerate e' orbital to be lower in energy than the (2)A(1)' state arising from singly occupying the nondegenerate a(1)' orbital. For W(3)O(9)(-), the (2)A(1) state was predicted to have essentially the same energy as the (2)A(1)' state at the CCSD(T) level with core-valence correlation corrections included and to be higher in energy or essentially isoenergetic with most DFT methods. The calculated VDEs from the CCSD(T) method are in reasonable agreement with the experimental values for both electronic states if estimates for the corrections due to basis set incompleteness are included. For M(3)O(9)(2-), the singlet state arising from doubly occupying the nondegenerate a(1)' orbital was predicted to be the most stable state for both M = Mo and W. However, whereas M(3)O(9)(2-) was predicted to be less stable than M(3)O(9)(-), W(3)O(9)(2-) was predicted to be more stable than W(3)O(9)(-).

  18. M3与M5的MICM鉴别

    Institute of Scientific and Technical Information of China (English)

    索翠平; 李寅; 赵霞

    2003-01-01

    @@ 急性早幼粒细胞自血病(M3型,acute promyelocytic leukemia,APL)和急性单核细胞白血病(M5型,acute monocytic leukemia,AMOL)同属于急性非淋巴细胞白血病.二者在临床与形态上均有相似之处,特别是细颗粒型急性早幼粒细胞白血病(M3b)在形态上更易被误诊为急性单核细胞白血病.但二者的治疗与预后却有很大的区别.在此,结合MICM分型原则对二者加以鉴别,以免造成误诊,导致不应有的后果.

  19. Structure and dynamics of the M3 muscarinic acetylcholine receptor

    Energy Technology Data Exchange (ETDEWEB)

    Kruse, Andrew C.; Hu, Jianxin; Pan, Albert C.; Arlow, Daniel H.; Rosenbaum, Daniel M.; Rosemond, Erica; Green, Hillary F.; Liu, Tong; Chae, Pil Seok; Dror, Ron O.; Shaw, David E.; Weis, William I.; Wess, Jürgen; Kobilka, Brian K. (Stanford); (NIH); (D.E. Shaw); (Hanyang); (UTSMC)

    2012-03-01

    Acetylcholine, the first neurotransmitter to be identified, exerts many of its physiological actions via activation of a family of G-protein-coupled receptors (GPCRs) known as muscarinic acetylcholine receptors (mAChRs). Although the five mAChR subtypes (M1-M5) share a high degree of sequence homology, they show pronounced differences in G-protein coupling preference and the physiological responses they mediate. Unfortunately, despite decades of effort, no therapeutic agents endowed with clear mAChR subtype selectivity have been developed to exploit these differences. We describe here the structure of the G{sub q/11}-coupled M3 mAChR ('M3 receptor', from rat) bound to the bronchodilator drug tiotropium and identify the binding mode for this clinically important drug. This structure, together with that of the G{sub i/o}-coupled M2 receptor, offers possibilities for the design of mAChR subtype-selective ligands. Importantly, the M3 receptor structure allows a structural comparison between two members of a mammalian GPCR subfamily displaying different G-protein coupling selectivities. Furthermore, molecular dynamics simulations suggest that tiotropium binds transiently to an allosteric site en route to the binding pocket of both receptors. These simulations offer a structural view of an allosteric binding mode for an orthosteric GPCR ligand and provide additional opportunities for the design of ligands with different affinities or binding kinetics for different mAChR subtypes. Our findings not only offer insights into the structure and function of one of the most important GPCR families, but may also facilitate the design of improved therapeutics targeting these critical receptors.

  20. The boundary RSOS \\mathcal{M}(3,5) model

    CERN Document Server

    Deeb, Omar El

    2015-01-01

    We consider the critical non-unitary minimal model {\\cal M}(3,5) with integrable boundaries. We analyze the patterns of zeros of the eigenvalues of the transfer matrix and then determine the spectrum of the critical theory through the Thermodynamic Bethe Ansatz (TBA) equations. We derive these equations for all excitations by solving, the TBA functional equation satisfied by the transfer matrices of the associated A_{4} RSOS lattice model of Forrester and Baxter in Regime III, then determine their corresponding energies. The excitations are classified in terms of (m,n) systems.

  1. 3000m3/h cutter-suction dredge

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    @@ In October 2004, the Fumin 9 3000 m3/h cutter-suction dredge co-designed by the Dutch IHC and Guangzhou Wenchong Shipyard went through a dock usability test and a 25 meter clean water test. The dredge is the largest of its kind in China, and the most advanced and most efficient cutter-suction dredge in the world. The IHC was responsible for the design of the ship till its working design was taken over by Guangzhou Wenchong Shipyard, the builder of the dredge, who had started its construction on October 23, 2003.

  2. Hydraulic supports for polishing TMT M3MP

    Science.gov (United States)

    Hu, Haifei; Qi, Erhui; Cole, Glen; Hu, Haixiang; Luo, Xiao; Ford, Virginia; Zhang, Xuejun

    2016-10-01

    For polishing the ultra-thin TMT M3MP, a polishing support system with 18 hydraulic supports (HS) is introduced. This work focuses on the designing and testing of these HSs. Firstly the design concept of HS system is discussed; then mechanical implementation of the HS structure is carried out, with special consideration of fluid cycling, work pressurization and the weight component. Afterward the piping installation and the de-gas process for the working fluid are implemented. Pressurization and stiffness are well checked before system integration for the single HS unit. Finally the support system is integrated for the polishing process.

  3. Measurement of the Radiative $K_{e3}$ Branching Ratio

    CERN Document Server

    Lai, A; Bevan, A; Dosanjh, R S; Gershon, T J; Hay, B; Kalmus, George Ernest; Lazzeroni, C; Munday, D J; Olaiya, E; Parker, M A; White, T O; Wotton, S A; Barr, G; Bocquet,; Ceccucci, A; Çuhadar-Dönszelmann, T; Cundy, Donald C; D'Agostini, G; Doble, Niels T; Falaleev, V; Gatignon, L; Gonidec, A; Gorini, B; Govi, G; Grafström, P; Kubischta, Werner; Mikulec, I; Lacourt, A; Norton, A; Palestini, S; Panzer-Steindel, B; Taureg, H; Velasco, M; Wahl, H; Cheshkov, C; Khristov, P Z; Kekelidze, Vladimir D; Litov, L; Madigozhin, D T; Molokanova, N A; Potrebenikov, Yu K; Stoynev, S; Zinchenko, A I; Knowles, I; Martin, V; Sacco, R; Walker, A; Contalbrigo, M; Dalpiaz, Pietro; Duclos, J; Frabetti, P L; Gianoli, A; Martini, M; Petrucci, F; Savrié, M; Bizzeti, A; Calvetti, M; Collazuol, G; Graziani, G; Iacopini, E; Lenti, M; Martelli, F; Veltri, M; Becker, H G; Eppard, K; Eppard, M; Fox, H; Kalter, A; Kleinknecht, K; Koch, U; Köpke, L; Lopes da Silva, P; Marouelli, P; Pellmann, I A; Peters, A; Renk, B; Schmidt, S A; Schönharting, V; Schué, Yu; Wanke, R; Winhart, A; Wittgen, M; Chollet, J C; Fayard, L; Iconomidou-Fayard, L; Ocariz, J; Unal, G; Wingerter-Seez, I; Anzivino, Giuseppina; Cenci, P; Imbergamo, E; Lubrano, P; Mestvirishvili, A; Nappi, A; Pepé, M; Piccini, M; Bertanza, L; Carosi, R; Casali, R; Cerri, C; Cirilli, M; Costantini, F; Fantechi, R; Giudici, Sergio; Mannelli, I; Pierazzini, G M; Sozzi, M; Chèze, J B; Cogan, J; De Beer, M; Debu, P; Formica, A; Granier de Cassagnac, R; Mazzucato, E; Peyaud, B; Turlay, René; Vallage, B; Holder, M; Maier, A; Ziolkowski, M; Arcidiacono, R; Biino, C; Cartiglia, N; Marchetto, F; Menichetti, E; Pastrone, N; Nassalski, J P; Rondio, Ewa; Szleper, M; Wislicki, W; Wronka, S; Dibon, Heinz; Fischer, G; Jeitler, Manfred; Markytan, Manfred; Neuhofer, G; Pernicka, M; Taurok, A; Widhalm, L

    2005-01-01

    We present a measurement of the relative branching ratio of the decay {K}^0 -> pi+-e-+ nu gamma ({K}_e3 gamma) with respect to {K}^0 -> pi+- e-+ nu (gamma) ({k}_e3 + k}_e3 gamma) decay. The result is based on observation of 19 000 {K}_e3 gamma and 5.6 . {10}^6 {K}_e3 decays. The value of branching ratio is Br({K}^0 _e3 gamma{E}^*_gamma > 30 MeV, {theta}^*_e gamma > 20 deg) / Br({K}^0_e3 = (0.964 +- {0.008}^+0.011_0.009)%. This result agrees with the theoretical predictions but is at variance with a recently published result.

  4. 针对MCU应用的Cortex-M3

    Institute of Scientific and Technical Information of China (English)

    费浙平

    2005-01-01

    传统上MCU领域一直由4/8位架构占据了主导地位,部分采用16位架构,而32位才刚起步,在多数人印象中它还是一种奢侈的高端应用。但近几年这种情况已有了很大变化,越来越多的设计采用32位MCU架构,而ARMCotex—M3的面世也为32位MCU应用带来更多可能。

  5. E3: Economy - Energy - Environment; Supporting Manufacturing Leadership through Sustainability

    Science.gov (United States)

    The E3 initiative is designed to help you thrive in a new business era focused on sustainability and, working together, to promote sustainable manufacturing and economic growth throughout the United States. Within the E3 framework, we can: - Drive Innovation - Increase Manufacturing Productivity - Boost Local Economies - Reduce Environmental Impacts - Foster Development - Conserve Energy and Resources This website provides information and tools for E3, including fact sheets, contacts, and calculators.

  6. Magnetic circular dichroism of porphyrin lanthanide M3+ complexes.

    Science.gov (United States)

    Andrushchenko, Valery; Padula, Daniele; Zhivotova, Elena; Yamamoto, Shigeki; Bouř, Petr

    2014-10-01

    Lanthanide complexes exhibit interesting spectroscopic properties yielding many applications as imaging probes, natural chirality amplifiers, and therapeutic agents. However, many properties are not fully understood yet. Therefore, we applied magnetic circular dichroism (MCD) spectroscopy, which provides enhanced information about the underlying electronic structure to a series of lanthanide compounds. The metals in the M(3+) state included Y, La, Eu, Tb, Dy, Ho, Er, Tm, Yb, and Lu; the spectra were collected for selected tetraphenylporphin (TPP) and octaethylporphin (OEP) complexes in chloroform. While the MCD and UV-VIS absorption spectra were dominated by the porphyrin signal, metal binding significantly modulated them. MCD spectroscopy was found to be better suited to discriminate between various species than absorption spectroscopy alone. The main features and trends in the lanthanide series observed in MCD and absorption spectra of the complexes could be interpreted at the Density Functional Theory (DFT) level, with effective core potentials on metal nuclei. The sum over state (SOS) method was used for simulation of the MCD intensities. The combination of the spectroscopy and quantum-chemical computations is important for understanding the interactions of the metals with the organic compounds.

  7. Hemopoietic tissue in newts flown aboard Foton M3

    Science.gov (United States)

    Domaratskaya, Elena I.; Almeida, Eduardo; Butorina, Nina N.; Nikonova, Tatyana M.; Grigoryan, Eleonora N.; Poplinskaya, Valentina A.; Souza, Kenneth; Skidmore, Mike

    The effect of 12-day spaceflight aboard the Foton-M3 biosatellite on the hematopoietic tissue of P. waltl newts was studied. These animals used at the same time in regeneration experiments after lens and tail tip amputation. In flight and synchronous groups there were performed video recording, temperature and radiation monitoring and continuous contact (via skin) with thymidine analog BrdU. We took differential blood counts and assessed histologically the liver in the flight (F), basal (BC) and synchronous (SC)control groups of animals. In the peripheral blood, we identified neutrophils, eosinophils, basophils, lymphocytes, and monocytes. Lymphocytes (L) and neutrophils (N) prevailed, accounting for about 60 and 20% of white blood cells, respectively. The spaceflight had no apparent effect on the differential blood count in the F group: neither the L and N contents nor the maturing to mature N - ratio differed from those in the control groups. No significant differences between F, SC and BC groups were observed with respect to the structure of hematopoietic areas and the liver morphology. As in Foton-M2, BrdU labeled cells revealed in blood as well as in the hemopoietic areas of the liver. However, in previous experiments performed at satellites Bion-10 and Foton-M2 the changes in peripheral blood contents were registered in operated F newts, and we supposed it could be the result of additive effects of spaceflight factors and stimulation of reparative potency and stress due to surgical operation. Possibly, the temperature conditions also may provide some influence on blood cell content of newts that belong to poikilothermic animals. Thus, in present experiment F and SC groups were reared in the same temperature regims, whereas it was nearly 3o C differences between SC and F groups exposed on Foton-M2. At the same time as it was found in experiments on Bion-11 and Foton-M2 spaceflight factors did not affect on differential blood counts of intact non

  8. Molecular insights into RBR E3 ligase ubiquitin transfer mechanisms.

    Science.gov (United States)

    Dove, Katja K; Stieglitz, Benjamin; Duncan, Emily D; Rittinger, Katrin; Klevit, Rachel E

    2016-08-01

    RING-in-between-RING (RBR) ubiquitin (Ub) ligases are a distinct class of E3s, defined by a RING1 domain that binds E2 Ub-conjugating enzyme and a RING2 domain that contains an active site cysteine similar to HECT-type E3s. Proposed to function as RING/HECT hybrids, details regarding the Ub transfer mechanism used by RBRs have yet to be defined. When paired with RING-type E3s, E2s perform the final step of Ub ligation to a substrate. In contrast, when paired with RBR E3s, E2s must transfer Ub onto the E3 to generate a E3~Ub intermediate. We show that RBRs utilize two strategies to ensure transfer of Ub from the E2 onto the E3 active site. First, RING1 domains of HHARI and RNF144 promote open E2~Ubs. Second, we identify a Ub-binding site on HHARI RING2 important for its recruitment to RING1-bound E2~Ub. Mutations that ablate Ub binding to HHARI RING2 also decrease RBR ligase activity, consistent with RING2 recruitment being a critical step for the RBR Ub transfer mechanism. Finally, we demonstrate that the mechanism defined here is utilized by a variety of RBRs.

  9. E3: Economy - Energy - Environment; Supporting Manufacturing Leadership through Sustainability

    Data.gov (United States)

    U.S. Environmental Protection Agency — The E3 initiative is designed to help you thrive in a new business era focused on sustainability and, working together, to promote sustainable manufacturing and...

  10. About E3: Economy – Energy – Environment

    Science.gov (United States)

    This page explains EPA's E3 – Economy, Energy, and Environment – program, a federal and local technical assistance initiative, helping manufacturers adapt and thrive with a focus on sustainability.

  11. E3 Ubiquitin Ligases Neurobiological Mechanisms: Development to Degeneration

    Directory of Open Access Journals (Sweden)

    Arun Upadhyay

    2017-05-01

    Full Text Available Cells regularly synthesize new proteins to replace old or damaged proteins. Deposition of various aberrant proteins in specific brain regions leads to neurodegeneration and aging. The cellular protein quality control system develop various defense mechanisms against the accumulation of misfolded and aggregated proteins. The mechanisms underlying the selective recognition of specific crucial protein or misfolded proteins are majorly governed by quality control E3 ubiquitin ligases mediated through ubiquitin-proteasome system. Few known E3 ubiquitin ligases have shown prominent neurodevelopmental functions, but their interactions with different developmental proteins play critical roles in neurodevelopmental disorders. Several questions are yet to be understood properly. How E3 ubiquitin ligases determine the specificity and regulate degradation of a particular substrate involved in neuronal proliferation and differentiation is certainly the one, which needs detailed investigations. Another important question is how neurodevelopmental E3 ubiquitin ligases specifically differentiate between their versatile range of substrates and timing of their functional modulations during different phases of development. The premise of this article is to understand how few E3 ubiquitin ligases sense major molecular events, which are crucial for human brain development from its early embryonic stages to throughout adolescence period. A better understanding of these few E3 ubiquitin ligases and their interactions with other potential proteins will provide invaluable insight into disease mechanisms to approach toward therapeutic interventions.

  12. Transport coefficients of black MQGP M3-branes

    Energy Technology Data Exchange (ETDEWEB)

    Dhuria, Mansi [Physical Research Laboratory, Theoretical Physics Division, Ahmedabad (India); Misra, Aalok [Indian Institute of Technology, Department of Physics, Roorkee, Uttaranchal (India)

    2015-01-01

    The Strominger-Yau-Zaslow (SYZ) mirror, in the 'delocalised limit' of Becker et al. (Nucl Phys B 702:207, 2004), of N D3-branes, M fractional D3-branes and N{sub f} flavour D7-branes wrapping a non-compact four-cycle in the presence of a black hole (BH) resulting in a non-Kahler resolved warped deformed conifold (NKRWDC) in Mia et al. (Nucl Phys B 839:187, 2010), was carried out in Dhuria and Misra (JHEP 1311:001, 2013) and resulted in black M3- branes. There are two parts in our paper. In the first we show that in the 'MQGP' limit discussed in Dhuria and Misra (JHEP 1311:001, 2013) a finite g{sub s} (and hence expected to be more relevant to QGP), finite g{sub s}M, N{sub f}, g{sub s}{sup 2}MN{sub f} and very large g{sub s}N, and very small (g,M{sup 2})/(N), we have the following. (i) The uplift, if valid globally (like Dasgupta et al., Nucl Phys B 755:21, 2006) for fractional D3 branes in conifolds, asymptotically goes to M5-branes wrapping a two-cycle (homologously a (large) integer sum of two-spheres) in AdS{sub 5} x M{sub 6}. (ii) Assuming the deformation parameter to be larger than the resolution parameter, by estimating the five SU(3) structure torsion (τ) classes W{sub 1,2,3,4,5} we verify that τ element of W{sub 5} in the large-r limit, implying the NKRWDC reduces to a warped Kahler deformed conifold. (iii) The local T{sup 3} of Dhuria and Misra (JHEP 1311:001, 2013) in the large-r limit satisfies the same conditions as the maximal T{sup 2}-invariant special Lagrangian three-cycle of T*S{sup 3} of Ionel and Min-OO (J Math 52(3), 2008), partly justifying use of SYZ-mirror symmetry in the ''delocalised limit'' of Becker et al. (Nucl Phys B 702:207, 2004) in Dhuria and Misra (JHEP 1311:001, 2013). In the second part of the paper, by either integrating out the angular coordinates of the non-compact four-cycle which a D7-brane wraps around, using the Ouyang embedding, in the DBI action of a D7-brane evaluated at infinite

  13. Effects of Modulating M3 Muscarinic Receptor Activity on Azoxymethane-Induced Liver Injury in Mice

    OpenAIRE

    2013-01-01

    Previously, we reported that azoxymethane (AOM)-induced liver injury is robustly exacerbated in M3 muscarinic receptor (M3R)-deficient mice. We used the same mouse model to test the hypothesis that selective pharmacological modulation of M3R activity regulates the liver injury response. Initial experiments confirmed that giving a selective M3R antagonist, darifenacin, to AOM-treated mice mimicked M3R gene ablation. Compared to vehicle controls, mice treated with the M3R antagonist had reduced...

  14. Structure of a RING E3 ligase and ubiquitin-loaded E2 primed for catalysis

    Science.gov (United States)

    Plechanovová, Anna; Jaffray, Ellis; Tatham, Michael H.; Naismith, James H.; Hay, Ronald T.

    2012-01-01

    SUMMARY Ubiquitin modification is mediated by a large family of specificity determining ubiquitin E3 ligases. To facilitate ubiquitin transfer, RING E3 ligases bind both substrate and a ubiquitin E2 conjugating enzyme linked to ubiquitin via a thioester bond, but the mechanism of transfer has remained elusive. Here we report the crystal structure of the dimeric RING of RNF4 in complex with E2 (UbcH5a) linked by an isopeptide bond to ubiquitin. While the E2 contacts a single protomer of the RING, ubiquitin is folded back onto the E2 by contacts from both RING protomers. The C-terminal tail of ubiquitin is locked into an active site groove on the E2 by an intricate network of interactions, resulting in changes at the E2 active site. This arrangement is primed for catalysis as it can deprotonate the incoming substrate lysine residue and stabilise the consequent tetrahedral transition state intermediate. PMID:22842904

  15. Radiative origin of solar scale and $U_{e3}$

    CERN Document Server

    Joshipura, A S

    2002-01-01

    We make a general study of possibility of generating the solar scale $\\Delta_{\\odot}$ and the CHOOZ angle $U_{e3}$ radiatively by assuming that they are zero at some high scale. The most general neutrino mass matrix leading to this result is determined in a CP conserving theory. This matrix contains four independent parameters which can be fixed in terms of physical observables. The standard weak radiative corrections then lead to non-zero $\\Delta_{\\odot}$ and $U_{e3}$ without drastically altering the other tree level results. As a consequence, both $\\Delta_{\\odot}$ and $U_{e3}$ are predicted in terms of other physically observable parameters. These predictions are insensitive to specific form of the neutrino mass matrix. The solar scale and $U_{e3}$ are strongly correlated with the effective neutrino mass $m_{ee}$ probed in neutrinoless double beta decay. In particular, the LMA solution to the solar neutrino problem arise for $m_{ee}$ close to the present experimental limit. An example of specific texture is...

  16. Summary of Model Predictions for $U_{e3}$

    CERN Document Server

    Joshipura, A S

    2004-01-01

    We present a short discussion on the expected magnitude of $|U_{e3}|$ in the context of various scenarios proposed to describe neutrino masses and mixing. Generic expectation is relatively large ($>0.05$) values for $\\ue3$ which occur in many well-motivated theoretical scenarios and models.

  17. Exception Processing of Cortex-M3%Cortex-M3的异常处理机制研究

    Institute of Scientific and Technical Information of China (English)

    方安平; 蔡俊宇

    2009-01-01

    详细阐述Cortex-M3异常的分类、优先级、进入和退出,以及在Cortex-M3异常处理机制中使用的新技术--迟到(late-arriving)和尾链(tail-chaining);最后,比较Cortex-M3和ARM7异常控制机制的区别,并量化分析迟到和尾链技术在异常处理中的优越性.

  18. CHANG'E-3 contingency scheme and trajectory

    Science.gov (United States)

    Liu, Lei; Cao, Jian-feng; Liu, Yong; Hu, Song-jie; Tang, Ge-shi; Xie, Jian-feng

    2015-02-01

    This paper addresses contingency trajectories of CHANG'E-3 in the case of a failure of the lunar brake, which is crucial to the CHANG'E-3 mission, i.e., the first Chinese lunar soft-landing and rover mission. Considering the flight-time and control-energy requirements placed on the contingency trajectories, the paper proposes a direct return method and a low-energy return method and develops the corresponding contingency trajectories based on the CHANG'E-3 cislunar transfer trajectory. The direct return method was studied on return style, flight time, control energy, and influence of maneuver time on energy. The low-energy return method was investigated using the method of invariant manifold calculations for a Lissajous orbit, the method of direct libration-point orbit transfer and injection, and the control strategy used for a low-energy trajectory. The results demonstrate that the control energy for direct return trajectories can be reduced using a certain flight course. When a flight time of less than half of a month is desired, a trajectory from the north celestial pole should be selected as a lunar approach trajectory for CHANG'E-3. Otherwise, a trajectory from the south celestial pole should be selected. Furthermore, these two trajectories have approximately equal velocity increments if their flight-time difference is close to half of a month. In the case of the low-energy return method, methods using approximate manifold calculations for a Lissajous orbit and the direct transfer and injection to a libration-point orbit are proposed and shown to be useful. CHANG'E-3 would return via the Sun-Earth L2 libration point and would require four maneuvers during its flight. The low-energy return method offers remarkable energy savings of up to 267 m/s compared to the direct return method. The methodology not only provides a contingency control technique for CHANG'E-3 and for future lunar missions, but it also serves as a beneficial supplement to the present studies

  19. Alteration of airway responsiveness mediated by receptors in ovalbumin-induced asthmatic E3 rats

    Institute of Scientific and Technical Information of China (English)

    Jing-wen LONG; Xu-dong YANG; Lei CAO; She-min LU; Yong-xiao CAO

    2009-01-01

    Aim:Airway hyperresponsiveness is a constant feature of asthma.The aim of the present study was to investigate airway hyperreactivity mediated by contractile and dilative receptors in an ovalbumin (OVA)-induced model of rat asthma.Methods:Asthmatic E3 rats were prepared by intraperitoneal injection with OVA/aluminum hydroxide and then challenged with intranasal instillation of OVA-PBS two weeks later.The myograph method was used to measure the responses of constriction and dilatation in the trachea,main bronchi and lobar bronchi.Results:In asthmatic E3 rata,β2 adrenoceptor-mediated relaxation of airway smooth muscle pre-contracted with 5-HT was inhibited,and there were no obvious difference in relaxation compared with normal E3 rats.Contraction of lobar bronchi mediated by 5-HT and sarafotoxin 6c was more potent than in the trachea or main bronchi.Airway contractions mediated by the endothelin (ET)A receptor,ETB receptor and M3 muscarinic receptor were augmented,and the augmented contraction was most obvious in lobar bronchi.The order of efficacy of contraction for lobar bronchi induced by agonists was ET-1,sarafotoxin 6c>ACh>5-HT.OX8 (an antibody against CD8+ T cells) strongly shifted and 0X35 (an antibody against CD4+ T cells) modestly shifted isoprenaline-induced concentration-relaxation curves in a nonparallel fashion to the left with an increased Rmax in asthmatic rats and sarafotoxin 6c-induced concentration-contractile curves to the right with a decreased Emax.Conclusion:The inhibition of airway relaxation and the augmentation of contraction mediated by receptors contribute to airway hyperresponsiveness and involve CD8+ and CD4+ T cells.

  20. The surface accessibility of the glycine receptor M2-M3 loop is increased in the channel open state.

    Science.gov (United States)

    Lynch, J W; Han, N L; Haddrill, J; Pierce, K D; Schofield, P R

    2001-04-15

    Mutations in the extracellular M2-M3 loop of the glycine receptor (GlyR) alpha1 subunit have been shown previously to affect channel gating. In this study, the substituted cysteine accessibility method was used to investigate whether a structural rearrangement of the M2-M3 loop accompanies GlyR activation. All residues from R271C to V277C were covalently modified by both positively charged methanethiosulfonate ethyltrimethylammonium (MTSET) and negatively charged methanethiosulfonate ethylsulfonate (MTSES), implying that these residues form an irregular surface loop. The MTSET modification rate of all residues from R271C to K276C was faster in the glycine-bound state than in the unliganded state. MTSES modification of A272C, L274C, and V277C was also faster in the glycine-bound state. These results demonstrate that the surface accessibility of the M2-M3 loop is increased as the channel transitions from the closed to the open state, implying that either the loop itself or an overlying domain moves during channel activation.

  1. Different Characteristics of the Bright Branches of the Globular Clusters M3 and M13

    CERN Document Server

    Cho, D H; Jeon, Y B; Sim, K J; Cho, Dong-Hwan; Lee, Sang-Gak; Jeon, Young-Beom; Sim, Kyung Jin

    2005-01-01

    We carried out wide-field BVI CCD photometric observations of the GCs M3 and M13 using the BOAO 1.8 m telescope equipped with a 2K CCD. We present CMDs of M3 and M13. We have found AGB bumps at V = 14.85 for M3 at V = 14.25 for M13. It is found that AGB stars in M3 are more concentrated near the bump, while those in M13 are scattered along the AGB sequence. We identified the RGB bump of M3 at V = 15.50 and that of M13 at V = 14.80. We have estimated the ratios R and R2 for M3 and M13 and found that of R for M3 is larger than that for M13 while R2's for M3 and M13 are similar when only normal HB stars are used in R and R2 for M13. However, we found that R's for M3 and M13 are similar while R2 for M3 is larger than that for M13 when all the HB stars are included in R and R2 for M13. We have compared the observed RGB LFs of M3 and M13 with the theoretical RGB LF of Bergbusch & VandenBerg at the same radial distances from the cluster centers as used in R and R2 for M3 and M13. We found "extra stars" belonging...

  2. Second Parameter Effects in and between M3 and Palomar 3

    CERN Document Server

    Catelan, M; Ferraro, F R

    2001-01-01

    We study the globular clusters M3 and Palomar 3 as a "second parameter (2ndP) pair," showing that: i) M3 has a surprisingly strong *internal* 2ndP; ii) The dispersion in mass on the Pal 3 horizontal branch (HB) is intrinsically very small, leading to the most apparent differences in HB morphology between M3 and Pal 3; iii) Ignoring the difference in HB mass dispersion between M3 and Pal 3, their relative HB types can be accounted for by a fairly small difference in age, of order 0.5-1 Gyr.

  3. Design Essentials of 80 m3 Diluted Acetaldehyde Storage Tank%浅谈80 m3稀乙醛储槽设计要点

    Institute of Scientific and Technical Information of China (English)

    白春山; 刘文元

    2009-01-01

    Combination 80 m3 thin acetaldehyde tank design, the paper focused on low-pressure tank-top cans bearing ring, tank walls, tank top and anchor set design and the method of calculating and comparing the general design of storage tanks were introduced.%结合80 m3稀乙醛储槽的设计,着重介绍低压储罐罐顶承压环、罐壁、罐顶以及锚栓设置的设计及其计算方法,并与一般储罐设计进行比较.

  4. 世代更迭 E3争锋

    Institute of Scientific and Technical Information of China (English)

    华尔兹

    2013-01-01

    《GT赛车6》来了!不同于《GT赛车5》经历的长时间等待,已经对PS3机能了如指掌的制作组将在今年冬天为大家带来全新的《GT赛车》!“《GT》系列”每一作都伴随着惊人的进化,相信已经看过E3的《GT赛车6》预告片的玩家已经激动不已了吧,

  5. Effects of Modulating M3 Muscarinic Receptor Activity on Azoxymethane-Induced Liver Injury in Mice

    Science.gov (United States)

    Khurana, Sandeep; Jadeja, Ravirajsinh; Twadell, William; Cheng, Kunrong; Rachakonda, Vikrant; Saxena, Neeraj; Raufman, Jean-Pierre

    2013-01-01

    Previously, we reported that azoxymethane (AOM)-induced liver injury is robustly exacerbated in M3 muscarinic receptor (M3R)-deficient mice. We used the same mouse model to test the hypothesis that selective pharmacological modulation of M3R activity regulates the liver injury response. Initial experiments confirmed that giving a selective M3R antagonist, darifenacin, to AOM-treated mice mimicked M3R gene ablation. Compared to vehicle controls, mice treated with the M3R antagonist had reduced survival and increased liver nodularity and fibrosis. We next assessed AOM-induced liver injury in mice treated with a selective M3R agonist, pilocarpine. After pilocarpine treatment, stimulation of post-M3R signaling in the liver was evidenced by ERK and AKT activation. In contrast to the damaging effects of the M3R antagonist, administering pilocarpine to AOM-treated mice significantly attenuated hepatic stellate cell activation, collagen deposition, bile ductule proliferation, and liver fibrosis and nodularity. As anticipated from these findings, livers from pilocarpine-treated mice exhibited reduced expression of key players in fibrosis (α1 collagen, α-smooth muscle actin, TGF-β1, PGDF, TGF-β1R, PGDFR) and decreased mRNA levels for molecules that regulate extracellular matrix formation (TIMP-1, TIMP-2, MMP-2, MMP-13). Cleaved caspase-3, nitrotyrosine and BrdU immunostaining provided evidence that pilocarpine treatment reduced hepatocyte apoptosis and oxidative stress, while increasing hepatocyte proliferation. Collectively, these findings identify several downstream mechanisms whereby M3R activation ameliorates toxic liver injury. These novel observations provide a proof-of-principle that selectively stimulating M3R activation to prevent or diminish liver injury is a therapeutic strategy worthy of further investigation. PMID:23707755

  6. Scale-up of industrial biodiesel production to 40 m3using a liquid lipase formulation

    DEFF Research Database (Denmark)

    Price, Jason; Nordblad, Mathias; Martel, Hannah H.

    2016-01-01

    In this work, we demonstrate the scale-up from an 80 L fed-batch scale to 40 m3 along with the design of a 4 m3continuous process for enzymatic biodiesel production catalysed by NS-40116 (a liquid formulation of a modified Thermomyces lanuginosus lipase). Based on the analysis of actual pilot pla...

  7. Residual stress in a M3:2 PM high speed steel; effect of mechanical loading

    DEFF Research Database (Denmark)

    Højerslev, Christian; Odén, Magnus; Carstensen, Jesper V.;

    2001-01-01

    X-ray lattice strains were investigated in an AISI M3:2 PM high-speed steel in the as heat treated condition and after exposure to alternating mechanical load. The volume changes during heat treatment were monitored with dilatometry. Hardened and tempered AISI M3:2 steel consists of tempered lath...

  8. Ubiquitin E3 ligase FIEL1 regulates fibrotic lung injury through SUMO-E3 ligase PIAS4.

    Science.gov (United States)

    Lear, Travis; McKelvey, Alison C; Rajbhandari, Shristi; Dunn, Sarah R; Coon, Tiffany A; Connelly, William; Zhao, Joe Y; Kass, Daniel J; Zhang, Yingze; Liu, Yuan; Chen, Bill B

    2016-05-30

    The E3 small ubiquitin-like modifier (SUMO) protein ligase protein inhibitor of activated STAT 4 (PIAS4) is a pivotal protein in regulating the TGFβ pathway. In this study, we discovered a new protein isoform encoded by KIAA0317, termed fibrosis-inducing E3 ligase 1 (FIEL1), which potently stimulates the TGFβ signaling pathway through the site-specific ubiquitination of PIAS4. FIEL1 targets PIAS4 using a double locking mechanism that is facilitated by the kinases PKCζ and GSK3β. Specifically, PKCζ phosphorylation of PIAS4 and GSK3β phosphorylation of FIEL1 are both essential for the degradation of PIAS4. FIEL1 protein is highly expressed in lung tissues from patients with idiopathic pulmonary fibrosis (IPF), whereas PIAS4 protein levels are significantly reduced. FIEL1 overexpression significantly increases fibrosis in a bleomycin murine model, whereas FIEL1 knockdown attenuates fibrotic conditions. Further, we developed a first-in-class small molecule inhibitor toward FIEL1 that is highly effective in ameliorating fibrosis in mice. This study provides a basis for IPF therapeutic intervention by modulating PIAS4 protein abundance.

  9. Spectrin’s chimeric E2/E3 enzymatic activity

    Science.gov (United States)

    Goodman, Steven R; Petrofes Chapa, Rachel

    2015-01-01

    In this minireview, we cover the discovery of the human erythrocyte α spectrin E2/E3 ubiquitin conjugating/ligating enzymatic activity and the specific cysteines involved. We then discuss the consequences when this activity is partially inhibited in sickle cell disease and the possibility that the same attenuation is occurring in multiple organ dysfunction syndrome. We finish by discussing the reasons for believing that nonerythroid α spectrin isoforms (I and II) also have this activity and the importance of testing this hypothesis. If correct, this would suggest that the nonerythroid spectrin isoforms play a major role in protein ubiquitination in all cell types. This would open new fields in experimental biology focused on uncovering the impact that this enzymatic activity has upon protein–protein interactions, protein turnover, cellular signaling, and many other functions impacted by spectrin, including DNA repair. PMID:26283706

  10. Akt is negatively regulated by the MULAN E3 ligase

    Institute of Scientific and Technical Information of China (English)

    Seunghee Bae; Jongdoo Kim; Hong-Duck Um; In-Chul Park; Su-Jae Lee; Seon Young Nam; Young-Woo Jin; Jae Ho Lee; Sungkwan An; Sun-Yong Kim; Jin Hyuk Jung; Yeongmin Yoon; Hwa Jun Cha; Hyunjin Lee; Karam Kim; Jongran Kim; In-Sook An

    2012-01-01

    The serine/threonine kinase Akt functions in multiple cellular processes,including cell survival and tumor development.Studies of the mechanisms that negatively regulate Akt have focused on dephosphorylation-mediated inactivation.In this study,we identified a negative regulator of Akt,MULAN,which possesses both a RING finger domain and E3 ubiquitin ligase activity.Akt was found to directly interact with MULAN and to be ubiquitinated by MULAN in vitro and in vivo.Other molecular assays demonstrated that phosphorylated Akt is a substantive target for both interaction with MULAN and ubiquitination by MULAN.The results of the functional studies suggest that the degradation of Akt by MULAN suppresses cell proliferation and viability.These data provide insight into the Akt ubiquitination signaling network.

  11. Multiple charge density wave states at the surface of TbT e3

    Science.gov (United States)

    Fu, Ling; Kraft, Aaron M.; Sharma, Bishnu; Singh, Manoj; Walmsley, Philip; Fisher, Ian R.; Boyer, Michael C.

    2016-11-01

    We studied TbT e3 using scanning tunneling microscopy (STM) in the temperature range of 298-355 K. Our measurements detect a unidirectional charge density wave (CDW) state in the surface Te layer with a wave vector consistent with that of the bulk qCDW=0.30 ±0.01 c* . However, unlike previous STM measurements, and differing from measurements probing the bulk, we detect two perpendicular orientations for the unidirectional CDW with no directional preference for the in-plane crystal axes (a or c axis) and no noticeable difference in wave vector magnitude. In addition, we find regions in which the bidirectional CDW states coexist. We propose that observation of two unidirectional CDW states indicates a decoupling of the surface Te layer from the rare-earth block layer below, and that strain variations in the Te surface layer drive the local CDW direction to the specific unidirectional or, in rare occurrences, bidirectional CDW orders observed. This indicates that similar driving mechanisms for CDW formation in the bulk, where anisotropic lattice strain energy is important, are at play at the surface. Furthermore, the wave vectors for the bidirectional order we observe differ from those theoretically predicted for checkerboard order competing with stripe order in a Fermi-surface nesting scenario, suggesting that factors beyond Fermi-surface nesting drive CDW order in TbT e3 . Finally, our temperature-dependent measurements provide evidence for localized CDW formation above the bulk transition temperature TCDW.

  12. COOLING METHOD OF SILUMINA CASTINGS AK15M3 AT VERTICAL CENTRIFUGAL CASTING

    Directory of Open Access Journals (Sweden)

    V. Yu. Stecenko

    2013-01-01

    Full Text Available The way of cooling of castings from silumin AK15M3 is developed at the vertical centrifugal casting, enabling to receive bimetallic blanks with high-disperse eutectic and hypereutectic microstructures and minimal allowance for machining.

  13. Complete Genome Sequence of the Novel Leech Symbiont Mucinivorans hirudinis M3T

    OpenAIRE

    Nelson, Michael C.; Bomar, Lindsey; Graf, Joerg

    2015-01-01

    Mucinivorans hirudinis M3T was isolated from the digestive tract of the medicinal leech, Hirudo verbana, and is the type species of a new genus within the Rikenellaceae. Here, we report the complete annotated genome sequence of this bacterium.

  14. Complete Genome Sequence of the Novel Leech Symbiont Mucinivorans hirudinis M3T.

    Science.gov (United States)

    Nelson, Michael C; Bomar, Lindsey; Graf, Joerg

    2015-02-05

    Mucinivorans hirudinis M3(T) was isolated from the digestive tract of the medicinal leech, Hirudo verbana, and is the type species of a new genus within the Rikenellaceae. Here, we report the complete annotated genome sequence of this bacterium.

  15. Posttranslational modifications of human M3 muscarinic acetylcholine receptor: zooming in its functional implications

    OpenAIRE

    Romero Fernández, Wilber

    2011-01-01

    The human M3 muscarinic acetylcholine receptor (M3R) regulates many important physiological roles in the central and peripheral nervous systems, and it is involved in the pathophysiology of several neurodegenerative and autoimmune diseases, representing attractive potential pharmacological target for intervention. However, the lack of structural information on this receptor hampered the development of new potent antagonist with increased selectivity and lower side effects. Such structural inf...

  16. M3B: A coarse grain model for the simulation of oligosaccharides and their water mixtures.

    Science.gov (United States)

    Goddard, William A.; Cagin, Tahir; Molinero, Valeria

    2003-03-01

    Water and sugar dynamics in concentrated carbohydrate solutions is of utmost importance in food and pharmaceutical technology. Water diffusion in concentrated sugar mixtures can be slowed down many orders of magnitude with respect to bulk water [1], making extremely expensive the simulation of these systems with atomistic detail for the required time-scales. We present a coarse grain model (M3B) for malto-oligosaccharides and their water mixtures. M3B speeds up molecular dynamics simulations about 500-1000 times with respect to the atomistic model while retaining enough detail to be mapped back to the atomistic structures with low uncertainty in the positions. The former characteristic allows the study of water and carbohydrate dynamics in supercooled and polydisperse mixtures with characteristic time scales above the nanosecond. The latter makes M3B well suited for combined atomistic-mesoscale simulations. We present the parameterization of M3B force field for water and a family of technologically relevant glucose oligosaccharides, the alpha-(1->4) glucans. The coarse grain force field is completely parameterized from atomistic simulations to reproduce the density, cohesive energy and structural parameters of amorphous sugars. We will show that M3B is capable to describe the helical character of the higher oligosaccharides, and that the water structure in low moisture mixtures shows the same features obtained with the atomistic and M3B models. [1] R Parker, SG Ring: Carbohydr. Res. 273 (1995) 147-55.

  17. Nuclear targeting of an endosomal E3 ubiquitin ligase.

    Science.gov (United States)

    Bocock, Jeffrey P; Carmicle, Stephanie; Madamba, Egbert; Erickson, Ann H

    2010-06-01

    Ring finger protein 13 (RNF13) is an E3 ubiquitin ligase embedded in endosome membranes. The protein undergoes constitutive post-translational proteolysis, making its detection difficult unless cells are incubated with a proteasome inhibitor to allow biosynthetic forms to accumulate. When cells were treated with phorbol 12-myristate 13-acetate (PMA), RNF13 avoided proteolysis. A similar stabilization was seen on ionomycin treatment of cells. Drug treatment stabilized both the full-length protein and a membrane-embedded C-terminal fragment generated following ectodomain shedding. Immunofluorescence staining revealed that PMA treatment caused the protein to accumulate in recycling endosomes, where it colocalized with transferrin receptor, and on the inner nuclear membrane, where it colocalized with lamin B. Expression of dominant-negative Rab11 inhibited nuclear localization, suggesting RNF13 was targeted to the inner nuclear membrane through recycling endosomes. New protein synthesis was necessary for this targeting. Nuclear localization was confirmed by immunoelectron microscopy and by purification of the inner nuclear membrane. Stress-induced transport of an endosomal protein to the inner nuclear membrane is a novel mechanism for introduction of regulatory proteins to the DNA environment. RNF13, with its ubiquitin ligase-active RING domain, has the potential to turn over key nuclear proteins in response to signals received at the plasma membrane.

  18. $\\pi_{e3}$ form factor $f_{-}$ near mass shell

    CERN Document Server

    Krivoruchenko, M I

    2014-01-01

    Generalized Ward-Takahashi identity (gWTI) in the pion sector for broken isotopic symmetry is derived and used for the model-independent calculation of the longitudinal form factor $f_{-}$ of the $\\pi_{e3}$ vector vertex. The on-shell $f_{-}$ is found to be proportional to the mass difference of pions and the difference between vector isospin $ T = 1 $ and scalar isospin $ T = 2 $ pion radii. A numerical estimate of the form factor gives a value two times higher than the earlier estimate in the quark model. Off-shell form factors are known to be ambiguous because of the gauge dependence and the freedom in parameterization of the fields. The near-mass-shell $f_{-}$ appears to be an exception, allowing the experimental verification of the gWTI consequences. We calculate the near-mass-shell $f_{-}$ using the gWTI and dispersion techniques. The results are discussed in the context of the conservation of vector current (CVC) condition.

  19. New M+, M3+-arsenates – the framework structures of AgM3+(HAsO42 (M3+ = Al, Ga and M+GaAs2O7 (M+ = Na, Ag

    Directory of Open Access Journals (Sweden)

    Karolina Schwendtner

    2017-05-01

    Full Text Available The crystal structures of hydrothermally synthesized silver(I aluminium bis[hydrogen arsenate(V], AgAl(HAsO42, silver(I gallium bis[hydrogen arsenate(V], AgGa(HAsO42, silver gallium diarsenate(V, AgGaAs2O7, and sodium gallium diarsenate(V, NaGaAs2O7, were determined from single-crystal X-ray diffraction data collected at room temperature. The first two compounds are representatives of the MCV-3 structure type known for KSc(HAsO42, which is characterized by a three-dimensional anionic framework of corner-sharing alternating M3+O6 octahedra (M = Al, Ga and singly protonated AsO4 tetrahedra. Intersecting channels parallel to [101] and [110] host the Ag+ cations, which are positionally disordered in the Ga compound, but not in the Al compound. The hydrogen bonds are relatively strong, with O...O donor–acceptor distances of 2.6262 (17 and 2.6240 (19 Å for the Al and Ga compounds, respectively. The two diarsenate compounds are representatives of the NaAlAs2O7 structure type, characterized by an anionic framework topology built of M3+O6 octahedra (M = Al, Ga sharing corners with diarsenate groups, and M+ cations (M = Ag hosted in the voids of the framework. Both structures are characterized by a staggered conformation of the As2O7 groups.

  20. 3 800 m3耙吸挖泥船的HVAC设计%HVAC design for a 3 800 m3 trailing suction dredger

    Institute of Scientific and Technical Information of China (English)

    戴菁; 赵骊; 陈维茂

    2007-01-01

    挖泥船的需求量与日俱增,逐渐形成系列船型.通过介绍3 800 m3耙吸挖泥船的HVAC设计系统,与以往挖泥船型比较,以及用户的评价,指出该船的空调系统设计思想和方法上的优点,为后续船提供了有益的参考.

  1. Muscarinic M3 receptors on structural cells regulate cigarette smoke-induced neutrophilic airway inflammation in mice

    NARCIS (Netherlands)

    Kistemaker, Loes E.M.; van Os, Ronald P.; Dethmers-Ausema, Albertina; Bos, I. Sophie T.; Hylkema, Machteld N.; van den Berge, Maarten; Hiemstra, Pieter S; Wess, Jürgen; Meurs, Herman; Kerstjens, Huib A.M.; Gosens, Reinoud

    2015-01-01

    Anticholinergics, blocking the muscarinic M-3 receptor, are effective bronchodilators for patients with chronic obstructive pulmonary disease. Recent evidence from M-3 receptor-deficient mice (M3R-/-) indicates that M-3 receptors also regulate neutrophilic inflammation in response to cigarette smoke

  2. Design of USB smart card reader based on Cortex-M3%基于Cortex-M3的智能卡USB读卡器设计

    Institute of Scientific and Technical Information of China (English)

    李冬霞; 张雪庆

    2010-01-01

    为了提高智能卡系统的通信速度和中断响应速度,设计了基于Cortex-M3和USB接口的智能卡读卡器系统.设计中采用具有ARM Cortex-M3内核的STM32F103R6T6等芯片进行相关的硬件设计,分别使用Keil和Visual C++6.0进行读卡器固件子系统程序和PC端子系统驱动程序开发,在此基础上,专门设计了测试程序用于测试系统的正确性和有效性.实验结果表明,该智能卡读卡器系统可实现计算机与智能卡的准确,高效通信.

  3. Renovation of stirring system in 300m3 L-lysine fermentor%300m3赖氨酸发酵罐搅拌系统改造

    Institute of Scientific and Technical Information of China (English)

    王远海

    2012-01-01

    以加强传质混合为目的提出300m3赖氨酸发酵罐搅拌系统改造方案,采用计算流体力学(CFD)数值模拟方法分析了搅拌系统轴功率、流型、传质混合能力,成功指导了搅拌系统改造,在电流增大的情况下,平均单罐产量提高2.44t,平均糖酸转化率提高约1个百分点.%To strengthen mass transfer and mixing for purpose, the reform scheme of stirring system in 300m3 L-lysine fermentor was proposed, CFD (Computational Fluid Dynamics) numerical simulation was used in analysing shaft power, flow pattern, mass transfer mixing ability of the stirring system, when current increased, the fermentation yield and L-lysine acid conversion rate of sugar was 2.44t and about 1% higher than the fermentor which not renovated.

  4. M3-receptor activation counteracts opioid-mediated apneusis, but the apneusis per se is not necessarily related to an impaired M3 mechanism in rats.

    Science.gov (United States)

    Niwa, Yuka; Haji, Akira

    2011-11-07

    Morphine slows the respiratory cycle due to a predominant prolongation of inspiration (apneusis) by postponing the spontaneous termination of inspiration (inspiratory off-switching). The present study investigates whether the morphine-induced apneusis results from impairment of cholinergic mechanisms in the central respiratory network. The efferent discharge was recorded from the phrenic nerve in artificially ventilated and anesthetized rats with vagotomy. All drugs were injected intravenously. The phrenic nerve displayed an augmenting discharge during inspiration and arrest of discharge during expiration in normal condition. Administration of morphine (0.3-10.0mg/kg) dose-dependently provoked apneusis characterized by a long-lasting, plateau inspiratory discharge of the phrenic nerve. It shortened the expiratory duration. Subsequent administration of physostigmine (0.1mg/kg) restored the morphine-induced apneusis to eupnea with a partial recovery of the augmenting inspiratory discharge. This modification of physostigmine was blocked by a non-specific muscarinic antagonist scopolamine (3.0mg/kg), leading to re-prolongation of inspiration. A similar antagonism was affected by an antagonist of M3 cholinergic receptors, 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, 1.0 and 10.0mg/kg) but not by an antagonist of M1 cholinergic receptors, pirenzepine (1.0 and 10.0mg/kg). These results demonstrate that the activation of endogenous M3 cholinergic mechanisms counteracts the morphine-induced apneusis. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. The application of pentaprism scanning technology on the manufacturing of M3MP

    Science.gov (United States)

    Qi, Erhui; Hu, Haixiang; Hu, Haifei; Cole, Glen; Luo, Xiao; Ford, Virginia; Zhang, Xuejun

    2016-10-01

    The PSS (pentaprism scanning system) has advantages of simple structure, needless of reference flat, be able of on-site testing, etc, it plays an important role in large flat reflective mirror's manufacturing, especially the high accuracy testing of low order aberrations. The PSS system measures directly the slope information of the tested flat surface. Aimed at the unique requirement of M3MP, which is the prototype mirror of the tertiary mirror in TMT (Thirty Meter Telescope) project, this paper analyzed the slope distribution of low order aberrations, power and astigmatism, which is very important in the manufacturing process of M3MP. Then the sample route lines of PSS are reorganized and new data process algorism is implemented. All this work is done to improve PSS's measure sensitivity of power and astigmatism, for guiding the manufacturing process of M3MP.

  6. Muscarinic M3 receptor subtype gene expression in the human heart.

    Science.gov (United States)

    Hellgren, I; Mustafa, A; Riazi, M; Suliman, I; Sylvén, C; Adem, A

    2000-01-20

    The heart is an important target organ for cholinergic function. In this study, muscarinic receptor subtype(s) in the human heart were determined using reverse transcription-polymerase chain reaction. Our results demonstrated muscarinic receptor M2 and M3 subtype RNA in left/right atria/ventricles of donor hearts. Receptor autoradiography analysis using selective muscarinic ligands indicated an absence of M1 receptor subtype in the human heart. The level of muscarinic receptor binding in atria was two to three times greater than in ventricles. Our results suggest that muscarinic receptors in the human heart are of the M2 and M3 subtypes. This is the first report of M3 receptors in the human myocardium.

  7. Tilting structures in inverse perovskites, M3TtO (M = Ca, Sr, Ba, Eu; Tt = Si, Ge, Sn, Pb).

    Science.gov (United States)

    Nuss, Jürgen; Mühle, Claus; Hayama, Kyouhei; Abdolazimi, Vahideh; Takagi, Hidenori

    2015-06-01

    Single-crystal X-ray diffraction experiments were performed for a series of inverse perovskites, M3TtO (M = Ca, Sr, Ba, Eu; Tt = tetrel element: Si, Ge, Sn, Pb) in the temperature range 500-50 K. For Tt = Sn, Pb, they crystallize as an 'ideal' perovskite-type structure (Pm3m, cP5); however, all of them show distinct anisotropies of the displacement ellipsoids of the M atoms at room temperature. This behavior vanishes on cooling for M = Ca, Sr, Eu, and the structures can be regarded as `ideal' cubic perovskites at 50 K. The anisotropies of the displacement ellipsoids are much more enhanced in the case of the Ba compounds. Finally, their structures undergo a phase transition at ∼ 150 K. They change from cubic to orthorhombic (Ibmm, oI20) upon cooling, with slightly tilted OBa6 octahedra, and bonding angles O-Ba-O ≃ 174° (100 K). For the larger Ba(2+) cations, the structural changes are in agreement with smaller tolerance factors (t) as defined by Goldschmidt. Similar structural behavior is observed for Ca3TtO. Smaller Tt(4-) anions (Si, Ge) introduce reduced tolerance factors. Both compounds Ca3SiO and Ca3GeO with cubic structures at 500 K, change into orthorhombic (Ibmm) at room temperature. Whereby, Ca3SiO is the only representative within the M3TtO family where three polymorphs can be found within the temperature range 500-50 K: Pm3m-Ibmm-Pbnm. They show tiny differences in the tilting of the OCa6 octahedra, expressed by O-Ca-O bond angles of 180° (500 K), ∼ 174° (295 K) and 170° (100 K). For larger M (Sr, Eu, Ba), together with smaller Tt (Si, Ge) atoms, pronounced tilting of the OM6 octahedra, and bonding angles of O-M-O ≃ 160° (295 K) are observed. They crystallize in the anti-GdFeO3 type of structure (Pbnm, oP20), and no phase transitions occur between 500 and 50 K. The observed phase transitions are all accompanied by multiple twinning, in terms of pseudo-merohedry or reticular pseudo-merohedry.

  8. M3 User's Manual. Version 3.0

    Energy Technology Data Exchange (ETDEWEB)

    Laaksoharju, Marcus (Geopoint AB, Sollentuna (Sweden)); Skaarman, Erik (Abscondo Utveckling, Bromma (Sweden)); Gomez, Javier B. (Univ. of Zaragoza (Spain). Geochemical modelling Group); Gurban, Ioana (3D Terra (Canada))

    2006-07-15

    This report describes the Multivariate Mixing and Mass balance calculations (M3). This new method and computer code is developed to trace the mixing and reaction processes in the groundwater. The aim of the M3 concept is to decode the often hidden and complex information gathered in the groundwater analytical data. The manual presents shortly the theory and practice behind the M3 method. The M3 computer code is also presented and emphasis is put on the reference manual. This includes detailed reference to the M3 program's abilities and limitations, installation procedures and all functions and operations that the program can perform. It also describes sample cases of how the program is used to analyse a test data set. This guide is part of the Help Files distributed together with M3. Two accompanying reports cover other aspects: - Concepts, Methods, and Mathematical Formulation, gives a complete description of the mathematical framework of M3 and introduces concepts and methods useful for the end user. - M3 version 3.0: Verification and Validation, gathers a collection of validation and verification exercises, designed to test each part of M3 code and to build confidence in its methodology. The M3 method has been tested and modified over several years. The development work has been supported by the Swedish Nuclear Fuel and Waste Management Company (SKB). The main test site for the model was the underground Aespoe Hard Rock Laboratory (HRL). The examples used in this manual are from a Aespoe international groundwater modelling co-operation project where one of the tools used was M3. The M3 concept has been applied on the data from SKB's site investigation programme and in data from Canada, Japan, Jordan, Gabon and Finland. The groundwater composition is a result of mixing processes and water-rock interaction. Standard groundwater models based on thermodynamic laws may not be applicable in a normal temperature groundwater system where equilibrium with many

  9. A Discussion of the High Energy Density Primary Battery Employed in the FOTON M3 Mission

    Science.gov (United States)

    Bennetti, A.; Reece, D.; Spurrett, R.; Schautz, M.; Green, K.

    2008-09-01

    In 2005, ABSL Space Products (ABSL) was contracted by QinetiQ to deliver the lithium sulfuryl chloride primary battery system for the FOTON M3 ESA (European Space Agency) mission. FOTON M3 was led by the ESA Directorate of Human Spaceflight & Exploration and carried a number of materials science, fluid physics and biology experiments as well as technology demonstration payloads. A number of the experiments required a very high energy density primary battery power source. This battery was manufactured by ABSL, and the mission was successfully completed in September 2007 following a twelve days orbiting in Low Earth Orbit (LEO).

  10. Development of RT-components for the M-3 Strawberry Harvesting Robot

    Science.gov (United States)

    Yamashita, Tomoki; Tanaka, Motomasa; Yamamoto, Satoshi; Hayashi, Shigehiko; Saito, Sadafumi; Sugano, Shigeki

    We are now developing the strawberry harvest robot called “M-3” prototype robot system under the 4th urgent project of MAFF. In order to develop the control software of the M-3 robot more efficiently, we innovated the RT-middleware “OpenRTM-aist” software platform. In this system, we developed 9 kind of RT-Components (RTC): Robot task sequence player RTC, Proxy RTC for image processing software, DC motor controller RTC, Arm kinematics RTC, and so on. In this paper, we discuss advantages of RT-middleware developing system and problems about operating the RTC-configured robotic system by end-users.

  11. Global Kinetic Analysis of Mammalian E3 Reveals pH-dependent NAD+/NADH Regulation, Physiological Kinetic Reversibility, and Catalytic Optimum.

    Science.gov (United States)

    Moxley, Michael A; Beard, Daniel A; Bazil, Jason N

    2016-02-05

    Mammalian E3 is an essential mitochondrial enzyme responsible for catalyzing the terminal reaction in the oxidative catabolism of several metabolites. E3 is a key regulator of metabolic fuel selection as a component of the pyruvate dehydrogenase complex (PDHc). E3 regulates PDHc activity by altering the affinity of pyruvate dehydrogenase kinase, an inhibitor of the enzyme complex, through changes in reduction and acetylation state of lipoamide moieties set by the NAD(+)/NADH ratio. Thus, an accurate kinetic model of E3 is needed to predict overall mammalian PDHc activity. Here, we have combined numerous literature data sets and new equilibrium spectroscopic experiments with a multitude of independently collected forward and reverse steady-state kinetic assays using pig heart E3. The latter kinetic assays demonstrate a pH-dependent transition of NAD(+) activation to inhibition, shown here, to our knowledge, for the first time in a single consistent data set. Experimental data were analyzed to yield a thermodynamically constrained four-redox-state model of E3 that simulates pH-dependent activation/inhibition and active site redox states for various conditions. The developed model was used to determine substrate/product conditions that give maximal E3 rates and show that, due to non-Michaelis-Menten behavior, the maximal flux is different compared with the classically defined kcat.

  12. 1500 m3立式圆筒形煤仓有限元计算%Finite Element Calculation of 1 500 m3 Vertical Cylindrical Bunker

    Institute of Scientific and Technical Information of China (English)

    汪志福; 陶保林; 孙文红

    2015-01-01

    Large cylindrical bunker is widely used in oil fired steam injection station project.An analysis of stress strength for the design of a 1 500 m3 vertical cylindrical bunker is given.A large general finite element software ANSYS is used to establish a actual size of the finite element nu-merical model,which connected with a coal bunker tank top,tank walls,bearing,cone bottom, consistent with steel support columns,using powerful border simulation and all kinds of applied load function,in a state filled with water + wind + snow + load cases,to calculate and check the various structural parts of coal bunker.The calculated results show that it has sufficient safe-ty margin and reliability.%大型圆筒式煤仓在油田燃煤注汽站工程中应用广泛,对某1500 m3立式圆筒形煤仓进行了应力强度分析。运用有限元软件 ANSYS 建立了与煤仓罐顶、罐壁、支座连接、锥底、支撑钢架以及立柱实际尺寸相一致的有限元数值计算模型,利用软件的边界模拟和各种荷载施加功能,针对煤仓各结构部分,在充水状态+风载荷+雪载荷+地震载荷工况下进行了应力计算和校核,结果表明,此煤仓具有足够的安全裕度及可靠性。

  13. Biophysical analysis of apolipoprotein E3 variants linked with development of type III hyperlipoproteinemia.

    Directory of Open Access Journals (Sweden)

    Dimitra Georgiadou

    Full Text Available BACKGROUND: Apolipoprotein E (apoE is a major protein of the lipoprotein transport system that plays important roles in lipid homeostasis and protection from atherosclerosis. ApoE is characterized by structural plasticity and thermodynamic instability and can undergo significant structural rearrangements as part of its biological function. Mutations in the 136-150 region of the N-terminal domain of apoE, reduce its low density lipoprotein (LDL receptor binding capacity and have been linked with lipoprotein disorders, such as type III hyperlipoproteinemia (HLP in humans. However, the LDL-receptor binding defects for these apoE variants do not correlate well with the severity of dyslipidemia, indicating that these variants may carry additional properties that contribute to their pathogenic potential. METHODOLOGY/PRINCIPAL FINDINGS: In this study we examined whether three type III HLP predisposing apoE3 variants, namely R136S, R145C and K146E affect the biophysical properties of the protein. Circular dichroism (CD spectroscopy revealed that these mutations do not significantly alter the secondary structure of the protein. Thermal and chemical unfolding analysis revealed small thermodynamic alterations in each variant compared to wild-type apoE3, as well as effects in the reversibility of the unfolding transition. All variants were able to remodel multillamelar 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC vesicles, but R136S and R145C had reduced kinetics. Dynamic light scattering analysis indicated that the variant R136S exists in a higher-order oligomerization state in solution. Finally, 1-anilinonaphthalene-8-sulfonic acid (ANS binding suggested that the variant R145C exposes a larger amount of hydrophobic surface to the solvent. CONCLUSIONS/SIGNIFICANCE: Overall, our findings suggest that single amino acid changes in the functionally important region 136-150 of apoE3 can affect the molecule's stability and conformation in solution and may

  14. E3 Success Story - Transforming and Promoting Sustainable Manufacturing in Alabama

    Science.gov (United States)

    Alabama E3 is expanding to other manufacturing sectors and expanding its scope. Alabama E3 now includes a workforce training and education component and is also developing a new innovation engineering green module that focuses on improving sustainability

  15. HST UV Observations of the Cores of M3 and M13

    CERN Document Server

    Ferraro, F R; Pecci, F F; Cacciari, C; Dorman, B; Rood, R T; Ferraro, Francesco R.; Paltrinieri, Barbara; Pecci, Flavio Fusi; Cacciari, Carla; Dorman, Ben; Rood, Robert T.

    1997-01-01

    We present preliminary results from HST/WFPC2 observations of the central regions of the of the Galactic globular clusters M13 and M3. The clusters are almost identical in most respects including chemical composition, but there are dramatic differences in both the horizontal branch (HB) and blue straggler (BSS) populations. The M13 HB has a long blue tail extending 4.5 mag in V, reaching well below the level of the main sequence turn-off. M3 has no such feature. M3 and M13 are thus an extreme case of the ``second parameter problem'' in HB morphology. Also present in the M13 HB are two gaps similar to those seen in the clusters NGC 6752 and NGC 2808. M3 has a specific frequency of BSS three times larger than that of M13. Our results imply that neither age nor cluster density, two popular second parameter candidates, are likely to be responsible for the observed differences.

  16. Experimental Conditions: SE37_S16_M3_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available opes SE37_S16 Blank (80% methanol) SE37_S16_M3 0mg [MassBase ID] MDLC1_43486 SE37_MS1 Metabolites extraction... with 80% methanol and analysis by LC-Orbitrap-MS SE37_DS1 Peak extraction for unlabeled data ...

  17. On the Family of Thue Equation |x3 + mx2y- (m + 3) xy2 + y3 |= k

    Institute of Scientific and Technical Information of China (English)

    XIA Jingbo; CHEN Jianhua; ZHANG Silan

    2006-01-01

    The family of cubic Thue equation which depend on two parameters | x3 + mx2 y- (m+3) xy2 + y3|=k is studied. Using rational approximation, we give a smaller upper bound of the solution of the equation, that is quite better than the present result. Moreover, we study two inequalities |x3 +mx2y- (m+3)xy2 +y3|=k≤2m+3 and |m3 +mm2y- (m+3)my2 + y3 | = k≤(2m+ 3)2 separately. Our result of upper bound make it easy to solve those inequalities by simple method of continuous fraction expansion.

  18. Divergent evolution of the M3A family of metallopeptidases in plants.

    Science.gov (United States)

    Kmiec, Beata; Teixeira, Pedro F; Murcha, Monika W; Glaser, Elzbieta

    2016-07-01

    Plants, as stationary organisms, have developed mechanisms allowing them efficient resource reallocation and a response to changing environmental conditions. One of these mechanisms is proteome remodeling via a broad peptidase network present in various cellular compartments including mitochondria and chloroplasts. The genome of the model plant Arabidopsis thaliana encodes as many as 616 putative peptidase-coding genes organized in 55 peptidase families. In this study, we describe the M3A family of peptidases, which comprises four members: mitochondrial and chloroplastic oligopeptidase (OOP), cytosolic oligopeptidase (CyOP), mitochondrial octapeptidyl aminopeptidase 1 (Oct1) and plant-specific protein of M3 family (PSPM3) of unknown function. We have analyzed the evolutionary conservation of M3A peptidases across plant species and the functional specialization of the three distinct subfamilies. We found that the subfamily-containing OOP and CyOP-like peptidases, responsible for oligopeptide degradation in the endosymbiotic organelles (OOP) or in the cytosol (CyOP), are highly conserved in all kingdoms of life. The Oct1-like peptidase subfamily involved in pre-protein maturation in mitochondria is conserved in all eukaryotes, whereas the PSPM3-like protein subfamily is strictly conserved in higher plants only and is of unknown function. Specific characteristics within PSPM3 sequences, i.e. occurrence of a N-terminal transmembrane domain and amino acid changes in distal substrate-binding motif, distinguish PSPM3 proteins from other members of M3A family. We performed peptidase activity measurements to analyze the role of substrate-binding residues in the different Arabidopsis M3A paralogs. © 2016 Scandinavian Plant Physiology Society.

  19. Apolipoprotein E3/E3 genotype decreases the risk of pituitary dysfunction after traumatic brain injury due to various causes: preliminary data.

    Science.gov (United States)

    Tanriverdi, Fatih; Taheri, Serpil; Ulutabanca, Halil; Caglayan, Ahmet Okay; Ozkul, Yusuf; Dundar, Munis; Selcuklu, Ahmet; Unluhizarci, Kursad; Casanueva, Felipe F; Kelestimur, Fahrettin

    2008-09-01

    Traumatic brain injury (TBI) is a devastating public health problem which may result in hypopituitarism. However, the mechanisms and the risk factors responsible for hypothalamo-pituitary dysfunction due to TBI are still unclear. Although APO E is one of the most abundant protein in hypothalamo-pituitary region, there is no study investigating the relation between APO E polymorphism and TBI-induced hypopituitarism. This study was undertaken to determine whether APO E genotypes modulate the pituitary dysfunction risk after TBI due to various causes, including traffic accident, boxing, and kickboxing. Ninety-three patients with TBI (mean age, 30.61 +/- 1.25 years) and 27 healthy controls (mean age, 29.03 +/- 1.70 years) were included in the study. Pituitary functions were evaluated, and APO E genotypes (E2/E2; E3/E3; E4/E4; E2/E3; E2/E4; E3/E4) were screened. Twenty-four of 93 subjects (25.8%) had pituitary dysfunction after TBI. The ratio of pituitary dysfunction was significantly lower in subjects with APO E3/E3 (17.7%) than the subjects without APO E3/E3 genotype (41.9%; p = 0.01), and the corresponding odds ratio was 0.29 (95% confidence interval [CI], 0.11-0.78). In conclusion, this study provides strong evidence for the first time that APO E polymorphism is associated with the development of TBI-induced pituitary dysfunction. Present data demonstrated that APO E3/E3 genotype decreases the risk of hypopituitarism after TBI. The demonstration of the association between the APO E polymorphism and TBI may provide a new point of view in this field and promote further studies.

  20. Genome-wide and functional annotation of human E3 ubiquitin ligases identifies MULAN, a mitochondrial E3 that regulates the organelle's dynamics and signaling.

    Directory of Open Access Journals (Sweden)

    Wei Li

    Full Text Available Specificity of protein ubiquitylation is conferred by E3 ubiquitin (Ub ligases. We have annotated approximately 617 putative E3s and substrate-recognition subunits of E3 complexes encoded in the human genome. The limited knowledge of the function of members of the large E3 superfamily prompted us to generate genome-wide E3 cDNA and RNAi expression libraries designed for functional screening. An imaging-based screen using these libraries to identify E3s that regulate mitochondrial dynamics uncovered MULAN/FLJ12875, a RING finger protein whose ectopic expression and knockdown both interfered with mitochondrial trafficking and morphology. We found that MULAN is a mitochondrial protein - two transmembrane domains mediate its localization to the organelle's outer membrane. MULAN is oriented such that its E3-active, C-terminal RING finger is exposed to the cytosol, where it has access to other components of the Ub system. Both an intact RING finger and the correct subcellular localization were required for regulation of mitochondrial dynamics, suggesting that MULAN's downstream effectors are proteins that are either integral to, or associated with, mitochondria and that become modified with Ub. Interestingly, MULAN had previously been identified as an activator of NF-kappaB, thus providing a link between mitochondrial dynamics and mitochondria-to-nucleus signaling. These findings suggest the existence of a new, Ub-mediated mechanism responsible for integration of mitochondria into the cellular environment.

  1. Antibody to the E3 Glycoprotein Protects Mice against Lethal Venezuelan Equine Encephalitis Virus Infection▿

    Science.gov (United States)

    Parker, Michael D.; Buckley, Marilyn J.; Melanson, Vanessa R.; Glass, Pamela J.; Norwood, David; Hart, Mary Kate

    2010-01-01

    Six monoclonal antibodies were isolated that exhibited specificity for a furin cleavage site deletion mutant (V3526) of Venezuelan equine encephalitis virus (VEEV). These antibodies comprise a single competition group and bound the E3 glycoprotein of VEEV subtype I viruses but failed to bind the E3 glycoprotein of other alphaviruses. These antibodies neutralized V3526 virus infectivity but did not neutralize the parental strain of Trinidad donkey (TrD) VEEV. However, the E3-specific antibodies did inhibit the production of virus from VEEV TrD-infected cells. In addition, passive immunization of mice demonstrated that antibody to the E3 glycoprotein provided protection against lethal VEEV TrD challenge. This is the first recognition of a protective epitope in the E3 glycoprotein. Furthermore, these results indicate that E3 plays a critical role late in the morphogenesis of progeny virus after E3 appears on the surfaces of infected cells. PMID:20926570

  2. Residual stress in a M3:2 PM high speed steel; effect of mechanical loading

    DEFF Research Database (Denmark)

    Højerslev, Christian; Odén, Magnus; Carstensen, Jesper V.

    2001-01-01

    X-ray lattice strains were investigated in an AISI M3:2 PM high-speed steel in the as heat treated condition and after exposure to alternating mechanical load. The volume changes during heat treatment were monitored with dilatometry. Hardened and tempered AISI M3:2 steel consists of tempered lath...... martensite and the carbides M6C,V8C7 and M23C6. In the as heat treated condition the stress state is triaxial. The primary carbides M6C and V8C7 experience a compressive state of stress. Exposure to an alternating mechanical load, changes the states of stress of V8C7 and tempered martensite, but does...... not appear to change the state of stress in M6C....

  3. The Abundance of Lithium in an AGB Star in the Globular Cluster M3 (NGC 5272)

    CERN Document Server

    Givens, R A

    2016-01-01

    A survey of red giants in the globular cluster M3 with the Hydra multi-object spectrograph on the WIYN 3.5-m telescope indicated a prominent Li I 6707 $\\AA$ feature in the red giant vZ 1050. Follow-up spectroscopy with the ARC 3.5-m telescope confirmed this observation and yielded a derived abundance of A(Li)$_{NLTE}$ = 1.6 $\\pm$ 0.05. In addition, the high oxygen and low sodium abundances measured from the same spectrum suggest that vZ 1050 is a first generation cluster star. The location vZ 1050 above the horizontal branch and blueward of the red giant branch in the cluster's color-magnitude diagram places vZ 1050 on M3's asymptotic giant branch. The likely source for the enhanced lithium abundance is the Cameron-Fowler mechanism operating in vZ 1050 itself.

  4. The Abundance of Lithium in an ABG Star in the Globular Cluster M3 (NGC 5272)

    Science.gov (United States)

    Givens, R. A.; Pilachowski, C. A.

    2016-12-01

    A survey of red giants in the globular cluster M3 with the Hydra multi-object spectrograph on the WIYN 3.5 m telescope indicated a prominent Li i 6707 Å feature in the red giant vZ 1050. Followup spectroscopy with the ARC 3.5 m telescope confirmed this observation and yielded a derived abundance of A(Li)NLTE = 1.6 ± 0.05. In addition, the high oxygen and low sodium abundances measured from the same spectrum suggest that vZ 1050 is a first generation cluster star. The location of vZ 1050 above the horizontal branch and blueward of the red giant branch in the cluster’s color-magnitude diagram places vZ 1050 on M3's asymptotic giant branch. The likely source for the enhanced lithium abundance is the Cameron-Fowler mechanism operating in vZ 1050 itself.

  5. M3A system (2000–2005 – operation and maintenance

    Directory of Open Access Journals (Sweden)

    G. Petihakis

    2006-05-01

    Full Text Available During the Pilot Phase of the Mediterranean Forecasting System (MFSPP (1998–2001 a prototype observing system (Mediterranean Moored Multi-sensor Array – M3A was designed, developed and operated in the Cretan Sea for continuous oceanographic measurements in real time. The main problems encountered were associated with biofouling, underwater and aerial communication and with the design of the surface buoy. In the second phase of the MFS project named Mediterranean Forecasting System Towards Environmental Predictions (MFSTEP (2001–2005, the aim was to solve those problems and to consolidate the M3A. During the approximately five years of operation there were 13 scheduled and 15 emergency visits with a total duration of 65 days. The acquired experience through the maintenance program proved that the continuous observation of a so important system with a relative low cost is feasible.

  6. Response of plasmaspheric configuration to substorms revealed by Chang’e 3

    Science.gov (United States)

    He, Han; Shen, Chao; Wang, Huaning; Zhang, Xiaoxin; Chen, Bo; Yan, Jun; Zou, Yongliao; Jorgensen, Anders M.; He, Fei; Yan, Yan; Zhu, Xiaoshuai; Huang, Ya; Xu, Ronglan

    2016-08-01

    The Moon-based Extreme Ultraviolet Camera (EUVC) of the Chang’e 3 mission provides a global and instantaneous meridian view (side view) of the Earth’s plasmasphere. The plasmasphere is one inner component of the whole magnetosphere, and the configuration of the plasmasphere is sensitive to magnetospheric activity (storms and substorms). However, the response of the plasmaspheric configuration to substorms is only partially understood, and the EUVC observations provide a good opportunity to investigate this issue. By reconstructing the global plasmaspheric configuration based on the EUVC images observed during 20–22 April 2014, we show that in the observing period, the plasmasphere had three bulges which were located at different geomagnetic longitudes. The inferred midnight transit times of the three bulges, using the rotation rate of the Earth, coincide with the expansion phase of three substorms, which implies a causal relationship between the substorms and the formation of the three bulges on the plasmasphere. Instead of leading to plasmaspheric erosion as geomagnetic storms do, substorms initiated on the nightside of the Earth cause local inflation of the plasmasphere in the midnight region.

  7. M3MS-16OR0401086 – Report on NEAMS Workbench Support for MOOSE Applications

    Energy Technology Data Exchange (ETDEWEB)

    Lefebvre, Robert A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Reactor and Nuclear Systems Division; Langley, Brandon R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Reactor and Nuclear Systems Division; Thompson, Adam B. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Reactor and Nuclear Systems Division

    2016-09-23

    This report summarizes the status of the Nuclear Energy Advanced Modeling and Simulation (NEAMS) Workbench from Oak Ridge National Laboratory (ORNL) and the integration of the MOOSE framework. This report marks the completion of NEAMS milestone M3MS-16OR0401086. This report documents the developed infrastructure to support the MOOSE framework applications, the applications’ results, visualization status, the collaboration that facilitated this progress, and future considerations.

  8. Relativistic electrons high doses at International Space Station and Foton M2/M3 satellites

    Science.gov (United States)

    Dachev, T. P.; Tomov, B.; Matviichuk, Yu.; Dimitrov, Pl.; Bankov, N.

    2009-12-01

    The paper presents observation of relativistic electrons. Data are collected by the Radiation Risk Radiometer-Dosimeters (R3D) B2/B3 modifications during the flights of Foton M2/M3 satellites in 2005 and 2007 as well as by the R3DE instrument at the European Technology Exposure Facility (EuTEF) on the Columbus External Payload Adaptor at the International Space Station (ISS) in the period February 20 - April 28, 2008. On the Foton M2/M3 satellites relativistic electrons are observed more frequently than on the ISS because of higher (62.8°) inclination of the orbit. At both Foton satellites the usual duration of the observations are a few minutes long. On the ISS the duration usually is about 1 min or less. The places of observations of high doses due to relativistic electrons are distributed mainly at latitudes above 50° geographic latitude in both hemispheres on Foton M2/M3 satellites. A very high maximum is found in the southern hemisphere at longitudinal range 0°-60°E. At the ISS the maximums are observed between 45° and 52° geographic latitude in both hemispheres mainly at longitudes equatorward from the magnetic poles. The measured absolute maximums of dose rates generated by relativistic electrons are found to be as follows: 304 μGy h -1 behind 1.75 g cm -2 shielding at Foton M2, 2314 μGy h -1 behind 0.71 g cm -2 shielding at Foton M3 and 19,195 μGy h -1 (Flux is 8363 cm -2 s -1) behind les than 0.4 g cm -2 shielding at ISS.

  9. New species of Triplocania Roesler with forewing M3 forked (Psocodea: 'Psocoptera': Ptiloneuridae), from Brazil.

    Science.gov (United States)

    Da Silva Neto, Alberto Moreira; Rafael, José Albertino; Aldrete, Alfonso N García

    2014-07-16

    Four new Brazilian species of Triplocania with forewing M3 forked are described and illustrated based on male specimens, namely: Triplocania lamasi n.sp. (Mato Grosso: Brazil), Triplocania mariateresae n.sp. (Rio de Janeiro: Brazil), Triplocania newi n.sp. (Tocantins: Brazil) and Triplocania plaumanni n.sp. (Santa Catarina: Brasil). They differ from all the other species in the genus, in which the males are known, by the hypandrium and phallosome structures.

  10. A novel antiarrhythmic target-M3-R/IKM3

    Institute of Scientific and Technical Information of China (English)

    Bao-fengYANG

    2004-01-01

    The total efficient rate of antiarrhythmic agents is only 30%to 60%, and the compounding problem is the lack of an effective therapy for some serious arrhythmias. Muscarinic receptors have been cloned and subdivided into the five subtypes M1, M2, M3,M4 and M5. And M2 receptors have long been believed to be the only functional subtype of muscarinic acetylcholine receptor (mAChR) in the heart, although recent studies have provided

  11. A picrotoxin-specific conformational change in the glycine receptor M2-M3 loop.

    Science.gov (United States)

    Hawthorne, Rebecca; Lynch, Joseph W

    2005-10-28

    The external loop linking the M2 and M3 transmembrane domains is crucial for coupling agonist binding to channel gating in the glycine receptor chloride channel (GlyR). A substituted cysteine accessibility scan previously showed that glycine activation increased the surface accessibility of 6 contiguous residues (Arg271-Lys276) toward the N-terminal end of the homomeric alpha1 GlyR M2-M3 loop. In the present study we used a similar approach to determine whether the allosteric antagonist, picrotoxin, could impose conformational changes to this domain that cannot be induced by varying agonist concentrations alone. Picrotoxin slowed the reaction rate of a sulfhydryl-containing compound (MTSET) with A272C, S273C, and L274C. Before interpreting this as a picrotoxin-specific conformational change, it was necessary to eliminate the possibility of steric competition between picrotoxin and MTSET. Accordingly, we showed that picrotoxin and the structurally unrelated blocker, bilobalide, were both trapped in the R271C GlyR in the closed state and that a point mutation to the pore-lining Thr6' residue abolished inhibition by both compounds. We also demonstrated that the picrotoxin dissociation rate was linearly related to the channel open probability. These observations constitute a strong case for picrotoxin binding in the pore. We thus conclude that the picrotoxin-specific effects on the M2-M3 loop are mediated allosterically. This suggests that the M2-M3 loop responds differently to the occupation of different binding sites.

  12. Development, Implementation and Evaluation of an M3 Community Health Curriculum

    Directory of Open Access Journals (Sweden)

    Staci Young, MS

    2004-03-01

    Full Text Available Objectives: This paper describes the development, implementation and evaluation of an M3 community health curriculum that responds to recent changes within the health care finance and delivery system. Methods: The new curriculum was developed based on AAMC recommendations, LCME requirements, a national review of undergraduate community health curricula, and an internal review of the integration of community health concepts in M3 clerkships. Results: The M3 curriculum teaches: 1 the importance of being a community responsive physician; 2 SES factors that influence health; 3 cultural competency; and 4 the role of physicians as health educators. Student evaluations for the first twelve months of implementation indicate that students are most satisfied with presentations and less satisfied with required readings and a patient interview project. Discussion: Most students agree that at the completion of the course they understand what it means to be a community-responsive physician, and they have developed skills to help them become more community responsive. Evaluation tools need to be developed to assess if students’ behavior has changed due to course participation.

  13. Performance of 500 m3 TankCell® at Kevitsa Cu-Ni-PGM concentrator

    Directory of Open Access Journals (Sweden)

    Mattsson Toni

    2016-01-01

    Full Text Available Outotec TankCell e500 flotation cell, with 500 m3 of efficient flotation volume, has been in operation since October 2014 at Kevitsa Cu-Ni-PGM concentrator as the first Cu rougher flotation cell. The 500 m3 flotation cell has proven to provide metallurgical superiority at very low specific power. On average the cell has recovered 71% of copper contained in the flotation feed. The cell has produced the concentrate with the Cu grade equal to 17% Cu. The typical specific power for the cell is around 0.4 kW/m3 (blower power not included. After the start-up of the cell the operating parameters have varied. The mixing speed have varied from 4.9 to 7.0 m/s and the superficial gas velocity from 0.3 to 1.5 cm/s. At various operating parameters the mixing, gas dispersion and metallurgical performance of the cell have been evaluated. In this paper a review of the hydrodynamic and metallurgical performance of the cell is presented. The paper focuses on the interactions of mixing intensity, bubble size and metallurgical performance in industrial application.

  14. Mice Lacking M1 and M3 Muscarinic Acetylcholine Receptors Have Impaired Odor Discrimination and Learning

    Science.gov (United States)

    Chan, Wilson; Singh, Sanmeet; Keshav, Taj; Dewan, Ramita; Eberly, Christian; Maurer, Robert; Nunez-Parra, Alexia; Araneda, Ricardo C.

    2017-01-01

    The cholinergic system has extensive projections to the olfactory bulb (OB) where it produces a state-dependent regulation of sensory gating. Previous work has shown a prominent role of muscarinic acetylcholine (ACh) receptors (mAChRs) in regulating the excitability of OB neurons, in particular the M1 receptor. Here, we examined the contribution of M1 and M3 mAChR subtypes to olfactory processing using mice with a genetic deletion of these receptors, the M1−/− and the M1/M3−/− knockout (KO) mice. Genetic ablation of the M1 and M3 mAChRs resulted in a significant deficit in odor discrimination of closely related molecules, including stereoisomers. However, the discrimination of dissimilar molecules, social odors (e.g., urine) and novel object recognition was not affected. In addition the KO mice showed impaired learning in an associative odor-learning task, learning to discriminate odors at a slower rate, indicating that both short and long-term memory is disrupted by mAChR dysfunction. Interestingly, the KO mice exhibited decreased olfactory neurogenesis at younger ages, a deficit that was not maintained in older animals. In older animals, the olfactory deficit could be restored by increasing the number of new born neurons integrated into the OB after exposing them to an olfactory enriched environment, suggesting that muscarinic modulation and adult neurogenesis could be two different mechanism used by the olfactory system to improve olfactory processing. PMID:28210219

  15. Goldschmidt crater and the Moon's north polar region: Results from the Moon Mineralogy Mapper (M3)

    Science.gov (United States)

    Cheek, L.C.; Pieters, C.M.; Boardman, J.W.; Clark, R.N.; Combe, J.-P.; Head, J.W.; Isaacson, P.J.; McCord, T.B.; Moriarty, D.; Nettles, J.W.; Petro, N.E.; Sunshine, J.M.; Taylor, L.A.

    2011-01-01

    Soils within the impact crater Goldschmidt have been identified as spectrally distinct from the local highland material. High spatial and spectral resolution data from the Moon Mineralogy Mapper (M3) on the Chandrayaan-1 orbiter are used to examine the character of Goldschmidt crater in detail. Spectral parameters applied to a north polar mosaic of M3 data are used to discern large-scale compositional trends at the northern high latitudes, and spectra from three widely separated regions are compared to spectra from Goldschmidt. The results highlight the compositional diversity of the lunar nearside, in particular, where feldspathic soils with a low-Ca pyroxene component are pervasive, but exclusively feldspathic regions and small areas of basaltic composition are also observed. Additionally, we find that the relative strengths of the diagnostic OH/H2O absorption feature near 3000 nm are correlated with the mineralogy of the host material. On both global and local scales, the strongest hydrous absorptions occur on the more feldspathic surfaces. Thus, M3 data suggest that while the feldspathic soils within Goldschmidt crater are enhanced in OH/H2O compared to the relatively mafic nearside polar highlands, their hydration signatures are similar to those observed in the feldspathic highlands on the farside. Copyright 2011 by the American Geophysical Union.

  16. The Moon Mineralogy (M3) Imaging Spectrometer: Early Assessment of the Spectral, Radiometric, Spatial and Uniformity Properties

    Science.gov (United States)

    Green, Robert O.; Pieters, C. M.; Boardman, J.; Barr, D.; Bruce, C.; Bousman, J.; Chatterjee, A.; Eastwood, M.; Essandoh, V.; Geier, S.; Glavich, T.; Green, R.; Haemmerle, V.; Hyman, S.; Hovland, L.; Koch, T.; Lee, K.; Lundeen, S.; Motts, E.; Mouroulis, P.; Paulson, S.; Plourde, K.; Racho, C.; Robinson, D.; Rodriquez, J.

    2009-01-01

    The Moon Mineralogy Mapper's (M3) is a high uniformity and high signal-to-noise ratio NASA imaging spectrometer that is a guest instrument on the Indian Chandrayaan-1 Mission to the Moon. The laboratory measured spectral, radiometric, spatial, and uniformity characteristics of the M3 instrument are given. The M3 imaging spectrometer takes advantage of a suite of critical enabling capabilities to achieve its measurement requirement with a mass of 8 kg, power usage of 15 W, and volume of 25X18X12 cm. The M3 detector and spectrometer are cooled by a multi-stage passive cooler. This paper presents early M3 performance assessment results.

  17. Effect of cation site-disorder on the structure and magneto-transport properties of Ln5/8M3/8MnO 3 manganites

    Science.gov (United States)

    Collado, J. A.; Frontera, C.; García-Muñoz, J. L.; Aranda, M. A. G.

    2005-06-01

    Five members of Ln5/8M3/8MnO 3 series with A-cation size variance ( σ2) ranging between 3×10 -4 and 71×10 -4 Å 2, and the same A-cation size =1.2025 Å, have been synthesized by the ceramic method. The five manganites are single phase and they crystallize in the Pnma perovskite superstructure. The five compositions display ferromagnetic-paramagnetic transitions at temperatures ranging between 130 and 270 K, for the highest and lowest variance sample, respectively. The samples with smaller variances show sharp magnetization transitions and the samples with the larger variances display broad transitions. These transitions have also been studied by differential scanning calorimetry, DSC, and some enthalpy changes are reported. The resistivity study indicates that all samples display the expected metal-to-insulator transitions at temperatures ranging between 140 and 270 K. The samples have been analysed at room temperature by ultra-high-resolution synchrotron powder diffraction and the structural and microstructural features are reported. Furthermore, Nd 5/8Sr 0.255Ca 0.12MnO 3 ( σ2=40×10-4 Å2) and Sm 0.225Nd 0.4Sr 0.308Ca 0.067MnO 3 ( σ2=53×10-4 Å2) samples have also been studied by synchrotron powder diffraction at 140 K, below the transition temperatures. Both samples are found to be single phase above and below the transition by ultra-high-resolution synchrotron powder diffraction. The microstructure of the samples has been investigated through Williamson-Hall plots. Sample broadenings are markedly anisotropic and strongly dominated by microstrains with average values of the Δ d/ d term close to 14×10 -4. A direct correlation is found between the microstrain values and the widths of the magnetization transitions.

  18. 10 CFR 830 Major Modification Determination for the ATR Diesel Bus (E-3) and Switchgear Replacement

    Energy Technology Data Exchange (ETDEWEB)

    Noel Duckwtiz

    2011-05-01

    Near term replacement of aging and obsolescent original ATR equipment has become important to ensure ATR capability in support of NE’s long term national missions. To that end, a mission needs statement has been prepared for a non-major system acquisition which is comprised of three interdependent subprojects. The first project, subject of this determination, will replace the existent diesel-electrical bus (E-3) and associated switchgear. More specifically, INL proposes transitioning ATR to 100% commercial power with appropriate emergency backup to include: • Provide commercial power as the normal source of power to the ATR loads currently supplied by diesel-electric power. • Provide backup power to the critical ATR loads in the event of a loss of commercial power. • Replace obsolescent critical ATR power distribution equipment, e.g., switchgear, transformers, motor control centers, distribution panels. Completion of this and two other age-related projects (primary coolant pump and motor replacement and emergency firewater injection system replacement) will resolve major age related operational issues plus make a significant contribution in sustaining the ATR safety and reliability profile. The major modification criteria evaluation of the project pre-conceptual design identified several issues make the project a major modification: 1. Evaluation Criteria #2 (Footprint change). The addition of a new PC-4 structure to the ATR Facility to house safety-related SSCs requires careful attention to maintaining adherence to applicable engineering and nuclear safety design criteria (e.g., structural qualification, fire suppression) to ensure no adverse impacts to the safety-related functions of the housed equipment. 2. Evaluation Criteria #3 (Change of existing process). The change to the strategy for providing continuous reliable power to the safety-related emergency coolant pumps requires careful attention and analysis to ensure it meets a project primary object

  19. Vasco da Gama 33000m3耙吸挖泥船

    Institute of Scientific and Technical Information of China (English)

    刘厚恕; 顾洁

    2001-01-01

    The 33000m3 Vasco da Gama was delivered to the owner in 2000, which is the largest trailing suction hopper dredger up to now. The vessel is designed for the following main functions: loading spoil with two side suction pipes at a depth of 45-60m; transporting the spoil at a speed of 16.Skn; dumping spoil through six pairs of bottom doors; self-discharging of spoil via floating pipeline; self-discharging of spoil through bow-jet nozzle; deep dredging at 131m with 5500kW submerged dredge pump. This paper fully described its arrangement, key dredging equipments and major design features,

  20. Deposition of CdTe films under microgravity: Foton M3 mission

    Energy Technology Data Exchange (ETDEWEB)

    Benz, K.W.; Croell, A. [Freiburger Materialforschungszentrum FMF, Albert-Ludwigs-Universitaet Freiburg (Germany); Zappettini, A.; Calestani, D. [CNR Parma, Instituto Materiali Speciali per Elettronica e Magnetismo IMEM, Fontani Parma (Italy); Dieguez, E. [Universidad Autonoma de Madrid (Spain). Departamento de Fisica de Materiales; Carotenuto, L.; Bassano, E. [Telespazio Napoli, Via Gianturco 31, 80146 Napoli (Italy); Fiederle, M.

    2009-10-15

    Experiments of deposition of CdTe films have been carried out under microgravity in the Russian Foton M3 mission. The influence of gravity has been studied with these experiments and compared to the results of simulations. The measured deposition rate could be confirmed by the theoretical results for lower temperatures. For higher temperatures the measured thickness of the deposited films was larger compared to the theoretical data. (copyright 2009 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  1. Postpartum Diagnosis of AML-M3: A Rare Case Report

    Directory of Open Access Journals (Sweden)

    Manjula Biradar

    2016-07-01

    Full Text Available A 27 year old female gravid 2, para 1, presented at 39 weeks of gestation with pain in abdomen going in for labour, and delivered healthy baby. The patient later had post-partum haemorrhage with Prothrombin Time (PT 10min, platelet count 70,000 cells/cumm. Peripheral smear showed shift to left with myeloblasts, promyelocytes. The diagnosis of Acute Myeloid Leukemia (AML was given and advised for bone marrow examination. The diagnosis AML-M3 was confirmed by marrow study. Unfortunately, patient went in for Disseminated Intravascular Coagulation (DIC and died 2 days after the diagnosis.

  2. Lunar Exploration Insights Recognized from Chandrayaan-1 M3 Imaging Spectrometer

    Science.gov (United States)

    Pieters, Carle; Green, Robert O.; Boardman, Joseph

    2016-07-01

    One of the most important lessons learned from the renaissance of lunar exploration over the last decade is that new discoveries and surprises occur with every new mission to the Moon. Although the color of the Moon had been measured using Earth-based telescopes even before Apollo, modern instruments sent to orbit the Moon provide a scope of inquiry unimaginable during the last century. Spacecraft have now been successfully sent to the Moon by six different space agencies from around the world and the number is growing. The Indian Chandrayaan- 1 spacecraft carried a suite of indigenous instruments as well as several guest instruments from other countries, including the Moon Mineralogy Mapper (M-cube) supplied by NASA. Even though Chandrayaan's lifetime in orbit was shortened by technical constraints, M3 provided a taste of the power of near-infrared imaging spectroscopy used for science and exploration at the Moon. Contrary to expectations, the lunar surface was discovered to be hydrated, which is now known to result from solar wind H combining with O of rocks and soil. Surficial hydration was found to be pervasive across the Moon and the limited data hint at both local concentrations and temporal variations. The prime objective of M3 was to characterize lunar mineralogy in a spatial context. Working in tandem with related instruments on JAXA's SELENE, M3 readily recognized and mapped known minerals from mare and highland terrains (pyroxenes, olivine) at high resolution, but also detected diagnostic properties of crystalline plagioclase which, when mapped across a spatial context, enabled the unambiguous identification of a massive crustal layer of plagioclase that clearly resulted from an early magma ocean. An additional surprise came with the discovery of a new rock type on the Moon that had not been recognized in samples returned by Apollo and Luna: a Mg-rich spinel anorthosite associated with material excavated from some of the greatest lunar depths. In

  3. Forsmark Site: M3 modelling and 2D visualisation of the hydrochemical parameters in Forsmark groundwater

    Energy Technology Data Exchange (ETDEWEB)

    Gurban, Ioana (3D Terra (Canada))

    2008-08-15

    This work represents the stage 2.3 of the hydrochemical evaluation and modelling of the Forsmark data. This comprises M3 modelling and 2D visualisation of the data along the boreholes. The following conclusions can be drawn: - M3 modelling helped to summarise and understand the data, by using as variables the major elements and the isotopes delta18O and deltaD. - Previous alternative models and the experience from Forsmark 1.2, 2.1 and 2.2, helped to clarify different previously unsolved issues such as: the use of variables, tests with different endmembers, the use of only groundwater data in order to build a bedrock hydrochemical model. - The visualisation of the mixing proportions along the boreholes helps to understand the distribution of the data in the domain and to check and compare the results of different models; and therefore to chose the model which best describes the measured data. - The different M3 modelling tests resulted in the following conclusions: a) When calculating mixing proportions only samples from the boreholes will be used, b) the altered meteoric end-member which best describes the more shallow groundwater compositions is defined by a representative upper bedrock sample; the Littorina end-member employed the existing modelled compositions; the Deep saline and glacial end-members compositions were tested by means of a feasibility study and employed in the modelling. - Three models were presented. All the models are good and can be used, but the best is to use the one that fits the conceptual model best and the hydrogeochemical understanding. - The use of Littorina, Glacial, Deep Saline and Altered Meteoric end-members makes possible the comparison of different sites such as Laxemar and Forsmark. - All the data used in the M3 modelling and the results of the modelling and visualisation along the boreholes are presented in SKB database SIMON. - The extended data do not affect the results of the modelling of the Forsmark 2.3 dataset (the

  4. (e, 3e) reactions at moderate energies visualization of average field effects in atom

    CERN Document Server

    Kuzakov, K A; Gusev, A A; Popov, Y V; Vinitsky, S I

    2002-01-01

    In the case of helium atom the theory is presented for quasi-elastic A (e, 3e) A sup + sup + and A (e, 3 -1e) A sup + sup + atomic reactions in the coplanar symmetric geometry at incident electron energy of several hundreds eV. The comparison with the recent (e, 3 - 1 e) experiment has allowed one to observe the effect of the mean atomic field as well as postcollisional effects.

  5. The Mediterranean Moored Multi-sensor Array (M3A: system development and initial results

    Directory of Open Access Journals (Sweden)

    K. Nittis

    Full Text Available Operational forecasting of ocean circulation and marine ecosystem fluctuations requires multi-parametric real-time measurements of physical and biochemical properties. The architecture of a system that is able to provide such measurements from the upper-thermocline layers of the Mediterranean Sea is described here. The system was developed for the needs of the Mediterranean Forecasting System and incorporates state-of-the-art sensors for optical and chemical measurements in the upper 100 m and physical measurements down to 500 m. Independent moorings that communicate via hydro-acoustic modems are hosting the sensors. The satellite data transfer and the large autonomy allow for the operation of the system in any open-ocean site. The system has been in pre-operational use in the Cretan Sea since January 2000. The results of this pilot phase indicate that multi-parametric real-time observations with the M3A system are feasible, if a consistent maintenance and re-calibration program is followed. The main limitations of the present configuration of M3A are related: (a to bio-fouling that primarily affects the turbidity and secondarily affects the other optical sensors, and (b to the limited throughput of the currently used satellite communication system.

    Key words. Atmospheric composition and structure (instruments and techniques. Oceanography: general (ocean prediction Oceanography: physical (upper ocean process

  6. Connexins and M3 Muscarinic Receptors Contribute to Heterogeneous Ca2+ Signaling in Mouse Aortic Endothelium

    Directory of Open Access Journals (Sweden)

    François-Xavier Boittin

    2013-02-01

    Full Text Available Background/Aims: Smooth muscle tone is controlled by Ca2+ signaling in the endothelial layer. Mouse endothelial cells are interconnected by gap junctions made of Connexin40 (Cx40 and Cx37, which allow the exchange of signaling molecules to coordinate their activity. Here, we investigated the role of Cx40 in the endothelial Ca2+ signaling of the mouse aorta. Methods: Ca2+ imaging was performed on intact aortic endothelium from both wild type (Cx40+/+ and Connexin40-deficient (Cx40 -/- mice. Results: Acetylcholine (ACh induced early fast and high amplitude Ca2+ transients in a fraction of endothelial cells expressing the M3 muscarinic receptors. Inhibition of intercellular communication using carbenoxolone or octanol fully blocked the propagation of ACh-induced Ca2+ transients toward adjacent cells in WT and Cx40-/- mice. As compared to WT, Cx40-/- mice displayed a reduced propagation of ACh-induced Ca2+ waves, indicating that Cx40 contributes to the spreading of Ca2+ signals. The propagation of those Ca2+ responses was not blocked by suramin, a blocker of purinergic ATP receptors, indicating that there is no paracrine effect of ATP release on the Ca2+ waves. Conclusions: Altogether our data show that Cx40 and Cx37 contribute to the propagation and amplification of the Ca2+ signaling triggered by ACh in endothelial cells expressing the M3 muscarinic receptors.

  7. HST Observations of Blue Straggler Stars in the Core of the Globular Cluster M3

    CERN Document Server

    Ferraro, F R; Pecci, F F; Cacciari, C; Dorman, B; Rood, R T; Buonanno, R; Corsi, C E; Burgarella, D; Laget, M

    1997-01-01

    The core of the Galactic Globular Cluster M3 (NGC 5272) has been observed with the WFPC2 through the filters F255W, F336W, F555W, and F814W. Using these observations along with a thorough reanalysis of earlier catalogs, we have produced a catalog of blue straggler stars (BSS) spanning the cluster. Earlier studies and the fainter part of our sample suffer severe selection biases. Our analysis is based on a more reliable bright global sample of 122 BSS. We confirm earlier suggestions that the radial BSS distribution in M3 is bimodal. It is strongly peaked in the center, has a clear dip 100--200" from the center, and rises again at larger radii. The observed distribution agrees with the dynamical model of Sigurdsson et al. (1994) which takes into account both star collisions and merging of primordial binaries for the origin of BSS. The observed luminosity functions of BSS in the inner and outer parts of the cluster are different. Interpreting these using the models of Bailyn & Pinsonneault (1995), we suggest...

  8. Scale-up of industrial biodiesel production to 40 m3using a liquid lipase formulation

    DEFF Research Database (Denmark)

    Price, Jason; Nordblad, Mathias; Martel, Hannah H.

    2016-01-01

    In this work, we demonstrate the scale-up from an 80 L fed-batch scale to 40 m3 along with the design of a 4 m3continuous process for enzymatic biodiesel production catalysed by NS-40116 (a liquid formulation of a modified Thermomyces lanuginosus lipase). Based on the analysis of actual pilot plant...... the fed-batch and CSTR cases. Given similar operating conditions, the CSTR operation on average, has a reaction time which is 1.3 times greater than the fed-batch operation. We also showed how the process metrics can be used to quickly estimate the selling price of the enzyme. Assuming a biodiesel selling...... price of 0.6 USD/kg and a one-time use of the enzyme (0.1% (w/woil) enzyme dosage); the enzyme can then be sold for 30 USD/kg which ensures that that the enzyme cost is not more than 5% of the biodiesel revenue. This article is protected by copyright. All rights reserved...

  9. M3A system (2000–2005 – operation and maintenance

    Directory of Open Access Journals (Sweden)

    G. Petihakis

    2007-01-01

    Full Text Available During the pilot phase of the Mediterranean Forecasting System (MFSPP (2000 2003, a prototype observing system (Mediterranean Moored Multi-sensor Array – M3A was designed, developed and operated in the Cretan Sea for continuous oceanographic measurements in real time. The main problems encountered were associated with biofouling, underwater and aerial communication and with the design of the surface buoy. In the second phase of the MFS project named Mediterranean Forecasting System Towards Environmental Predictions (MFSTEP (2003–2005, the aim was to solve those problems and to consolidate the M3A. For the minimisation of biofouling a pilot field study was performed and the techniques of bromine solution and copper shielding were evaluated. Additionally, the oligotrophy of the Aegean Sea dictated the need to ignore factory calibrations and to perform site-specific laboratory calibrations of the sensors. This procedure was proved necessary and produced calibration coefficients that gave results comparable to the measurements obtained with the laboratory analysis method. During the approximately five years of operation, there were 13 scheduled and 15 emergency visits, with a total duration of 65 days. The acquired experience through the maintenance program proved that the continuous observation of such a very important system with a relative low cost is feasible.

  10. Machining risk of beryllium disease and sensitization with median exposures below 2 micrograms/m3.

    Science.gov (United States)

    Kreiss, K; Mroz, M M; Newman, L S; Martyny, J; Zhen, B

    1996-07-01

    We examined the prevalence of beryllium sensitization in relation to work process and beryllium exposure measurements in a beryllia ceramics plant that had operated since 1980. We interviewed 136 employees (97.8% of the workforce), ascertained beryllium sensitization with the beryllium lymphocyte proliferation blood test, and reviewed historical industrial hygiene measurements. Of eight beryllium-sensitized employees (5.9%), six (4.4% of participating employees) had granulomatous disease on transbronchial lung biopsy. Machinists had a sensitization rate of 14.3% compared to a rate of 1.2% among other employees. Machining had significantly higher general area and breathing zone measurements than did other processes in the time period in which most beryllium-sensitized cases had started machining work. Daily weighted average (DWA) estimates of exposure for matching processes also exceeded estimates for other work processes in that time period, with a median DWA of 0.9 microgram/m3. Machining process DWAs accounted for the majority of DWAs exceeding the 2.0 micrograms/m3 OSHA standard, with 8.1% of machining DWAs above the standard. We conclude that lowering machining process-related exposures may be important to lowering risk of beryllium disease.

  11. Intricate Crystal Structure of Dihydrolipoamide Dehydrogenase (E3) with its Binding Protein: Multiple Copies, Dynamic and Static Disorders

    Science.gov (United States)

    Makal, A.; Hong, Y. S.; Potter, R.; Vettaikkorumakankauv, A. K.; Korotchkina, L. G.; Patel, M. S.; Ciszak, E.

    2004-01-01

    Human E3 and binding protein E3BP are two components of the pyruvate dehydrogenase complex. Crystallization of E3 with 221-amino acid fragment of E3BP (E3BPdd) led to crystals that diffracted to a resolution of 2.6 Angstroms. Structure determination involved molecular replacement using a dimer of E3 homolog as a search model and de novo building of the E3BPdd peptide. Solution was achieved by inclusion of one E3 dimer at a time, followed by refinement until five E3 dimers were located. This complete content of E3 provided electron density maps suitable for tracing nine peptide chains of E3BPdd, eight of them being identified with partial occupancies. Final content of the asymmetric unit consists of five E3 dimers, each binding one E3BPdd molecule. In four of these molecular complexes, E3BPdd is in static disorder resulting in E3BPdd binding to either one or the other monomer of the E3 dimer. However, E3BPdd of the fifth E3 dimer forms specific contacts that lock it at one monomer. In addition to this static disorder, E3BPdd reveals high mobility in the limited space of the crystal lattice. Support from NIH and NASA.

  12. E3 ubiquitin ligase UBR5 drives the growth and metastasis of triple negative breast cancer.

    Science.gov (United States)

    Liao, Liqiu; Song, Mei; Li, Xin; Tang, Lili; Zhang, Tuo; Zhang, Lixing; Pan, Yihang; Chouchane, Lotfi; Ma, Xiaojing

    2017-03-22

    Patients with triple negative breast cancers (TNBC) are at high risk for recurrence and metastasis at an early time despite standard treatment, underscoring the need for novel therapeutic modalities. Here we report for the first time a distinctive and profound role of the E3 ubiquitin ligase UBR5 in the growth and metastasis of TNBC. An analysis of primary TNBC specimen by whole exon sequencing revealed strong gene amplifications of UBR5 associated with the disease. UBR5 overexpression in TNBC tissues was confirmed at mRNA and protein levels. CRISPR/Cas9-mediated deletion of ubr5 in an experimental murine mammary carcinoma model of TNBC dramatically abrogated tumor growth and metastasis in vivo, which could be reversed completely via reconstitution with wild type UBR5 but not a catalytically inactive mutant. Loss of UBR5 caused an impairment in angiogenesis within the tumor, associated with increased apoptosis, necrosis, and growth arrest. Absence of UBR5 in the tumor triggered aberrant epithelial to mesenchymal transition (EMT), principally via abrogated expression of E-cadherin, which resulted in severely reduced tumor metastasis to secondary organs. Use of NOD/SCID mice revealed that tumor-derived UBR5 facilitated tumor growth in a manner completely dependent upon immune cells in the microenvironment, whereas it promoted metastasis in a tumor cell-autonomous fashion. Our findings unveil UBR5 as a novel and critical regulator of tumor growth, metastasis, and immune response, and highlight the potential for UBR5 as an effective therapeutic target for the treatment of highly aggressive breast and ovarian cancers that fail conventional therapy.

  13. Procedure Redesign Methods : E3-Control: a redesign methodology for control procedures

    NARCIS (Netherlands)

    Liu, J.; Hofman, W.J.; Tan, Y.H.

    2011-01-01

    This chapter highlights the core research methodology, e3-control, that is applied throughout the ITAIDE project for the purpose of control procedure redesign. We present the key concept of the e3-control methodology and its technical guidelines. Based on the output of this chapter, domain experts

  14. Characterization of atherosclerotic lesions in apo E3-leiden transgenic mice

    NARCIS (Netherlands)

    Leppänen, P.; Luoma, J.S.; Hofker, M.H.; Havekes, L.M.; Ylä-Herttuala, S.

    1998-01-01

    Apo E3-leiden transgenic mice express human dysfunctional apo E variant and develop hyperlipidemia and atherosclerosis on a high fat/high cholesterol diet. We characterized diet-induced atherosclerotic lesions in apo E3-leiden transgenic mice using immunocytochemical methods in order to examine foam

  15. Data of evolutionary structure change: 1Q95E-3GD5E [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1Q95E-3GD5E 1Q95 3GD5 E E ANPLYQKHIISINDLSRDDLNLVLATAAKLKANPQPELL...KHKVIASCFFEASTRTRLSFETSMHRLGASVVGFSDSANTSLGKKGETLADTISVISTYVDAIVMRHPQEGAARLATEFSGNVPVLNAGDGSNQHPTQTLLDLFTIQETQGRLDNLHVAMVGD...TELEEYAHYAG-IPVINALTD-HEHPCQVVADLLTIRENFGRLAGLKLAYVGDG--NNVAHSLLLGCAKVG-MSIAVATPEGFTPDPAVSARASEIAGRTGAEVQIL-...line> ILE CA 374 ALA CA 275 THR CA 238 3GD...5 E 3GD5E

  16. Characterization of atherosclerotic lesions in apo E3-leiden transgenic mice

    NARCIS (Netherlands)

    Leppänen, P.; Luoma, J.S.; Hofker, M.H.; Havekes, L.M.; Ylä-Herttuala, S.

    1998-01-01

    Apo E3-leiden transgenic mice express human dysfunctional apo E variant and develop hyperlipidemia and atherosclerosis on a high fat/high cholesterol diet. We characterized diet-induced atherosclerotic lesions in apo E3-leiden transgenic mice using immunocytochemical methods in order to examine foam

  17. Procedure Redesign Methods : E3-Control: a redesign methodology for control procedures

    NARCIS (Netherlands)

    Liu, J.; Hofman, W.J.; Tan, Y.H.

    2011-01-01

    This chapter highlights the core research methodology, e3-control, that is applied throughout the ITAIDE project for the purpose of control procedure redesign. We present the key concept of the e3-control methodology and its technical guidelines. Based on the output of this chapter, domain experts m

  18. Map-Based Cloning of the Gene Associated With the Soybean Maturity Locus E3

    Science.gov (United States)

    Watanabe, Satoshi; Hideshima, Rumiko; Xia, Zhengjun; Tsubokura, Yasutaka; Sato, Shusei; Nakamoto, Yumi; Yamanaka, Naoki; Takahashi, Ryoji; Ishimoto, Masao; Anai, Toyoaki; Tabata, Satoshi; Harada, Kyuya

    2009-01-01

    Photosensitivity plays an essential role in the response of plants to their changing environments throughout their life cycle. In soybean [Glycine max (L.) Merrill], several associations between photosensitivity and maturity loci are known, but only limited information at the molecular level is available. The FT3 locus is one of the quantitative trait loci (QTL) for flowering time that corresponds to the maturity locus E3. To identify the gene responsible for this QTL, a map-based cloning strategy was undertaken. One phytochrome A gene (GmPhyA3) was considered a strong candidate for the FT3 locus. Allelism tests and gene sequence comparisons showed that alleles of Misuzudaizu (FT3/FT3; JP28856) and Harosoy (E3/E3; PI548573) were identical. The GmPhyA3 alleles of Moshidou Gong 503 (ft3/ft3; JP27603) and L62-667 (e3/e3; PI547716) showed weak or complete loss of function, respectively. High red/far-red (R/FR) long-day conditions enhanced the effects of the E3/FT3 alleles in various genetic backgrounds. Moreover, a mutant line harboring the nonfunctional GmPhyA3 flowered earlier than the original Bay (E3/E3; PI553043) under similar conditions. These results suggest that the variation in phytochrome A may contribute to the complex systems of soybean flowering response and geographic adaptation. PMID:19474204

  19. A design principle underlying the paradoxical roles of E3 ubiquitin ligases

    Science.gov (United States)

    Lee, Daewon; Kim, Minjin; Cho, Kwang-Hyun

    2014-07-01

    E3 ubiquitin ligases are important cellular components that determine the specificity of proteolysis in the ubiquitin-proteasome system. However, an increasing number of studies have indicated that E3 ubiquitin ligases also participate in transcription. Intrigued by the apparently paradoxical functions of E3 ubiquitin ligases in both proteolysis and transcriptional activation, we investigated the underlying design principles using mathematical modeling. We found that the antagonistic functions integrated in E3 ubiquitin ligases can prevent any undesirable sustained activation of downstream genes when E3 ubiquitin ligases are destabilized by unexpected perturbations. Interestingly, this design principle of the system is similar to the operational principle of a safety interlock device in engineering systems, which prevents a system from abnormal operation unless stability is guaranteed.

  20. Overview of the membrane-associated RING-CH (MARCH) E3 ligase family.

    Science.gov (United States)

    Bauer, Johannes; Bakke, Oddmund; Morth, J Preben

    2016-12-14

    E3 ligases are critical checkpoints for protein ubiquitination, a signal that often results in protein sorting and degradation but has also been linked to regulation of transcription and DNA repair. In line with their key role in cellular trafficking and cell-cycle control, malfunction of E3 ligases is often linked to human disease. Thus, they have emerged as prime drug targets. However, the molecular basis of action of membrane-bound E3 ligases is still unknown. Here, we review the current knowledge on the membrane-embedded MARCH E3 ligases (MARCH-1-6,7,8,11) with a focus on how the transmembrane regions can contribute via GxxxG-motifs to the selection and recognition of other membrane proteins as substrates for ubiquitination. Further understanding of the molecular parameters that govern target protein recognition of MARCH E3 ligases will contribute to development of strategies for therapeutic regulation of MARCH-induced ubiquitination.

  1. E3 ubiquitin ligases as drug targets and prognostic biomarkers in melanoma

    Directory of Open Access Journals (Sweden)

    Kristina Bielskienė

    2015-01-01

    E3 ligases are of interest as drug targets for their ability to regulate proteins stability and functions. Compared to the general proteasome inhibitor bortezomib, which blocks the entire protein degradation, drugs that target a particular E3 ligase are expected to have better selectivity with less associated toxicity. Components of different E3 ligases complexes (FBW7, MDM2, RBX1/ROC1, RBX2/ROC2, cullins and many others are known as oncogenes or tumor suppressors in melanomagenesis. These proteins participate in regulation of different cellular pathways and such important proteins in cancer development as p53 and Notch. In this review we summarized published data on the role of known E3 ligases in the development of melanoma and discuss the inhibitors of E3 ligases as a novel approach for the treatment of malignant melanomas.

  2. VARIABILITY STUDIES IN M3 GENERATION IN BLACKGRAM (VIGNA MUNGO (L.HEPPER

    Directory of Open Access Journals (Sweden)

    M P MESHRAM

    2013-12-01

    Full Text Available In the present study, pure line seeds of black gram variety viz. T-9, TPU-4 and one promising genotype AKU-18 was treated with gamma irradiation (15kR, 25kR and 35kR with the objective to assess the variability in M3 generation.. Highest GCV and PCV and high estimates of heritability were recorded for the characters sprouting percentage, number of pods plant-1 and grain yield plant-1 (g. High heritability accompanied with high genetic advance was recorded for number of pods plant-1 governed by additive gene effects and therefore selection based on phenotypic performance will be useful to improve character in future.

  3. Trimble M3 1” and South Nts-362R Total Station Angle Measurement Accuracy Analysis

    Directory of Open Access Journals (Sweden)

    Oleniacz Grzegorz

    2017-03-01

    Full Text Available The main purpose of this study was to obtain information about the actual precision of angle measurements with two instruments (Trimble M3 1 "and South NTS-362R, realizable in given measurement conditions. This object is achieved by using a simplified method of testing instruments contained in the PN-ISO 17123-3 standard [1]. This is a continuation of research described in [2], carried out on the same test base, but this time in a different, less favorable field conditions. The use of the same instrument has created an opportunity to compare and analyze the measurement results. The scope of work includes the measurement and results preparation along with statistical processing of the obtained results for both instruments.

  4. Half lives of spherical proton emitters using density dependent M3Y interaction

    CERN Document Server

    Chowdhury, P R; Basu, D N

    2005-01-01

    The proton radioactivity lifetimes of spherical proton emitters from the ground and the isomeric states are calculated using the microscopic nucleon-nucleus interaction potentials. The daughter nuclei density distributions are folded with a realistic density dependent M3Y effective interaction supplemented by a zero-range pseudo-potential. The density dependence parameters of the interaction are extracted from the nuclear matter calculations. The saturation energy per nucleon used for nuclear matter calculations is determined from the co-efficient of the volume term of Bethe-Weizsacker mass formula which is evaluated by fitting the recent experimental and estimated atomic mass excesses from Audi-Wapstra-Thibault atomic mass table by minimizing the mean square deviation. The quantum mechanical tunneling probability is calculated within the WKB approximation. Spherical charge distributions are used for calculating the Coulomb interaction potentials. These calculations provide good estimates for the observed pro...

  5. Electrodialytic remediation of CCA-treated waste wood in a 2 m3 pilot plant

    DEFF Research Database (Denmark)

    Christensen, Iben Vernegren; Pedersen, Anne Juul; Ottosen, Lisbeth M.;

    2006-01-01

    Waste wood that has been treated with chromated-copper-arsenate (CCA) poses a potential environmental problem due to the content of copper, chromium and arsenic. A pilot plant for electrodialytic remediation of up to 2 m3 wood has been designed and tested and the results are presented here. Several...... fractions. The best remediation efficiency was obtained in an experiment with an electrode distance of 60 cm, and 100 kg wood chips. In this experiment 87% copper, 81% chromium and > 95% arsenic were removed. One other experiment was also analysed for arsenic. In this experiment the distance between...... the working electrodes was 1.5 m and here 95% As was removed. The results showed that arsenic may be the easiest removable of the copper, chromium and arsenic investigated here. This is very encouraging since arsenic is the CCA components of most environmental concern....

  6. Variable Star Status of Two Stars: V204 and I-I-39 in M3

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The star I-I-42 (=vZ1390), a cluster member in M3, located near the red edge of the instability strip of the horizontal branch, was discovered by Roberts and Sandage as a low amplitude variable, it was designated as V204 in the "second catalogue of variable stars in globular clusters", but its coordinates given in all versions of this catalogue are wrong since 1955. We argue that V204 is indeed a low amplitude HB variable star, located near to the red edge of the instability strip, with a period of 0.74785d and an amplitude of about 0.04 mag in V. We also find that the red cluster member star I-I-39 is a low amplitude variable with a period of 1.16d and amplitude of about 0.03 mag in V which might be pulsating at the second overtone.

  7. Modeling of lithium granule injection in NSTX using M3D-C1

    Science.gov (United States)

    Fil, A.; Kolemen, E.; Ferraro, N.; Jardin, S.; Parks, P. B.; Lunsford, R.; Maingi, R.

    2017-05-01

    In this paper, we present simulations of pedestal control by lithium granule injection (LGI) in NSTX. A model for small granule ablation has been implemented in the M3D-C1 code (Jardin et al 2012 Comput. Sci. Discovery 5 014002), allowing the simulation of realistic lithium granule injections. 2D and 3D simulations of Li injections in NSTX H-mode plasmas are performed and the effect of granule size, injection angle and velocity on the pedestal gradient increase is studied. The amplitude of the local pressure perturbation caused by the granules is found to be highly dependent on the solid granule size. Adjusting the granule injection velocity allows one to inject more particles at the pedestal top. 3D simulations show the destabilization of high order MHD modes whose amplitude is directly linked to the localized pressure perturbation, which is found to depend on the toroidal localization of the granule density source.

  8. CH5M3D: an HTML5 program for creating 3D molecular structures.

    Science.gov (United States)

    Earley, Clarke W

    2013-11-18

    While a number of programs and web-based applications are available for the interactive display of 3-dimensional molecular structures, few of these provide the ability to edit these structures. For this reason, we have developed a library written in JavaScript to allow for the simple creation of web-based applications that should run on any browser capable of rendering HTML5 web pages. While our primary interest in developing this application was for educational use, it may also prove useful to researchers who want a light-weight application for viewing and editing small molecular structures. Molecular compounds are drawn on the HTML5 Canvas element, with the JavaScript code making use of standard techniques to allow display of three-dimensional structures on a two-dimensional canvas. Information about the structure (bond lengths, bond angles, and dihedral angles) can be obtained using a mouse or other pointing device. Both atoms and bonds can be added or deleted, and rotation about bonds is allowed. Routines are provided to read structures either from the web server or from the user's computer, and creation of galleries of structures can be accomplished with only a few lines of code. Documentation and examples are provided to demonstrate how users can access all of the molecular information for creation of web pages with more advanced features. A light-weight (≈ 75 kb) JavaScript library has been made available that allows for the simple creation of web pages containing interactive 3-dimensional molecular structures. Although this library is designed to create web pages, a web server is not required. Installation on a web server is straightforward and does not require any server-side modules or special permissions. The ch5m3d.js library has been released under the GNU GPL version 3 open-source license and is available from http://sourceforge.net/projects/ch5m3d/.

  9. Effects of the A-site cation number on the properties of Ln5/8M3/8MnO 3 manganites

    Science.gov (United States)

    Collado, J. A.; García-Muñoz, J. L.; Aranda, M. A. G.

    2010-05-01

    The properties of manganites can be tuned by changing the doping level x in Ln1-xM xMnO 3. A second mechanism allows tuning of magnetic and electronic properties, for fixed x values, by varying the average A-cation radius, . Moreover, for fixed x and values, the changes in the A-cation size variance, σ2, also modify the ferromagnetic and metal-insulator transition temperatures. Here, we investigate the influence of the number of A-site cations on Ln5/8M3/8MnO 3 manganites, where x, and σ2 values are kept constant, and in the absence of phase separation phenomena. We have found that the number of cation species at the A site ( N A) has a strong influence on the width of the ferromagnetic and metal-insulator transitions, and a small influence on the average transition temperature. This behavior is opposite to that observed for increasing values of the variance σ2 in manganites, with the same x and values, where average transition temperatures are strongly reduced.

  10. M3 Macrophages Stop Division of Tumor Cells In Vitro and Extend Survival of Mice with Ehrlich Ascites Carcinoma.

    Science.gov (United States)

    Kalish, Sergey; Lyamina, Svetlana; Manukhina, Eugenia; Malyshev, Yuri; Raetskaya, Anastasiya; Malyshev, Igor

    2017-01-26

    BACKGROUND M1 macrophages target tumor cells. However, many tumors produce anti-inflammatory cytokines, which reprogram the anti-tumor M1 macrophages into the pro-tumor M2 macrophages. We have hypothesized that the problem of pro-tumor macrophage reprogramming could be solved by using a special M3 switch phenotype. The M3 macrophages, in contrast to the M1 macrophages, should respond to anti-inflammatory cytokines by increasing production of pro-inflammatory cytokines to retain its anti-tumor properties. Objectives of the study were to form an M3 switch phenotype in vitro and to evaluate the effect of M3 macrophages on growth of Ehrlich ascites carcinoma (EAC) in vitro and in vivo. MATERIAL AND METHODS Tumor growth was initiated by an intraperitoneal injection of EAC cells into C57BL/6J mice. RESULTS 1) The M3 switch phenotype can be programed by activation of M1-reprogramming pathways with simultaneous inhibition of the M2 phenotype transcription factors, STAT3, STAT6, and/or SMAD3. 2) M3 macrophages exerted an anti-tumor effect both in vitro and in vivo, which was superior to anti-tumor effects of cisplatin or M1 macrophages. 3) The anti-tumor effect of M3 macrophages was due to their anti-proliferative effect. CONCLUSIONS Development of new biotechnologies for restriction of tumor growth using in vitro reprogrammed M3 macrophages is very promising.

  11. M3 Macrophages Stop Division of Tumor Cells In Vitro and Extend Survival of Mice with Ehrlich Ascites Carcinoma

    Science.gov (United States)

    Kalish, Sergey; Lyamina, Svetlana; Manukhina, Eugenia; Malyshev, Yuri; Raetskaya, Anastasiya; Malyshev, Igor

    2017-01-01

    Background M1 macrophages target tumor cells. However, many tumors produce anti-inflammatory cytokines, which reprogram the anti-tumor M1 macrophages into the pro-tumor M2 macrophages. We have hypothesized that the problem of pro-tumor macrophage reprogramming could be solved by using a special M3 switch phenotype. The M3 macrophages, in contrast to the M1 macrophages, should respond to anti-inflammatory cytokines by increasing production of pro-inflammatory cytokines to retain its anti-tumor properties. Objectives of the study were to form an M3 switch phenotype in vitro and to evaluate the effect of M3 macrophages on growth of Ehrlich ascites carcinoma (EAC) in vitro and in vivo. Material/Methods Tumor growth was initiated by an intraperitoneal injection of EAC cells into C57BL/6J mice. Results 1) The M3 switch phenotype can be programed by activation of M1-reprogramming pathways with simultaneous inhibition of the M2 phenotype transcription factors, STAT3, STAT6, and/or SMAD3. 2) M3 macrophages exerted an anti-tumor effect both in vitro and in vivo, which was superior to anti-tumor effects of cisplatin or M1 macrophages. 3) The anti-tumor effect of M3 macrophages was due to their anti-proliferative effect. Conclusions Development of new biotechnologies for restriction of tumor growth using in vitro reprogrammed M3 macrophages is very promising. PMID:28123171

  12. Chemokine Binding Protein M3 of Murine Gammaherpesvirus 68 Modulates the Host Response to Infection in a Natural Host

    Science.gov (United States)

    Hughes, David J.; Kipar, Anja; Leeming, Gail H.; Bennett, Elaine; Howarth, Deborah; Cummerson, Joanne A.; Papoula-Pereira, Rita; Flanagan, Brian F.; Sample, Jeffery T.; Stewart, James P.

    2011-01-01

    Murine γ-herpesvirus 68 (MHV-68) infection of Mus musculus-derived strains of mice is an attractive model of γ-herpesvirus infection. Surprisingly, however, ablation of expression of MHV-68 M3, a secreted protein with broad chemokine-binding properties in vitro, has no discernable effect during experimental infection via the respiratory tract. Here we demonstrate that M3 indeed contributes significantly to MHV-68 infection, but only in the context of a natural host, the wood mouse (Apodemus sylvaticus). Specifically, M3 was essential for two features unique to the wood mouse: virus-dependent inducible bronchus-associated lymphoid tissue (iBALT) in the lung and highly organized secondary follicles in the spleen, both predominant sites of latency in these organs. Consequently, lack of M3 resulted in substantially reduced latency in the spleen and lung. In the absence of M3, splenic germinal centers appeared as previously described for MHV-68-infected laboratory strains of mice, further evidence that M3 is not fully functional in the established model host. Finally, analyses of M3's influence on chemokine and cytokine levels within the lungs of infected wood mice were consistent with the known chemokine-binding profile of M3, and revealed additional influences that provide further insight into its role in MHV-68 biology. PMID:21445235

  13. Chemokine binding protein M3 of murine gammaherpesvirus 68 modulates the host response to infection in a natural host.

    Directory of Open Access Journals (Sweden)

    David J Hughes

    2011-03-01

    Full Text Available Murine γ-herpesvirus 68 (MHV-68 infection of Mus musculus-derived strains of mice is an attractive model of γ-herpesvirus infection. Surprisingly, however, ablation of expression of MHV-68 M3, a secreted protein with broad chemokine-binding properties in vitro, has no discernable effect during experimental infection via the respiratory tract. Here we demonstrate that M3 indeed contributes significantly to MHV-68 infection, but only in the context of a natural host, the wood mouse (Apodemus sylvaticus. Specifically, M3 was essential for two features unique to the wood mouse: virus-dependent inducible bronchus-associated lymphoid tissue (iBALT in the lung and highly organized secondary follicles in the spleen, both predominant sites of latency in these organs. Consequently, lack of M3 resulted in substantially reduced latency in the spleen and lung. In the absence of M3, splenic germinal centers appeared as previously described for MHV-68-infected laboratory strains of mice, further evidence that M3 is not fully functional in the established model host. Finally, analyses of M3's influence on chemokine and cytokine levels within the lungs of infected wood mice were consistent with the known chemokine-binding profile of M3, and revealed additional influences that provide further insight into its role in MHV-68 biology.

  14. Soluble M3 proteins of murine gammaherpesviruses 68 and 72 expressed in Escherichia coli: analysis of chemokine-binding properties.

    Science.gov (United States)

    Matúšková, R; Pančík, P; Štibrániová, I; Belvončíková, P; Režuchová, I; Kúdelová, M

    2015-12-01

    M3 protein of murine gammaherpesvirus 68 (MHV-68) was identified as a viral chemokine-binding protein 3 (vCKBP-3) capable to bind a broad spectrum of chemokines and their receptors. During both acute and latent infection MHV-68 M3 protein provides a selective advantage for the virus by inhibiting the antiviral and inflammatory response. A unique mutation Asp307Gly was identified in the M3 protein of murine gammaherpesvirus 72 (MHV-72), localized near chemokine-binding domain. Study on chemokine-binding properties of MHV-72 M3 protein purified from medium of infected cells implied reduced binding to some chemokines when compared to MHV-68 M3 protein. It was suggested that the mutation in the M3 protein might be involved in the attenuation of immune response to infection with MHV-72. Recently, Escherichia coli cells were used to prepare native recombinant M3 proteins of murine gammaherpesviruses 68 and 72 (Pančík et al., 2013). In this study, we assessed the chemokine-binding properties of three M3 proteins prepared in E. coli Rosetta-gami 2 (DE3) cells, the full length M3 protein of both MHV-68 and MHV-72 and MHV-68 M3 protein truncated in the signal sequence (the first 24 aa). They all displayed binding activity to human chemokines CCL5 (RANTES), CXCL8 (IL-8), and CCL3 (MIP-1α). The truncated MHV-68 M3 protein had more than twenty times reduced binding activity to CCL5, but only about five and three times reduced binding to CXCL8 and CCL3 when compared to its full length counterpart. Binding of the full length MHV-72 M3 protein to all chemokines was reduced when compared to MHV-68 M3 protein. Its binding to CCL5 and CCL3 was reduced over ten and seven times. However, its binding to CXCL8 was only slightly reduced (64.8 vs 91.8%). These data implied the significance of the signal sequence and also of a single mutation (at aa 307) for efficient M3 protein binding to some chemokines.

  15. Structure of the HHARI catalytic domain shows glimpses of a HECT E3 ligase.

    Directory of Open Access Journals (Sweden)

    Donald E Spratt

    Full Text Available The ubiquitin-signaling pathway utilizes E1 activating, E2 conjugating, and E3 ligase enzymes to sequentially transfer the small modifier protein ubiquitin to a substrate protein. During the last step of this cascade different types of E3 ligases either act as scaffolds to recruit an E2 enzyme and substrate (RING, or form an ubiquitin-thioester intermediate prior to transferring ubiquitin to a substrate (HECT. The RING-inBetweenRING-RING (RBR proteins constitute a unique group of E3 ubiquitin ligases that includes the Human Homologue of Drosophila Ariadne (HHARI. These E3 ligases are proposed to use a hybrid RING/HECT mechanism whereby the enzyme uses facets of both the RING and HECT enzymes to transfer ubiquitin to a substrate. We now present the solution structure of the HHARI RING2 domain, the key portion of this E3 ligase required for the RING/HECT hybrid mechanism. The structure shows the domain possesses two Zn²⁺-binding sites and a single exposed cysteine used for ubiquitin catalysis. A structural comparison of the RING2 domain with the HECT E3 ligase NEDD4 reveals a near mirror image of the cysteine and histidine residues in the catalytic site. Further, a tandem pair of aromatic residues exists near the C-terminus of the HHARI RING2 domain that is conserved in other RBR E3 ligases. One of these aromatic residues is remotely located from the catalytic site that is reminiscent of the location found in HECT E3 enzymes where it is used for ubiquitin catalysis. These observations provide an initial structural rationale for the RING/HECT hybrid mechanism for ubiquitination used by the RBR E3 ligases.

  16. The BIOPAN experiment MARSTOX II of the FOTON M-3 mission

    Science.gov (United States)

    Rettberg, P.; Moeller, R.; Rabbow, E.; Panitz, C.; Horneck, G.; Meyer, C.; Lammer, H.; Douki, T.; Cadet, J.

    2008-09-01

    The experiment MARSTOX II on FOTON M-3 mission (September 14 - 26, 2007) was a further step in the study of the Responses of Organisms to the Martian Environment (ROME) which already started with first ground-based experiments in Mars simulation chambers and with the space experiment MARSTOX I, flown in 2005 in the ESA facility BIOPAN (Fig. 1) on FOTON M-2. The survivability of bacterial spores of B. subtilis, a well-characterized model system for highly resistant microorganisms, was investigated under the extreme environmental conditions as they exist on the surface of Mars. By use of exterrestrial UV radiation and cut-off filters the photoprotection and potential UV-phototoxicity of different minerals of the Martian soil were investigated.In MARSTOX II two further aspects were addressed (i) the influence of different concentrations of dust in the Martian atmosphere, which change the solar irradiance on the surface significantly compared to vacuum exposure under the same conditions (experiment parts 'DUST MARS' and 'DUST SPACE'), and (ii) the survivability of spores under martian atmosphere and pressure exposed to a mars-like spectral irradiance compared to vacuum exposure under the same conditions (experiment parts 'MIXED MARS' and 'MIXED SPACE') (Fig. 2 and 3). After exposure to space during the FOTON M-3 mission the sample analysis was performed at CEA in Grenoble, F, and at DLR in Cologne, D, together with parallel samples from the corresponding ground control experiment performed in the space simulation facilities at DLR. As biological endpoints in these investigations survival and UV-induced DNAphotoproducts were analysed.From the results of MARSTOX II the following conclusions can be drawn: (i) Spores mixed with martian soil analogue are protected only to a low degree against UV radiation. The protective effect of several defined layers of spores mixed with Martian soil analogue were quantified. (ii) The two investigated martian soil analogues, MRS07 (47

  17. CH5M3D: an HTML5 program for creating 3D molecular structures

    Science.gov (United States)

    2013-01-01

    Background While a number of programs and web-based applications are available for the interactive display of 3-dimensional molecular structures, few of these provide the ability to edit these structures. For this reason, we have developed a library written in JavaScript to allow for the simple creation of web-based applications that should run on any browser capable of rendering HTML5 web pages. While our primary interest in developing this application was for educational use, it may also prove useful to researchers who want a light-weight application for viewing and editing small molecular structures. Results Molecular compounds are drawn on the HTML5 Canvas element, with the JavaScript code making use of standard techniques to allow display of three-dimensional structures on a two-dimensional canvas. Information about the structure (bond lengths, bond angles, and dihedral angles) can be obtained using a mouse or other pointing device. Both atoms and bonds can be added or deleted, and rotation about bonds is allowed. Routines are provided to read structures either from the web server or from the user’s computer, and creation of galleries of structures can be accomplished with only a few lines of code. Documentation and examples are provided to demonstrate how users can access all of the molecular information for creation of web pages with more advanced features. Conclusions A light-weight (≈ 75 kb) JavaScript library has been made available that allows for the simple creation of web pages containing interactive 3-dimensional molecular structures. Although this library is designed to create web pages, a web server is not required. Installation on a web server is straightforward and does not require any server-side modules or special permissions. The ch5m3d.js library has been released under the GNU GPL version 3 open-source license and is available from http://sourceforge.net/projects/ch5m3d/. PMID:24246004

  18. Real-time monitoring of genetically modified Chlamydomonas reinhardtii during the Foton M3 space mission

    Science.gov (United States)

    Lambreva, M.; Rea, G.; Antonacci, A.; Serafini, A.; Damasso, M.; Pastorelli, S.; Margonelli, A.; Johanningmeier, U.; Bertalan, I.; Pezzotti, G.; Giardi, M. T.

    2008-09-01

    Long-term space exploration, colonization or habitation requires biological life support systems capable to cope with the deleterious space environment. The use of oxygenic photosynthetic microrganisms is an intriguing possibility mainly for food, O2 and nutraceutical compounds production. The critical points of utilizing plants- or algae-based life support systems are the microgravity and the ionizing radiation, which can influence the performance of these organisms. The aim of the present study was to assess the effects of space environment on the photosynthetic activity of various microrganisms and to select space stresstolerant strains. Photosystem II D1 protein sitedirected and random mutants of the unicellular green alga Chlamydomonas reinhardtii [1] were used as a model system to test and select the amino acid substitutions capable to account for space stress tolerance. We focussed our studies also on the accumulation of the Photosystem II photoprotective carotenoids (the xantophylls violaxanthin, anteraxanthin and zeaxanthin), powerful antioxidants that epidemiological studies demonstrated to be human vision protectors. For this purpose some mutants modified at the level of enzymes involved in the biosynthesis of xanthophylls were included in the study [2]. To identify the consequences of the space environment on the photosynthetic apparatus the changes in the Photosystem II efficiency were monitored in real time during the ESA-Russian Foton- M3 mission in September 2007. For the space flight a high-tech, multicell fluorescence detector, Photo-II, was designed and built by the Centre for Advanced Research in Space Optics in collaboration with Kayser-Italy, Biosensor and DAS. Photo-II is an automatic device developed to measure the chlorophyll fluorescence and to provide a living conditions for several different algae strains (Fig.1). Twelve different C. reinhardti strains were analytically selected and two replications for each strain were brought to space

  19. The Swift/UVOT Stars Survey. II. RR Lyrae Stars in M 3 and M 15

    CERN Document Server

    Siegel, Michael H; Balzer, Benjamin G; Hagen, Lea M Z

    2015-01-01

    We present the first results of an near-ultraviolet (NUV) survey of RR Lyrae stars from the Ultraviolet Optical Telescope (UVOT) aboard the Swift Gamma-Ray Burst Mission. It is well-established that RR Lyrae have large amplitudes in the far- and near-ultraviolet. We have used UVOT's unique wide-field NUV imaging capability to perform the first systematic NUV survey of variable stars in the Galactic globular clusters M 3 and M 15. We identify 280 variable stars, comprising 275 RR Lyrae, two anomalous Cepheids, one classical Cepheid, one SX Phoenicis star and one possible long-period or irregular variable. Only two of these are new discoveries. We compare our results to previous investigations and find excellent agreement in the periods with significantly larger amplitudes in the NUV. We map out, for the first time, an NUV Bailey diagram from globular clusters, showing the usual loci for fundamental mode RRab and first overtone RRc pulsators. We show the unique sensitivity of NUV photometry to both the temperat...

  20. THE SWIFT UVOT STARS SURVEY. II. RR LYRAE STARS IN M3 AND M15

    Energy Technology Data Exchange (ETDEWEB)

    Siegel, Michael H.; Porterfield, Blair L.; Balzer, Benjamin G.; Hagen, Lea M. Z., E-mail: siegel@astro.psu.edu, E-mail: blp14@psu.edu, E-mail: bgb5080@psu.edu, E-mail: lea.zernow.hagen@gmail.com [Pennsylvania State University, Department of Astronomy, 525 Davey Laboratory, University Park, PA 16802 (United States)

    2015-10-15

    We present the first results of a near-ultraviolet (NUV) survey of RR Lyrae stars from the Ultraviolet Optical Telescope (UVOT) on board the Swift Gamma-ray Burst Mission. It is well-established that RR Lyrae stars have large amplitudes in the far- and near-ultraviolet. We have used UVOT’s unique wide-field NUV imaging capability to perform the first systematic NUV survey of variable stars in the Galactic globular clusters M3 and M15. We identify 280 variable stars, comprised of 275 RR Lyrae, 2 anomalous Cepheids, 1 classical Cepheid, 1 SX Phoenicis star, and 1 possible long-period or irregular variable. Only two of these are new discoveries. We compare our results to previous investigations and find excellent agreement in the periods with significantly larger amplitudes in the NUV. We map out, for the first time, an NUV Bailey diagram from globular clusters, showing the usual loci for fundamental mode RRab and first overtone RRc pulsators. We show the unique sensitivity of NUV photometry to both the temperatures and the surface gravities of RR Lyrae stars. Finally, we show evidence of an NUV period–metallicity–luminosity relationship. Future investigations will further examine the dependence of NUV pulsation parameters on metallicity and Oosterhoff classification.

  1. Molecular Modeling of the M3 Acetylcholine Muscarinic Receptor and Its Binding Site

    Science.gov (United States)

    Martinez-Archundia, Marlet; Cordomi, Arnau; Garriga, Pere; Perez, Juan J.

    2012-01-01

    The present study reports the results of a combined computational and site mutagenesis study designed to provide new insights into the orthosteric binding site of the human M3 muscarinic acetylcholine receptor. For this purpose a three-dimensional structure of the receptor at atomic resolution was built by homology modeling, using the crystallographic structure of bovine rhodopsin as a template. Then, the antagonist N-methylscopolamine was docked in the model and subsequently embedded in a lipid bilayer for its refinement using molecular dynamics simulations. Two different lipid bilayer compositions were studied: one component palmitoyl-oleyl phosphatidylcholine (POPC) and two-component palmitoyl-oleyl phosphatidylcholine/palmitoyl-oleyl phosphatidylserine (POPC-POPS). Analysis of the results suggested that residues F222 and T235 may contribute to the ligand-receptor recognition. Accordingly, alanine mutants at positions 222 and 235 were constructed, expressed, and their binding properties determined. The results confirmed the role of these residues in modulating the binding affinity of the ligand. PMID:22500107

  2. [Gerbil experiment in the flight of spacecraft "Foton-M3"].

    Science.gov (United States)

    Il'in, E A; Smirnov, I A; Soldatov, P E; Orlov, O I

    2009-01-01

    The 12-d mission of Russian spacecraft Foton-M3 in September of 2007 was used as an opportunity to fly an experiment with 12 male gerbils (Meriones unguiculatus) at the age of 4-4.5 mos. and mean body weight of 51.6 grams. Considering the behavior pattern of these animals, selection and preparation of the experimental groups continued in the course of 2.5-3 months. The flight animals were contained in module Kontur-L outfitted with a self-sustained system of life support. In orbit, the animals received a palletized hydrogenous feed. The physiological and hygienic parameters of the gerbil environment during the flight complied with the official standards. Analysis of the video recorded behavior of animals in microgravity showed that virtually throughout the flight they moved chaotically along the cage never attempting to stabilize position catching at the wire netting of the cage. The animals were decapitated in 21-24 hours after landing. The investigations showed that structural and functional changes in gerbil organs and tissues were generally of the same type as in rats following fights of comparable duration. However, some differences between the animals were attributed to the specifics of water turnover in gerbils.

  3. [Handling and maintenance of gerbils during the spacecraft Foton-M3 mission].

    Science.gov (United States)

    Soldatov, P E; Smirnov, I A; Il'in, E A; Gur'eva, T S; Mednikova, E I; Smolenskaia, T S; Lysenko, L A; Kaminskaia, E V

    2009-01-01

    Pressurized low-sized module Kontur with an independent life support system (LSS) was developed by the Institute of Biomedical Problems cooperatively with the Special Design Bureau of Experimental Equipment to house gerbils (Meriones unguiculatus) aboard robotic technology-purpose spacecraft. Design of the module precludes pollution of the environment The fully equipped module weighs 69 kg; average daily power consumption is 62 watts. The environmental parameters for 12 animals flown on Foton-M3 in the period of September 14-26, 2007 were controlled within the following ranges: pO2 - 143-156 mm Hg, (mean 150 mm Hg), pCO2 - 0.76 mm Hg maximum (mean 0.64 mm Hg), temperature - 23-28 degrees C (mean 26.7 degrees C), relative humidity - 29% and 57% at the beginning and end of the flight, respectively (mean 39%). The animals consumed the palletized food prepared of natural products with a moisture content of approx. 20%. The day-night periods were 12 hrs. long. The daytime video recording of the animals went on continuously in the throughout the flight. The experiment showed that the module meets the requirements of experiments with mammals aboard returnable robotic spacecraft and piloted space stations. At the moment, the model is being redesigned for a 30-day BION-M1 mission.

  4. [Glycogen content in gerbil's liver following the spacecraft Foton-M3 mission].

    Science.gov (United States)

    Atiakshin, D A; Bykov, E G; Il'in, E A; Pashkov, A N

    2009-01-01

    Glycogen cytochemistry and distribution in hepatocytes of the classic liver lobules were studied in three groups of gerbils Meriones unguiculatus: vivarium, synchronous control and flown in the 12-d Foton-M3 mission. The control animals were shown to have the central glycogen distribution with a large pool of polysaccharides found in hepatocytes of the pericentral and intermediate lobules and a small pool in the periportal area. Glycogen in hepatocyte plasm was within the physiological norm in the alpha- and beta-granules, typically localized on the cell periphery. Exposure to the spaceflight conditions decreased significantly glycogen concentrations in each functional region of the hepatic lobules and reduced the gradient of polysaccharide distribution from the portal triads toward the central vein. In parallel, high glycogen heterogeneity formed in adjacent hepatocytes and loci. The presence of glycosomes evidenced disturbance of carbohydrates metabolism. In addition, intracellular topography of glycogen granules in cytoplasm was altered. Trends of glycogen in gerbils of the synchronous control were similar to the space flown animals but much less pronounced.

  5. [Jejunum intersticium in mongolian gerbils after the flight on spacecraft Foton-M3].

    Science.gov (United States)

    Atiashkin, D A; Bykov, É G; Il'in, E A; Pashkov, A N

    2012-01-01

    Methods of light optical microscopy were used to explore histoarchitectonics, topography and tinctorial properties of the extracellular phase of fibers of jejunum wall intersticium in Mongolian gerbils following 12-day orbital flight aboard Foton-M3, ground-based simulation of the spaceflight factors in the KONTUR-L facility, and in the group of biological control Postflight destructive changes were found in reticulin fibers (type-III collagen) of villi stroma, intercrypt intersticium and submucosa. Local acidophilia and fiber homogenization formed in type I collagen present in the intestinal subserous layer, muscular layers endomysium and submucose against the background of progressing edema and arterial, venous plethora and lymphostasis. Elastic component of the intersticium was disarranged in the structures of internal elastic membrane of submucous vessels, fragmented and partly reduced. Simulation of the orbital factors, except for microgravity, in the KONTUR-L facility called forth similar, although less often and diffuse, changes in intersticium fibers. The results of examination of intestinal intersticium fibers in the vivarium control gerbils discovered expressed species characters that should be taken into account by investigators, especially when comparing with data obtained from other animal species.

  6. [Rna content of gerbil hepatocytes after the flight aboard space platform Foton-M3].

    Science.gov (United States)

    Atiashkin, D A; Bykov, E G; Il'in, E A; Pashkov, A N

    2010-01-01

    The paper compares and contrasts the results of measuring the hepatocyte cytoplasm area and RNA content in 35 gerbils in three series of experiments, i.e. the vivarium control, modeled space flight (synchronous control) and exposure to the factors of 12-d Foton-M3 orbital flight. Central, intermediate and peripheral zones of hepatic lobes were subjected to histological and histochemical analyses to measure the hepatocyte cytoplasm area; the RNA content was determined from the level of cytoplasm basophilia after azure staining. Cytometric and cytophotometric investigations were performed using image analyzer Video-7-Test-Morpho. In the vivarium animals, hepatocytes with the largest cytoplasm localized predominantly in the intermediate and central zones of the lobes. Judging from the results of microdensitometry, the RNA content was particularly high in binucleate hepatocytes of the intermediate zone. In the synchronous control, hepatocytes tended to grow in size, in the peripheral zone specifically, whereas RNA content was largely equal no matter hepatocyte topography. After space flight, cytoplasm enlargement transcended this process in the vivarium animals. The cytoplasm RNA content along the entire liver parenchyma made a significant decrease equally as compared with the vivarium and synchronous control animals.

  7. Molecular Modeling of the M3 Acetylcholine Muscarinic Receptor and Its Binding Site

    Directory of Open Access Journals (Sweden)

    Marlet Martinez-Archundia

    2012-01-01

    Full Text Available The present study reports the results of a combined computational and site mutagenesis study designed to provide new insights into the orthosteric binding site of the human M3 muscarinic acetylcholine receptor. For this purpose a three-dimensional structure of the receptor at atomic resolution was built by homology modeling, using the crystallographic structure of bovine rhodopsin as a template. Then, the antagonist N-methylscopolamine was docked in the model and subsequently embedded in a lipid bilayer for its refinement using molecular dynamics simulations. Two different lipid bilayer compositions were studied: one component palmitoyl-oleyl phosphatidylcholine (POPC and two-component palmitoyl-oleyl phosphatidylcholine/palmitoyl-oleyl phosphatidylserine (POPC-POPS. Analysis of the results suggested that residues F222 and T235 may contribute to the ligand-receptor recognition. Accordingly, alanine mutants at positions 222 and 235 were constructed, expressed, and their binding properties determined. The results confirmed the role of these residues in modulating the binding affinity of the ligand.

  8. [2 fatal cases of acute myeloid leukemia (M3, M4) during pregnancy].

    Science.gov (United States)

    Aragona, M; Asmundo, A

    1995-04-01

    Two cases of unexpected post-partum death of women with acute leukemia are described. In the first case (1st pregnancy) the diagnosis (acute promyelocytic leukemia: M3) was performed one week before delivery and death occurred 3 days later, because of hemorrhagic and renal DIC complication. Since one month before hospitalization, laboratory exams indicated a serious hematological pathology and no further exams were carried out by the physicians, elements of professional fault were recognized in them, considering that because of the diagnostic omission it was impossible to make an early diagnosis and thus perform to specific therapy, adopted only in the terminal phase. This specific therapy is able to determine remission from most cases of acute promyelocytic leukemia. In the second case (2nd pregnancy) the diagnosis (acute myelomonocytic leukemia: M4) was performed only postmortem because, during the whole pregnancy, no signs of disease were evident. After a few hours from the spontaneous delivery, death occurred as a result of an intractable + hemorrhagic syndrome caused by primary hyperfibrinolysis and repeated episodes of cardiac arrest, without possibility of recognizing it. The medical procedures for this case, both throughout pregnancy and terminal phases, appeared free of censure.

  9. Experimental Study of Ultralight (<300 kg/m3 Foamed Concrete

    Directory of Open Access Journals (Sweden)

    Xianjun Tan

    2014-01-01

    Full Text Available A type of ultralight (<300 kg/m3 foamed concrete (FC, which can be used as a new energy-conservation and environmental-protection building material and is particularly suitable for the thermal-insulation engineering of building external walls, was produced. The influences of different mixing amounts of fly ash, fly ash activator, WC (WC ratio, and foaming agent (FA on the compressive strength of FC were reported. The experimental study indicated that (1 the addition of fly ash reduced the strength of the FC and that the appropriate mixing amount of fly ash in this ultralight FC system should not exceed 45%; (2 with the increasing of fly ash activator, the strength of the FC sample is notably enhanced and the appropriate mixing amount of fly ash activator is 2.5%; (3 the optimized proportion of WC ratio is 0.45, and the FC that was produced according to this proportion has relatively high compressive strength; (4 by increasing the mixing amount of FA, the compressive strength of the FC notably decreases, and the optimal mixing amount of FA in this experiment is 3.5%.

  10. Discovery of a wide planetary-mass companion to the young M3 star GU PSC

    Energy Technology Data Exchange (ETDEWEB)

    Naud, Marie-Eve; Artigau, Étienne; Malo, Lison; Albert, Loïc; Doyon, René; Lafrenière, David; Gagné, Jonathan; Boucher, Anne [Département de physique and Observatoire du Mont-Mégantic, Université de Montréal, Montréal H3C 3J7 (Canada); Saumon, Didier [Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Morley, Caroline V. [Department of Astronomy and Astrophysics, University of California, Santa Cruz, CA 95064 (United States); Allard, France; Homeier, Derek [Centre de Recherche Astrophysique de Lyon, UMR 5574 CNRS, Université de Lyon, École Normale Supérieure de Lyon, 46 Allée d' Italie, F-69364 Lyon Cedex 07 (France); Beichman, Charles A.; Gelino, Christopher R., E-mail: naud@astro.umontreal.ca [Infrared Processing and Analysis Center, MS 100-22, California Institute of Technology, Pasadena, CA 91125 (United States)

    2014-05-20

    We present the discovery of a comoving planetary-mass companion ∼42'' (∼2000 AU) from a young M3 star, GU Psc, a likely member of the young AB Doradus Moving Group (ABDMG). The companion was first identified via its distinctively red i – z color (>3.5) through a survey made with Gemini-S/GMOS. Follow-up Canada-France-Hawaii Telescope/WIRCam near-infrared (NIR) imaging, Gemini-N/GNIRS NIR spectroscopy and Wide-field Infrared Survey Explorer photometry indicate a spectral type of T3.5 ± 1 and reveal signs of low gravity which we attribute to youth. Keck/Adaptive Optics NIR observations did not resolve the companion as a binary. A comparison with atmosphere models indicates T {sub eff} = 1000-1100 K and log g = 4.5-5.0. Based on evolution models, this temperature corresponds to a mass of 9-13 M {sub Jup} for the age of ABDMG (70-130 Myr). The relatively well-constrained age of this companion and its very large angular separation to its host star will allow its thorough characterization and will make it a valuable comparison for planetary-mass companions that will be uncovered by forthcoming planet-finder instruments such as Gemini Planet Imager and SPHERE 9.

  11. Magnetic and dynamical photospheric disturbances observed during an M3.2 solar flare

    CERN Document Server

    Kuckein, C; Sainz, R Manso

    2015-01-01

    This letter reports on a set of full-Stokes spectropolarimetric observations in the near infrared He I 10830 A spectral region covering the pre-, flare, and post-flare phases of an M3.2 class solar flare. The flare originated on 2013 May 17 and belonged to active region NOAA 11748. We detected strong He I 10830 A emission in the flare. The red component of the He I triplet peaks at an intensity ratio to the continuum of about 1.86. During the flare, He I Stokes V is substantially larger and appears reversed compared to the usually larger Si I Stokes V profile. The photospheric Si I inversions of the four Stokes profiles reveal the following: (1) the magnetic field strength in the photosphere decreases or is even absent during the flare phase, as compared to the pre-flare phase. However, this decrease is not permanent. After the flare the magnetic field recovers its pre-flare configuration in a short time (i.e., in 30 minutes after the flare). (2) In the photosphere, the line-of-sight velocities show a regular...

  12. GRAVITAS : General Relativistic Astrophysics VIa Timing And Spectroscopy: An ESA M3 mission proposal

    CERN Document Server

    Nandra, Kirpal; Fabian, Andy; Strueder, Lothar; Willingale, Richard; Watson, Mike; Jonker, Peter; Kunieda, Hideyo; Miniutti, Giovanni; Motch, Christian; Predehl, Peter

    2011-01-01

    GRAVITAS is an X-ray observatory, designed and optimised to address the ESA Cosmic Vision theme of "Matter under extreme conditions". It was submitted as a response to the call for M3 mission proposals. The concept centres around an X-ray telescope of unprecedented effective area, which will focus radiation emitted from close to the event horizon of black holes or the surface of neutron stars. To reveal the nature and behaviour of matter in the most extreme astrophysical environments, GRAVITAS targets a key feature in the X-ray spectra of compact objects: the iron Kalpha line at ~6.5 keV. The energy, profile, and variability of this emission line, and the properties of the surrounding continuum emission, shaped by General Relativity (GR) effects, provide a unique probe of gravity in its strong field limit. Among its prime targets are hundreds of supermassive black holes in bright Active Galactic Nuclei (AGN), which form the perfect laboratory to help understand the physical processes behind black hole growth....

  13. Overtone and multi-mode RR Lyrae stars in the globular cluster M3

    CERN Document Server

    Jurcsik, J; Hajdu, G; Sódor, Á; Nuspl, J; Kolenberg, K; Fűrész, G; Moór, A; Kun, E; Pál, A; Bakos, J; Kelemen, J; Kovács, T; Kriskovics, L; Sárneczky, K; Szalai, T; Szing, A; Vida, K

    2015-01-01

    The overtone and multi-mode RR Lyrae stars in the globular cluster M3 are studied using a 200-d long, $B,V$ and $I_{\\mathrm C}$ time-series photometry obtained in 2012. 70\\% of the 52 overtone variables observed show some kind of multi-periodicity (additional frequency at ${f_{0.61}}={f_{\\mathrm {1O}}}/0.61$ frequency ratio, Blazhko effect, double/multi-mode pulsation, period doubling). A signal at 0.587 frequency ratio to the fundamental-mode frequency is detected in the double-mode star, V13, which may be identified as the second radial overtone mode. If this mode-identification is correct, than V13 is the first RR Lyrae star showing triple-mode pulsation of the first three radial modes. Either the Blazhko effect or the ${f_{0.61}}$ frequency (or both of these phenomena) appear in 7 double-mode stars. The $P_{\\mathrm{1O}}/P_{\\mathrm{F}}$ period ratio of RRd stars showing the Blazhko effect are anomalous. A displacement of the main frequency component at the fundamental-mode with the value of modulation freq...

  14. Discovery of a wide planetary-mass companion to the young M3 star GU Psc

    CERN Document Server

    Naud, Marie-Eve; Malo, Lison; Albert, Loïc; Doyon, René; Lafrenière, David; Gagné, Jonathan; Saumon, Didier; Morley, Caroline V; Allard, France; Homeier, Derek; Beichman, Charles A; Gelino, Christopher R; Boucher, Anne

    2014-01-01

    We present the discovery of a co-moving planetary-mass companion ~42" (~2000 AU) from a young M3 star, GU Psc, likely member of the young AB Doradus Moving Group (ABDMG). The companion was first identified via its distinctively red i - z color (> 3.5) through a survey made with Gemini-S/GMOS. Follow-up Canada-France-Hawaii Telescope/WIRCam near-infrared (NIR) imaging, Gemini-N/GNIRS NIR spectroscopy and Wide-field Infrared Survey Explorer photometry indicate a spectral type of T3.5+-1 and reveal signs of low gravity which we attribute to youth. Keck/Adaptive Optics NIR observations did not resolve the companion as a binary. A comparison with atmosphere models indicates Teff = 1000-1100 K and logg = 4.5-5.0. Based on evolution models, this temperature corresponds to a mass of 9-13 MJup for the age of ABDMG (70-130 Myr). The relatively well-constrained age of this companion and its very large angular separation to its host star will allow its thorough characterization and will make it a valuable comparison for ...

  15. IFR safety tests M2 and M3 in TREAT: data and analysis

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, W R; Lo, R K; Bauer, T H; Froehle, P H; Helenberg, H W; Morman, J A; Stanford, G S; Wright, A E

    1985-06-01

    TREAT tests M2 and M3 were performed to obtain information on the characteristics of metal-alloy reactor fuel under slow transient overpower accident conditions, in particular, the margin to cladding breach and the axial self-extrusion of fuel within intact cladding. The tests used U-5Fs fuel pins irradiated to burnup levels of 0.3 at. %, 4.5 at. % and 7.9 at. %. Each pin was located in a separte flowtube and cooled by flowing sodium. In one test, a pin of each burnup was heated to incipient cladding breach. In the other, pins of the medium and high burnup levels wer heated to slightly beyond breach. Pre- and post-failure fuel motions were monitored by the fast-neutron hodoscope. The time and axial location of cladding breach were determined from the test-loop instrumentation. Computations of fuel extrusion and cladding failure are desribed. The models used in the computations include effects of retained fission gas expansion, vaporization of the sodium-bond annulus in low burnup fuel, and cladding-wall thinning by eutectic formation.

  16. Structural and Thermodynamic Properties of M3W3N (M=Fe, Co, Ni)

    Institute of Scientific and Technical Information of China (English)

    CHEN Yi; SHEN Jiang; CHEN Nan-Xian

    2009-01-01

    @@ Ternary transition metal nitrides, Fe3W3N, Co3W3N, and Ni3W3N, are studied by the use of interatomic po-tentials acquired from lattice inversion. The study indicates that Fe3W3N would be more stable than the other compounds in the family of intermetallic tungsten nitrides. The investigation of phonon density of states indi-cates that the lower frequency modes are mostly excited by the metal atoms, and the higher frequency modes are mostly excited by the nitrogen atoms. A qualitative analysis is carried out with the relevant potentials for the phase stability and vibrational modes.

  17. E3 Success Story - Whirlpool Trains Staff on Lean and Green Advantage

    Science.gov (United States)

    Whirlpool Corporation invited Green Suppliers Network representatives to its Monterrey facility to provide training on the Lean and Green Advantage. The project sought to expand E3 initiatives to every part of the company's operations.

  18. E3 Success Story - Advancing Performance in Sustainability and Workforce Development

    Science.gov (United States)

    E3: North Carolina advances performance in sustainability and workforce development strategies for the state's manufacturers. The initiative helps communities and manufacturers address energy and sustainability challenges by leveraging expertise.

  19. Bioinformatics analysis identifies several intrinsically disordered human E3 ubiquitin-protein ligases

    DEFF Research Database (Denmark)

    Boomsma, Wouter Krogh; Nielsen, Sofie Vincents; Lindorff-Larsen, Kresten

    2016-01-01

    The ubiquitin-proteasome system targets misfolded proteins for degradation. Since the accumulation of such proteins is potentially harmful for the cell, their prompt removal is important. E3 ubiquitin-protein ligases mediate substrate ubiquitination by bringing together the substrate with an E2...... ubiquitin-conjugating enzyme, which transfers ubiquitin to the substrate. For misfolded proteins, substrate recognition is generally delegated to molecular chaperones that subsequently interact with specific E3 ligases. An important exception is San1, a yeast E3 ligase. San1 harbors extensive regions...... of intrinsic disorder, which provide both conformational flexibility and sites for direct recognition of misfolded targets of vastly different conformations. So far, no mammalian ortholog of San1 is known, nor is it clear whether other E3 ligases utilize disordered regions for substrate recognition. Here, we...

  20. Structure and function of Parkin E3 ubiquitin ligase reveals aspects of RING and HECT ligases

    National Research Council Canada - National Science Library

    Riley, B E; Lougheed, J C; Callaway, K; Velasquez, M; Brecht, E; Nguyen, L; Shaler, T; Walker, D; Yang, Y; Regnstrom, K; Diep, L; Zhang, Z; Chiou, S; Bova, M; Artis, D R; Yao, N; Baker, J; Yednock, T; Johnston, J A

    2013-01-01

    Parkin is a RING-between-RING E3 ligase that functions in the covalent attachment of ubiquitin to specific substrates, and mutations in Parkin are linked to Parkinson's disease, cancer and mycobacterial infection...

  1. Protein microarrays for the identification of praja1 e3 ubiquitin ligase substrates.

    Science.gov (United States)

    Loch, Christian M; Eddins, Michael J; Strickler, James E

    2011-06-01

    Although they are the primary determinants of substrate specificity, few E3-substrate pairs have been positively identified, and few E3's profiled in a proteomic fashion. Praja1 is an E3 implicated in bone development and highly expressed in brain. Although it has been well studied relative to the majority of E3's, little is known concerning the repertoire of proteins it ubiquitylates. We sought to identify high confidence substrates for Praja1 from an unbiased proteomic profile of thousands of human proteins using protein microarrays. We first profiled Praja1 activity against a panel of E2's to identify its optimal partner in vitro. We then ubiquitylated multiple, identical protein arrays and detected putative substrates with reagents that vary in ubiquitin recognition according to the extent of chain formation. Gene ontology clustering identified putative substrates consistent with information previously known about Praja1 function, and provides clues into novel aspects of this enzyme's function.

  2. Comparison of human and porcine gastric clasp and sling fiber contraction by M2 and M3 muscarinic receptors.

    Science.gov (United States)

    Vegesna, Anil K; Braverman, Alan S; Miller, Larry S; Tallarida, Ronald J; Tiwana, Mansoor I; Khayyam, Umar; Ruggieri, Michael R

    2010-04-01

    To compare the gastroesophageal junction of the human with the pig, M(2) and M(3) receptor densities and the potencies of M(2) and M(3) muscarinic receptor subtype selective antagonists were determined in gastric clasp and sling smooth muscle fibers. Total muscarinic and M(2) receptors are higher in pig than human clasp and sling fibers. M(3) receptors are higher in human compared with pig sling fibers but lower in human compared with pig clasp fibers. Clasp fibers have fewer M(3) receptors than sling fibers in both humans and pigs. Similar to human clasp fibers, pig clasp fibers contract significantly less than pig sling fibers. Analysis of the methoctramine Schild plot suggests that M(2) receptors are involved in mediating contraction in pig clasp and sling fibers. Darifenacin potency suggests that M(3) receptors mediate contraction in pig sling fibers and that M(2) and M(3) receptors mediate contraction in pig clasp fibers. Taken together, the data suggest that both M(2) and M(3) muscarinic receptors mediate the contraction in both pig clasp and sling fibers similar to human clasp and sling fibers.

  3. Ghosts of Milky Way's past: the globular cluster ESO 37-1 (E 3)

    CERN Document Server

    Marcos, R de la Fuente; Bidin, C Moni; Ortolani, S; Carraro, G

    2015-01-01

    Context. In the Milky Way, most globular clusters are highly conspicuous objects that were found centuries ago. However, a few dozen of them are faint, sparsely populated systems identified largely during the second half of the past century. One of the faintest is ESO 37-1 (E 3) and as such it remains poorly studied, with no spectroscopic observations published so far, although it was discovered in 1976. Aims. We investigate the globular cluster E 3 in an attempt to better constrain its fundamental parameters. Spectroscopy of stars in the field of E 3 is shown here for the first time. Methods. Deep, precise VI CCD photometry of E 3 down to V=26 mag is presented and analyzed. Low resolution, medium signal-to-noise ratio spectra of 9 candidate members are studied to derive radial velocity and metallicity. Proper motions from the UCAC4 catalogue are used to explore the kinematics of the bright members of E 3. Results. Isochrone fitting indicates that E 3 is probably very old, with an age of about 13 Gyr; its dis...

  4. MAGNETIC AND DYNAMICAL PHOTOSPHERIC DISTURBANCES OBSERVED DURING AN M3.2 SOLAR FLARE

    Energy Technology Data Exchange (ETDEWEB)

    Kuckein, C. [Leibniz-Institut für Astrophysik Potsdam (AIP), An der Sternwarte 16, D-14482, Potsdam (Germany); Collados, M.; Sainz, R. Manso, E-mail: ckuckein@aip.de [Instituto de Astrofísica de Canarias (IAC), Vía Láctea s/n, E-38205, La Laguna, Tenerife (Spain)

    2015-02-01

    This Letter reports on a set of full-Stokes spectropolarimetric observations in the near-infrared He i 10830 Å spectral region covering the pre-flare, flare, and post-flare phases of an M3.2 class solar flare. The flare originated on 2013 May 17 and belonged to active region NOAA 11748. We detected strong He i 10830 Å emission in the flare. The red component of the He i triplet peaks at an intensity ratio to the continuum of about 1.86. During the flare, He i Stokes V is substantially larger and appears reversed compared to the usually larger Si i Stokes V profile. The photospheric Si i inversions of the four Stokes profiles reveal the following: (1) the magnetic field strength in the photosphere decreases or is even absent during the flare phase, as compared to the pre-flare phase. However, this decrease is not permanent. After the flare, the magnetic field recovers its pre-flare configuration in a short time (i.e., 30 minutes after the flare). (2) In the photosphere, the line of sight velocities show a regular granular up- and downflow pattern before the flare erupts. During the flare, upflows (blueshifts) dominate the area where the flare is produced. Evaporation rates of ∼10{sup −3} and ∼10{sup −4} g cm{sup −2} s{sup −1} have been derived in the deep and high photosphere, respectively, capable of increasing the chromospheric density by a factor of two in about 400 s.

  5. Signal transduction by M3 muscarinic acetylcholine receptor in prostate cancer

    Science.gov (United States)

    GUO, LIQIANG; LIU, YUQIANG; DING, ZHIBO; SUN, WENDONG; YUAN, MINGZHEN

    2016-01-01

    The present study aimed to investigate the potential mechanisms used during signal transduction by M3 muscarinic acetylcholine receptor (CHRM3) in prostate cancer. The microarray datasets of GSE3325, including 5 clinically localized primary prostate cancers and 4 benign prostate tissues, were downloaded from the Gene Expression Omnibus database. The differentially-expressed genes (DEGs) in primary prostate cancer tissues compared with benign controls were screened using the Limma package. Gene Ontology and pathway enrichment analyses were performed using the Database for Annotation Visualization and Integrated Discovery. Next, a protein-protein interaction (PPI) network was constructed. Additionally, microRNAs (miRNAs) associated with DEGs were predicted and miRNA-target DEG analysis was performed using a Web-based Gene Set Analysis Toolkit. Finally, the PPI network and the miRNA-target DEG network were integrated using Cytoscape. In total, 224 DEGs were screened in the prostate cancer tissues, including 113 upregulated and 111 downregulated genes. CHRM3 and epidermal growth factor (EGF) were enriched in the regulation of the actin cytoskeleton. EGF and v-myc avian myelocytomatosis viral oncogene homolog (Myc) were enriched in the mitogen-activated protein kinase (MAPK) signaling pathway. EGF with the highest degree of connectivity was the hub node in the PPI network, and miR-34b could interact with Myc directly in the miRNA-target DEG network. EGF and Myc may exhibit significant roles in the progression of prostate cancer via regulation of the actin cytoskeleton and the MAPK signaling pathway. CHRM3 may activate these two pathways in prostate cancer progression. Thus, these two key factors and pathways may be crucial mechanisms during signal transduction by CHRM3 in prostate cancer. PMID:26870222

  6. Simulation of VANAM M3 test using MELCOR 1.8.3

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Sung Won; Kim, Hee Dong [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1996-07-01

    A standard problem is defined as a comparison between experimental and analytical results in the field of reactor safety research. The detailed comparison of the data permits conclusions for the reliability and precision of computer simulations of postulated accidents and contributions to the development and improvement of reactor safety computer codes. Following a suggestion of the Federal Republic of Germany, the OECD-CSNI agreed to offer the experiment VANAM M3 at the Battelle Model Containment (BMC), an experiment on thermohydraulics and aerosol behavior in a containment, as International Standard Problem No. 37 (ISP 37). The general objectives of the ISP 37 are to analyse the thermohydraulics of a containment atmosphere and the distribution and settlement of aerosol after a high pressure path with depressurization by pressurizer relief valve discharge. Steam condensation at the aerosol particles(condensation in volume) is enhanced by the hygroscopic properties of the aerosol materials, even in case of limited steam supply. The originally small, low-density NaOH particles are converted to solution droplets by steam condensation, the increasing droplet mass significantly enhancing aerosol depletion by gravity settlement. As a result, higher depletion rate have been obtained for the NaOH aerosol than for the SnO{sub 2} aerosol in M2. The MELCOR code, version 1.8.3, has been used for the simulation of this experiment, and the results are compared with the results of other calculations at GRS. The objectives of this report are to contribute to the efficient use of MELCOR code and understanding of the aerosol behavior. 12 tabs., 19 figs., 11 refs. (Author).

  7. Agronomic Characterization of Wheat Mutants (Triticum aestivum of M3 Generation Planted in Sukabumi

    Directory of Open Access Journals (Sweden)

    Laela Sari

    2016-11-01

    Full Text Available The purpose of this study was to identify the selection criteria to obtain a superior mutant derived from the wheat plants of such varieties as Dewata, Selayar and Alibey, adaptive in medium land. The analysis of agronomic growth characters showed a significantly effect on a growth percentage of the initial growth (8 mutants, flowering time (1 mutant, panicle stem length (15 mutants, number of panicles (7 mutants, the number of grains per panicle (8 mutants, grain weight observed (8 mutants, grain weight per genotype (6 mutants, leaf area (2 mutants and leaf greenness (5 mutants. The effects on the characters of ripe time, harvest, panicle length and plant height were not significant. The mutants of Dewata, Selayar and Alibey could be selected based on the characters of panicle stem length, number of grains per panicle and grain weight per observation because these characters generated more mutants than the other characters. The correlation analysis between the characters of growth and yield components of wheat mutants showed that the number of grains per panicle was positively correlated with the grain weight observed, while the length of panicle stem was positively correlated with grain weight per genotype, number of panicles and leaf area. Hopefully some mutants produced could adapt to the tropical medium land, thus adding to the diversity of wheat germplasm in Indonesia, thereby reducing the import of wheat to Indonesia.How to CiteSari, L., Purwito, A., Sopandie, D., Purnamaningsih, R. & Sudarmonowati, E. (2016. Agronomic Characterization of Wheat Mutants (Triticum aestivum of M3 Generation Planted in Sukabumi. Biosaintifika: Journal of Biology & Biology Education, 8(3, 353-361. 

  8. Remote compositional analysis of lunar olivine-rich lithologies with Moon Mineralogy Mapper (M3) spectra

    Science.gov (United States)

    Isaacson, P.J.; Pieters, C.M.; Besse, S.; Clark, R.N.; Head, J.W.; Klima, R.L.; Mustard, J.F.; Petro, N.E.; Staid, M.I.; Sunshine, J.M.; Taylor, L.A.; Thaisen, K.G.; Tompkins, S.

    2011-01-01

    A systematic approach for deconvolving remotely sensed lunar olivine-rich visible to near-infrared (VNIR) reflectance spectra with the Modified Gaussian Model (MGM) is evaluated with Chandrayaan-1 Moon Mineralogy Mapper (M 3) spectra. Whereas earlier studies of laboratory reflectance spectra focused only on complications due to chromite inclusions in lunar olivines, we develop a systematic approach for addressing (through continuum removal) the prominent continuum slopes common to remotely sensed reflectance spectra of planetary surfaces. We have validated our continuum removal on a suite of laboratory reflectance spectra. Suites of olivine-dominated reflectance spectra from a small crater near Mare Moscoviense, the Copernicus central peak, Aristarchus, and the crater Marius in the Marius Hills were analyzed. Spectral diversity was detected in visual evaluation of the spectra and was quantified using the MGM. The MGM-derived band positions are used to estimate the olivine's composition in a relative sense. Spectra of olivines from Moscoviense exhibit diversity in their absorption features, and this diversity suggests some variation in olivine Fe/Mg content. Olivines from Copernicus are observed to be spectrally homogeneous and thus are predicted to be more compositionally homogeneous than those at Moscoviense but are of broadly similar composition to the Moscoviense olivines. Olivines from Aristarchus and Marius exhibit clear spectral differences from those at Moscoviense and Copernicus but also exhibit features that suggest contributions from other phases. If the various precautions discussed here are weighed carefully, the methods presented here can be used to make general predictions of absolute olivine composition (Fe/Mg content). Copyright ?? 2011 by the American Geophysical Union.

  9. ns2np4 (n = 4, 5) lone pair triplets whirling in M*F2E3 (M* = Kr, Xe): Stereochemistry and ab initio analyses

    Science.gov (United States)

    Galy, Jean; Matar, Samir F.

    2017-02-01

    The stereochemistry of ns2np4 (n = 4, 5) lone pair LP characterizing noble gas Kr and Xe (labeled M*) in M*F2 difluorides is examined within coherent crystal chemistry and ab initio visualizations. M*2+ in such oxidation state brings three lone pairs (E) and difluorides are formulated M*F2E3. The analyses use electron localization function (ELF) obtained within density functional theory calculations showing the development of the LP triplets whirling {E3} quantified in the relevant chemical systems. Detailed ELF data analyses allowed showing that in α KrF2E3 and isostructural XeF2E3 difluorides the three E electronic clouds merge or hybridize into a torus and adopt a perfect gyration circle with an elliptical section, while in β KrF2 the network architecture deforms the whole torus into an ellipsoid shape. Original precise metrics are provided for the torus in the different compounds under study. In KrF2 the geometric changes upon β → α phase transition is schematized and mechanisms for the transformation with temperature or pressure are proposed. The results are further highlighted by electronic band structure calculations which show similar features of equal band gaps of 3 eV in both α and β KrF2 and a reorganization of frontier orbitals due to the different orientations of the F-Kr-F linear molecule in the two tetragonal structures.

  10. Peculiarities of lens and tail regeneration detected in newts after spaceflight aboard Foton M3

    Science.gov (United States)

    Grigoryan, Eleonora N.; Almeida, Eduardo; Poplinskaya, Valentina; Novikova, Julia; Domaratskaya, Elena; Aleinikova, Karina; Souza, Kenneth; Skidmore, Mike; Grigoryan, Eleonora N.

    In September 2007 the joint, 12 day long experiment was carried out aboard Russian satellite Foton M3. The goal of the experiment was to study eye lens, tail and forelimb toe regeneration in adult 16 newts (Pl. waltl.) operated 10 days before taking-off. In spaceflight and synchronous ground control we used video recording, temperature and irradiation control, as well as constant availability of thymidine analog BrdU for its absorption via animals' skin. New techniques allowed us to analyze animals' behavior in hyperand microgravity periods of time, to take proper account of spaceflight factors, and measure accumulated pools of DNA-synthesizing cells in regenerating tissues. All tissue specimens obtained from animals were isolated in the day of landing and then prepared for morphological, immunochemical and molecular investigations. Synchronous control was shifted for two days and reproduced flight conditions except changes of gravity influence. As a result in flown animals as compared with synchronous ground control we found lens regeneration of 0.5-1 stage speeded up and an increased BrdU+ (S-phase) cell number in eye cornea, growth zone, limbus and newly forming lens. These features of regeneration were accompanied by an increase of FGF2 expression in eye growth zone and heat shock protein (HSP90) induction purely in retinal macroglial cells of regenerating eyes. Toe regeneration rate was equal and achieved the stage of accomplished healing of amputation area in both groups - "flown" and control animals. We found no essential differences in tail regeneration rate and tail regenerate sizes in the newts exposed to space and on ground. In both groups tail regeneration reached the stage IV-V when tail length and square were around 4.4 mm and 15.5 mm2, correspondingly. However we did observe remarkable changes of tail regenerate form and some of pigmentation. Computer morphometrical analysis showed that only in ground control animals the evident dorso

  11. Compositional diversity of near-, far-side transitory zone around Naonobu, Webb and Sinus Successus craters: Inferences from Chandrayaan-1 Moon Mineralogy Mapper (M3) data

    Indian Academy of Sciences (India)

    Rishikesh Bharti; D Ramakrishnan; K D Singh

    2014-02-01

    This study investigated the potential of Moon Mineralogy Mapper (M3) data for studying compositional variation in the near-, far-side transition zone of the lunar surface. For this purpose, the radiance values of the M3 data were corrected for illumination and emission related effects and converted to apparent reflectance. Dimensionality of the calibrated reflectance image cube was reduced using Independent Component Analysis (ICA) and endmembers were extracted by using Pixel Purity Index (PPI) algorithm. The selected endmembers were linearly unmixed and resolved for mineralogy using United States Geological Survey (USGS) library spectra of minerals. These mineralogically resolved endmembers were used to map the compositional variability within, and outside craters using Spectral Angle Mapper (SAM) algorithm. Cross validation for certain litho types was attempted using band ratios like Optical Maturity (OMAT), Color Ratio Composite and Integrated Band Depth ratio (IBD). The identified lithologies for highland and basin areas match well with published works and strongly support depth related magmatic differentiation. Prevalence of pigeonite-basalt, pigeonite-norite and pyroxenite in crater peaks and floors are unique to the investigated area and are attributed to local, lateral compositional variability in magma composition due to pressure, temperature, and rate of cooling.

  12. Evidence of an Antimicrobial Peptide Signature Encrypted in HECT E3 Ubiquitin Ligases

    Science.gov (United States)

    Candido-Ferreira, Ivan Lavander; Kronenberger, Thales; Sayegh, Raphael Santa Rosa; Batista, Isabel de Fátima Correia; da Silva Junior, Pedro Ismael

    2017-01-01

    The ubiquitin-proteasome pathway (UPP) is a hallmark of the eukaryotic cell. In jawed vertebrates, it has been co-opted by the adaptive immune system, where proteasomal degradation produces endogenous peptides for major histocompatibility complex class I antigen presentation. However, proteolytic products are also necessary for the phylogenetically widespread innate immune system, as they often play a role as host defense peptides (HDPs), pivotal effectors against pathogens. Here, we report the identification of the arachnid HDP oligoventin, which shares homology to a core member of the UPP, E3 ubiquitin ligases. Oligoventin has broad antimicrobial activity and shows strong synergy with lysozymes. Using computational and phylogenetic approaches, we show high conservation of the oligoventin signature in HECT E3s. In silico simulation of HECT E3s self-proteolysis provides evidence that HDPs can be generated by fine-tuned 26S proteasomal degradation, and therefore are consistent with the hypothesis that oligoventin is a cryptic peptide released by the proteolytic processing of an Nedd4 E3 precursor protein. Finally, we compare the production of HDPs and endogenous antigens from orthologous HECT E3s by proteasomal degradation as a means of analyzing the UPP coupling to metazoan immunity. Our results highlight the functional plasticity of the UPP in innate and adaptive immune systems as a possibly recurrent mechanism to generate functionally diverse peptides. PMID:28119686

  13. A novel role of Drosophila cytochrome P450-4e3 in permethrin insecticide tolerance.

    Science.gov (United States)

    Terhzaz, Selim; Cabrero, Pablo; Brinzer, Robert A; Halberg, Kenneth A; Dow, Julian A T; Davies, Shireen-A

    2015-12-01

    The exposure of insects to xenobiotics, such as insecticides, triggers a complex defence response necessary for survival. This response includes the induction of genes that encode key Cytochrome P450 monooxygenase detoxification enzymes. Drosophila melanogaster Malpighian (renal) tubules are critical organs in the detoxification and elimination of these foreign compounds, so the tubule response induced by dietary exposure to the insecticide permethrin was examined. We found that expression of the gene encoding Cytochrome P450-4e3 (Cyp4e3) is significantly up-regulated by Drosophila fed on permethrin and that manipulation of Cyp4e3 levels, specifically in the principal cells of the Malpighian tubules, impacts significantly on the survival of permethrin-fed flies. Both dietary exposure to permethrin and Cyp4e3 knockdown cause a significant elevation of oxidative stress-associated markers in the tubules, including H2O2 and lipid peroxidation byproduct, HNE (4-hydroxynonenal). Thus, Cyp4e3 may play an important role in regulating H2O2 levels in the endoplasmic reticulum (ER) where it resides, and its absence triggers a JAK/STAT and NF-κB-mediated stress response, similar to that observed in cells under ER stress. This work increases our understanding of the molecular mechanisms of insecticide detoxification and provides further evidence of the oxidative stress responses induced by permethrin metabolism.

  14. A Dual E3 Mechanism for Rub1 Ligation to Cdc53

    Energy Technology Data Exchange (ETDEWEB)

    Scott, Daniel C.; Monda, Julie K.; Grace, Christy R.R.; Duda, David M.; Kriwacki, Richard W.; Kurz, Thimo; Schulman, Brenda A. (Dundee); (SJCH)

    2010-09-16

    In ubiquitin-like protein (UBL) cascades, a thioester-linked E2 {approx} UBL complex typically interacts with an E3 enzyme for UBL transfer to the target. Here we demonstrate a variant mechanism, whereby the E2 Ubc12 functions with two E3s, Hrt1 and Dcn1, for ligation of the UBL Rub1 to Cdc53's WHB subdomain. Hrt1 functions like a conventional RING E3, with its N terminus recruiting Cdc53 and C-terminal RING activating Ubc12Rub1. Dcn1's potentiating neddylation domain (Dcn1{sup P}) acts as an additional E3, reducing nonspecific Hrt1-mediated Ubc12 {approx} Rub1 discharge and directing Ubc12's active site to Cdc53. Crystal structures of Dcn1{sup P}-Cdc53{sup WHB} and Ubc12 allow modeling of a catalytic complex, supported by mutational data. We propose that Dcn1's interactions with both Cdc53 and Ubc12 would restrict the otherwise flexible Hrt1 RING-bound Ubc12 {approx} Rub1 to a catalytically competent orientation. Our data reveal mechanisms by which two E3s function synergistically to promote UBL transfer from one E2 to a target.

  15. Electron delocalization and relaxation behavior in Cu-doped B i2S e3 films

    Science.gov (United States)

    Li, Mingze; Wang, Zhenhua; Yang, Liang; Li, Da; Yao, Q. R.; Rao, G. H.; Gao, Xuan P. A.; Zhang, Zhidong

    2017-08-01

    C uxB i2S e3 is known for superconductivity due to Cu intercalation in the van der Waals gaps between the quintuple layers of B i2S e3 at x >0.10 . Here we report the synthesis and transport properties of Cu-doped C uxB i2S e3 films prepared by the chemical-vapor-deposition (CVD) method with 0.11 ≥x ≥0 . It is found that the insulatinglike temperature-dependent resistivity of polycrystalline C uxB i2S e3 films exhibits a marked metallic downturn and an increase of carrier concentration below ˜37 K. There is also a time-dependent slow relaxation behavior in the resistance at low temperature. These effects might be related to the strong hybridization between C u+ and C u2 + conduction bands from the intercalated C u+ and substituted C u2 + sites in B i2S e3 films. The findings here have important implications for the understanding and development of doping-induced superconductivity in topological insulators.

  16. SAP is required for the development of innate phenotype in H2-M3-restricted CD8+ T cells1

    Science.gov (United States)

    Bediako, Yaw; Bian, Yao; Zhang, Hong; Cho, Hoonsik; Stein, Paul L.; Wang, Chyung-Ru

    2012-01-01

    H2-M3-restricted T cells have a pre-activated surface phenotype, rapidly expand and produce cytokines upon stimulation and as such, are classified as innate T cells. Unlike most innate T cells, M3-restricted T cells also express CD8αβ co-receptors and a diverse TCR repertoire: hallmarks of conventional MHC Ia-restricted CD8+ T cells. Although iNKT cells are also innate lymphocytes, they are selected exclusively on hematopoietic cells (HC), while M3-restricted T cells can be selected on either hematopoietic or thymic epithelial cells (TEC). Moreover, their phenotypes differ depending on what cells mediate their selection. Though there is a clear correlation between selection on HC and development of innate phenotype, the underlying mechanism remains unclear. SAP is required for the development of iNKT cells and mediates signals from SLAM receptors that are exclusively expressed on HC. Based on their dual selection pathway, M3-restricted T cells present a unique model for studying the development of innate T cell phenotype. Using both polyclonal and transgenic mouse models we demonstrate that while M3-restricted T cells are capable of developing in the absence of SAP, SAP is required for HC-mediated selection, development of pre-activated phenotype and heightened effector functions of M3-restricted T cells. These findings are significant because they directly demonstrate the need for SAP in HC-mediated acquisition of innate T cell phenotype and suggest that due to their SAP-dependent HC-mediated selection, M3-restricted T cells develop a pre-activated phenotype and an intrinsic ability to proliferate faster upon stimulation, allowing for an important role in the early response to infection. PMID:23041566

  17. The centrosomal E3 ubiquitin ligase FBXO31-SCF regulates neuronal morphogenesis and migration.

    Directory of Open Access Journals (Sweden)

    Mayur Vadhvani

    Full Text Available Neuronal development requires proper migration, polarization and establishment of axons and dendrites. Growing evidence identifies the ubiquitin proteasome system (UPS with its numerous components as an important regulator of various aspects of neuronal development. F-box proteins are interchangeable subunits of the Cullin-1 based E3 ubiquitin ligase, but only a few family members have been studied. Here, we report that the centrosomal E3 ligase FBXO31-SCF (Skp1/Cullin-1/F-box protein regulates neuronal morphogenesis and axonal identity. In addition, we identified the polarity protein Par6c as a novel interaction partner and substrate targeted for proteasomal degradation in the control of axon but not dendrite growth. Finally, we ascribe a role for FBXO31 in dendrite growth and neuronal migration in the developing cerebellar cortex. Taken together, we uncovered the centrosomal E3 ligase FBXO31-SCF as a novel regulator of neuronal development.

  18. RBR E3 ubiquitin ligases: new structures, new insights, new questions.

    Science.gov (United States)

    Spratt, Donald E; Walden, Helen; Shaw, Gary S

    2014-03-15

    The RBR (RING-BetweenRING-RING) or TRIAD [two RING fingers and a DRIL (double RING finger linked)] E3 ubiquitin ligases comprise a group of 12 complex multidomain enzymes. This unique family of E3 ligases includes parkin, whose dysfunction is linked to the pathogenesis of early-onset Parkinson's disease, and HOIP (HOIL-1-interacting protein) and HOIL-1 (haem-oxidized IRP2 ubiquitin ligase 1), members of the LUBAC (linear ubiquitin chain assembly complex). The RBR E3 ligases share common features with both the larger RING and HECT (homologous with E6-associated protein C-terminus) E3 ligase families, directly catalysing ubiquitin transfer from an intrinsic catalytic cysteine housed in the C-terminal domain, as well as recruiting thioester-bound E2 enzymes via a RING domain. Recent three-dimensional structures and biochemical findings of the RBRs have revealed novel protein domain folds not previously envisioned and some surprising modes of regulation that have raised many questions. This has required renaming two of the domains in the RBR E3 ligases to more accurately reflect their structures and functions: the C-terminal Rcat (required-for-catalysis) domain, essential for catalytic activity, and a central BRcat (benign-catalytic) domain that adopts the same fold as the Rcat, but lacks a catalytic cysteine residue and ubiquitination activity. The present review discusses how three-dimensional structures of RBR (RING1-BRcat-Rcat) E3 ligases have provided new insights into our understanding of the biochemical mechanisms of these important enzymes in ubiquitin biology.

  19. Fluorescence study of domain structure and lipid interaction of human apolipoproteins E3 and E4.

    Science.gov (United States)

    Mizuguchi, Chiharu; Hata, Mami; Dhanasekaran, Padmaja; Nickel, Margaret; Okuhira, Keiichiro; Phillips, Michael C; Lund-Katz, Sissel; Saito, Hiroyuki

    2014-12-01

    Human apolipoprotein E (apoE) isoforms exhibit different conformational stabilities and lipid-binding properties that give rise to altered cholesterol metabolism among the isoforms. Using Trp-substituted mutations and site- directed fluorescence labeling, we made a comprehensive comparison of the conformational organization of the N- and C-terminal domains and lipid interactions between the apoE3 and apoE4 isoforms. Trp fluorescence measurements for selectively Trp-substituted variants of apoE isoforms demonstrated that apoE4 adopts less stable conformations in both the N- and C-terminal domains compared to apoE3. Consistent with this, the conformational reorganization of the N-terminal helix bundle occurs at lower guanidine hydrochloride concentration in apoE4 than in apoE3 as monitored by fluorescence resonance energy transfer (FRET) from Trp residues to acrylodan attached at the N-terminal helix. Upon binding of apoE3 and apoE4 variants to egg phosphatidylcholine small unilamellar vesicles, similar changes in Trp fluorescence or FRET efficiency were observed for the isoforms, indi- cating that the opening of the N-terminal helix bundle occurs similarly in apoE3 and apoE4. Introduction of mutations into the C-terminal domain of the apoE isoforms to prevent self-association and maintain the monomeric state resulted in great increase in the rate of binding of the C-terminal helices to a lipid surface. Overall, our results demonstrate that the different conformational organizations of the N- and C-terminal domains have a minor effect on the steady-state lipid-binding behavior of apoE3 and apoE4: rather, self-association property is a critical determinant in the kinetics of lipid binding through the C-terminal helices of apoE isoforms.

  20. Case study of the interdisciplinary integration in an IST-E3 project

    DEFF Research Database (Denmark)

    Jørgensen, Ulrik

    2002-01-01

    Case study of a specific IST-E3 project funded by the EU commissions 5th framework program. The case study highlights the difficulties in integrating different disciplinary approaches and suggests that a more openended research strategy should be applied by the commission.......Case study of a specific IST-E3 project funded by the EU commissions 5th framework program. The case study highlights the difficulties in integrating different disciplinary approaches and suggests that a more openended research strategy should be applied by the commission....

  1. Monitoring of high-risk pregnancies using E3 and HPL

    Energy Technology Data Exchange (ETDEWEB)

    Bieglmayer, Ch.; Spona, J.

    1981-01-01

    Routine determinations of HPL and E3 together with other clinical and laboratory checks offer usable information on the state of pregnancy and assist the doctor in taking decisions on the use of therapeutical measures. The anamnesis, the presence of placental insufficiency of EPH-gestosis are important indications for monitoring the pregnancy using HPL and E3. A commercial RIA apparatus (Centria 2) allowing the determination of HPL in a mere hour was compared with our established laboratory method. In 140 determinations, the correlation was r=0.75. Considering its capacity and method, the instrument seems to be more suitable for a small specialized laboratory.

  2. Folding Behaviour for Proteins BBL and E3BD with Gō-like Models

    Institute of Scientific and Technical Information of China (English)

    ZUO Guang-Hong; ZHANG Jian; WANG Jun; WANG Wei

    2005-01-01

    @@ Folding behaviour of protein BBL and its homologue domain E3BD are studied by using an off-lattice Gō-like model. It is found that the folding behaviours of these two proteins are different. Protein BBL folds in a downhill manner, which is consistent with experiments. In contrast, protein E3BD folds cooperatively and has a bimodal distribution of the Q values (the similarity to the native state). By analysing the native structures of the two proteins, it is found that the difference in folding behaviours can be attributed to the different structural features described by the number of nonlocal contacts per residue.

  3. 1750m3高炉煤气除尘改造及TRT发电技术的应用%De-dusting System Improvement and TRT Technology Application on the 1750m3 Blast Furnaces

    Institute of Scientific and Technical Information of China (English)

    曹海刚; 许强

    2012-01-01

    介绍了济钢2座1750m3高炉煤气湿法改干法涂尘及TRT发电的主体设备、主要技术参数及取得的经济效益。%On the two 1750m3 blast furnaces of Jinan Iron and Steel Co., the wet BFG de-ducting system is replaced with the dry de-dusting system and the TRT generation unit is installed. These equipment and their technical data and economic benefits are presented.

  4. Horizontal-Branch Models and the Second-Parameter Effect. IV. The Case of M3 and Palomar 3

    CERN Document Server

    Catelan, M; Rood, R T

    2001-01-01

    We present a detailed analysis of the "second-parameter pair" of globular clusters M3 (NGC 5272) and Palomar 3. Our main results can be summarized as follows: i) The horizontal-branch (HB) morphology of M3 is significantly bluer in its inner regions (observed with the Hubble Space Telescope) than in the cluster outskirts (observed from the ground), i.e., M3 has an internal second parameter. Most plausibly the mass loss on the red giant branch (RGB) has been more efficient in the inner than in the outer regions of the cluster. ii) The dispersion in mass of the Pal 3 HB is found to be very small -- consistent with zero -- and we argue that this is unlikely to be due to a statistical fluctuation. It is this small mass dispersion that leads to the most apparent difference in the HB morphologies of M3 and Pal 3. iii) The relative HB types of M3 and Pal 3, as measured by mean colors or parameters involving the number of blue, variable, and red HB stars, can easily be accounted for by a fairly small difference in ag...

  5. Acetylcholine acts through M3 muscarinic receptor to activate the EGFR signaling and promotes gastric cancer cell proliferation

    Science.gov (United States)

    Yu, Huangfei; Xia, Hongwei; Tang, Qiulin; Xu, Huanji; Wei, Guoqing; Chen, Ying; Dai, Xinyu; Gong, Qiyong; Bi, Feng

    2017-01-01

    Acetylcholine (ACh), known as a neurotransmitter, regulates the functions of numerous fundamental central and peripheral nervous system. Recently, emerging evidences indicate that ACh also plays an important role in tumorigenesis. However, little is known about the role of ACh in gastric cancer. Here, we reported that ACh could be auto-synthesized and released from MKN45 and BGC823 gastric cancer cells. Exogenous ACh promoted cell proliferation in a does-dependent manner. The M3R antagonist 4-DAMP, but not M1R antagonist trihexyphenidyl and M2/4 R antagonist AFDX-116, could reverse the ACh-induced cell proliferation. Moreover, ACh, via M3R, activated the EGFR signaling to induce the phosphorylation of ERK1/2 and AKT, and blocking EGFR pathway by specific inhibitor AG1478 suppressed the ACh induced cell proliferation. Furthermore, the M3R antagonist 4-DAMP and darifenacin could markedly inhibit gastric tumor formation in vivo. 4-DAMP could also significantly enhance the cytotoxic activity of 5-Fu against the MKN45 and BGC823 cells, and induce the expression of apoptosis-related proteins such as Bax and Caspase-3. Together, these findings indicated that the autocrine ACh could act through M3R and the EGFR signaling to promote gastric cancer cells proliferation, targeting M3R or EGFR may provide us a potential therapeutic strategy for gastric cancer treatment. PMID:28102288

  6. Genetic environments of the transferable plasmid-mediated blaCTX-M-3 gene in Serratia marcescens isolates.

    Science.gov (United States)

    Chu, Pei-Yu; Peng, Chien-Fang

    2014-01-01

    In this study, genetic environments of the transferable plasmid-mediated blaCTX-M-3 gene were characterized among 14 isolates of cefotaxime-resistant Serratia marcescens using PCR and BLAST DNA sequence analysis. A total of 3 types of genetic architectures in the regions surrounding this blaCTX-M-3 gene were identified. Type I architecture was characterized by the presence of a complete insertion sequence of tnpA-ISEcp1, identified as interrupting a reverse IS26 sequence in the upstream region of the blaCTX-M-3 gene. A reverse-directional orf477 fragment was located downstream of the blaCTX-M-3 gene, which was in the same direction of the mucA gene. A common region containing the orf513 element was located upstream of the mucA gene. Moreover, a copy of the 3'-CS2 element was located immediately upstream of the orf513 element. A novel complex class 1 integron was characterized by the presence of the dfrA19 gene, which was flanked by two copies of class 1 integrons. This is the first report to describe the dfrA19 gene within a novel complex class 1 integron in S. marcescens isolates from Taiwan. This novel complex class 1 integron structure was located distantly upstream of the blaCTX-M-3 gene.

  7. Hypocholesterolemic effects of Kluyveromyces marxianus M3 isolated from Tibetan mushrooms on diet-induced hypercholesterolemia in rat

    Directory of Open Access Journals (Sweden)

    Yuanhong Xie

    2015-06-01

    Full Text Available To investigate the effects of Kluyveromyces marxianus M3 isolated from Tibetan mushrooms on diet-induced hypercholesterolemia in rats, female Wistar rats were fed a high-cholesterol diet (HCD for 28 d to generate hyperlipidemic models. Hyperlipidemic rats were assigned to four groups, which were individually treated with three different dosages of K. marxianus M3+HCD or physiological saline+HCD via oral gavage for 28 d. The total cholesterol (TC, triglycerides (TG, high-density lipoprotein cholesterol (HDL-C, and low-density lipoprotein cholesterol (LDL-C levels in the serum and liver of the rats were measured using commercially available enzyme kits. In addition, the liver morphology was also examined using hematoxylin and eosin staining and optical microscopy. According to our results, the serum and liver TC, TG, LDL-C levels and atherogenic index (AI were significantly decreased in rats orally administered K. marxianus M3 (p <0.01, and the HDL-C levels and anti atherogenic index (AAI were significantly increased (p <0.01 compared to the control group. Moreover, K. marxianus M3 treatment also reduced the build-up of lipid droplets in the liver and exhibited normal hepatocytes, suggesting a protective effect of K. marxianus M3 in hyperlipidemic rats.

  8. Hypocholesterolemic effects of Kluyveromyces marxianus M3 isolated from Tibetan mushrooms on diet-induced hypercholesterolemia in rat.

    Science.gov (United States)

    Xie, Yuanhong; Zhang, Hongxing; Liu, Hui; Xiong, Lixia; Gao, Xiuzhi; Jia, Hui; Lian, Zhengxing; Tong, Nengsheng; Han, Tao

    2015-06-01

    To investigate the effects of Kluyveromyces marxianus M3 isolated from Tibetan mushrooms on diet-induced hypercholesterolemia in rats, female Wistar rats were fed a high-cholesterol diet (HCD) for 28 d to generate hyperlipidemic models. Hyperlipidemic rats were assigned to four groups, which were individually treated with three different dosages of K. marxianus M3+HCD or physiological saline+HCD via oral gavage for 28 d. The total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels in the serum and liver of the rats were measured using commercially available enzyme kits. In addition, the liver morphology was also examined using hematoxylin and eosin staining and optical microscopy. According to our results, the serum and liver TC, TG, LDL-C levels and atherogenic index (AI) were significantly decreased in rats orally administered K. marxianus M3 (p <0.01), and the HDL-C levels and anti atherogenic index (AAI) were significantly increased (p <0.01) compared to the control group. Moreover, K. marxianus M3 treatment also reduced the build-up of lipid droplets in the liver and exhibited normal hepatocytes, suggesting a protective effect of K. marxianus M3 in hyperlipidemic rats.

  9. EFFECT OF Nb ON THE MICROSTRUCTURE AND PROPERTIES OF SPRAY FORMED M3 HIGH SPEED STEEL%Nb对喷射成形M3型高速钢组织和性能的影响

    Institute of Scientific and Technical Information of China (English)

    于一鹏; 黄进峰; 崔华; 蔡元华; 张济山

    2012-01-01

    为了利用NbC的高硬度和高热稳定性,并避免其在凝固过程中的过分长大,采用喷射成形快速凝固技术制备了M3型高速钢和以Nb代V的M3型高速钢.利用SEM,EDX和XRD等方法研究了Nb对喷射成形M3型高速钢沉积态组织的影响;利用SRV高温摩擦磨损试验机和三维白光干涉表面形貌仪研究了Nb对喷射成形M3型高速钢摩擦磨损性能的影响.结果表明,用等原子分数的Nb替代V,可大幅增加沉积态中一次MC型碳化物,减少一次M2C型碳化物,同时由于喷射成形高冷速的作用,使得MC碳化物尺寸减小,分布更弥散;这些MC型碳化物的存在是M3型高速钢的抗磨粒磨损性能提高的主要原因,但其对抗氧化性能并无贡献,在高载荷时抗氧化剥落磨损能力增加不明显;Nb对提高M3高速钢回火稳定性也有明显的作用.%Spray forming with a short process chains has been proven to be a powerful tool for the production of high-alloyed materials. Niobium, as a strong former for the carbide, will mainly form primary MC carbides, such as NbC, which can be formed via the reaction between Nb and C atoms at the beginning of solidification, and it can act as the inoculants and refine the cast structure of steel which can mainly form primary MC carbides. M3 high speed steel with or without Nb addition were prepared via spray forming. The effect of Nb on the microstructure of spray formed M3 high speed steel was investigated by SEM, EDX and XRD methods; the friction performances of these two steels were studied by SRV high temperature tribometer and 3D white-light interfering profilometer. The results show that the amount of primary MC carbides can increase sharply while the reduction of the amount of primary M2C due to the substitution of 2% Nb for 1% V (mass fraction) in M3 high speed steel. For the high cooling rate during the spray forming, the primary MC carbides can be refined and dispersed. Large number of primary MC carbides

  10. High temperature EPR study of the M3Fe4V6O24 (M = Cu, Zn, Mg and Mn

    Directory of Open Access Journals (Sweden)

    Guskos Niko

    2016-09-01

    Full Text Available Electron paramagnetic resonance (EPR spectra of M3Fe4V6O24 (M = Cu, Zn, Mg and Mn compounds in high temperature range (293 K to 493 K have been investigated. The role of magnetic (Cu, Mn and non-magnetic (Zn, Mg ions in M3Fe4V6O24 structure in formation of magnetic resonance spectra was studied. Temperature dependence of EPR parameters: resonance field, linewidth and integrated intensity were examined. Similarities and differences in temperature behavior of these parameters has been discussed in terms of different relaxation mechanisms and magnetic interactions in the spin systems. An important role of additional magnetic ions (M = Mn or Cu in the M3Fe4V6O24 structure has been identified and its consequences considered.

  11. Expression of the M3 Muscarinic Receptor on Orexin Neurons that Project to the Rostral Ventrolateral Medulla.

    Science.gov (United States)

    Dai, Yu-Wen E; Lee, Yen-Hsien; Chen, Jennifer Y S; Lin, Yen-Kuang; Hwang, Ling-Ling

    2016-05-01

    Activation of central cholinergic receptors causes a pressor response in rats, and the hypothalamus is important for this response. Projections from hypothalamic orexin neurons to the rostral ventrolateral medulla (RVLM) are involved in sympatho-excitation of the cardiovascular system. A small population of orexin neurons is regulated by cholinergic inputs through M3 muscarinic acetylcholine receptor (M3 R). To elucidate whether the M3 R on orexin neurons is involved in cardiosympathetic regulation through the RVLM, we examined the presence of the M3 R on retrograde-labeled RVLM-projecting orexin neurons. The retrograde tracer was unilaterally injected into the RVLM. Within the hypothalamus, retrograde-labeled neurons were located predominantly ipsilateral to the injection side. In the anterior hypothalamus (-1.5 to -2.3 mm to the bregma), retrograde-labeled neurons were densely distributed in the paraventricular nuclei and scattered in the retrochiasmatic area. At -2.3 to -3.5 mm from the bregma, labeled neurons were located in the regions where orexin neurons were situated, that is, the tuberal lateral hypothalamic area, perifornical area, and dorsomedial nuclei. Very few retrograde-labeled neurons were observed in the hypothalamus at -3.5 to -4.5 mm from the bregma. About 19.5% ± 1.6% of RVLM-projecting neurons in the tuberal hypothalamus were orexinergic. The M3 R was present on 18.7% ± 3.0% of RVLM-projecting orexin neurons. Injection of a muscarinic agonist, oxotremorine, in the perifornical area resulted in a pressor response, which was attenuated by a pretreatment of atropine. We conclude that cholinergic inputs to orexin neurons may be involved in cardiosympathetic regulation through the M3 R on the orexin neurons that directly project to the RVLM.

  12. Ophthalmic epidemiology in Europe : the "European Eye Epidemiology" (E3) consortium

    NARCIS (Netherlands)

    Delcourt, Cecile; Korobelnik, Jean-Francois; Buitendijk, Gabrielle H. S.; Foster, Paul J.; Hammond, Christopher J.; Piermarocchi, Stefano; Peto, Tunde; Jansonius, Nomdo; Mirshahi, Alireza; Hogg, Ruth E.; Bretillon, Lionel; Topouzis, Fotis; Deak, Gabor; Grauslund, Jakob; Broe, Rebecca; Souied, Eric H.; Creuzot-Garcher, Catherine; Sahel, Jose; Daien, Vincent; Lehtimaki, Terho; Hense, Hans-Werner; Prokofyeva, Elena; Oexle, Konrad; Rahi, Jugnoo S.; Cumberland, Phillippa M.; Schmitz-Valckenberg, Steffen; Fauser, Sascha; Bertelsen, Geir; Hoyng, Carel; Bergen, Arthur; Silva, Rufino; Wolf, Sebastian; Lotery, Andrew; Chakravarthy, Usha; Fletcher, Astrid; Klaver, Caroline C. W.

    The European Eye Epidemiology (E3) consortium is a recently formed consortium of 29 groups from 12 European countries. It already comprises 21 population-based studies and 20 other studies (case-control, cases only, randomized trials), providing ophthalmological data on approximately 170,000

  13. Bioinformatics analysis identifies several intrinsically disordered human E3 ubiquitin-protein ligases

    DEFF Research Database (Denmark)

    Boomsma, Wouter Krogh; Nielsen, Sofie Vincents; Lindorff-Larsen, Kresten;

    2016-01-01

    conduct a bioinformatics analysis to examine >600 human and S. cerevisiae E3 ligases to identify enzymes that are similar to San1 in terms of function and/or mechanism of substrate recognition. An initial sequence-based database search was found to detect candidates primarily based on the homology...

  14. Total Synthesis and Tentative Structural Elucidation of Cryptomoscatone E3: Interplay of Experimental and Computational Studies.

    Science.gov (United States)

    Novaes, Luiz F T; Sarotti, Ariel M; Pilli, Ronaldo A

    2015-12-18

    A successful combination of computational chemistry and total synthesis was explored to tentatively elucidate the absolute configuration of cryptomoscatone E3, a polyketide isolated from the Brazilian tree Cryptocarya mandiocanna. Two independent synthetic approaches are discussed based on asymmetric allylation, ring closing metathesis, and aldol reactions.

  15. Yeast SREBP cleavage activation requires the Golgi Dsc E3 ligase complex.

    Science.gov (United States)

    Stewart, Emerson V; Nwosu, Christine C; Tong, Zongtian; Roguev, Assen; Cummins, Timothy D; Kim, Dong-Uk; Hayles, Jacqueline; Park, Han-Oh; Hoe, Kwang-Lae; Powell, David W; Krogan, Nevan J; Espenshade, Peter J

    2011-04-22

    Mammalian lipid homeostasis requires proteolytic activation of membrane-bound sterol regulatory element binding protein (SREBP) transcription factors through sequential action of the Golgi Site-1 and Site-2 proteases. Here we report that while SREBP function is conserved in fungi, fission yeast employs a different mechanism for SREBP cleavage. Using genetics and biochemistry, we identified four genes defective for SREBP cleavage, dsc1-4, encoding components of a transmembrane Golgi E3 ligase complex with structural homology to the Hrd1 E3 ligase complex involved in endoplasmic reticulum-associated degradation. The Dsc complex binds SREBP and cleavage requires components of the ubiquitin-proteasome pathway: the E2-conjugating enzyme Ubc4, the Dsc1 RING E3 ligase, and the proteasome. dsc mutants display conserved aggravating genetic interactions with components of the multivesicular body pathway in fission yeast and budding yeast, which lacks SREBP. Together, these data suggest that the Golgi Dsc E3 ligase complex functions in a post-ER pathway for protein degradation.

  16. Motion of Bishop Frenet Offsets of Ruled Surfaces in E3

    Directory of Open Access Journals (Sweden)

    H. N. Abd-Ellah

    2015-01-01

    Full Text Available The main goal of this paper is to study the motion of two associated ruled surfaces in Euclidean 3-space E3. In particular, the motion of Bishop Frenet offsets of ruled surfaces is investigated. Additionally, the characteristic properties for such ruled surfaces are given. Finally, an application is presented and plotted using computer aided geometric design.

  17. Selectivity of E2-E3 interactions in the human ubiquitin system

    NARCIS (Netherlands)

    van Wijk, S.J.L.

    2010-01-01

    Highly selective interactions between ubiquitin-conjugating enzymes and RING-type E3 ligases are crucial for the adequate and efficient action of ubiquitin and ubiquitin-like pathways. Within these cascades, E2 enzymes provide a connecting link between activation and the final covalent conjugation,

  18. Ophthalmic epidemiology in Europe : the "European Eye Epidemiology" (E3) consortium

    NARCIS (Netherlands)

    Delcourt, Cecile; Korobelnik, Jean-Francois; Buitendijk, Gabrielle H. S.; Foster, Paul J.; Hammond, Christopher J.; Piermarocchi, Stefano; Peto, Tunde; Jansonius, Nomdo; Mirshahi, Alireza; Hogg, Ruth E.; Bretillon, Lionel; Topouzis, Fotis; Deak, Gabor; Grauslund, Jakob; Broe, Rebecca; Souied, Eric H.; Creuzot-Garcher, Catherine; Sahel, Jose; Daien, Vincent; Lehtimaki, Terho; Hense, Hans-Werner; Prokofyeva, Elena; Oexle, Konrad; Rahi, Jugnoo S.; Cumberland, Phillippa M.; Schmitz-Valckenberg, Steffen; Fauser, Sascha; Bertelsen, Geir; Hoyng, Carel; Bergen, Arthur; Silva, Rufino; Wolf, Sebastian; Lotery, Andrew; Chakravarthy, Usha; Fletcher, Astrid; Klaver, Caroline C. W.

    2016-01-01

    The European Eye Epidemiology (E3) consortium is a recently formed consortium of 29 groups from 12 European countries. It already comprises 21 population-based studies and 20 other studies (case-control, cases only, randomized trials), providing ophthalmological data on approximately 170,000 Europea

  19. Biochemical function of typical and variant Arabidopsis thaliana U-box E3 ubiquitin-protein ligases

    DEFF Research Database (Denmark)

    Wiborg, Jakob; O'Shea, Charlotte; Skriver, Karen

    2008-01-01

    The variance of the U-box domain in 64 Arabidopsis thaliana (thale cress) E3s (ubiquitin-protein ligases) was used to examine the interactions between E3s and E2s (ubiquitin-conjugating enzymes). E2s and E3s are components of the ubiquitin protein degradation pathway. Seven U-box proteins were...

  20. Novel E3 ubiquitin ligases that regulate histone protein levels in the budding yeast Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Rakesh Kumar Singh

    Full Text Available Core histone proteins are essential for packaging the genomic DNA into chromatin in all eukaryotes. Since multiple genes encode these histone proteins, there is potential for generating more histones than what is required for chromatin assembly. The positively charged histones have a very high affinity for negatively charged molecules such as DNA, and any excess of histone proteins results in deleterious effects on genomic stability and cell viability. Hence, histone levels are known to be tightly regulated via transcriptional, posttranscriptional and posttranslational mechanisms. We have previously elucidated the posttranslational regulation of histone protein levels by the ubiquitin-proteasome pathway involving the E2 ubiquitin conjugating enzymes Ubc4/5 and the HECT (Homologous to E6-AP C-Terminus domain containing E3 ligase Tom1 in the budding yeast. Here we report the identification of four additional E3 ligases containing the RING (Really Interesting New Gene finger domains that are involved in the ubiquitylation and subsequent degradation of excess histones in yeast. These E3 ligases are Pep5, Snt2 as well as two previously uncharacterized Open Reading Frames (ORFs YKR017C and YDR266C that we have named Hel1 and Hel2 (for Histone E3 Ligases respectively. Mutants lacking these E3 ligases are sensitive to histone overexpression as they fail to degrade excess histones and accumulate high levels of endogenous histones on histone chaperones. Co-immunoprecipitation assays showed that these E3 ligases interact with the major E2 enzyme Ubc4 that is involved in the degradation related ubiquitylation of histones. Using mutagenesis we further demonstrate that the RING domains of Hel1, Hel2 and Snt2 are required for histone regulation. Lastly, mutants corresponding to Hel1, Hel2 and Pep5 are sensitive to replication inhibitors. Overall, our results highlight the importance of posttranslational histone regulatory mechanisms that employ multiple E3

  1. Study and Implementation of Floating-point Operations Based on Cortex-M3 Core%Cortex-M3内核浮点型运算的研究与实现

    Institute of Scientific and Technical Information of China (English)

    梅静静; 王申良

    2011-01-01

    通过分析Cortex-M3内核的结构与浮点型格式,充分利用Cortex-M3内核中的分支预测、单周期乘法、硬件除法等众多功能强大的特性,使用Thumb-2指令集实现了单精度浮点型的加、减、乘、除与比较运算,并给出了加减法运算的流程图和除法运算的源程序.%By analyzing the Cortex-M3 core structure and floating-point format, this paper uses the Thumb-2 instruction set to achieve addition, subtraction, multiplication, division and comparison operations of single-precision floating-point numbers, making full use of such powerful features of Cortex-M3 core as branch prediction, single-cycle multiplication and hardware division. The flow chart of addition and subtraction operations, as well as the source program of division operation, is provided.

  2. TREATMENT OF ABNORMAL TEMPERATURE RISE OF 1 800 m3 BF HEARTH%宣钢1800 m3高炉炉缸温度异常升高的处理

    Institute of Scientific and Technical Information of China (English)

    武建新; 匡祎

    2014-01-01

    This paper is aimed at the abnormal temperature rise of the 1800m3 BF hearth carbon bricks . Through correct diagnosis of furnace body corrosion condition , such measures are taken as increasing tita-nium load into the furnace , enhancing cooling intensity , enhancing tap -hole maintenance to guarantee tap-hole depth , changing field on time while tapping and so on , many hidden safety troubles are elimi-nated , and long-time and smooth operation of the 1 800 m3 BF is guaranteed .%针对2013年1月16日宣钢1800 m3高炉炉缸碳砖温度大幅度异常升高。通过正确诊断炉体侵蚀状况,采取提高入炉钛负荷、提高冷却强度、加强铁口维护保证铁口深度、出铁及时倒场等多项护炉措施,消除了安全隐患,保证了1800 m3高炉炉况长期稳定顺行。

  3. M3(Au,Ge)19 and M(3.25)(Au,Ge)18 (M = Ca, Yb): distinctive phase separations driven by configurational disorder in cubic YCd6-type derivatives.

    Science.gov (United States)

    Lin, Qisheng; Corbett, John D

    2010-05-17

    Exploratory syntheses in the M-Au-Ge (M = Ca, Yb) systems have led to the discovery of two cleanly separated non-stoichiometric phases M(3)Au(approximately 14.4)Ge(approximately 4.6) (I) and M(3.25)Au(approximately 12.7)Ge(approximately 5.3) (II). Single crystal X-ray studies reveal that both (space group Im3) feature body-centered-cubic packing of five-shell multiply endohedral clusters that resemble those in the parent YCd(6) (= Y(3)Cd(18)) and are akin to approximate phases in other quasicrystal systems. However, differences resulting from various disorders in these are distinctive. The innermost cluster in the M(3)Au(approximately 14.4)Ge(approximately 4.6) phase (I) remains a disordered tetrahedron, as in the YCd(6) parent. In contrast, its counterpart in the electron-richer M(3.25)Au(approximately 12.7)Ge(approximately 5.3) phase (II) is a "rattling" M atom. The structural differentiations between I and II exhibit strong correlations between lattice parameters, cluster sizes, particular site occupancies, and valence electron counts.

  4. Pathfinding the Flight Advanced Stirling Convertor Design with the ASC-E3

    Science.gov (United States)

    Wong, Wayne A.; Wilson, Kyle; Smith, Eddie; Collins, Josh

    2012-01-01

    The Advanced Stirling Convertor (ASC) was initially developed by Sunpower, Inc. under contract to NASA Glenn Research Center (GRC) as a technology development project. The ASC technology fulfills NASA's need for high efficiency power convertors for future Radioisotope Power Systems (RPS). Early successful technology demonstrations between 2003 to 2005 eventually led to the expansion of the project including the decision in 2006 to use the ASC technology on the Advanced Stirling Radioisotope Generator (ASRG). Sunpower has delivered 22 ASC convertors of progressively mature designs to date to GRC. Currently, Sunpower with support from GRC, Lockheed Martin Space System Company (LMSSC), and the Department of Energy (DOE) is developing the flight ASC-F in parallel with the ASC-E3 pathfinders. Sunpower will deliver four pairs of ASC-E3 convertors to GRC which will be used for extended operation reliability assessment, independent validation and verification testing, system interaction tests, and to support LMSSC controller verification. The ASC-E3 and -F convertors are being built to the same design and processing documentation and the same product specification. The initial two pairs of ASC-E3 are built before the flight units and will validate design and processing changes prior to implementation on the ASC-F flight convertors. This paper provides a summary on development of the ASC technology and the status of the ASC-E3 build and how they serve the vital pathfinder role ahead of the flight build for ASRG. The ASRG is part of two of the three candidate missions being considered for selection for the Discovery 12 mission.

  5. Comparative study of AISI M3:2 high speed steel produced through different techniques of manufacturing; Estudo comparativo de acos rapidos AISI M3:2 produzidos por diferentes processos de fabricacao

    Energy Technology Data Exchange (ETDEWEB)

    Araujo Filho, Oscar Olimpio de

    2006-07-01

    In this work AISI M3:2 high speed steels obtained through different techniques of manufacturing, submitted to the same heat treatment procedure were evaluated by measuring their mechanical properties of transverse rupture strength and hardness. Sinter 23 obtained by hot isostatic pressing (HIP), VWM3C obtained by the conventional route and a M3:2 high speed steel obtained by cold compaction of water atomized powders and vacuum sintered with and without the addition of a small quantity of carbon were evaluated after the same heat treatment procedure. The vacuum sintered M3:2 high speed steel can be an alternative to the more expensive high speed steel produced by hot isostatic pressing and with similar properties presented by the conventional one. The characterization of the vacuum sintered M3:2 high speed steel was performed by measuring the densities of the green compacts and after the sintering cycle. The sintering produced an acceptable microstructure and densities near to the theoretical. The transverse rupture strength was evaluated by means of three point bending tests and the hardness by means of Rockwell C and Vickers tests. The technique of scanning electronic microscopy (SEM) was used to evaluate the microstructure and to establish a relation with the property of transverse rupture strength. The structure was determined by means of X-ray diffraction (XRD) patterns and the retained austenite was detected to all the conditions of heat treatment. The main contribution of this work is to establish a relation between the microstructure and the mechanical property of transverse rupture strength and to evaluate the AISI M3:2 vacuum sintered high speed steel as an alternative to the similar commercial high speed steels. (author)

  6. Development and validation of a UHPLC-MS/MS method for simultaneous quantitation the plasma concentration of Sabarubicin and its alcohol metabolite M3 in Chinese small cell lung cancer patients.

    Science.gov (United States)

    Zhang, Yan; Liu, Peng; Li, Ning; Wu, Di; Feng, Yun; Song, Yuanyuan; Shi, Yuankai; Han, Xiaohong

    2016-07-01

    To support a novel anthracycline agent - Sabarubicin's pharmacokinetics study in Chinese small cell lung cancer patients, a rapid, sensitive, and high throughput ultra-performance liquid chromatography tandem mass spectrometry method using Doxorubicin hydrochloride as internal standard (IS) was developed and validated for simultaneously quantifying Sabarubicin and its alcohol metabolite M3 in human plasma. Plasma samples were pre-extracted with n-hexane to remove hydrophobic interferences and the target compounds were extracted into a 1ml mixture of chloroform and isopropanol (1:1, v/v) and separated on an ACQUITY UPLC BEH Shield RP18 (100mm×2.1mm, 1.7μm) column with gradient mobile phase composed of acetonitrile and water containing 0.1% formic acid. Detection was performed by electrospray ionization in the positive ionization mode under multiple reaction monitoring of the transitions at m/z 644→130 for Sabarubicin, m/z 646→333.2 for M3, and m/z 544→360 for IS. For Sabarubicin and M3, calibration curves over 2-400ng/ml and 0.5-100ng/ml could achieve excellent linearity respectively(r>0.99). Intra- and inter-day precisions were 1.5%-9.1% and 2.2%-12.8%, and accuracy were -9.6% to 0.7% and -4.8% to 5.9% for Sabarubicin and M3 respectively at four concentration levels. The mean recovery for Sabarubicin was 62.4%, 71.9% for M3, and 58.8% for IS. This method was completely validated and successfully applied in the pharmacokinetics study of Sabarubicin and M3 in Chinese small cell lung cancer patients.

  7. Reactor Dosimetry Applications Using RAPTOR-M3G:. a New Parallel 3-D Radiation Transport Code

    Science.gov (United States)

    Longoni, Gianluca; Anderson, Stanwood L.

    2009-08-01

    The numerical solution of the Linearized Boltzmann Equation (LBE) via the Discrete Ordinates method (SN) requires extensive computational resources for large 3-D neutron and gamma transport applications due to the concurrent discretization of the angular, spatial, and energy domains. This paper will discuss the development RAPTOR-M3G (RApid Parallel Transport Of Radiation - Multiple 3D Geometries), a new 3-D parallel radiation transport code, and its application to the calculation of ex-vessel neutron dosimetry responses in the cavity of a commercial 2-loop Pressurized Water Reactor (PWR). RAPTOR-M3G is based domain decomposition algorithms, where the spatial and angular domains are allocated and processed on multi-processor computer architectures. As compared to traditional single-processor applications, this approach reduces the computational load as well as the memory requirement per processor, yielding an efficient solution methodology for large 3-D problems. Measured neutron dosimetry responses in the reactor cavity air gap will be compared to the RAPTOR-M3G predictions. This paper is organized as follows: Section 1 discusses the RAPTOR-M3G methodology; Section 2 describes the 2-loop PWR model and the numerical results obtained. Section 3 addresses the parallel performance of the code, and Section 4 concludes this paper with final remarks and future work.

  8. Lead generation using pharmacophore mapping and three-dimensional database searching: application to muscarinic M(3) receptor antagonists.

    Science.gov (United States)

    Marriott, D P; Dougall, I G; Meghani, P; Liu, Y J; Flower, D R

    1999-08-26

    By using a pharmacophore model, a geometrical representation of the features necessary for molecules to show a particular biological activity, it is possible to search databases containing the 3D structures of molecules and identify novel compounds which may possess this activity. We describe our experiences of establishing a working 3D database system and its use in rational drug design. By using muscarinic M(3) receptor antagonists as an example, we show that it is possible to identify potent novel lead compounds using this approach. Pharmacophore generation based on the structures of known M(3) receptor antagonists, 3D database searching, and medium-throughput screening were used to identify candidate compounds. Three compounds were chosen to define the pharmacophore: a lung-selective M(3) antagonist patented by Pfizer and two Astra compounds which show affinity at the M(3) receptor. From these, a pharmacophore model was generated, using the program DISCO, and this was used subsequently to search a UNITY 3D database of proprietary compounds; 172 compounds were found to fit the pharmacophore. These compounds were then screened, and 1-[2-(2-(diethylamino)ethoxy)phenyl]-2-phenylethanone (pA(2) 6.67) was identified as the best hit, with N-[2-(piperidin-1-ylmethyl)cycohexyl]-2-propoxybenz amide (pA(2) 4. 83) and phenylcarbamic acid 2-(morpholin-4-ylmethyl)cyclohexyl ester (pA(2) 5.54) demonstrating lower activity. As well as its potency, 1-[2-(2-(diethylamino)ethoxy)phenyl]-2-phenylethanone is a simple structure with limited similarity to existing M(3) receptor antagonists.

  9. Light Distribution in the E3 and E4 Scintillation Counters of the ATLAS Tile Calorimeter

    CERN Document Server

    Hsu, Catherine

    2013-01-01

    The Tile Calorimeter (TileCal) of the ATLAS experiment is an important component of the ATLAS calorimetry because they play a crucial role in the search for new particles. The E3 and E4 are crack scintillators of TileCal that extend into the gap region between the EM barrel and EM endcaps. They thus sample the energy of the EM showers produced by particles interacting with the dead material in the EM calorimeters and with the inner detector cables. This project focuses on the study of the light collection uniformity in the E3 and E4 scintillating tiles using low energy electrons as the ionising particles. It is important to have uniform light response in the tiles because it would ensure a good energy resolution for the dead region. However, many factors affect the uniform light collection within the scintillating tiles.

  10. A Bacterial Inhibitor of Host Programmed Cell Death Defenses is an E3 Ubiquitin Ligase

    Energy Technology Data Exchange (ETDEWEB)

    Janjusevic,R.; Abramovitch, R.; Martin, G.; Stebbins, C.

    2005-01-01

    The Pseudomonas syringae protein AvrPtoB is translocated into plant cells, where it inhibits immunity-associated programmed cell death (PCD). The structure of a C-terminal domain of AvrPtoB that is essential for anti-PCD activity reveals an unexpected homology to the U-box and RING-finger components of eukaryotic E3 ubiquitin ligases, and we show that AvrPtoB has ubiquitin ligase activity. Mutation of conserved residues involved in the binding of E2 ubiquitin-conjugating enzymes abolishes this activity in vitro, as well as anti-PCD activity in tomato leaves, which dramatically decreases virulence. These results show that Pseudomonas syringae uses a mimic of host E3 ubiquitin ligases to inactivate plant defenses.

  11. The E3 ubiquitin ligase CTRIP controls CLOCK levels and PERIOD oscillations in Drosophila.

    Science.gov (United States)

    Lamaze, Angélique; Lamouroux, Annie; Vias, Carine; Hung, Hsiu-Cheng; Weber, Frank; Rouyer, François

    2011-06-01

    In the Drosophila circadian clock, the CLOCK/CYCLE complex activates the period and timeless genes that negatively feedback on CLOCK/CYCLE activity. The 24-h pace of this cycle depends on the stability of the clock proteins. RING-domain E3 ubiquitin ligases have been shown to destabilize PERIOD or TIMELESS. Here we identify a clock function for the circadian trip (ctrip) gene, which encodes a HECT-domain E3 ubiquitin ligase. ctrip expression in the brain is mostly restricted to clock neurons and its downregulation leads to long-period activity rhythms in constant darkness. This altered behaviour is associated with high CLOCK levels and persistence of phosphorylated PERIOD during the subjective day. The control of CLOCK protein levels does not require PERIOD. Thus, CTRIP seems to regulate the pace of the oscillator by controlling the stability of both the activator and the repressor of the feedback loop.

  12. Petrology and oxygen isotope compositions of chondrules in E3 chondrites

    Science.gov (United States)

    Weisberg, Michael K.; Ebel, Denton S.; Connolly, Harold C.; Kita, Noriko T.; Ushikubo, Takayuki

    2011-11-01

    Chondrules in E3 chondrites differ from those in other chondrite groups. Many contain near-pure endmember enstatite (Fs metal, Cr-bearing troilite, and, in some cases Mg, Mn- and Ca-sulfides. Olivine and more FeO-rich pyroxene grains are present but much less common than in ordinary or carbonaceous chondrite chondrules. In some cases, the FeO-rich grains contain dusty inclusions of metal. The oxygen three-isotope ratios (δ 18O, δ 17O) of olivine and pyroxene in chondrules from E3 chondrites, which are measured using a multi-collection SIMS, show a wide range of values. Most enstatite data plots on the terrestrial fractionation (TF) line near whole rock values and some plot near the ordinary chondrite region on the 3-isotope diagram. Pyroxene with higher FeO contents (˜2-10 wt.% FeO) generally plots on the TF line similar to enstatite, suggesting it formed locally in the EC (enstatite chondrite) region and that oxidation/reduction conditions varied within the E3 chondrite chondrule-forming region. Olivine shows a wide range of correlated δ 18O and δ 17O values and data from two olivine-bearing chondrules form a slope ˜1 mixing line, which is approximately parallel to but distinct from the CCAM (carbonaceous chondrite anhydrous mixing) line. We refer to this as the ECM (enstatite chondrite mixing) line but it also may coincide with a line defined by chondrules from Acfer 094 referred to as the PCM (Primitive Chondrite Mineral) line ( Ushikubo et al., 2011). The range of O isotope compositions and mixing behavior in E3 chondrules is similar to that in O and C chondrite groups, indicating similar chondrule-forming processes, solid-gas mixing and possibly similar 16O-rich precursors solids. However, E3 chondrules formed in a distinct oxygen reservoir. Internal oxygen isotope heterogeneity was found among minerals from some of the chondrules in E3 chondrites suggesting incomplete melting of the chondrules, survival of minerals from previous generations of

  13. 高顶压技术在莱钢1000m3高炉的应用%Application of High Top Pressure Technology in Laigang 1000 m3 Blast Furnace

    Institute of Scientific and Technical Information of China (English)

    王丰巧

    2015-01-01

    高压操作是强化高炉冶炼的一项重要措施,利于高炉炉况稳定顺行、提高煤气利用率,莱钢1000 m3高炉通过加强原料管理、增加鼓风动能、加强炉前管理等措施提高炉顶压力,取得了显著的经济效益。%High pressure operation is an important measure to strengthen the blast furnace smelting of blast furnace, can be conducive to the stable operation and the exploitation rate of gas.By improving raw material management, increasing the en-ergy of blast furnace, strengthening management measures to strengthen blast furnace top pressure, remarkable economic benefits has been achieved for Laigang 1000 m3 furnace.

  14. Development of Protection System Preventing 60 000 m3 Air Compressor from Stall%60000m3空压机喘振保护系统的研发

    Institute of Scientific and Technical Information of China (English)

    李学波

    2014-01-01

    This article describes the reason and harm of air compressor stall in detail ,and elaborates the principle of the anti-stall control system .A protection system for 60 000 m3 air compressor is set up .By using the function of DCS and PLC ,we can make the control of compressor fast and reliable .This work has important reference value to the other anti-stall control systems .%简述了喘振的原理及危害。详细阐述了防喘振系统的控制原理,并建立了60000 m3空压机的保护系统,利用DCS和PLC的强大功能实现快速可靠的控制,对其他系统的防喘振控制有着重要的参考价值。

  15. Shark (Prionace glauca) elastoidin: characterization of its collagen as [alpha 1(E)]3 homotrimers.

    Science.gov (United States)

    Kimura, S; Uematsu, Y; Miyauchi, Y

    1986-01-01

    A new type of collagen was isolated from elastoidin of great blue shark by limited pepsin digestion. The collagen alpha chain of elastoidin, designated alpha 1(E), was very similar in electrophoretic and chromatographic behavior and amino acid composition to shark skin alpha 1(I) chain, but they were genetically-distinct on the basis of CNBr-peptide maps. The collagen molecule of elastoidin was shown to be an [alpha 1(E)]3 homotrimer.

  16. The substrate binding domains of human SIAH E3 ubiquitin ligases are now crystal clear

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Qi; Wang, Zhongduo; Hou, Feng; Harding, Rachel; Huang, Xinyi; Dong, Aiping; Walker, John R.; Tong, Yufeng

    2017-01-01

    Seven in absentia homologs (SIAHs) comprise a family of highly conserved E3 ubiquitin ligases that play an important role in regulating signalling pathways in tumorigenesis, including the DNA damage repair and hypoxia response pathways. SIAH1 and SIAH2 have been found to function as a tumour repressor and a proto-oncogene, respectively, despite the high sequence identity of their substrate binding domains (SBDs). Ubiquitin-specific protease USP19 is a deubiquitinase that forms a complex with SIAHs and counteracts the ligase function. Much effort has been made to find selective inhibitors of the SIAHs E3 ligases. Menadione was reported to inhibit SIAH2 specifically. We used X-ray crystallography, peptide array, bioinformatic analysis, and biophysical techniques to characterize the structure and interaction of SIAHs with deubiquitinases and literature reported compounds. We solved the crystal structures of SIAH1 in complex with a USP19 peptide and of the apo form SIAH2. Phylogenetic analysis revealed the SIAH/USP19 complex is conserved in evolution. We demonstrated that menadione destabilizes both SIAH1 and SIAH2 non-specifically through covalent modification. The SBDs of SIAH E3 ligases are structurally similar with a subtle stability difference. USP19 is the only deubiquitinase that directly binds to SIAHs through the substrate binding pocket. Menadione is not a specific inhibitor for SIAH2. The crystallographic models provide structural insights into the substrate binding of the SIAH family E3 ubiquitin ligases that are critically involved in regulating cancer-related pathways. Our results suggest caution should be taken when using menadione as a specific SIAH2 inhibitor.

  17. M3 version 3.0: Verification and validation; Hydrochemical model of ground water at repository site

    Energy Technology Data Exchange (ETDEWEB)

    Gomez, Javier B. (Dept. of Earth Sciences, Univ. of Zaragoza, Zaragoza (Spain)); Laaksoharju, Marcus (Geopoint AB, Sollentuna (Sweden)); Skaarman, Erik (Abscondo, Bromma (Sweden)); Gurban, Ioana (3D-Terra (Canada))

    2009-01-15

    Hydrochemical evaluation is a complex type of work that is carried out by specialists. The outcome of this work is generally presented as qualitative models and process descriptions of a site. To support and help to quantify the processes in an objective way, a multivariate mathematical tool entitled M3 (Multivariate Mixing and Mass balance calculations) has been constructed. The computer code can be used to trace the origin of the groundwater, and to calculate the mixing proportions and mass balances from groundwater data. The M3 code is a groundwater response model, which means that changes in the groundwater chemistry in terms of sources and sinks are traced in relation to an ideal mixing model. The complexity of the measured groundwater data determines the configuration of the ideal mixing model. Deviations from the ideal mixing model are interpreted as being due to reactions. Assumptions concerning important mineral phases altering the groundwater or uncertainties associated with thermodynamic constants do not affect the modelling because the calculations are solely based on the measured groundwater composition. M3 uses the opposite approach to that of many standard hydrochemical models. In M3, mixing is evaluated and calculated first. The constituents that cannot be described by mixing are described by reactions. The M3 model consists of three steps: the first is a standard principal component analysis, followed by mixing and finally mass balance calculations. The measured groundwater composition can be described in terms of mixing proportions (%), while the sinks and sources of an element associated with reactions are reported in mg/L. This report contains a set of verification and validation exercises with the intention of building confidence in the use of the M3 methodology. At the same time, clear answers are given to questions related to the accuracy and the precision of the results, including the inherent uncertainties and the errors that can be made

  18. M3 version 3.0: Verification and validation; Hydrochemical model of ground water at repository site

    Energy Technology Data Exchange (ETDEWEB)

    Gomez, Javier B. (Dept. of Earth Sciences, Univ. of Zaragoza, Zaragoza (Spain)); Laaksoharju, Marcus (Geopoint AB, Sollentuna (Sweden)); Skaarman, Erik (Abscondo, Bromma (Sweden)); Gurban, Ioana (3D-Terra (Canada))

    2009-01-15

    Hydrochemical evaluation is a complex type of work that is carried out by specialists. The outcome of this work is generally presented as qualitative models and process descriptions of a site. To support and help to quantify the processes in an objective way, a multivariate mathematical tool entitled M3 (Multivariate Mixing and Mass balance calculations) has been constructed. The computer code can be used to trace the origin of the groundwater, and to calculate the mixing proportions and mass balances from groundwater data. The M3 code is a groundwater response model, which means that changes in the groundwater chemistry in terms of sources and sinks are traced in relation to an ideal mixing model. The complexity of the measured groundwater data determines the configuration of the ideal mixing model. Deviations from the ideal mixing model are interpreted as being due to reactions. Assumptions concerning important mineral phases altering the groundwater or uncertainties associated with thermodynamic constants do not affect the modelling because the calculations are solely based on the measured groundwater composition. M3 uses the opposite approach to that of many standard hydrochemical models. In M3, mixing is evaluated and calculated first. The constituents that cannot be described by mixing are described by reactions. The M3 model consists of three steps: the first is a standard principal component analysis, followed by mixing and finally mass balance calculations. The measured groundwater composition can be described in terms of mixing proportions (%), while the sinks and sources of an element associated with reactions are reported in mg/L. This report contains a set of verification and validation exercises with the intention of building confidence in the use of the M3 methodology. At the same time, clear answers are given to questions related to the accuracy and the precision of the results, including the inherent uncertainties and the errors that can be made

  19. Restoration of Bottom Plate Leakage at 80,000 m3 Wiggins Gasholder%8万m3威金斯煤气柜柜底板泄漏修复

    Institute of Scientific and Technical Information of China (English)

    董永涛

    2015-01-01

    8万m3威金斯柜在生产运行中柜底板发生泄漏,采取临时措施封堵后效果不佳,为了避免事态扩大停柜检修,针对柜底板蜂窝状腐蚀,以托补钢板的形式予以加强,消除煤气泄漏的安全隐患.

  20. HSV-1 ICP0: An E3 Ubiquitin Ligase That Counteracts Host Intrinsic and Innate Immunity

    Directory of Open Access Journals (Sweden)

    Mirna Perusina Lanfranca

    2014-05-01

    Full Text Available The herpes simplex virus type 1 (HSV-1 encoded E3 ubiquitin ligase, infected cell protein 0 (ICP0, is required for efficient lytic viral replication and regulates the switch between the lytic and latent states of HSV-1. As an E3 ubiquitin ligase, ICP0 directs the proteasomal degradation of several cellular targets, allowing the virus to counteract different cellular intrinsic and innate immune responses. In this review, we will focus on how ICP0’s E3 ubiquitin ligase activity inactivates the host intrinsic defenses, such as nuclear domain 10 (ND10, SUMO, and the DNA damage response to HSV-1 infection. In addition, we will examine ICP0’s capacity to impair the activation of interferon (innate regulatory mediators that include IFI16 (IFN γ-inducible protein 16, MyD88 (myeloid differentiation factor 88, and Mal (MyD88 adaptor-like protein. We will also consider how ICP0 allows HSV-1 to evade activation of the NF-κB (nuclear factor kappa B inflammatory signaling pathway. Finally, ICP0’s paradoxical relationship with USP7 (ubiquitin specific protease 7 and its roles in intrinsic and innate immune responses to HSV-1 infection will be discussed.

  1. Identification of Arabidopsis MYB56 as a novel substrate for CRL3(BPM) E3 ligases.

    Science.gov (United States)

    Chen, Liyuan; Bernhardt, Anne; Lee, JooHyun; Hellmann, Hanjo

    2015-02-01

    Controlled stability of proteins is a highly efficient mechanism to direct diverse processes in living cells. A key regulatory system for protein stability is given by the ubiquitin proteasome pathway, which uses E3 ligases to mark specific proteins for degradation. In this work, MYB56 is identified as a novel target of a CULLIN3 (CUL3)-based E3 ligase. Its stability depends on the presence of MATH-BTB/POZ (BPM) proteins, which function as substrate adaptors to the E3 ligase. Genetic studies have indicated that MYB56 is a negative regulator of flowering, while BPMs positively affect this developmental program. The interaction between BPMs and MYB56 occurs at the promoter of FLOWERING LOCUS T (FT), a key regulator in initiating flowering in Arabidopsis, and results in instability of MYB56. Overall the work establishes MYB transcription factors as substrates of BPM proteins, and provides novel information on components that participate in controlling flowering time in plants. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

  2. Construction of new operation interface for the LABIHS simulator using the ELIPSE E3 studio software

    Energy Technology Data Exchange (ETDEWEB)

    Augusto, Silas C.; Oliveira, Mauro V., E-mail: silas@ien.gov.b, E-mail: mvitor@ien.gov.b [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2011-07-01

    The Human-System Interface Laboratory (LABIHS), located at the Instituto de Engenharia Nuclear (IEN), has a compact simulator that simulate the processes of a pressurized water reactor nuclear power plant of 930 MWe of power. This simulator is composed by a HP-UX workstation computer, where the simulation software runs, and a set of computer stations, that represent an advanced control room, where the simulator is operated by software control panels that represent several systems of the simulated nuclear power plant. The current HSIs for the LABIHS simulator was built using iLog software tool. The development of new human-system interfaces (HSIs) for the simulator is one of the research fields of LABIHS. This paper presents the screen components development process for a new HSI for the LABIHS simulator, using the software Elipse{sup TM} E3 Studio. These new components developed using the E3 Studio are similar to the ones used in the current simulator interface. The article shows some comparisons between the component and screen development with Elipse{sup TM} E3 Studio processes and using iLog Studio. (author)

  3. MDM2 is a novel E3 ligase for HIV-1 Vif

    Directory of Open Access Journals (Sweden)

    Tomonaga Mitsunori

    2009-01-01

    Full Text Available Abstract The human immunodeficiency virus type 1 (HIV-1 Vif plays a crucial role in the viral life cycle by antagonizing a host restriction factor APOBEC3G (A3G. Vif interacts with A3G and induces its polyubiquitination and subsequent degradation via the formation of active ubiquitin ligase (E3 complex with Cullin5-ElonginB/C. Although Vif itself is also ubiquitinated and degraded rapidly in infected cells, precise roles and mechanisms of Vif ubiquitination are largely unknown. Here we report that MDM2, known as an E3 ligase for p53, is a novel E3 ligase for Vif and induces polyubiquitination and degradation of Vif. We also show the mechanisms by which MDM2 only targets Vif, but not A3G that binds to Vif. MDM2 reduces cellular Vif levels and reversely increases A3G levels, because the interaction between MDM2 and Vif precludes A3G from binding to Vif. Furthermore, we demonstrate that MDM2 negatively regulates HIV-1 replication in non-permissive target cells through Vif degradation. These data suggest that MDM2 is a regulator of HIV-1 replication and might be a novel therapeutic target for anti-HIV-1 drug.

  4. Instanton induced Yukawa couplings from distant E3 and E(-1) instantons

    Energy Technology Data Exchange (ETDEWEB)

    Goodsell, Mark D. [Sorbonne Universités, UPMC Univ Paris 06, UMR 7589, LPTHE,F-75005, Paris (France); CNRS, UMR 7589, LPTHE,F-75005, Paris (France); Witkowski, Lukas T. [Institute for Theoretical Physics, University of Heidelberg,Philosophenweg 19, 69120 Heidelberg (Germany)

    2016-01-07

    We calculate non-perturbative contributions to Yukawa couplings on D3-branes at orbifold singularities due to E3 and fractional E(-1) instantons which do not intersect the visible sector branes. While distant E3 instantons on bulk cycles typically contribute to Yukawa couplings, we find that distant fractional E(-1) can also give rise to new Yukawa couplings. However, fractional E(-1) instantons only induce Yukawa couplings if they are located at a singularity which shares a collapsed homologous two-cycle with the singularity supporting the visible sector. The non-perturbative contributions to Yukawa couplings exhibit a different flavour structure than the tree-level Yukawa couplings and, as a result, they can be sources of flavour violation. This is particularly relevant for schemes of moduli stabilisation which rely on superpotential contributions from E3 instantons, such as KKLT or the Large Volume Scenario. As a byproduct of our analysis, we shed some new light on the properties of annulus diagrams with matter field insertions in stringy instanton calculus.

  5. Arabidopsis HIGH PLOIDY2 sumoylates and stabilizes flowering locus C through its E3 ligase activity

    Directory of Open Access Journals (Sweden)

    Jun Soo eKwak

    2016-04-01

    Full Text Available Flowering Locus C (FLC, a floral repressor, plays an important role in flowering. The mechanisms regulating FLC gene expression and protein function have been studied extensively; however, post-translational regulation of FLC remains unclear. Here, we identified Arabidopsis HIGH PLOIDY2 (HPY2 as an E3 SUMO ligase for FLC. In vitro and vivo pull-down assays showed that FLC physically interacts with HPY2. In vitro assays showed that the stimulation of FLC sumoylation by HPY2 was dependent on SUMO-activating enzyme E1 and -conjugating enzyme E2, indicating that HPY2 was an E3 SUMO ligase for FLC. In transgenic plants, inducible HPY2 overexpression increased the concentration of FLC, indicating that HPY2 stabilized FLC through direct sumoylation. Flowering time in hpy2-2 mutants was shorter than in wild-type plants under long- and short-day conditions, with a greater effect under short-day conditions, and FLC was downregulated in hpy2-2 mutants. These data indicate that HPY2 regulates FLC function and stability at both the transcriptional and post-translational levels through its E3 SUMO ligase activity.

  6. 基于ARM Cortex-M3的步进电机线性速度控制的实现%The Realization of Linear Speed Control of Stepper Motor Based on ARM Cortex-M3

    Institute of Scientific and Technical Information of China (English)

    罗鑫; 张峰

    2009-01-01

    Conex-M3是ARM公司最新推出的基于ARMy7体系架构的处理核.步进电机已被广泛的应用于速度、位置等控制领域.本文实现了基于Codex-M3内核处理器的步进电机的线性速度控制.针对步进电机控制过程中易出现的失步和过冲现象,提出了一种步进电机加减速控制算法.首先,在Codex-M3内核处理器上移植了μCOS-Ⅱ实时操作系统.在此基础上,利用系统的API接口函数用程序实现了加减速控制算法,并最终实现了对两路步进电机的控制.

  7. Photometric characterization of the Chang'e-3 landing site using LROC NAC images

    Science.gov (United States)

    Clegg-Watkins, R. N.; Jolliff, B. L.; Boyd, A.; Robinson, M. S.; Wagner, R.; Stopar, J. D.; Plescia, J. B.; Speyerer, E. J.

    2016-07-01

    China's robotic Chang'e-3 spacecraft, carrying the Yutu rover, touched down in Mare Imbrium on the lunar surface on 14 December 2013. The Lunar Reconnaissance Orbiter (LRO) Narrow Angle Camera (NAC) imaged the site both before and after landing. Multi-temporal NAC images taken before and after the landing, phase-ratio images made from NAC images taken after the landing, and Hapke photometric techniques were used to evaluate surface changes caused by the disturbance of regolith at the landing site (blast zone) by the descent engines of the Chang'e-3 spacecraft. The reflectance of the landing site increased by 10 ± 1% (from I/F = 0.040 to 0.044 at 30° phase angle) as a result of the landing, a value similar to reflectance increases estimated for the Apollo, Luna, and Surveyor landing sites. The spatial extent of the disturbed area at the Chang'e-3 landing site, 2530 m2, also falls close to what is predicted on the basis of correlations between lander mass, thrust, and blast zone areas for the historic landed missions. A multi-temporal ratio image of the Chang'e-3 landing site reveals a main blast zone (slightly elongate in the N-S direction; ∼75 m across N-S and ∼43 m across in the E-W direction) and an extended diffuse, irregular halo that is less reflective than the main blast zone (extending ∼40-50 m in the N-S direction and ∼10-15 m in the E-W direction beyond the main blast zone). The N-S elongation of the blast zone likely resulted from maneuvering during hazard avoidance just prior to landing. The phase-ratio image reveals that the blast zone is less backscattering than surrounding undisturbed areas. The similarities in magnitude of increased reflectance between the Chang'e-3 landing site and the Surveyor, Apollo, and Luna landing sites suggest that lunar soil reflectance changes caused by interaction with rocket exhaust are not significantly altered over a period of 40-50 years. The reflectance changes are independent of regolith composition

  8. GEM-E3: A computable general equilibrium model applied for Switzerland

    Energy Technology Data Exchange (ETDEWEB)

    Bahn, O. [Paul Scherrer Inst., CH-5232 Villigen PSI (Switzerland); Frei, C. [Ecole Polytechnique Federale de Lausanne (EPFL) and Paul Scherrer Inst. (Switzerland)

    2000-01-01

    The objectives of the European Research Project GEM-E3-ELITE, funded by the European Commission and coordinated by the Centre for European Economic Research (Germany), were to further develop the general equilibrium model GEM-E3 (Capros et al., 1995, 1997) and to conduct policy analysis through case studies. GEM-E3 is an applied general equilibrium model that analyses the macro-economy and its interaction with the energy system and the environment through the balancing of energy supply and demand, atmospheric emissions and pollution control, together with the fulfillment of overall equilibrium conditions. PSI's research objectives within GEM-E3-ELITE were to implement and apply GEM-E3 for Switzerland. The first objective required in particular the development of a Swiss database for each of GEM-E3 modules (economic module and environmental module). For the second objective, strategies to reduce CO{sub 2} emissions were evaluated for Switzerland. In order to develop the economic, PSI collaborated with the Laboratory of Applied Economics (LEA) of the University of Geneva and the Laboratory of Energy Systems (LASEN) of the Federal Institute of Technology in Lausanne (EPFL). The Swiss Federal Statistical Office (SFSO) and the Institute for Business Cycle Research (KOF) of the Swiss Federal Institute of Technology (ETH Zurich) contributed also data. The Swiss environmental database consists mainly of an Energy Balance Table and of an Emission Coefficients Table. Both were designed using national and international official statistics. The Emission Coefficients Table is furthermore based on know-how of the PSI GaBE Project. Using GEM-E3 Switzerland, two strategies to reduce the Swiss CO{sub 2} emissions were evaluated: a carbon tax ('tax only' strategy), and the combination of a carbon tax with the buying of CO{sub 2} emission permits ('permits and tax' strategy). In the first strategy, Switzerland would impose the necessary carbon tax to achieve

  9. [Biological experiments in flights of unmanned space craft Foton-M2 and Foton-M3].

    Science.gov (United States)

    Ilyin, E A

    2013-01-01

    Missions of unmanned spacecraft Foton-M2 (2005) and Foton-M3 (2007) of 16 and 12 days in duration, respectively, provided an opportunity to conduct the Russian/US experiments with snails (Helix lucorum and Helix aspera), newts (Pleurodeles waltli), geckos (Pachydactilus turneri) and microorganisms (Streptomyces lividans 66, E. coli and others). Besides, Foton-M3 carried a Russian experiment with Mongolian gerbils (Meriones unguiculatus). Objectives of the space experiments were to study the micro-g effects on the living systems' behavior, structure and functioning, post-traumatic regeneration of bone and organs, stable inheritance of plasmid pIJ 702, and melanin pigment synthesis by streptomycets. The survey paper presents the major findings of a large team of investigators.

  10. Electrochemical properties of mixed conducting (La,M)(CoFe) oxide perovskites (M=3DSr, Ca, and Ba)

    Energy Technology Data Exchange (ETDEWEB)

    Stevenson, J.W.; Armstrong, T.R.; Bates, J.L. [and others

    1996-04-01

    Electrical properties and oxygen permeation properties of solid mixed-conducting electrolytes (La,M)(CoFe) oxide perovskites (M=3DSr, Ca, and Ba) have been characterized. These materials are potentially useful as passive membranes to separate high purity oxygen from air and as the cathode in a fuel cell. Dilatometric linear expansion measurements were performed as a function of temperature and oxygen partial pressure to evaluate the stability.

  11. The Armys M-1 Abrams, M-2/M-3 Bradley, and M-1126 Stryker: Background and Issues for Congress

    Science.gov (United States)

    2016-04-05

    entered service with the Army in 1980; the M-2/M-3 Bradley Fighting Vehicle in 1981; and the Stryker Combat Vehicle in 2001. Under current Army... Under current Army modernization plans, the Army envisions all three vehicles in service with Active and National Guard forces beyond FY2028...Information from this section, unless otherwise noted, is taken from Jane’s Armour and Artillery, 2011-2012, pp.177- 185, and the author’s personal

  12. Inhalation by design: dual pharmacology β-2 agonists/M3 antagonists for the treatment of COPD.

    Science.gov (United States)

    Jones, Lyn H; Baldock, Helen; Bunnage, Mark E; Burrows, Jane; Clarke, Nick; Coghlan, Michele; Entwistle, David; Fairman, David; Feeder, Neil; Fulton, Craig; Hilton, Laura; James, Kim; Jones, Rhys M; Kenyon, Amy S; Marshall, Stuart; Newman, Sandra D; Osborne, Rachel; Patel, Sheena; Selby, Matthew D; Stuart, Emilio F; Trevethick, Michael A; Wright, Karen N; Price, David A

    2011-05-01

    This paper describes the successful design and development of dual pharmacology β-2 agonists-M3 antagonists, for the treatment of chronic obstructive pulmonary disorder using the principles of 'inhalation by design'. A key feature of this work is the combination of balanced potency and pharmacodynamic duration with desirable pharmacokinetic and material properties, whilst keeping synthetic complexity to a minimum. Copyright © 2010 Elsevier Ltd. All rights reserved.

  13. Implications for Damage Recognition during Dpo4-Mediated Mutagenic Bypass of m1G and m3C Lesions

    Energy Technology Data Exchange (ETDEWEB)

    Rechkoblit, Olga; Delaney, James C.; Essigmann, John M.; Patel, Dinshaw J. (MIT); (MSKCC)

    2012-05-08

    DNA is susceptible to alkylation damage by a number of environmental agents that modify the Watson-Crick edge of the bases. Such lesions, if not repaired, may be bypassed by Y-family DNA polymerases. The bypass polymerase Dpo4 is strongly inhibited by 1-methylguanine (m1G) and 3-methylcytosine (m3C), with nucleotide incorporation opposite these lesions being predominantly mutagenic. Further, extension after insertion of both correct and incorrect bases, introduces additional base substitution and deletion errors. Crystal structures of the Dpo4 ternary extension complexes with correct and mismatched 3'-terminal primer bases opposite the lesions reveal that both m1G and m3C remain positioned within the DNA template/primer helix. However, both correct and incorrect pairing partners exhibit pronounced primer terminal nucleotide distortion, being primarily evicted from the DNA helix when opposite m1G or misaligned when pairing with m3C. Our studies provide insights into mechanisms related to hindered and mutagenic bypass of methylated lesions and models associated with damage recognition by repair demethylases.

  14. Drop by drop backscattered signal of a 50 × 50 × 50 m3 volume: A numerical experiment

    Science.gov (United States)

    Gires, A.; Tchiguirinskaia, I.; Schertzer, D.

    2016-09-01

    The goal of this paper is to analyse the influence of individual drop positions on a backscattered radar signal. This is achieved through a numerical experiment: a 3D rain drop field generator is developed and implemented over a volume of 50 × 50 × 50 m3, and then the sum of the electromagnetic waves backscattered by its hydrometeors is computed. Finally the temporal evolution over 1 s is modelled with simplistic assumptions. For the rainfall generator, the liquid water content (LWC) distribution is represented with the help of a multiplicative cascade down to 0.5 m, below which it is considered as homogeneous. Within each 0.5 × 0.5 × 0.5 m3 patch, liquid water is distributed into drops, located randomly uniformly according to a pre-defined drop size distribution (DSD). Such configuration is compared with the one consisting of the same drops being uniformly distributed over the entire 50 × 50 × 50 m3 volume. Due to the fact that the radar wave length is much smaller than the size of a rainfall "patch", it appears that, in agreement with the theory, we retrieve an exponential distribution for potential measures on horizontal reflectivity. Much thinner dispersion is noticed for differential reflectivity. We show that a simple ballistic assumption for drop velocities does not enable the reproduction of radar observations, and turbulence should be taken into account. Finally the sensitivity of these outputs to the various model parameters is quantified.

  15. Analysis on establishing Chang'E-3 landing site as a reflectance calibration target

    Science.gov (United States)

    Liu, Bin; Fu, Xiaohui; Zeng, Xingguo; Yao, Meijuan; Zhang, Hongbo; Su, Yan; Zhao, Shu; Xue, Xiping; Li, Chunlai; Zou, Yongliao

    2015-04-01

    Recent lunar orbital observations suggested that the surface reflectance calculated based on the Apollo 16 standard area and Apollo 16 sample laboratory measurement is significantly different from its true value [1-3], one reason is the composition and maturity differences between the 62231 sampling site and the Apollo 16 standard site existed, the other reason is the physical properties of the returned lunar sample, such as porosity, have been changed during the sampling operations. So more new standard targets on the Moon, besides the widely used Apollo 16 area, are needed for imaging spectrometers on lunar missions to improve their reflectance calibration accuracies. The Chang'E-3 VIS/NIR Imaging Spectrometer (VNIS), which is just fixed at the front of the Yutu rover [4], equipped with a white spectralon panel as reflectance calibration standard, can perform in situ multispectral observations around the Chang'E-3 landing site without altering the physical and mineralogical natures of lunar soils. Therefore, it provides an opportunity to establish a new reliable standard target for in-flight reflectance calibration. The reflectance calibration target should be compositional homogeneous, the topography of which must be flat, and the reflectance should be identical with no nearby units of other different materials. As we have known, Chang'e-3 probe landed on the Mare Imbrium basin in the east part of Sinus Iridum, the landing site is relatively flat at a spatial coverage of ~660km2, and this region belongs to Eratosthenian low-Ti/high-Ti mare basalts [5-6]. According to much higher resolution topography data, elemental data and reflectance data of Chang'E-2 and Chang'E-3[7-8], we preliminary analyse the possibility on establishing Chang'E-3 landing site as a reflectance calibration target. Firstly, the overall terrain of the 4 km×4 km area around the landing site is flat, but there are still three bigger craters existed. Secondly, the composition on Chang'E-3

  16. Endoplasmic Reticulum Exit of Golgi-resident Defective for SREBP Cleavage (Dsc) E3 Ligase Complex Requires Its Activity.

    Science.gov (United States)

    Raychaudhuri, Sumana; Espenshade, Peter J

    2015-06-01

    Layers of quality control ensure proper protein folding and complex formation prior to exit from the endoplasmic reticulum. The fission yeast Dsc E3 ligase is a Golgi-localized complex required for sterol regulatory element-binding protein (SREBP) transcription factor activation that shows architectural similarity to endoplasmic reticulum-associated degradation E3 ligases. The Dsc E3 ligase consists of five integral membrane proteins (Dsc1-Dsc5) and functionally interacts with the conserved AAA-ATPase Cdc48. Utilizing an in vitro ubiquitination assay, we demonstrated that Dsc1 has ubiquitin E3 ligase activity that requires the E2 ubiquitin-conjugating enzyme Ubc4. Mutations that specifically block Dsc1-Ubc4 interaction prevent SREBP cleavage, indicating that SREBP activation requires Dsc E3 ligase activity. Surprisingly, Golgi localization of the Dsc E3 ligase complex also requires Dsc1 E3 ligase activity. Analysis of Dsc E3 ligase complex formation, glycosylation, and localization indicated that Dsc1 E3 ligase activity is specifically required for endoplasmic reticulum exit of the complex. These results define enzyme activity-dependent sorting as an autoregulatory mechanism for protein trafficking.

  17. An integrated design of the payload for Chang'e 3 Lunar Rover

    Science.gov (United States)

    Zhouchangyi, Zhouchangyi

    Chang’e 3 detector is launched in China Xichang Satellite Launch Center on December 2, 2013. Its project task was a complete success. CE-3 detector achieved a soft landing and started its lunar exploration andinspection. It is composed of the lander and Rover (Yutu). This paper introduces an integrated designing payload of Chang’e 3 Lunar Rover. Chang’e 3 Lunar Rover is allocated with infrared imaging spectrometer,moon-measuring radar, Alpha Particle X-ray Spectrometer(APXS), panoramic camera and other payloads. The infrared spectrometer is used to analyse the infrared spectrum and take images of the patrolling areas, to analyse the mineral composition and distribution of the lunar surface, and to do a comprehensive study of the energy sources and mineral sources.The radar is used for inspecting the thickness and structure of the lunar soil on the patrolling path as well as probing the structure of the shallow lunar crust. The APXS will use the method of alpha-particle-induced X-ray fluorescence to study in detail the composition of soil in specific areas. The panoramic camera is for obtaining three-dimensional images of the lunar surface around the patrolling path, accomplishing the inspection of near landscapes and topographic analysis. Limited by the total weight, the Rover is equipped with a payload controller, through which an integrated design consisting of the power supply, data processing, electronic units, operating management and other functions of the payload is done, to realize the centralized power supply, centralized management, centralized data processing, centralized operating controlling and centralized interfaces with the integrated electronic system of the Rover.

  18. Topographic modeling and analysis of the landing site of Chang'E-3 on the Moon

    Science.gov (United States)

    Wu, Bo; Li, Fei; Ye, Lei; Qiao, Si; Huang, Jun; Wu, Xueying; Zhang, He

    2014-11-01

    The Chinese lunar probe Chang'E-3, carrying the “Jade Rabbit” lunar rover, successfully landed in the Sinus Iridum area on the Moon on December 14, 2013. This paper presents the characterization activities that were done for the selection of the landing area, including topographic modeling and analysis based on multisource lunar remote sensing data. Seven meter-resolution Chang'E-2 imagery and Lunar Orbiter Laser Altimeter data were integrated to generate a digital elevation model (DEM) with a resolution of 20 m for the entire Sinus Iridum landing area. Long baseline slopes were assessed according to this DEM for all of this area. Lunar Reconnaissance Orbiter narrow-angle camera images and 1.5 m-resolution Chang'E-2 imagery were used to derive DEMs with higher resolution (4 m) at several local regions within the Sinus Iridum landing area. Slope analyses at lander footprint scale (˜8 m) were performed in these local regions. Craters were detected from the DEMs and the derived orthophotos, and size-frequency distributions were generated. Crater morphological statistics, including the depth/diameter ratios, rim height/diameter ratios and wall slopes, were analyzed. The results showed that the Sinus Iridum landing area is relatively flat. Most of the area has slopes of less than 15°. The steeper slopes are mainly alongside craters and ridges. The crater size-frequency distribution is close to the equilibrium distribution. The crater ages, as indicated by their morphological statistics, vary from mature to relatively fresh in different regions. These topographic modeling and analysis results were used for strategic planning to identify the landing site for the Chang'E-3 and made a useful contribution to the success of the Chang'E-3 mission.

  19. Momentum correlation of the final-state wavefunction for (e, 3e) collisions on helium

    Institute of Scientific and Technical Information of China (English)

    Zhang Sui- Meng

    2004-01-01

    Based on our earlier paper, the momentum correlation of the four bodies in the final state is further considered for (e, 3e) processes on helium. A fivefold differential cross section (FDCS) for electron-impact double ionization of helium is calculated by use of the modified model for high incident energy (1-5.6keV). It has been found that the present results give a better description for the experimental data, as compared with the results of our earlier paper.

  20. The Processing and Analysis of Lunar Penetrating Radar Channel-1 Data from Chang'E-3

    Directory of Open Access Journals (Sweden)

    Gao Yun-ze

    2015-10-01

    Full Text Available Lunar Penetrating Radar (LPR, which is one of the most important science payloads onboard the Chang'E-3 (CE-3 rover, is used to obtain electromagnetic image less than 100 m beneath the lunar surface. This paper describes the system composition and working mechanism of the LPR and presents a detailed analysis of its data. We investigated special signal-processing methods and present the result of channel-1 data. The result shows that the effective echo occurs at depths greater than 100 m. Moreover, an unusual reflection exists at depth of 40 m, which may be the boundary of two geological units beneath the lunar surface.

  1. Structure of the DDB1-CRBN E3 ubiquitin ligase in complex with thalidomide

    OpenAIRE

    Fischer, Eric S.; Böhm, Kerstin; Lydeard, John R.; Yang, Haidi; Stadler, Michael B.; Cavadini, Simone; Nagel, Jane; Serluca, Fabrizio; Acker, Vincent; Lingaraju, Gondichatnahalli M.; Tichkule, Ritesh B.; Schebesta, Michael; Forrester, William C.; Schirle, Markus; Hassiepen, Ulrich

    2015-01-01

    In the 1950s the drug thalidomide administered as a sedative to pregnant women led to the birth of thousands of children with multiple defects. Despite its teratogenicity, thalidomide and its derivatives lenalidomide and pomalidomide (together known as Immunomodulatory Drugs: IMiDs) recently emerged as effective treatments for multiple myeloma and 5q-dysplasia. IMiDs target the CUL4-RBX1-DDB1-CRBN (CRL4CRBN) E3 ubiquitin ligase and promote the ubiquitination of Ikaros/Aiolos transcription fac...

  2. CHANG'E-3 Active Particle-induced X-ray Spectrometer: ground verification test

    Science.gov (United States)

    Guo, Dongya; Peng, Wenxi; Cui, XingZhu; Wang, Huanyu

    The Active Particle-induced X-ray Spectrometer (APXS) is one of the payloads of Chang’E-3 rover Yutu, with which the major elemental composition of lunar soils and rocks can be measured on site. In order to assess the instrument performance and the accuracy of determination, ground verification test was carried out with two blind samples(basaltic rock, powder). Details of the experiments and data analysis method are discussed. The results show that the accuracy of quantitative analysis for major elements(Mg,Al,Si,K,Ca,Ti,Fe) is better than 15%.

  3. The E3 Ligase CHIP Mediates Ubiquitination and Degradation of Mixed-Lineage Kinase 3

    OpenAIRE

    Blessing, Natalya A.; Brockman, April L.; Chadee, Deborah N.

    2014-01-01

    Mixed-lineage kinase 3 (MLK3) activates mitogen-activated protein kinase (MAPK) signaling pathways and has important functions in migration, invasion, proliferation, tumorigenesis, and apoptosis. We investigated the role of the E3 ligase carboxyl terminus of Hsc70-interacting protein (CHIP) in the regulation of MLK3 protein levels. We show that CHIP interacts with MLK3 and, together with the E2 ubiquitin-conjugating enzyme UbcH5 (UbcH5a, -b, -c, or -d), ubiquitinates MLK3 in vitro. CHIP or Hs...

  4. A prediction for |U{sub e3}| from patterns in the charged lepton spectra

    Energy Technology Data Exchange (ETDEWEB)

    Ferrandis, Javier; Pakvasa, Sandip

    2004-09-22

    It is shown that empirical relations between the charged lepton spectra and the quark spectra together with a bimaximal or near bimaximal neutrino mixing matrix necessarily imply that there is a contribution to |U{sub e3}| given by {theta}{sub C}/ 3{radical}2 {approx} {radical}(m{sub e}/2m{sub {mu}}) {approx} 0.052, where {theta}{sub C}is the Cabibbo angle. This prediction could be tested in the near future reactor experiments. The charged lepton mixing also generates a less robust prediction for the angle {theta}{sub 23} and a small contribution to the phase {delta}.

  5. Design of Instrument Lathe Control System Based on CORTEX-M3 Technology%基于CORTEX-M3技术的仪表车床控制系统设计

    Institute of Scientific and Technical Information of China (English)

    李香泉; 刘浪; 洪耀球

    2012-01-01

    采用了基于CORTEX-M3核的STM32F103VCT6 ARM芯片作为核心,实现4轴步进电机控制功能,同时系统还实现了与基于MODBUS RTU协议的文本显示或工业触摸屏的通信功能,以及获取相关输入信号和控制继电器功能.

  6. 8×104m3威金斯转炉煤气柜密封膜破损修复处理%Renovation the Broken Sealing Membrane of 8×104m3 Wiggins Converter Gas Tank

    Institute of Scientific and Technical Information of China (English)

    王树奇; 张军; 刘芳荣

    2013-01-01

    文章介绍了8× 104m3威金斯转炉煤气柜发生密封膜破损泄漏事故,分析了密封膜损坏的原因分析.希望通过此次事故,能提高运行人员和点检人员对八万转炉煤气柜的高度认识和密切关注,在以后的工作当中,避免此类事情的发生.

  7. The influence of polymorphisms of glutathione S-transferases M1 and M3 on the development of human urothelial cancer.

    Science.gov (United States)

    Golka, Klaus; Schmidt, Tobias; Seidel, Thilo; Dietrich, Holger; Roemer, Hermann C; Lohlein, Dietrich; Reckwitz, Thomas; Sokeland, Jurgen; Weistenhofer, Wobbeke; Blaszkewicz, Meinolf; Selinski, Silvia

    2008-01-01

    Cigarette smoking is the most important risk factor for development of transitional cell carcinoma of the urinary bladder. The effect of polymorphisms of glutathione S-transferases M1 (GSTM1) and M3 (GSTM3) on the influence of cigarette smoking on urinary bladder carcinogenesis was investigated. In total, 293 bladder cancer patients from hospitals in Dortmund and Wittenberg as well as 176 patients without any malignancy from a Department of Surgery from Dortmund were genotyped for GSTM1 and GSTM3 according to standard PCR/RFLP methods. Smoking habits were quantified by a standardized interview. The proportion of GSTM1 negative cases was 63% in the entire bladder cancer cases group compared to 50% in controls. The GSTM3*A/*A genotype was 76% in cancer cases versus 74% in controls. Smokers and ex-smokers were overrepresented in bladder cancer cases. A significant association between smoking status and GSTM1 or GSTM3 genotype was not detected. The elevated proportion of GSTM1 negative bladder cancer cases shows an effect of this polymorphic enzyme on development of bladder cancer. In contrast to other studies, an influence of GSTM1 on the risk due to cigarette smoking was not observed.

  8. Phase transitions

    CERN Document Server

    Solé, Ricard V

    2011-01-01

    Phase transitions--changes between different states of organization in a complex system--have long helped to explain physics concepts, such as why water freezes into a solid or boils to become a gas. How might phase transitions shed light on important problems in biological and ecological complex systems? Exploring the origins and implications of sudden changes in nature and society, Phase Transitions examines different dynamical behaviors in a broad range of complex systems. Using a compelling set of examples, from gene networks and ant colonies to human language and the degradation o

  9. Blocking an N-terminal acetylation–dependent protein interaction inhibits an E3 ligase

    Energy Technology Data Exchange (ETDEWEB)

    Scott, Daniel C.; Hammill, Jared T.; Min, Jaeki; Rhee, David Y.; Connelly, Michele; Sviderskiy, Vladislav O.; Bhasin, Deepak; Chen, Yizhe; Ong, Su-Sien; Chai, Sergio C.; Goktug, Asli N.; Huang, Guochang; Monda, Julie K.; Low, Jonathan; Kim, Ho Shin; Paulo, Joao A.; Cannon, Joe R.; Shelat, Anang A.; Chen, Taosheng; Kelsall, Ian R.; Alpi, Arno F.; Pagala, Vishwajeeth; Wang, Xusheng; Peng, Junmin; Singh , Bhuvanesh; Harper, J. Wade; Schulman, Brenda A.; Guy, R. Kip (MSKCC); (Dundee); (SJCH); (Harvard-Med); (MXPL)

    2017-06-05

    N-terminal acetylation is an abundant modification influencing protein functions. Because ~80% of mammalian cytosolic proteins are N-terminally acetylated, this modification is potentially an untapped target for chemical control of their functions. Structural studies have revealed that, like lysine acetylation, N-terminal acetylation converts a positively charged amine into a hydrophobic handle that mediates protein interactions; hence, this modification may be a druggable target. We report the development of chemical probes targeting the N-terminal acetylation–dependent interaction between an E2 conjugating enzyme (UBE2M or UBC12) and DCN1 (DCUN1D1), a subunit of a multiprotein E3 ligase for the ubiquitin-like protein NEDD8. The inhibitors are highly selective with respect to other protein acetyl-amide–binding sites, inhibit NEDD8 ligation in vitro and in cells, and suppress anchorage-independent growth of a cell line with DCN1 amplification. Overall, our data demonstrate that N-terminal acetyl-dependent protein interactions are druggable targets and provide insights into targeting multiprotein E2–E3 ligases.

  10. Treatability study of Tank E-3-1 waste: mixed waste stream SR-W049

    Energy Technology Data Exchange (ETDEWEB)

    Langton, C.A. [Westinghouse Savannah River Company, AIKEN, SC (United States)

    1997-08-21

    Treatability studies were conducted for tank E-3-1 waste which was previously characterized in WSRC-RP-87-0078. The waste was determined to be mixed waste because it displayed the characteristic of metal toxicity for Hg and Cr and was also contaminated with low levels of radionuclides. Two types of treatments for qualifying this waste suitable for land disposal were evaluated: ion exchange and stabilization with hydraulic materials (portland cement, slag and magnesium phosphate cement). These treatments were selected for testing because: (1) Both treatments can be carried out as in-drum processes., (2) Cement stabilization is the RCRA/LDR best developed available technology (BDAT) for Hg (less than 280 mg/L) and for Cr., and (3) Ion exchange via Mag-Sep is a promising alternative technology for in drum treatment of liquid wastes displaying metal toxicity. Cement stabilization of the E-3-1 material ( supernate and settled solids) resulted in waste forms which passed the TCLP test for both Hg and Cr. However, the ion exchange resins tested were ineffective in removing the Hg from this waste stream. Consequently, cement stabilization is recommended for a treatment of the five drums of the actual waste.

  11. The E3 Ligase CHIP Mediates p21 Degradation to Maintain Radioresistance.

    Science.gov (United States)

    Biswas, Kuntal; Sarkar, Sukumar; Du, Kangping; Brautigan, David L; Abbas, Tarek; Larner, James M

    2017-06-01

    Lung cancer resists radiotherapy, making it one of the deadliest forms of cancer. Here, we show that human lung cancer cell lines can be rendered sensitive to ionizing radiation (IR) by RNAi knockdown of C-terminus of Hsc70-interacting protein (CHIP/STUB1), a U-box-type E3 ubiquitin ligase that targets a number of stress-induced proteins. Mechanistically, ubiquitin-dependent degradation of the cyclin-dependent kinase (CDK) inhibitor, p21 protein, is reduced by CHIP knockdown, leading to enhanced senescence of cells in response to exposure to IR. Cellular senescence and sensitivity to IR is prevented by CRISPR/Cas9-mediated deletion of the p21 gene (CDKN1A) in CHIP knockdown cells. Conversely, overexpression of CHIP potentiates p21 degradation and promotes greater radioresistance of lung cancer cells. In vitro and cell-based assays demonstrate that p21 is a novel and direct ubiquitylation substrate of CHIP that also requires the CHIP-associated chaperone HSP70. These data reveal that the inhibition of the E3 ubiquitin ligase CHIP promotes radiosensitivity, thus suggesting a novel strategy for the treatment of lung cancer.Implications: The CHIP-HSP70-p21 ubiquitylation/degradation axis identified here could be exploited to enhance the efficacy of radiotherapy in patients with non-small cell lung cancer. Mol Cancer Res; 15(6); 651-9. ©2017 AACR. ©2017 American Association for Cancer Research.

  12. Structure of the DDB1-CRBN E3 ubiquitin ligase in complex with thalidomide.

    Science.gov (United States)

    Fischer, Eric S; Böhm, Kerstin; Lydeard, John R; Yang, Haidi; Stadler, Michael B; Cavadini, Simone; Nagel, Jane; Serluca, Fabrizio; Acker, Vincent; Lingaraju, Gondichatnahalli M; Tichkule, Ritesh B; Schebesta, Michael; Forrester, William C; Schirle, Markus; Hassiepen, Ulrich; Ottl, Johannes; Hild, Marc; Beckwith, Rohan E J; Harper, J Wade; Jenkins, Jeremy L; Thomä, Nicolas H

    2014-08-07

    In the 1950s, the drug thalidomide, administered as a sedative to pregnant women, led to the birth of thousands of children with multiple defects. Despite the teratogenicity of thalidomide and its derivatives lenalidomide and pomalidomide, these immunomodulatory drugs (IMiDs) recently emerged as effective treatments for multiple myeloma and 5q-deletion-associated dysplasia. IMiDs target the E3 ubiquitin ligase CUL4-RBX1-DDB1-CRBN (known as CRL4(CRBN)) and promote the ubiquitination of the IKAROS family transcription factors IKZF1 and IKZF3 by CRL4(CRBN). Here we present crystal structures of the DDB1-CRBN complex bound to thalidomide, lenalidomide and pomalidomide. The structure establishes that CRBN is a substrate receptor within CRL4(CRBN) and enantioselectively binds IMiDs. Using an unbiased screen, we identified the homeobox transcription factor MEIS2 as an endogenous substrate of CRL4(CRBN). Our studies suggest that IMiDs block endogenous substrates (MEIS2) from binding to CRL4(CRBN) while the ligase complex is recruiting IKZF1 or IKZF3 for degradation. This dual activity implies that small molecules can modulate an E3 ubiquitin ligase and thereby upregulate or downregulate the ubiquitination of proteins.

  13. Noninvasive visualization of adenovirus replication with a fluorescent reporter in the E3 region.

    Science.gov (United States)

    Ono, Hidetaka A; Le, Long P; Davydova, Julia G; Gavrikova, Tatyana; Yamamoto, Masato

    2005-11-15

    To overcome the inefficacy and undesirable side effects of current cancer treatment strategies, conditionally replicative adenoviruses have been developed to exploit the unique mechanism of oncolysis afforded by tumor-specific viral replication. Despite rapid translation into clinical trials and the established safety of oncolytic adenoviruses, the in vivo function of these agents is not well understood due to lack of a noninvasive detection system for adenovirus replication. To address this issue, we propose the expression of a reporter from the adenovirus E3 region as a means to monitor replication. Adenovirus replication reporter vectors were constructed with the enhanced green fluorescent protein (EGFP) gene placed in the deleted E3 region under the control of the adenoviral major late promoter while retaining expression of the adenovirus death protein to conserve the native oncolytic capability of the virus. Strong EGFP fluorescence was detected from these vectors in a replication-dependent manner, which correlated with viral DNA replication. Fluorescence imaging in vivo confirmed the ability to noninvasively detect fluorescent signal during replication, which generally corresponded with the underlying level of viral DNA replication. EGFP representation of viral replication was further confirmed by Western blot comparison with the viral DNA content in the tumors. Imaging reporter expression controlled by the adenoviral major late promoter provides a viable approach to noninvasively monitor adenovirus replication in preclinical studies and has the potential for human application with clinically relevant imaging reporters.

  14. Diagramming Transactive Building Business Cases: Using Principles of e3 Value to Document Valuation Studies

    Energy Technology Data Exchange (ETDEWEB)

    Hammerstrom, Donald J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Makhmalbaf, Atefe [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Marinovici, Maria C. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2016-12-30

    Energy management in buildings is becoming more transactive. Pacific Northwest National Laboratory and the U.S. Department of Energy Building Technologies Office recently defined innovative use cases wherein market-like mechanisms are used to manage energy within buildings, between buildings, and between buildings and third-party entities, such as power utilities. A next step toward defining a set of transactive use cases in the buildings domain is to carefully diagram the corresponding business cases to capture details of transactions among all stakeholders and their economic value propositions. The principles of e3-value diagramming are applied in this report toward creating business value diagrams. These principles are extended to be consistent with Universal Modeling Language use-case diagrams. Example diagrams are presented for a subset of buildings-domain use cases that were introduced in an earlier Pacific Northwest National Laboratory report. The diagrams are intended to clearly represent an understanding of the transactions through which individual entities accumulate value in their respective use cases, and the diagrams should therefore support economic valuation studies. The report reviews some of the foundational principles of e3 value and includes authors’ insights concerning the formulation of these diagrams using Universal Modeling Language as a more systematic modeling approach.

  15. No Evidence for Multiple Stellar Populations in the Low-mass Galactic Globular Cluster E 3

    Science.gov (United States)

    Salinas, Ricardo; Strader, Jay

    2015-08-01

    Multiple stellar populations are a widespread phenomenon among Galactic globular clusters. Even though the origin of the enriched material from which new generations of stars are produced remains unclear, it is likely that self-enrichment will be feasible only in clusters massive enough to retain this enriched material. We searched for multiple populations in the low mass (M˜ 1.4× {10}4 {M}⊙ ) globular cluster E3, analyzing SOAR/Goodman multi-object spectroscopy centered on the blue cyanogen (CN) absorption features of 23 red giant branch stars. We find that the CN abundance does not present the typical bimodal behavior seen in clusters hosting multistellar populations, but rather a unimodal distribution that indicates the presence of a genuine single stellar population, or a level of enrichment much lower than in clusters that show evidence for two populations from high-resolution spectroscopy. E3 would be the first bona fide Galactic old globular cluster where no sign of self-enrichment is found. Based on observations obtained at the Southern Astrophysical Research (SOAR) Telescope, which is a joint project of the Ministério da Ciência, Tecnologia, e Inovação (MCTI) da República Federativa do Brasil, the US National Optical Astronomy Observatory (NOAO), the University of North Carolina at Chapel Hill (UNC), and Michigan State University (MSU).

  16. Rock size-frequency distribution analysis at the Chang'E-3 landing site

    Science.gov (United States)

    Di, Kaichang; Xu, Bin; Peng, Man; Yue, Zongyu; Liu, Zhaoqin; Wan, Wenhui; Li, Lichun; Zhou, Jianliang

    2016-01-01

    This paper presents a comprehensive analysis of the rock size-frequency distribution at the Chang'E-3 landing site. Using 84 Navcam stereo images acquired at 7 waypoints by the Yutu rover and an interactive stereo image processing system, a total of 582 rocks larger than 0.05 m in diameter were identified and measured. The statistical results of the size-frequency distribution show that the cumulative fractional area covered by rocks versus their diameter follows a simple exponential function and has a convex-up shape on log-log graphs with the slope increasing with diameter. The cumulative number of rocks versus diameter derived by numerically integrating the cumulative fractional area also shows a good fit with the data. A diameter-height relationship was also determined from height and diameter ratios. The observed rock statistics were also compared with those from other lunar missions, including the Surveyor, Apollo, and Lunokhod missions; results suggest that the rock distribution at the Chang'E-3 landing site is similar to that found by Surveyor III.

  17. No evidence for multiple stellar populations in the low-mass Galactic globular cluster E 3

    CERN Document Server

    Salinas, Ricardo

    2015-01-01

    Multiple stellar populations are a widespread phenomenon among Galactic globular clusters. Even though the origin of the enriched material from which new generations of stars are produced remains unclear, it is likely that self-enrichment will be feasible only in clusters massive enough to retain this enriched material. We searched for multiple populations in the low mass (M~1.4 x 10^4 M_sun) globular cluster E 3, analyzing SOAR/Goodman multi-object spectroscopy centered on the blue CN absorption features of 23 red giant branch stars. We find that the CN abundance does not present the typical bimodal behavior seen in clusters hosting multi stellar populations, but rather a unimodal distribution that indicates the presence of a genuine single stellar population, or a level of enrichment much lower than in clusters that show evidence for two populations from high-resolution spectroscopy. E 3 would be the first bona fide Galactic old globular cluster where no sign of self-enrichment is found.

  18. Self-clearance mechanism of mitochondrial E3 ligase MARCH5 contributes to mitochondria quality control.

    Science.gov (United States)

    Kim, Song-Hee; Park, Yong-Yea; Yoo, Young-Suk; Cho, Hyeseong

    2016-01-01

    MARCH5, a mitochondrial E3 ubiquitin ligase, controls mitochondrial dynamics proteins and misfolded proteins, and has been proposed to play a role in mitochondria quality control. However, it remains unclear how mutant MARCH5 found in cancer tissues is removed from cells. Here, we show that mutation in the MARCH5 ligase domain increased its half-life fourfold, resulting in a drastic increase in its protein level. Abnormal accumulation of the E3 ligase-defective MARCH5 mutants MARCH5(H43W) and MARCH5(C65/68S) was diminished by overexpression of active MARCH5(WT) ; the mutant proteins were degraded through the ubiquitin-proteasome pathway. Coimmunoprecipitation revealed that MARCH5 forms homodimers, and that substitution of Gly to Leu at the first putative GxxxG dimerization motif, but not the second, resulted in a loss of dimeric interaction. Moreover, overexpression of the dimerization-defective mutant MARCH5(4GL) could not decrease the level of accumulated MARCH5(H43W) , suggesting that dimerization of MARCH5 is necessary for self-clearance. Abnormal accumulation of MARCH5(H43W) and mitochondrial hyperfusion led to NF-ĸB activation, which was suppressed by overexpression of MARCH5(WT) . Together, the data reveal a self-protective mechanism involving MARCH5, which can target its own dysfunctional mutant for degradation in order to maintain mitochondrial homeostasis.

  19. MARCH1 E3 Ubiquitin Ligase Dampens the Innate Inflammatory Response by Modulating Monocyte Functions in Mice.

    Science.gov (United States)

    Galbas, Tristan; Raymond, Maxime; Sabourin, Antoine; Bourgeois-Daigneault, Marie-Claude; Guimont-Desrochers, Fanny; Yun, Tae Jin; Cailhier, Jean-François; Ishido, Satoshi; Lesage, Sylvie; Cheong, Cheolho; Thibodeau, Jacques

    2017-01-15

    Ubiquitination was recently identified as a central process in the pathogenesis and development of numerous inflammatory diseases, such as obesity, atherosclerosis, and asthma. Treatment with proteasomal inhibitors led to severe side effects because ubiquitination is heavily involved in a plethora of cellular functions. Thus, new players regulating ubiquitination processes must be identified to improve therapies for inflammatory diseases. In addition to their role in adaptive immunity, endosomal MHC class II (MHCII) molecules were shown to modulate innate immune responses by fine tuning the TLR4 signaling pathway. However, the role of MHCII ubiquitination by membrane associated ring-CH-type finger 1 (MARCH1) E3 ubiquitin ligase in this process remains to be assessed. In this article, we demonstrate that MARCH1 is a key inhibitor of innate inflammation in response to bacterial endotoxins. The higher mortality of March1(-/-) mice challenged with a lethal dose of LPS was associated with significantly stronger systemic production of proinflammatory cytokines and splenic NK cell activation; however, we did not find evidence that MARCH1 modulates LPS or IL-10 signaling pathways. Instead, the mechanism by which MARCH1 protects against endotoxic shock rests on its capacity to promote the transition of monocytes from Ly6C(Hi) to Ly6C(+/-) Moreover, in competitive bone marrow chimeras, March1(-/-) monocytes and polymorphonuclear neutrophils outcompeted wild-type cells with regard to bone marrow egress and homing to peripheral organs. We conclude that MARCH1 exerts MHCII-independent effects that regulate the innate arm of immunity. Thus, MARCH1 might represent a potential new target for emerging therapies based on ubiquitination reactions in inflammatory diseases.

  20. lOT Data Acquisition Substation for forestry ecology monitor Based on Cortex- M3%Cortex—M3的生态物联网数据采集分站设计

    Institute of Scientific and Technical Information of China (English)

    李骏慧; 陶华; 俞哲伟; 宋军

    2011-01-01

    The IOT(Internet of things)data acquisition substation for forestry ecology monitor is proposed, which employs the Cortex- M3 processor as the CPU. Digital temperature humidity sensor, smoke sensor, C()2 sensor and digital luminance sensor are employed to acquire the environment information which is related with forestry ecology. Then the sensors data are collected by LM3S811 and ID of substation is added to data packet. Further more, LM3SSll transmits the data packet to servers using RF module.%以Cortex—M3处理器LM3S811为核心,设计了面向森林生态监测的物联网数据采集终端分站系统。通过单总线数字式温湿度传感器、烟雾传感器、CO2传感器和环境光亮度传感器分别采集温度、湿度、可燃性颗粒物、CO2含量和光照等与林木生态相关的环境信息和林场防火的相关信息。由LM3S81l处理器处理并添加分站ID和校验码后,采用无线模块传送给服务器。

  1. 100 m3/min往复式空压机长周期安全稳定运行研究%Study on Long, Safe and Stable Operation of 100 m3/min Reciprocating Air Compressor

    Institute of Scientific and Technical Information of China (English)

    陈山

    2015-01-01

    介绍了安徽晋煤中能化工股份有限公司100 m3/min往复式空压机的工况,针对影响机组长周期稳定、安全运行的问题,采取了优化设备结构和工艺结构的措施,优化结果表明:年创造经济效益16.28万元,实现了节能降耗的目的。%This paper introduces the working conditions of 100 m3/min reciprocating air compressor of Anhui Jinmei Zhongneng Chemical Co. , Ltd. To solve the problem affecting long, safe and stable operation of the unit, the author optimizes the structures of the equipment and the process. The opti-mization results show that it has gained 162 800 RMB yuan/a economic benefit and achieved its energy-saving and consumption-reducing purpose.

  2. 石家庄陕鼓2×40000m^3/h空分设备设计优化%Optimized design of Shijiazhuang Shaanxi Blower Group 2 ×40000m^3/h air separation plant

    Institute of Scientific and Technical Information of China (English)

    张岑; 卢子学

    2012-01-01

    At design stage of Shijiazhuang Shaanxi Blower Group 2 ×40000m^3/h air separation plants, it found unreasonable design in the nitrogen compression and supply system, air compressor vent silencer, and connection mode for feeding boosted air to plate-fin type heat exchanger, as well as the factors impairing stable and safe operation of the product continuous supply and air separation plant. Here, the optimization measures taken for the unreasonable factors are described, which puts a sound basis for stable run of the air separation plant.%在石家庄陕鼓2×40000m^3/h空分设备设计阶段,发现氮气压缩和供应系统、空压机放空消声器以及增压空气进板翅式换热器的连接方式设计不舍理,存在影响产品连续供应和空分设备稳定、安全运行的因素。介绍对这些不合理因素所采取的优化措施,为空分设备建成后稳定运行奠定基础。

  3. 3500m3/h绞吸挖泥船甲板机舱振动分析与优化%Analysis and Optimization of Deck Cabin Vibration in 3 500 m3/h Cutter Suction Dredger

    Institute of Scientific and Technical Information of China (English)

    王炜

    2015-01-01

    针对3500 m3/h绞吸式挖泥船的甲板机舱异常振动问题,建立机舱结构有限元模型,进行振动模态分析,发现甲板下支柱与柴油机工作频率耦合引起的共振是导致甲板机舱异常振动的主要原因,进行甲板机舱结构和立柱位置的优化,检测表明,优化后的结构有效避开了共振频率,振动速度峰值和加速度大幅下降,优化效果良好。%In view of abnormal vibration on deck engine room of 3 500 m3/h cutter suction dredger, the FE structural model of the engine room is established.Via the analysis of mode of vibration, resonance coupling of working frequency of the diesel en-gine with the pillar under deck is the primary cause for abnormal vibration of deck engine room.So the location of pillars is rede-signed to avoid the resonant frequency.The test results verify that the peaks of vibration acceleration and velocity are sharply de-creased;the effects of optimization are satisfactory.

  4. Logic control of molecular sieve purification system of 65000m3· h-1 air separation plant%65000m3·h-1空分设备分子筛纯化系统逻辑控制

    Institute of Scientific and Technical Information of China (English)

    朱玉芹

    2012-01-01

    The structure and technical process of molecular sieve purification system of 65000m3/ an air separation plant of Hebi coal and electeicity 600 ktpa methanol project are briefed, automatic valve closing / opening logical control of molecular sieve purification system, automatic / manual operation sequence control program,implementation of the sequence control program and optimized reform of the sequence control configuration program of the molecular sieve absorber in accordance with site operation conditions are described.%简介鹤壁煤电股份有限公司化工分公司空分厂65000m3·h-1空分设备分子筛纯化系统结构和工艺流程,介绍分子筛纯化系统阀门自动开关控制逻辑、顺控程序自动/手动运行、顺控程序执行过程,以及根据现场生产运行实际情况,对分子筛吸附器顺控组态程序进行的优化改进.

  5. Design of Low-cost LCD Touch Screen Based on Cortex-M3%基于Cortex-M3的低成本液晶触摸屏设计

    Institute of Scientific and Technical Information of China (English)

    张勇; 邹卫军

    2014-01-01

    选用NXP公司内置LCD控制器的Cortex-M3处理器LPC1788作为主控,设计了一种低成本的液晶触摸屏。介绍了四线电阻式触摸屏与LPC1788的接口设计,移植emWin图形界面库为GUI提供支持。实际运用证明,低成本液晶触摸屏运行稳定,界面设计便捷。%This paper provides a Iow-cost LCD Touch Screen design which use LPC1788 as the processor.LPC1788 which is de-signed by NXP,is a SoC based on Cortex-M3 CPU and contains a buiId-in LCD controI er,and introduces the interface of 4-wire resistive touch pad with LPC1788.In addition,transpIant the graphicaI interface Iibrary emWin to provide best support for the design of GUI.The practicaI appIication shows this screen works stabIy and makes the interface design convenient.

  6. 基于ARM Cortex M3内核TFT触摸屏无线遥控设计%On Wireless Remote Control System Design Based on the ARM Cortex M3 core TFT Touch Screen

    Institute of Scientific and Technical Information of China (English)

    李金赐; 梁九兴

    2012-01-01

    The designing is based on Bluetooth communication through the ARM Contex M3 core microprocessor STM32F103VET6 and TEF color LCD touch screen to design a touch-screen remote control.This kind of remote control,through touching the controls displayed on the TFT color LCD of the host computer,triggers variety of control signals and then wireless Bluetooth module sends control signals.%本设计是建立在蓝牙通信下通过ARM Cortex M3内核的微处理器STM32F103VET6与TFT彩色液晶触摸屏来设计一种触摸屏遥控器。该遥控器通过触摸上位机TFT彩色液晶触摸屏上显示的各个控件来触发各种控制信号;无线蓝牙模块发送各种控制信号。

  7. Design and Realization of GUI Based on ARM Cortex-M3%基于ARM Cortex-M3的图形用户界面设计和实现

    Institute of Scientific and Technical Information of China (English)

    韩定

    2015-01-01

    采用基于Cortex-M3内核的LPC1788为主控芯片和320(RGB)*480 pixels的带触摸点阵液晶屏,应用emWin图形库设计了一款简单易用的小型人机交互界面,并提供大容量的图片存储空间和可扩展字库存储空间,便于用户使用,可以广泛应用于家庭自动化和工业控制领域。%The ARM Cortex-M3 kernel processor LPC1788 and 320*480 pixels LCD with touch is used to design a small Graphical User Interface. EmWin is a kind of open source software, which is used to GUI embedded system. It can be widely used in home automation and industrial control.

  8. 年产5000m3意杨LVL主材及设备量的计算与配置%Calculation and Configuration of Main Material and Equipment Quantity for Annual 5000m3 Populus LVL

    Institute of Scientific and Technical Information of China (English)

    蒋瞻

    2012-01-01

      LVL has become the fastest kind of wooden composite material product in the current woodworking industry. The configuration of materials and equipment of an enterprise located in Northern Jiangsu that manufactures 5000 m 3 Populus LVL annually is introduced, with emphasis placed on relevant design calculation and configuration of such main materials as veneer and adhesive and such main equipment as presses, with the aim to provide reference for China’s small and medium-sized plywood manufacturing enterprises in term of design of the materials and equipment for manufacturing Populus LVL products.%  LVL已成为当今木材加工行业发展速度最快的一种木质复合材料产品。介绍了苏北一家年产5000m3意杨LVL企业的加工材料与设备配置情况,着重对单板、胶黏剂主材及压机等主要设备进行了相关的设计计算与配置,为我国制造胶合板的中小型企业做好意杨LVL产品的主材及其设备的设计工作提供参考。

  9. DISCUSSION ABOUT HEAT BALANCE CALCULATION AND ENERGY SAVING FOR 2500 m3 BLAST FURNACE%承钢2500 m3高炉热平衡测算与节能探讨

    Institute of Scientific and Technical Information of China (English)

    王秀英

    2014-01-01

    以承钢3座2 500 m3高炉为研究对象,用第一总热平衡测试法进行了高炉热平衡测算.结果表明:承钢2 500 m3高炉近年来节能主要是降低了冷却软熔带带走热量约0.29 GJ/tFe,减少煤气带走热量约0.12 GJ/tFe,降低瓦斯灰带走热量约0.04 GJ/tFe.从测算结果可以看出,因高炉工艺优化吨铁耗风量降低后,收入项中热风带入的热量减少约0.4 GJ/tFe,碳素氧化带入的热量减少约0.12 GJ/tFe.介绍了承钢高炉近年采用的节能技术及应用效果,根据热平衡测算结果和目前的前沿节能技术,提出了承钢高炉进一步降低能耗的措施.

  10. Scale-up of industrial biodiesel production to 40 m(3) using a liquid lipase formulation.

    Science.gov (United States)

    Price, Jason; Nordblad, Mathias; Martel, Hannah H; Chrabas, Brent; Wang, Huali; Nielsen, Per Munk; Woodley, John M

    2016-08-01

    In this work, we demonstrate the scale-up from an 80 L fed-batch scale to 40 m(3) along with the design of a 4 m(3) continuous process for enzymatic biodiesel production catalyzed by NS-40116 (a liquid formulation of a modified Thermomyces lanuginosus lipase). Based on the analysis of actual pilot plant data for the transesterification of used cooking oil and brown grease, we propose a method applying first order integral analysis to fed-batch data based on either the bound glycerol or free fatty acid content in the oil. This method greatly simplifies the modeling process and gives an indication of the effect of mixing at the various scales (80 L to 40 m(3) ) along with the prediction of the residence time needed to reach a desired conversion in a CSTR. Suitable process metrics reflecting commercial performance such as the reaction time, enzyme efficiency, and reactor productivity were evaluated for both the fed-batch and CSTR cases. Given similar operating conditions, the CSTR operation on average, has a reaction time which is 1.3 times greater than the fed-batch operation. We also showed how the process metrics can be used to quickly estimate the selling price of the enzyme. Assuming a biodiesel selling price of 0.6 USD/kg and a one-time use of the enzyme (0.1% (w/woil ) enzyme dosage); the enzyme can then be sold for 30 USD/kg which ensures that that the enzyme cost is not more than 5% of the biodiesel revenue. Biotechnol. Bioeng. 2016;113: 1719-1728. © 2016 Wiley Periodicals, Inc.

  11. Theoretical study of neutral and charged Sc{sub n{<=}2}-(benzene){sub m{<=}3} clusters

    Energy Technology Data Exchange (ETDEWEB)

    Maynez-Rojas, Miguel; Castro, Miguel, E-mail: castro@quetzal.pquim.unam.mx [Universidad Nacional Autonoma de Mexico, Departamento de Fisica y Quimica Teorica, DEPg. Facultad de Quimica (Mexico)

    2013-01-15

    Interactions of benzene molecules with scandium atoms, Sc{sub n{<=}2}-(C{sub 6}H{sub 6}){sub m{<=}3}, in the gas phase were studied by means of density functional theory. All-electron calculations were performed using the B3LYP hybrid functional in concert with 6-311+G(d,p) orbital basis sets for the Sc, C, and H atoms. Multiple-decker sandwich (MDS) structures are identified as the ground states for Sc{sub n{<=}2}-(C{sub 6}H{sub 6}){sub m{<=}3}, where the ligands are attached to the metal through Sc-C bonding, formed between the 3d electrons and the {pi}-clouds of the benzene rings. Significant distortion is produced on the absorbed benzene molecules by the metal-ligand bonding. Rice ball structures also appeared, but they were found at higher energies, in such a way that essentially MDS isomers may emerge in the molecular beams. Even the low number of valence electrons (3d{sup 2}4s{sup 1}) of the Sc atom; sextuple coordinations are formed, but they show different Sc-C bond lengths, diminishing the symmetry of neutral and charged clusters. The estimated ionization energies, in near agreement with experimental data, and electron affinities, suggest delocalization of the valence electrons through the network of 3d-{pi} bonds of Sc{sub 1,2}-(C{sub 6}H{sub 6}){sub m{<=}3}. The binding energies decrease with the absorption of more benzene molecules, and in some cases increase as more metal atoms are added to the cluster.

  12. Adsorption of aromatics on the (111) surface of PtM and PtM3 (M = Fe, Ni) alloys

    Energy Technology Data Exchange (ETDEWEB)

    Hensley, Alyssa; Schneider, Sebastian; Wang, Yong; McEwen, Jean-Sabin

    2015-09-18

    The adsorption of benzene and phenol was studied on PtM and PtM3 (111) surfaces, with M being either Ni or Fe. Under vacuum, the most favorable near surface structures showed an enrichment in Pt over the M species. An analysis of the electronic structure of the metal species in the clean surfaces with different near surface structures was done with the d-band model and showed that the Pt's d-states are significantly shifted away from the Fermi level due to the Pt-M interactions while the M species' d-states were less affected, with Ni's d-band shifting closer to the Fermi level and Fe's d-band shifting away from the Fermi level. The adsorption of aromatics, benzene and phenol, on several near surface structures for the PtM and PtM3 (111) surfaces showed that higher surface M concentrations resulted in a stronger adsorption due to the larger amount of charge transferred between the adsorbate and surface. However, compared to the adsorption of benzene and phenol on monometallic surfaces, the adsorption of these species on the PtM and PtM3 (111) surfaces was significantly weakened. Overall, our results show that the observed behavior of these Pt/Fe and Pt/Ni alloys is similar to that seen for the previously studied Pd/Fe surfaces. Furthermore, balancing the weakly adsorbing Pt surface species with the more strongly interacting Fe or Ni species can lead to the tailored adsorption of aromatics with applications in both hydrodeoxygenation and hydrogenation reactions by increasing the desorption rate of wanted aromatic products.

  13. Syntheses, crystal structure and magnetic properties of Rm+nCo5m+3nB2n

    Institute of Scientific and Technical Information of China (English)

    梁敬魁; 陈怡; 陈小龙

    2001-01-01

    The phase relations at the 600℃ and 700℃ isothermal sections of the ternary systems R-Co-B for R= Nd, Pr and R = Sm, Gd respectively were summarized in this paper. For Rm+ n Co5m+3n B2n, two new types ofcompounds R3Co13B2(R=Pr, Nd, Sm, Gd, Dy, Ho, Er, Y) (m=2, n=1) andR5Co19B6(R=Pr, Nd) (m=2,n = 3 ) were synthesized by utilizing the principle of structural combination. Their crystalstructures and easymagnetization direction were determined by X-ray powder diffraction, and structures were refined by the Rietveldmethod. The Curie temperature Tc, saturation magnetization M8 and anisotropic field HA of the new compounds weremeasured using a vibrating-sample magnetometer, an extraction sample magnetometer and M(H) - H curves of samplesin different magnetization directions respectively. The Tc and Ms of Rm + n Co5 m + 3 n B2n increase with increasing values of mat a given n value. HA increases with an increase in n when m is kept invariable. The effects of the substitution of Ni for Co on the magnetic properties of Nd13 Co15- x Nix B2 were also investigated. It was found that TsR decreased monotonously as the concentration of Ni increased, and at x = 3 the easy magnetization direction becomes axial at room temperature. The relations between crystal structure and magnetic properties of Rm + nCo5m+ 3nB2n and the possible routes of synthesizing permanent magnetic materials are also discussed.

  14. Successful management of pulmonary hemorrhage and aspergillosis in a patient with acute myeloid leukemia (AML-M3

    Directory of Open Access Journals (Sweden)

    Hulya Gunbatar

    2015-01-01

    Full Text Available A 35-year-old man presented with a one month history of gingival bleeding. He was diagnosed with Acute Myeloid Leukemia (AML-M3. During treatment he developed alveolar hemorrhage for which he was treated with a steroid. After the steroid treatment he developed a nodule, a cavitary lesion and atelectasia in the left lung. He was treated with voriconazole. After therapy with voriconazole his lesion significantly decreased. This case illustrates the efficacy and safety of antifungal therapy with voriconazole for aspergillosis complicated by AML.

  15. Successful management of pulmonary hemorrhage and aspergillosis in a patient with acute myeloid leukemia (AML-M3).

    Science.gov (United States)

    Gunbatar, Hulya; Demir, Cengiz; Kara, Erdal; Esen, Ramazan; Sertogullarindan, Bunyamin; Asker, Selvi

    2015-01-01

    A 35-year-old man presented with a one month history of gingival bleeding. He was diagnosed with Acute Myeloid Leukemia (AML-M3). During treatment he developed alveolar hemorrhage for which he was treated with a steroid. After the steroid treatment he developed a nodule, a cavitary lesion and atelectasia in the left lung. He was treated with voriconazole. After therapy with voriconazole his lesion significantly decreased. This case illustrates the efficacy and safety of antifungal therapy with voriconazole for aspergillosis complicated by AML.

  16. Relativistic many-body calculations of lifetimes, rates, and line strengths of multipole transitions between 3l-1 4l' states in Ni-like ions

    Energy Technology Data Exchange (ETDEWEB)

    Safronova, U I; Safronova, A S; Beiersdorfer, P

    2007-10-08

    Transition rates and line strengths are calculated for electric-multipole (E2 and E3) and magnetic-multipole (M1, M2, and M3) transitions between 3s{sup 2}3p{sup 6}3d{sup 10}, 3s{sup 2}3p{sup 6}3d{sup 9}4l, 3s{sup 2}3p{sup 5}3d{sup 10}4l, and 3s3p{sup 6}3d{sup 10}4l states (with 4l = 4s, 4p, 4d, and 4f) in Ni-like ions with the nuclear charges ranging from Z = 34 to 100. Relativistic many-body perturbation theory (RMBPT), including the Breit interaction, is used to evaluate retarded multipole matrix elements. Transition energies used in the calculation of line strengths and transition rates are from second-order RMBPT. Lifetimes of the 3s{sup 2}3p{sup 6}3d{sup 9}4s levels are given for Z = 34-100. Taking into account that calculations were performed in a very broad range of Z, most of the data are presented in graphs as Z-dependencies. The full set of data is given only for Ni-like W ion. In addition, we also give complete results for the 3d4s{sup 3}D{sub 2}-3d4s {sup 3}D{sub 1} magnetic-dipole transition, as the transition may be observed in future experiments, which measure both transition energies and radiative rates. These atomic data are important in the modeling of radiation spectra from Ni-like multiply-charged ions generated in electron beam ion trap experiments as well as for laboratory plasma diagnostics including fusion research.

  17. Mutations in the DNA-binding domain of NR2E3 affect in vivo dimerization and interaction with CRX.

    Directory of Open Access Journals (Sweden)

    Raphael Roduit

    Full Text Available BACKGROUND: NR2E3 (PNR is an orphan nuclear receptor essential for proper photoreceptor determination and differentiation. In humans, mutations in NR2E3 have been associated with the recessively inherited enhanced short wavelength sensitive (S- cone syndrome (ESCS and, more recently, with autosomal dominant retinitis pigmentosa (adRP. NR2E3 acts as a suppressor of the cone generation program in late mitotic retinal progenitor cells. In adult rod photoreceptors, NR2E3 represses cone-specific gene expression and acts in concert with the transcription factors CRX and NRL to activate rod-specific genes. NR2E3 and CRX have been shown to physically interact in vitro through their respective DNA-binding domains (DBD. The DBD also contributes to homo- and heterodimerization of nuclear receptors. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed NR2E3 homodimerization and NR2E3/CRX complex formation in an in vivo situation by Bioluminescence Resonance Energy Transfer (BRET(2. NR2E3 wild-type protein formed homodimers in transiently transfected HEK293T cells. NR2E3 homodimerization was impaired in presence of disease-causing mutations in the DBD, except for the p.R76Q and p.R104W mutant proteins. Strikingly, the adRP-linked p.G56R mutant protein interacted with CRX with a similar efficiency to that of NR2E3 wild-type and p.R311Q proteins. In contrast, all other NR2E3 DBD-mutant proteins did not interact with CRX. The p.G56R mutant protein was also more effective in abolishing the potentiation of rhodospin gene transactivation by the NR2E3 wild-type protein. In addition, the p.G56R mutant enhanced the transrepression of the M- and S-opsin promoter, while all other NR2E3 DBD-mutants did not. CONCLUSIONS/SIGNIFICANCE: These results suggest different disease mechanisms in adRP- and ESCS-patients carrying NR2E3 mutations. Titration of CRX by the p.G56R mutant protein acting as a repressor in trans may account for the severe clinical phenotype in adRP patients.

  18. Structural analysis of lunar subsurface with Chang'E-3 lunar penetrating radar

    Science.gov (United States)

    Lai, Jialong; Xu, Yi; Zhang, Xiaoping; Tang, Zesheng

    2016-01-01

    Geological structure of the subsurface of the Moon provides valuable information on lunar evolution. Recently, Chang'E-3 has utilized lunar penetrating radar (LPR), which is equipped on the lunar rover named as Yutu, to detect the lunar geological structure in Northern Imbrium (44.1260N, 19.5014W) for the first time. As an in situ detector, Chang'E-3 LPR has relative higher horizontal and vertical resolution and less clutter impact compared to spaceborne radars and earth-based radars. In this work, we analyze the LPR data at 500 MHz transmission frequency to obtain the shallow subsurface structure of the landing area of Chang'E-3 in Mare Imbrium. Filter method and amplitude recovery algorithms are utilized to alleviate the adverse effects of environment and system noises and compensate the amplitude losses during signal propagation. Based on the processed radar image, we observe numerous diffraction hyperbolae, which may be caused by discrete reflectors beneath the lunar surface. Hyperbolae fitting method is utilized to reverse the average dielectric constant to certain depth (ε bar). Overall, the estimated ε bar increases with the depth and ε bar could be classified into three categories. Average ε bar of each category is 2.47, 3.40 and 6.16, respectively. Because of the large gap between the values of ε bar of neighboring categories, we speculate a three-layered structure of the shallow surface of LPR exploration region. One possible geological picture of the speculated three-layered structure is presented as follows. The top layer is weathered layer of ejecta blanket with its average thickness and bound on error is 0.95±0.02 m. The second layer is the ejecta blanket of the nearby impact crater, and the corresponding average thickness is about 2.30±0.07 m, which is in good agreement with the two primary models of ejecta blanket thickness as a function of distance from the crater center. The third layer is regarded as a mixture of stones and soil. The

  19. The Horizontal Branch in the UV Colour Magnitude Diagrams. II. The case of M3, M13 and M79

    CERN Document Server

    Dalessandro, Emanuele; Ferraro, Francesco R; Mucciarelli, Alessio; Cassisi, Santi

    2012-01-01

    We present a detailed comparison between far-UV/optical colour Magnitude Diagrams obtained with high-resolution Hubble Space Telescope data and suitable theoretical models for three Galactic Globular Clusters: M3, M13 and M79. These systems represents a classical example of clusters in the intermediate metallicity regime that, even sharing similar metal content and age, show remarkably different Horizontal Branch morphologies. As a consequence, the observed differences in the colour distributions of Horizontal Branch stars cannot be interpreted in terms of either first (metallicity) or a second parameter such as age. We investigate here the possible role of variations of initial Helium abundance (Y). Thanks to the use of a proper setup of far-UV filters, we are able to put strong constraints on the maximum Y (Y_{max}) values compatible with the data. We find differences Delta Y_{max} ~ 0.02-0.04 between the clusters with M13 showing the largest value (Y_{max} ~ 0.30) and M3 the smallest (Y_{max} ~ 0.27). In g...

  20. Novel roles of Skp2 E3 ligase in cellular senescence, cancer progression, and metastasis

    Institute of Scientific and Technical Information of China (English)

    Guocan Wang; Chia-Hsin Chan; Yuan Gao; Hui-Kuan Lin

    2012-01-01

    S-phase kinase-associated protein 2 (Skp2) belongs to the F-box protein family.It is a component of the SCF E3 ubiquitin ligase complex.Skp2 has been shown to regulate cellular proliferation by targeting several cell cycle-regulated proteins for ubiquitination and degradation,including cyclin-dependent kinase inhibitor p27.Skp2 has also been demonstrated to display an oncogenic function since its overexpression has been observed in many human cancers.This review discusses the recent discoveries on the novel roles of Skp2 in regulating cellular senescence,cancer progression,and metastasis,as well as the therapeutic potential of targeting Skp2 for human cancer treatment.

  1. RING finger palmitoylation of the endoplasmic reticulum Gp78 E3 ubiquitin ligase.

    Science.gov (United States)

    Fairbank, Maria; Huang, Kun; El-Husseini, Alaa; Nabi, Ivan R

    2012-07-30

    Gp78 is an E3 ubiquitin ligase within the endoplasmic reticulum-associated degradation pathway. We show that Flag-tagged gp78 undergoes sulfhydryl cysteine palmitoylation (S-palmitoylation) within the RING finger motif, responsible for its ubiquitin ligase activity. Screening of 19 palmitoyl acyl transferases (PATs) identified five that increased gp78 RING finger palmitoylation. Endoplasmic reticulum (ER)-localized Myc-DHHC6 overexpression promoted the peripheral ER distribution of Flag-gp78 while RING finger mutation and the palmitoylation inhibitor 2-bromopalmitate restricted gp78 to the central ER. Palmitoylation of RING finger cysteines therefore regulates gp78 distribution to the peripheral ER. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  2. K-shell (e, 3e) double ionization of beryllium by relativistic electrons

    Energy Technology Data Exchange (ETDEWEB)

    Becher, M; Joulakian, B [Universite Paul Verlaine-Metz, Laboratoire de Physique Moleculaire et des Collisions, Member FR CNRS 2843 Jean Barriol 1 Bd Arago, 57078 Metz Cedex 3 (France)

    2009-03-28

    The (e, 3e) process, producing hollow metastable Be{sup 2+}(2s{sup 2}) by very energetic electrons (>100 keV), is studied by using a relativistic procedure based on the application of the first term of the Born series for the determination of the corresponding fully differential cross section. The very fast projectile electron, impinging on the K shell of the neutral beryllium, is described by Dirac plane-wave solutions with the appropriate wave vectors. All atomic electrons and the two final-state-bound electrons are taken into account by non-relativistic Jastrow-type correlated functions. The two slow ejected electrons in the continuum are described by the fully correlated three-Coulomb (3C) function. The comparison of the results with those obtained by our recent non-relativistic approach shows the necessity of the introduction of the relativistic treatment.

  3. Analysis of observational data from Extreme Ultra-Violet Camera onboard Chang'E-3 mission

    Science.gov (United States)

    Yan, Yan; Wang, Hua-Ning; He, Han; He, Fei; Chen, Bo; Feng, Jian-Qing; Ping, Jin-Song; Shen, Chao; Xu, Rong-Lan; Zhang, Xiao-Xin

    2016-02-01

    The Extreme Ultra-Violet Camera (hereafter EUVC) is a scientific payload onboard the lander of the Chang'E-3 (hereafter CE-3) mission launched on December 1st, 2013. Centering on a spectral band around 30.4 nm, EUVC provides the global images of the Earth's plasmasphere from the meridian view, with a spatial resolution of 0.1 R_{oplus} in 150 × 150 pixels and a cadence of 10 minutes. Along with the data being publicly released online, some unsettled issues in the early stage have been clarified, including the geometrical preparations, the refined approach on the coefficient K for the background, and the alignment among the images. A demo of data after all the above processes is therefore presented as a guidance for users who are studying the structure and dynamics of the plasmasphere.

  4. TRIM E3 ligases interfere with early and late stages of the retroviral life cycle.

    Directory of Open Access Journals (Sweden)

    Pradeep D Uchil

    2008-02-01

    Full Text Available Members of the TRIpartite interaction Motif (TRIM family of E3 ligases have been shown to exhibit antiviral activities. Here we report a near comprehensive screen for antiretroviral activities of 55 TRIM proteins (36 human, 19 mouse. We identified approximately 20 TRIM proteins that, when transiently expressed in HEK293 cells, affect the entry or release of human immunodeficiency virus 1 (HIV, murine leukemia virus (MLV, or avian leukosis virus (ALV. While TRIM11 and 31 inhibited HIV entry, TRIM11 enhanced N-MLV entry by interfering with Ref1 restriction. Strikingly, many TRIM proteins affected late stages of the viral life cycle. Gene silencing of endogenously expressed TRIM 25, 31, and 62 inhibited viral release indicating that they play an important role at late stages of the viral life cycle. In contrast, downregulation of TRIM11 and 15 enhanced virus release suggesting that these proteins contribute to the endogenous restriction of retroviruses in cells.

  5. [Suppression of E3 ubiquitin ligase Cbl-b in interleukin-1 signaling].

    Science.gov (United States)

    Yu, Jiang-Tian; Bu, Xin; Zhao, Hu; Su, Jin

    2015-08-25

    The present study aims to investigate the effect of Cbl-b, a member of E3 ubiquitin ligase family, on interleukin-1 (IL-1) pathway in synoviocytes. The protein expression levels of Cbl-b and IL-1-induced matrix metalloproteinase 13 (MMP-13) in synoviocytes were analyzed by Western blot. Collagen substrates were incubated with the conditioned medium collected from synoviocytes cultures and then subjected to SDS-PAGE for analysis of collagen degradation. The results showed that compared with wild-type cells, Cbl-b-deficient cells expressed more MMP-13 protein and had enhanced ability to degrade collagens under IL-1 stimulation. These data suggest that Cbl-b may negatively regulate IL-1-triggered degradation of collagen matrix in synoviocytes.

  6. Structure and aggregation proclivity of C12E3 in aqueous solution

    Science.gov (United States)

    Zahariev, Ts.; Ivanova, A.; Velinova, M.; Tadjer, A.

    2013-01-01

    Olygo(ethylene glycol) alkyl ethers - CxEy are well known for their high surface activity and rich phase behavior. These substances exhibit some unusual aggregation characteristics in aqueous solution even at concentrations well below CMC attributed to the formation of pre-aggregates of small size, e.g., dimers. To verify this, a series of C12E3 dimers with initial geometries taken from coarse-grained molecular dynamics simulations is subject to geometry optimization with two quantum chemical methods: DFT and ONIOM in implicit water solvent. The resulting structures are classified into groups based on structural parameters. Their stability is assessed by relative and binding energy and rationalized in terms of molecular characteristics. All studied dimers are stable and various mutual alignments of the surfactants therein are feasible. The loss of surface area is outlined as the predominant stabilizing factor. Substantial number of the structures is suitable for further aggregation.

  7. Design and Environmental Verification of Chang'E-3 Moon-night Survival Device for APXS

    Science.gov (United States)

    Chen, D. Y.; Wu, J.; Hu, Y. M.; Chang, J.; Gong, Y. Z.; Cai, M. S.; Wang, H. Y.; Zhang, J. Y.; Cui, X. Z.; Wang, J. Y.

    2015-09-01

    The Active Particle X-ray Spectrum (APXS) is one of the 4 scientific payloads of Chang'E-3 (CE-3) Lunar Rover, of which the scientific object is to identify the elements of lunar soil and rock samples. In this paper, the moon-night temperature of the moon surface will be described, and due to the cold environment the APXS will undergo after its landing. Thus, a specialized instrument which is named the moon-night survival device using the Radioisotope Heat Unit (RHU) as its heater source is designed to ensure APXS storage temperature requirements with limited sources on the satellite. In the end, a series of environmental tests are performed, and the installation of RHU on the launch tower as well as the status of the APXS working on orbit is presented since its launching in 2013.

  8. Design and Experimental Verification of Chang'E-3 Moon-night Survival Device for APXS

    Science.gov (United States)

    Deng-yi, Chen; Jian, Wu; Yi-ming, Hu; Jin, Chang; Yi-zhong, Gong; Ming-sheng, Cai; Huan-yu, Wang; Jia-yu, Zhang; Xing-zhu, Cui; Jin-zhou, Wang

    2016-07-01

    The Active Particle X-ray Spectrometer (APXS) is one of the 4 scientific payloads of Chang'E-3 (CE-3) Lunar Rover, of which the scientific object is to identify the elements of lunar soil and rock samples by a carried radioactive source to trigger and detect the characteristic X-ray from them. According to the extreme temperature environment of the APXS and under the restriction of limited resources, this paper presents the design and analysis of the moon-night survival device RHU (radioisotope heating unit) for the APXS, and describes the corresponding environmental tests on its structure dynamics and moon-night survival. Finally, its reinstallation on the launch tower and the preliminary result of its on-orbit operation are introduced.

  9. Lunar soil strength estimation based on Chang'E-3 images

    Science.gov (United States)

    Gao, Yang; Spiteri, Conrad; Li, Chun-Lai; Zheng, Yong-Chun

    2016-11-01

    Chang'E-3 (CE-3) was the third mission by China to explore the Moon which had landed two spacecraft, the CE-3 lander and Yutu rover on the lunar surface in late 2013. The paper presents analytical results of high-resolution terrain data taken by CE-3's onboard cameras. The image data processing aims to extract sinkage profiles of the wheel tracks during the rover traverse. Further analysis leads to derivation or estimation of lunar soil physical properties (in terms of strength and stiffness) based on the wheel sinkage, despite the fact Yutu does not possess in situ soil measurement instruments. Our findings indicate that the lunar soil at the CE-3 landing site has similar stiffness to what is measured at the Luna 17 landing site but has much less strength compared to the Apollo 15 landing site.

  10. Speed Measurement and Motion Analysis of Chang'E-3 Rover Based on Differential Phase Delay

    Science.gov (United States)

    Chao, Pan; Qing-hui, Liu; Xin, Zheng; Qing-bao, He; Ya-jun, Wu

    2016-04-01

    On 14th December 2013, the Chang'E-3 made a successful soft landing on the lunar surface, and then carried out the tasks of separating the lander and the rover, and taking pictures of each other. With the same beam VLBI (Very Long Baseline Interferometry) technique to observe the signals transmitted by the lander and the rover simultaneously, the differential phase delay between them is calculated, which can reflect the minor changes of the rover's position on a scale of a few centimeters. Based on the high sensitivity of differential phase delay, the rover's speeds during 5 movements are obtained with an average of 0.056 m/s. The relationship between the rover's shake in the moving process and the lunar terrain is analyzed by using the spectrum of the residual of the differential phase delay after the first-order polynomial fitting.

  11. Cullin4B/E3-ubiquitin ligase negatively regulates -catenin

    Indian Academy of Sciences (India)

    Rachana Tripathi; Satya Keerthi Kota; Usha K Srinivas

    2007-09-01

    -catenin is the key transducer of Wingless-type MMTV integration site family member (Wnt) signalling, upregulation of which is the cause of cancer of the colon and other tissues. In the absence of Wnt signals, -catenin is targeted to ubiquitin–proteasome-mediated degradation. Here we present the functional characterization of E3-ubiquitin ligase encoded by cul4B. RNAi-mediated knock-down of Cul4B in a mouse cell line C3H T10 (1/2) results in an increase in -catenin levels. Loss-of-function mutation in Drosophila cul4 also shows increased -catenin/Armadillo levels in developing embryos and displays a characteristic naked-cuticle phenotype. Immunoprecipitation experiments suggest that Cul4B and -catenin are part of a signal complex in Drosophila, mouse and human. These preliminary results suggest a conserved role for Cul4B in the regulation of -catenin levels.

  12. Ret Finger Protein: An E3 Ubiquitin Ligase Juxtaposed to the XY Body in Meiosis

    Directory of Open Access Journals (Sweden)

    Isabelle Gillot

    2009-01-01

    Full Text Available During prophase I of male meiosis, the sex chromosomes form a compact structure called XY body that associates with the nuclear membrane of pachytene spermatocytes. Ret Finger Protein is a transcriptional repressor, able to interact with both nuclear matrix-associated proteins and double-stranded DNA. We report the precise and unique localization of Ret Finger Protein in pachytene spermatocytes, in which Ret Finger Protein takes place of lamin B1, between the XY body and the inner nuclear membrane. This localization of Ret Finger Protein does not seem to be associated with O-glycosylation or sumoylation. In addition, we demonstrate that Ret Finger Protein contains an E3 ubiquitin ligase activity. These observations lead to an attractive hypothesis in which Ret Finger Protein would be involved in the positioning and the attachment of XY body to the nuclear lamina of pachytene spermatocytes.

  13. 安钢10万m3威金斯气柜利用效率探讨与应用%Efficiency Analysis and Application of Anyang Iron and Steel 100 000 m3 Wiggins Gasholder

    Institute of Scientific and Technical Information of China (English)

    于海顺; 王志峰; 王祥凯; 张文杰; 赵卫兵

    2015-01-01

    As to the operating situation of Augang 100 000 Wiggins gas holder, this paper analyzes the efficiency factors of Wiggins gesholder, and puts forward improving weasuers, including establishing a liaision mechauism, adjusting part programs of micro oxygen analzer before gasholder in gasholder control system to improve the gas-holder efficiency.%针对安钢10万m3威金斯气柜运行现状,对影响威金斯气柜利用效率的因素进行了探讨,并提出了建立联络机制、调整气柜控制系统中气柜进口前微氧分析仪的部分程序等改进措施。采取有效措施后提高了气柜的利用效率。

  14. Chang'e 3 and Jade Rabbit's: observations and the landing zone

    Science.gov (United States)

    Ping, Jinsong

    Chang’E-3 was launched and landed on the near side of the Moon in December 2013. It is realizing the 2nd phase of Chinese lunar scientific exploration projects. Together with the various in-situ optical observations around the landing sites, the mission carried 4 kinds of radio science experiments, cover the various lunar scientific disciplines as well as lunar surface radio astronomy studies. The key payloads onboard the lander and rover include the near ultraviolet telescope, extreme ultraviolet cameras, ground penetrating radar, very low frequency radio spectrum analyzer, which have not been used in earlier lunar landing missions. Optical spectrometer, Alpha Paticle X-ray spectrometer and Gama Ray spectrometer is also used. The mission is using extreme ultraviolet camera to observe the sun activity and geomagnetic disturbances on geo-space plasma layer of extreme ultraviolet radiation, studying space weather in the plasma layer role in the process; the mission also carries the first time lunar base optical astronomical observations. Most importantly, the topography, landforms and geological structure has been explored in detail. Additionally, the very precise Earth-Moon radio phase ranging technique was firstly tested and realized in this mission. It may increase the study of lunar dyanmics together with LLR technique. Similar to Luna-Glob landers, together with the VLBI radio beacons, the radio transponders are also set on the Chang’E-3. Transponder will receive the uplink X band radio wave transmitted from the two newly constructed Chinese deep space stations, where the high quality hydrogen maser atomic clocks have been used as local time and frequency standard. Radio science receivers have been developed by updating the multi-channel open loop Doppler receiver developed for VLBI and Doppler tracking in Yinghuo-1 and Phobos-Glob Martian missions. This experiment will improve the study of lunar dynamics, by means of measuring the lunar physical liberations

  15. Immersive Virtual Moon Scene System Based on Panoramic Camera Data of Chang'E-3

    Science.gov (United States)

    Gao, X.; Liu, J.; Mu, L.; Yan, W.; Zeng, X.; Zhang, X.; Li, C.

    2014-12-01

    The system "Immersive Virtual Moon Scene" is used to show the virtual environment of Moon surface in immersive environment. Utilizing stereo 360-degree imagery from panoramic camera of Yutu rover, the system enables the operator to visualize the terrain and the celestial background from the rover's point of view in 3D. To avoid image distortion, stereo 360-degree panorama stitched by 112 images is projected onto inside surface of sphere according to panorama orientation coordinates and camera parameters to build the virtual scene. Stars can be seen from the Moon at any time. So we render the sun, planets and stars according to time and rover's location based on Hipparcos catalogue as the background on the sphere. Immersing in the stereo virtual environment created by this imaged-based rendering technique, the operator can zoom, pan to interact with the virtual Moon scene and mark interesting objects. Hardware of the immersive virtual Moon system is made up of four high lumen projectors and a huge curve screen which is 31 meters long and 5.5 meters high. This system which take all panoramic camera data available and use it to create an immersive environment, enable operator to interact with the environment and mark interesting objects contributed heavily to establishment of science mission goals in Chang'E-3 mission. After Chang'E-3 mission, the lab with this system will be open to public. Besides this application, Moon terrain stereo animations based on Chang'E-1 and Chang'E-2 data will be showed to public on the huge screen in the lab. Based on the data of lunar exploration,we will made more immersive virtual moon scenes and animations to help the public understand more about the Moon in the future.

  16. Chaperone-dependent E3 ligase CHIP ubiquitinates and mediates proteasomal degradation of soluble guanylyl cyclase.

    Science.gov (United States)

    Xia, Tian; Dimitropoulou, Christiana; Zeng, Jingmin; Antonova, Galina N; Snead, Connie; Venema, Richard C; Fulton, David; Qian, Shuibing; Patterson, Cam; Papapetropoulos, Andreas; Catravas, John D

    2007-11-01

    The nitric oxide receptor soluble guanylyl cyclase (sGC) exists in multimeric protein complexes, including heat shock protein (HSP) 90 and endothelial nitric oxide synthase. Inhibition of HSP90 by geldanamycin causes proteasomal degradation of sGC protein. In this study, we have investigated whether COOH terminus of heat shock protein 70-interacting protein (CHIP), a co-chaperone molecule that is involved in protein folding but is also a chaperone-dependent ubiquitin E3 ligase, could play a role in the process of degradation of sGC. Transient overexpression of CHIP in COS-7 cells degraded heterologous sGC in a concentration-related manner; this downregulation of sGC was abrogated by the proteasome inhibitor MG-132. Transfection of tetratricopeptide repeats and U-box domain CHIP mutants attenuated sGC degradation, suggesting that both domains are indispensable for CHIP function. Results from immunoprecipitation and indirect immunofluorescent microscopy experiments demonstrated that CHIP is associated with sGC, HSP90, and HSP70 in COS-7 cells. Furthermore, CHIP increased the association of HSP70 with sGC. In in vitro ubiquitination assays using purified proteins and ubiquitin enzymes, E3 ligase CHIP directly ubiquitinated sGC; this ubiquitination was potentiated by geldanamycin in COS-7 cells, followed by proteasomal degradation. In rat aortic smooth muscle cells, endogenous sGC was also degraded by adenovirus-infected wild-type CHIP but not by the chaperone interaction-deficient K30A CHIP, whereas CHIP, but not K30A, attenuated sGC expression in, and nitric oxide donor-induced relaxation of, rat aortic rings, suggesting that CHIP plays a regulatory role under physiological conditions. This study reveals a new mechanism for the regulation of sGC, an important mediator of cellular and vascular function.

  17. Lenalidomide Stabilizes the Erythropoietin Receptor by Inhibiting the E3 Ubiquitin Ligase RNF41.

    Science.gov (United States)

    Basiorka, Ashley A; McGraw, Kathy L; De Ceuninck, Leentje; Griner, Lori N; Zhang, Ling; Clark, Justine A; Caceres, Gisela; Sokol, Lubomir; Komrokji, Rami S; Reuther, Gary W; Wei, Sheng; Tavernier, Jan; List, Alan F

    2016-06-15

    In a subset of patients with non-del(5q) myelodysplastic syndrome (MDS), lenalidomide promotes erythroid lineage competence and effective erythropoiesis. To determine the mechanism by which lenalidomide promotes erythropoiesis, we investigated its action on erythropoietin receptor (EpoR) cellular dynamics. Lenalidomide upregulated expression and stability of JAK2-associated EpoR in UT7 erythroid cells and primary CD71+ erythroid progenitors. The effects of lenalidomide on receptor turnover were Type I cytokine receptor specific, as evidenced by coregulation of the IL3-Rα receptor but not c-Kit. To elucidate this mechanism, we investigated the effects of lenalidomide on the E3 ubiquitin ligase RNF41. Lenalidomide promoted EpoR/RNF41 association and inhibited RNF41 auto-ubiquitination, accompanied by a reduction in EpoR ubiquitination. To confirm that RNF41 is the principal target responsible for EpoR stabilization, HEK293T cells were transfected with EpoR and/or RNF41 gene expression vectors. Steady-state EpoR expression was reduced in EpoR/RNF41 cells, whereas EpoR upregulation by lenalidomide was abrogated, indicating that cellular RNF41 is a critical determinant of drug-induced receptor modulation. Notably, shRNA suppression of CRBN gene expression failed to alter EpoR upregulation, indicating that drug-induced receptor modulation is independent of cereblon. Immunohistochemical staining showed that RNF41 expression decreased in primary erythroid cells of lenalidomide-responding patients, suggesting that cellular RNF41 expression merits investigation as a biomarker for lenalidomide response. Our findings indicate that lenalidomide has E3 ubiquitin ligase inhibitory effects that extend to RNF41 and that inhibition of RNF41 auto-ubiquitination promotes membrane accumulation of signaling competent JAK2/EpoR complexes that augment Epo responsiveness. Cancer Res; 76(12); 3531-40. ©2016 AACR.

  18. Chang'E-3 data pre-processing system based on scientific workflow

    Science.gov (United States)

    tan, xu; liu, jianjun; wang, yuanyuan; yan, wei; zhang, xiaoxia; li, chunlai

    2016-04-01

    The Chang'E-3(CE3) mission have obtained a huge amount of lunar scientific data. Data pre-processing is an important segment of CE3 ground research and application system. With a dramatic increase in the demand of data research and application, Chang'E-3 data pre-processing system(CEDPS) based on scientific workflow is proposed for the purpose of making scientists more flexible and productive by automating data-driven. The system should allow the planning, conduct and control of the data processing procedure with the following possibilities: • describe a data processing task, include:1)define input data/output data, 2)define the data relationship, 3)define the sequence of tasks,4)define the communication between tasks,5)define mathematical formula, 6)define the relationship between task and data. • automatic processing of tasks. Accordingly, Describing a task is the key point whether the system is flexible. We design a workflow designer which is a visual environment for capturing processes as workflows, the three-level model for the workflow designer is discussed:1) The data relationship is established through product tree.2)The process model is constructed based on directed acyclic graph(DAG). Especially, a set of process workflow constructs, including Sequence, Loop, Merge, Fork are compositional one with another.3)To reduce the modeling complexity of the mathematical formulas using DAG, semantic modeling based on MathML is approached. On top of that, we will present how processed the CE3 data with CEDPS.

  19. 高铝渣对济钢3200m3高炉冶炼的影响%Influence of High Al2O3 Slag on Operation of 3 200 m3 BF in Jinan Steel

    Institute of Scientific and Technical Information of China (English)

    王军

    2015-01-01

    To the characteristics of high Al2O3 slag with higher viscosity, poor liquidity, and poor desulphurization ability, by adjusting the thermal system and distributing system, the Mg/Al ratio in the slag is controlled lager than 0.6 by increasing the MgO content in sintering, the MgO content in the slag is made between 8%-11%, the overall operation of 3 200 m3 BF in Jinan Steel can fit smelting requirement with high Al2O3 slag. Under the condition of slag ratio increase by 43 kg/t, the silicon in the pig iron was decreased, the desulphurization ability of the slag was strengthened and third grade iron was eliminated basically.%针对高铝渣特有的黏度高、流动性差、脱硫能力差的特点,济钢3 200 m3高炉通过调整热制度和布料制度,在烧结时提高MgO含量,控制渣中镁铝比>0.6,使渣中MgO含量在8%~11%,高炉的整体操作炉型适应了高铝渣的冶炼要求.在渣铁比升高43 kg/t的条件下,高炉生铁含硅降低,炉渣脱硫能力增强,基本杜绝了三类铁.

  20. New Technology Adopted and Operation Practice in No.3 3 200 m3 BF in Laiwu Steel%莱钢3#3200 m3高炉采用的新技术及生产实践

    Institute of Scientific and Technical Information of China (English)

    贾利军; 孟淑敏; 王冰

    2016-01-01

    In the paper, a series of new process and technology adopted in newly built No.3 3 200 m3 BF in laiwu steel are introduced, such as comprehensive technology of blast furnace longevity,multi nozzle type and fixed hopper of PW bell-less top, technology of axial cyclone deduster plus automatically discharging ash system, environmental INBA slag granulation technology, the dehumidified blast technology of BF and so on. The blast furnace was started up smoothly and reached the design product, in addition, all kinds of operation experience was happened, for example, intensified smelting, high coal ratio, large ore batch, limited production, wind-off without plan. The results were verified that every system ran normally and had better technical and economic index.%介绍了莱钢3#3200 m3高炉采用的长寿综合技术、多流嘴式料流分配器+固定料罐的PW无料钟炉顶设备、轴流旋风除尘器+吸排罐车自动卸灰系统、环保型INBA法渣处理技术、高炉脱湿鼓风技术等设计特点,高炉顺利开炉达产,历经强化冶炼、高煤比、大矿批、限产、无计划休风等不同操作实践,炉况顺行良好,各工艺系统运行正常,取得了良好的技术经济指标。

  1. Portable and Smart Ultrasonic Fluid Level Meter Based on ARM Cortex- M3%基于ARM Cortex - M3便携式智能超声波液位计

    Institute of Scientific and Technical Information of China (English)

    张根宝; 李秀平; 庞苏娟

    2012-01-01

    为了准确测量环境恶劣工业生产中的液位以保证生产效率,通过研究超声波测距工作原理,采用新型高性能、低功耗和低成本的ARM - Cortex M3内核微控制器,结合超声波技术、红外传输与DS1820温度补偿修正设计了一款便携式智能超声波液位计.其采用的先进微处理器以及无线传输的方式,简化了硬件电路,优化了软件编程.研究表明:该液位计设计提高了液位测量精度、实时性、灵活性与快速性.%To measure fluid level in poor industrial production conditions accurately for ensuring production efficiency,a portable intelligent correction ultrasonic fluid level meter was designed by studying the working principle of ultrasonic distance measurement. New high-performance, low power and low-cost ARM-Cortex M3 microcontroller core, combined with ultrasonic technology, infrared transmission and DS1820 temperature compensation were used in the level meter. The use of advanced microprocessor and wireless transmission, simplified hardware and optimized software programming. Studies show that the design of this fluid level gauge improved accuracy,timeliness,flexibility and rapidity of the level measurement.

  2. 莱钢3号3200 m3高炉设计创新与实践%Design innovation and practice of No. 3200 m3 BF in Laigang

    Institute of Scientific and Technical Information of China (English)

    王冰; 孟淑敏; 贾利军

    2016-01-01

    莱钢3号3200m3高炉设计采用了串罐无料钟炉顶、软水密闭循环冷却、炉体全覆盖冷却壁、铜冷却壁、 UCAR热压小块炭砖、改进型顶燃式热风炉、环保型INBA渣处理、轴流式旋风除尘器、环保平坦化出铁场、全干法布袋除尘、高富氧喷煤等一系列先进实用、成熟可靠、清洁环保、高效长寿的新技术设备,为实现高炉“高效、优质、低耗、长寿、环保”的目标打下了坚实的基础。%A series of advanced and suitable , mature and reliable , clean and environmentally friendly, high efficiency and long campaign techniques were adopted in the design of No. 3 3200m3 BF in Laiwu Steel, such as BLT, closed loop soft water cooling, complete coverage of furnace body cooling stave, copper cooling staves, UCAR hot pressing small pieces of carbon brick, improved top combus-tion hot blast stove, environmental friendly INBA slag treatment, axial cyclone deduster, green flat cast house, completely dry method bag deduster, high oxygen enrichment PCI, all the new technolo-gies mentioned above has laid a solid foundation for blast the target of high efficiency, high quality, low consumption, long campaign and clean environmental protection.

  3. Hearth Erosion Situation Analysis for the 1 750 m3 Blast Furnace in Jinan Steel%济钢1750 m3高炉炉缸侵蚀情况分析

    Institute of Scientific and Technical Information of China (English)

    张小伟; 张熙玮

    2015-01-01

    通过对生产条件及炉缸结构相同的济钢1#、3#1750 m3高炉炉缸侵蚀情况进行调查,发现1#高炉炉缸呈浅锅底—象脚状侵蚀,扒炉实测表明,炉缸、炉底交接处侵蚀最为严重,炭砖残存厚度最薄处仅为300 mm;3#高炉铁口附近炭砖出现不同程度裂纹,侵蚀严重处炭砖残存厚度600 mm。建议考虑炭砖的微孔度,使用高可靠性热电偶,降低炉底冷却水流量,增加炉缸冷却水流量等,以提高高炉寿命。%The hearth erosion of Jinan Steel’s No.1 and No.3 1 750 m3 BF have been investigated, although they have the same production conditions and hearth structure. It is found that the No.1 blast furnace hearth pale pot is like the foot-shaped erosion, griddle test shows junction of hearth and bottom are the most serious erosion position, the remaining thickness of the thinnest carbon brick is only 300 mm. The carbon bricks near the iron mouth of the No.3 BF have cracked to some extent, the remaining carbon brick thickness of severe erosion is 600 mm. To improve and prolong the life of the blast furnace, it is suggested that to apply the porous carbon bricks and high reliability thermocouples, reduce the cooling water flow for bottom, increase the cooling water flow of the hearth etc.

  4. Design of on-broad diagnose terminal with real-time warning based on CORTEX-M3%基于CORTEX-M3的实时车载诊断预警系统的设计

    Institute of Scientific and Technical Information of China (English)

    陈鲤文; 邹复民

    2013-01-01

    The design of ODB-II standard framework is based on embedded real-time operation and it can be realized on Cortex-M3 CPU core with uc/os II operating system. We have successful read real-time OBD-II data of vehicles from PC monitor and gather accident codes and sensor data through CAN bus, which can be used to evaluate the health of the automobiles, preventive against trouble, deduce the cost of driving and improve the driving safety. The advantage to the device is taking full account of all sorts of vehicle buses and put forward a kind of resolved scheme about remote on-boarded diagnosis in complicated vehicle circumstance.%基于嵌入式实时操作系统的OBD-Ⅱ诊断协议框架,以Cortex-M3为内核,采用uc/os Ⅱ操作系统实现了ISO15765协议,成功通过CAN总线读取了车辆的OBD-Ⅱ系统数据,通过上位机监控窗口,能实时检查汽车故障码与汽车传感器数据.可在此基础上评价汽车健康状况,并可对故障及早预防,降低行车成本,提供行车安全性;本设计充分考虑中国汽车市场主流总线发展的情况,提供了在复杂的车载环境下远程车载诊断设备的解决方案.

  5. THE INFLUENCE OF THE INGOT MOLD COOLING ON THE STRUCTURE OF SILUMINA CASTINGS AK15M3 AT VERTICAL CENTRIFUGAL CASTING

    Directory of Open Access Journals (Sweden)

    V. Yu. Stecenko

    2013-01-01

    Full Text Available Influence of ways of the mold cooling on structure of castings with diameter of 135 mm from AK15M3 silumin at vertical centrifugal casting is investigated. It is established that for production of castings with diameter 135 mm from AK15M3 silumin with high mechanical and tribotechnical properties it is necessary to apply a shaped mould with water-spray cooling at expense of cooler of 0,42 m3/h.

  6. Role of SKP1-CUL1-F-Box-Protein (SCF) E3 Ubiquitin Ligases in Skin Cancer

    Institute of Scientific and Technical Information of China (English)

    Chuan-Ming Xie; Wenyi Wei; Yi Sun

    2013-01-01

    Many biological processes such as cell proliferation,differentiation,and cell death depend precisely on the timely synthesis and degradation of key regulatory proteins.While protein synthesis can be regulated at multiple levels,protein degradation is mainly controlled by the ubiquitin-proteasome system (UPS),which consists of two distinct steps:(1) ubiquitylation of targeted protein by E1 ubiquitin-activating enzyme,E2 ubiquitin-conjugating enzyme and E3 ubiquitin ligase,and (2) subsequent degradation by the 26S proteasome.Among all E3 ubiquitin ligases,the SCF (SKP1-CUL1-F-box protein) E3 ligases are the largest family and are responsible for the turnover of many key regulatory proteins.Aberrant regulation of SCF E3 ligases is associated with various human diseases,such as cancers,including skin cancer.In this review,we provide a comprehensive overview of all currently published data to define a promoting role of SCF E3 ligases in the development of skin cancer.The future directions in this area of research are also discussed with an ultimate goal to develop small molecule inhibitors of SCF E3 ligases as a novel approach for the treatment of human skin cancer.Furthermore,altered components or substrates of SCF E3 ligases may also be developed as the biomarkers for early diagnosis or predicting prognosis.

  7. A hybrid toxin from bacteriophage f1 attachment protein and colicin E3 has altered cell receptor specificity.

    OpenAIRE

    Jakes, K S; Davis, N G; Zinder, N D

    1988-01-01

    A hybrid protein was constructed in vitro which consists of the first 372 amino acids of the attachment (gene III) protein of filamentous bacteriophage f1 fused, in frame, to the carboxy-terminal catalytic domain of colicin E3. The hybrid toxin killed cells that had the F-pilus receptor for phage f1 but not F- cells. The activity of the hybrid protein was not dependent upon the presence of the colicin E3 receptor, BtuB protein. The killing activity was colicin E3 specific, since F+ cells expr...

  8. [Morphological changes in gastric wall of mongolian gerbils following the 12-day orbital flight aboard Foton-M3].

    Science.gov (United States)

    Atiashkin, D A; Bykov, É G

    2012-01-01

    Gastric wall of Meriones unguiculatus is distinguished by species-specific properties arising from the peculiar proportion of interstitium, muscle and epithelial tissues. Exposure to the factors of the 12-d Foton-M3 flight led to microfocal lesions of the mucous coat, dystrophic developments in the acid glands, dissociation of the mucous barrier function and deterioration of its biosynthetic function. Modifications of the tinctorial properties of the interstitium reticulum in every stomach layer progressed concurrently with reductions in prismatic epithelium height, as well as in mucous and muscular layer thickness. It is assumed that existence in the low gravity aboard the Biosat stimulated involutory processes in the gastric wall. Animals of the ground synchronous control conducted in the flight equipment mockup (Kontur-L) exhibited though similar yet less pronounced changes.

  9. Elements in the canine distemper virus M 3' UTR contribute to control of replication efficiency and virulence.

    Directory of Open Access Journals (Sweden)

    Danielle E Anderson

    Full Text Available Canine distemper virus (CDV is a negative-sense, single-stranded RNA virus within the genus Morbillivirus and the family Paramyxoviridae. The Morbillivirus genome is composed of six transcriptional units that are separated by untranslated regions (UTRs, which are relatively uniform in length, with the exception of the UTR between the matrix (M and fusion (F genes. This UTR is at least three times longer and in the case of CDV also highly variable. Exchange of the M-F region between different CDV strains did not affect virulence or disease phenotype, demonstrating that this region is functionally interchangeable. Viruses carrying the deletions in the M 3' UTR replicated more efficiently, which correlated with a reduction of virulence, suggesting that overall length as well as specific sequence motifs distributed throughout the region contribute to virulence.

  10. Conversión de diagramas de procesos en diagramas de casos de usos usando AToM3

    Directory of Open Access Journals (Sweden)

    CARLOS M. ZAPATA J.

    2005-01-01

    Full Text Available Toda pieza de software se origina en el modelo verbal, con el cual se pueden definir los diferentes modelos conceptuales que acerquen el problema a una solución. Las herramientas convencionales para la construcción de los modelos conceptuales no toman en consideración las diferentes reglas de consistencia que se pueden presentar entre los diferentes modelos. En este artículo se emplea el AToM3 como herramienta para la definición de los meta-modelos del diagrama de procesos y el diagrama de casos de uso, con el fin de reexpresar el primero para obtener algunos elementos básicos del segundo.

  11. Anomalous Hall hysteresis in T m3F e5O12/Pt with strain-induced perpendicular magnetic anisotropy

    Science.gov (United States)

    Tang, Chi; Sellappan, Pathikumar; Liu, Yawen; Xu, Yadong; Garay, Javier E.; Shi, Jing

    2016-10-01

    We demonstrate robust interface strain-induced perpendicular magnetic anisotropy in atomically flat ferrimagnetic insulator T m3F e5O12 (TIG) films grown with pulsed laser deposition on a substituted G d3G a5O12 substrate which maximizes the tensile strain at the interface. In bilayers consisting of Pt and TIG, we observe large squared Hall hysteresis loops over a wide range of thicknesses of Pt at room temperature. When a thin Cu layer is inserted between Pt and TIG, the Hall hysteresis magnitude decays but stays finite as the thickness of Cu increases up to 5 nm. However, if the Cu layer is placed atop Pt instead, the Hall hysteresis magnitude is consistently larger than when the Cu layer with the same thickness is inserted in between for all Cu thicknesses. These results suggest that both the proximity-induced ferromagnetism and spin current contribute to the anomalous Hall effect.

  12. Photometric and spectroscopic observations of the F3+M3 eclipsing binary T-Lyr0-08070

    CERN Document Server

    Cakirli, O; Sipahi, E

    2012-01-01

    The multi-color photometric and spectroscopic observations of the newly discovered eclipsing binary T-Lyr0-08070 were obtained. The resultant light and radial velocities were analysed and the absolute parameters of the components were determined. The system is composed of an F3 and an M3 main-sequence stars. Masses and radii were estimated to be 1.37$\\pm$0.23 M$_{\\odot}$ and 1.60$\\pm$0.09 R$_{\\odot}$ for the primary and 0.32$\\pm$0.04 M$_{\\odot}$ and 0.86$\\pm$0.06R$_{\\odot}$ for the secondary star. The less massive secondary component has a radius at least two times larger with respect to its mass. Using the BVJHK magnitudes of the system we estimated an interstellar reddening of 0.22 mag and a distance to the system as 479$\\pm$36 pc.

  13. Moment Tensors and their Uncertainties for M3 Earthquakes in the Geysers, California, from Waveform Modeling and First Motions

    Science.gov (United States)

    Guilhem, A.; Dreger, D. S.; Hutchings, L. J.; Johnson, L.

    2012-12-01

    We investigate moment tensor solutions and their uncertainties for magnitude (M) ~3 earthquakes located in the northwest Geysers geothermal field, California. We are exploiting an unusual opportunity where data for M~3 events have been recorded by three different networks and have moment tensor solutions calculated by three different methods. We solve for both deviatoric and full moment tensor solutions. The data sets include local short-period instruments (4.5 Hz) of the 30 stations of the Lawrence Berkeley National Laboratory (LBNL), with which we obtain waveform inversion solutions at relatively high frequencies (i.e., up to 2.5 Hz), and regionally distributed broadband stations operated by the Berkeley Seismological Laboratory (BSL), with which are used to provide waveform inversion solutions with data filtered at longer periods (i.e., > 10 sec). We also utilize the LBNL data to obtain moment tensor solutions by fitting the P-wave first motions. The USGS, LBNL, and BSL obtain different event locations, utilize different velocity models, and analyze different frequency bands and wave types (i.e., body waves for LBNL method and primarily surface waves for the BSL analysis). Preliminary results indicate that the BSL and LBNL waveform modeling analyses give similar results in terms of nodal plane characteristics, moment magnitude, and moment tensor decomposition. Analysis of the P-wave first motions recorded by LBNL stations can illuminate complexities in the source processes when compared to waveform moment tensor solutions. We discuss uncertainties in the source inversions that use broadband and/or short-period waveform modeling, and in the source inversions from first motions only. We also combine the different datasets and compare their individual importance as they can help illustrate the complex source processes happening in the Geysers. This study introduces the possibility to interpret the seismic sources as complex processes in which both shear and tensile

  14. Tessellations & Transitions.

    Science.gov (United States)

    Cassidy, Joan

    1998-01-01

    Describes two sixth-grade lessons on the work of M. C. Escher: (1) the first lesson instructs students on tessellations, or tiles that interlock in a repeated pattern; (2) the second lesson explores Escher's drawings of transitions from two- to three-dimensional space. (DSK)

  15. Presidential Transitions

    Science.gov (United States)

    2006-06-09

    Morton Mintz and Stuart Auerbach, “Ford Solicits Suggestions on No. 2 Man,” Washington Post, Aug. 11, 1974, p. A1. 64 Fred Austin, “Ford Begins Move...representatives of the federal departments and agencies to ensure a smooth transition. Management and organizational issues should be CRS-23 105 Carl Brauer

  16. Helix 8 and the i3 loop of the muscarinic M3 receptor are crucial sites for its regulation by the Gβ5-RGS7 complex.

    Science.gov (United States)

    Karpinsky-Semper, Darla; Tayou, Junior; Levay, Konstantin; Schuchardt, Brett J; Bhat, Vikas; Volmar, Claude-Henry; Farooq, Amjad; Slepak, Vladlen Z

    2015-02-01

    The muscarinic M3 receptor (M3R) is a Gq-coupled receptor and is known to interact with many intracellular regulatory proteins. One of these molecules is Gβ5-RGS7, the permanently associated heterodimer of G protein β-subunit Gβ5 and RGS7, a regulator of G protein signaling. Gβ5-RGS7 can attenuate M3R-stimulated release of Ca(2+) from intracellular stores or enhance the influx of Ca(2+) across the plasma membrane. Here we show that deletion of amino acids 304-345 from the central portion of the i3 loop renders M3R insensitive to regulation by Gβ5-RGS7. In addition to the i3 loop, interaction of M3R with Gβ5-RGS7 requires helix 8. According to circular dichroism spectroscopy, the peptide corresponding to amino acids 548-567 in the C-terminus of M3R assumes an α-helical conformation. Substitution of Thr553 and Leu558 with Pro residues disrupts this α-helix and abolished binding to Gβ5-RGS7. Introduction of the double Pro substitution into full-length M3R (M3R(TP/LP)) prevents trafficking of the receptor to the cell surface. Using atropine or other antagonists as pharmacologic chaperones, we were able to increase the level of surface expression of the TP/LP mutant to levels comparable to that of wild-type M3R. However, M3R-stimulated calcium signaling is still severely compromised. These results show that the interaction of M3R with Gβ5-RGS7 requires helix 8 and the central portion of the i3 loop.

  17. Cassini Plasma Spectrometer Ion Observations Close to Enceladus: E3, E5 and E7

    Science.gov (United States)

    Tokar, R. L.; Johnson, R. E.; Thomsen, M. F.; Wilson, R. J.; Crary, F. J.; Young, D. T.; Goldstein, R.; Reisenfeld, D. B.; Sittler, E. C.; Coates, A. J.; Paty, C. S.; Jia, Y.; Omidi, N.; Russell, C.

    2009-12-01

    The Cassini Plasma Spectrometer (CAPS) detected freshly-produced water-group ions (O+, OH+, H2O+, H3O+) and heavier water dimer ions (HxO2)+ very close to Enceladus where the plasma begins to emerge from the south polar plume (1). The data were obtained during two close (52 and 25 km) flybys of Enceladus in 2008 (E3 and E5) and are consistent with measurements from the Cassini Ion Neutral Mass Spectrometer (INMS). The ions are observed in CAPS detectors looking in the Cassini ram direction close to the ram kinetic energy, indicative of a nearly stagnant plasma flow in the plume. North of Enceladus the plasma slowing commences about 4 to 6 Enceladus radii away, while south of Enceladus signatures of the plasma interaction with the plume are detected 22 Enceladus radii away. Here we review and contrast these observations including the E7 flyby (anticipated Nov. 2, 2009). E7 is planned for a closest approach ~103 km south of Enceladus and CAPS should detect ions at rest with respect to Enceladus and over a broad range of gyrophase angles. Plasma fluid parameters both upstream and downstream of these encounters are extracted from the CAPS data. In addition, we compare the CAPS ion measurements with both fluid and 3D hybrid simulations. The MHD simulations (BATSRUS) are tuned to agree with Cassini Magnetometer (MAG) observations during the encounters then compared with CAPS observations. For example, for the E3 encounter the CAPS/BATSRUS comparison is striking, with features reproduced such as: the overall spatial scale of the interaction, the slowing of the ion flow within the dust plume to less than 5 km/s with respect to Enceladus, the temperature, flow and density signature of the geometric wake, and the flow perturbation along the magnetic field due to wake expansion. For E5, BATSRUS tuned against MAG suggests a 15 km/s bulk plasma flow toward Saturn during the encounter. We search for signatures of this flow in the CAPS ion data. 1.) Tokar,R.L. et al. Geophys. Res

  18. Design of Dynamic Electrocardiogram Based on ARM Cortex-M3%基于ARM Cortex-M3的动态心电图机设计

    Institute of Scientific and Technical Information of China (English)

    谢建华; 刘海波; 刘瑞芳

    2012-01-01

    In order to enrich the product categories and function of the dynamic electrocardiogram,a new type of dynamic electrocardiogram product based on ARM (Advanced RISC Machines) Cortex-M3 is developed. The system hardware consists a processor minimum system,bioelectricity amplification module, storage module,LCD(Liquid Crstal Display) and touch screen module,high speed USB interface and the power module. For the system software, the platform was build based on CooCox CoOS embedded realtime operating system, the file system and USB middleware. The man-machine interface is realized by transplanting uC/GUI. The experiment results showed that the system could be used to control ECG signal collection,great capacity data storage and high-speed upload. The graphical user interface and real time waveform display are the innovative points.%针对目前动态心电图机产品种类和功能单一的现状,研制了基于ARM(Advanced RISC Machines) Cortex-M3的新型动态心电图机.硬件主要由处理器最小系统、生物电放大模块、存储模块、LCD (Liquid Cgstal Display)和触摸屏模块、高速USB接口和电源模块构成.软件开发基于CooCox CoOS嵌入式实时操作系统,同时使用了文件系统和USB等中间件.移植uC/GUI实现人机接口设计.测试结果表明,该系统不但实现了心电信号采集、大容量数据存储和高速上传的功能,而且创新性地增加了图形用户界面和实时波形显示功能.

  19. Car Design of WiFi Internet of Things Based on SCM Cortex-M3%基于Cortex-M3单片机的WiFi物联网小车的设计

    Institute of Scientific and Technical Information of China (English)

    汤莉莉; 黄伟; 王春波; 方规

    2014-01-01

    使用无线互联网WiFi技术,采集小车上传感器的相关数据,并做相应的处理和控制,实现远程控制和监控功能。研究的范围包括Cortex-M3内核的LPC1768单片机软件的编程,单片机温度、速度、视屏的采集处理和传输,电脑软件的编程, Windows环境下的视屏处理、模拟速度表盘和模拟温度计的设计与实现以及TCP/IP通信实现等。方案采用自下而上的模块化编程方法,对温度和速度测试模块进行了模拟测试,对WiFi通信机制做了大量的数据分析,实现用电脑软件通过无线WiFi控制小车的运动、采集相关信息并显示等功能。%The purpose of this design is to use wireless Internet WiFi technology to collect the related data of car sensor,perform appropriate process and control,and ultimately realize remote control and monitoring functions.The study covers the SCM LPC1768 soft-ware programming of Cortex-M3 core,and the temperature,speed,screen capture processing and transmission of SCM,together with the design and implementation of screen processing,analog dial of speed,analog thermometer and TCP/IP communication under Windows environments.The scheme uses a bottom-up modular programming method to implement the simulation and test for temperature and speed testing module,perform much of data analysis of WiFi communication mechanism,and finally use computer software to achieve the control the car′s movement,collect and display relevant information through wireless WiFi.

  20. Design of mine DC electrical prospecting instrument based on ARM Cortex-M3 core%基于ARM Cortex-M3内核矿井直流电法仪的研制

    Institute of Scientific and Technical Information of China (English)

    宁殿艳; 张仲礼; 王继矿; 汪凯斌; 李超

    2011-01-01

    DC electrical prospecting instrument has played an important role in preventing mine water disaster, but the traditional DC electrical prospecting instrument has some disadvantages such as high power consumption, small storage capacity, hard operation and difficulty to carry, for it is mostly developed utilizing MCS -51 microcontroller. These restrict the application of DC electrical prospecting instrument to a certain extent. This article begins with the working principle of mine DC electrical, improves the traditional DC electrical prospecting instrument utilizing STM32 microcomputer based on Cortex - M3 core and 24 - bit Σ - A ADC component, and redesigns the hardware and software of mine DC eldetrieal instrument. The improved instrument has the advantage of high accuracy, low cost, low power consumption, large storage capacity, convenient communication and friendly man-machine interface compared with traditional DC electrical prospecting instrument.%直流电法仪在预防煤矿水害中发挥重要作用,但传统直流电法仪的核心芯片多采用51系列单片机,具有功耗大、存储容量小、操作不方便,难以携带等缺点,在一定程度上制约了直流电法仪的应用.文中从矿井直流电法仪的工作原理出发,采用基于ARM Cortex-M3内核的STM32处理器和基于Σ-Δ技术的24位高分辨率ADC器件对传统矿井直流电法仪进行了升级、改造,重新设计了硬件电路和软件程序.与传统矿井直流电法仪相比,新设计的直流电法仪具有精度高、成本低、功耗小、存储容量大、通讯方便和人机界面友好等优点.

  1. Initial clinical evaluation of radiolabeled MX-DTPA humanized BrE-3 antibody in patients with advanced breast cancer.

    Science.gov (United States)

    Kramer, E L; Liebes, L; Wasserheit, C; Noz, M E; Blank, E W; Zabalegui, A; Melamed, J; Furmanski, P; Peterson, J A; Ceriani, R L

    1998-07-01

    To evaluate radiometal-labeled humanized BrE-3 (huBrE-3) monoclonal antibody as a radioimmunolocalization and therapeutic agent in breast cancer patients, tumor localization, pharmacokinetics, radiation dosimetry, and immunogenicity of (111)In-labeled combined 1-p-isothiocyanatobenzyl 3-methyl- and 1-p-isothiocyanatobenzyl 4-methyldiethylenetriamine pentaacetic acid (MX-DTPA) huBrE-3 were studied. Seven women with BrE-3 antigen-positive, metastatic breast carcinoma underwent (111)In huBrE-3 infusion (5 mCi; 50 mg), followed by serial gamma camera imaging and plasma sampling. Region of interest analysis of images was used to make radiation absorbed dose estimates for (111)In huBrE-3. Data were extrapolated to 90Y huBrE-3. Human anti-human antibody (HAHA) response was measured in serum samples obtained up to 3 months after infusion. Patients tolerated infusions well. Seventy-six percent of 105 known sites of disease were identified on planar and single-photon emission computed tomography scans. For six of seven patients, a biexponential model fit the plasma time-activity curve best with an average T1/2alpha=10.6+/-8.5 (SD) h and average T1/2beta=114.2+/-39.2 h. Radiation absorbed dose estimates for (111)In huBrE-3 for whole body averaged 0.53+/-.08 rads/mCi. Dose estimates for 90Y huBrE-3 for marrow averaged 8.4+/-11.9 rads/mCi, and for tumors, 70+/-31.5 rads/mCi. Liver radioactivity uptake averaged 19.7+/-8.8% injected dose at 24 h after infusion, translating into an average radiation absorbed dose 21.1+/-12 rads/90Y mCi administered. Only one of seven patients demonstrated a low level of HAHA response. Although the plasma half-lives are longer and marrow dose higher for radiolabeled huBrE-3 compared with the murine construct, the excellent tumor localization, good tumor dosimetry, and low immunogenicity support the use of 90Y-huBrE-3 antibody for radioimmunotherapy of breast cancer.

  2. 77 FR 76598 - Notice of Receipt of Petition for Decision That Nonconforming 2006-2010 BMW M3 Passenger Cars Are...

    Science.gov (United States)

    2012-12-28

    ... vehicles that are not already so equipped; and (b) replacement of any non U.S.- model air bags, air bag...-2010 BMW M3 Passenger Cars Are Eligible for Importation AGENCY: National Highway Traffic Safety...-2010 BMW M3 passenger cars that were not originally manufactured to comply with all applicable Federal...

  3. The Arabidopsis MIEL1 E3 ligase negatively regulates ABA signalling by promoting protein turnover of MYB96

    OpenAIRE

    Lee, Hong Gil; Seo, Pil Joon

    2016-01-01

    The phytohormone abscisic acid (ABA) regulates plant responses to various environmental challenges. Controlled protein turnover is an important component of ABA signalling. Here we show that the RING-type E3 ligase MYB30-INTERACTING E3 LIGASE 1 (MIEL1) regulates ABA sensitivity by promoting MYB96 turnover in Arabidopsis. Germination of MIEL1-deficient mutant seeds is hypersensitive to ABA, whereas MIEL1-overexpressing transgenic seeds are less sensitive. MIEL1 can interact with MYB96, a regul...

  4. Ophthalmic epidemiology in Europe: the "European Eye Epidemiology" (E3) consortium.

    Science.gov (United States)

    Delcourt, Cécile; Korobelnik, Jean-François; Buitendijk, Gabriëlle H S; Foster, Paul J; Hammond, Christopher J; Piermarocchi, Stefano; Peto, Tunde; Jansonius, Nomdo; Mirshahi, Alireza; Hogg, Ruth E; Bretillon, Lionel; Topouzis, Fotis; Deak, Gabor; Grauslund, Jakob; Broe, Rebecca; Souied, Eric H; Creuzot-Garcher, Catherine; Sahel, José; Daien, Vincent; Lehtimäki, Terho; Hense, Hans-Werner; Prokofyeva, Elena; Oexle, Konrad; Rahi, Jugnoo S; Cumberland, Phillippa M; Schmitz-Valckenberg, Steffen; Fauser, Sascha; Bertelsen, Geir; Hoyng, Carel; Bergen, Arthur; Silva, Rufino; Wolf, Sebastian; Lotery, Andrew; Chakravarthy, Usha; Fletcher, Astrid; Klaver, Caroline C W

    2016-02-01

    The European Eye Epidemiology (E3) consortium is a recently formed consortium of 29 groups from 12 European countries. It already comprises 21 population-based studies and 20 other studies (case-control, cases only, randomized trials), providing ophthalmological data on approximately 170,000 European participants. The aim of the consortium is to promote and sustain collaboration and sharing of data and knowledge in the field of ophthalmic epidemiology in Europe, with particular focus on the harmonization of methods for future research, estimation and projection of frequency and impact of visual outcomes in European populations (including temporal trends and European subregions), identification of risk factors and pathways for eye diseases (lifestyle, vascular and metabolic factors, genetics, epigenetics and biomarkers) and development and validation of prediction models for eye diseases. Coordinating these existing data will allow a detailed study of the risk factors and consequences of eye diseases and visual impairment, including study of international geographical variation which is not possible in individual studies. It is expected that collaborative work on these existing data will provide additional knowledge, despite the fact that the risk factors and the methods for collecting them differ somewhat among the participating studies. Most studies also include biobanks of various biological samples, which will enable identification of biomarkers to detect and predict occurrence and progression of eye diseases. This article outlines the rationale of the consortium, its design and presents a summary of the methodology.

  5. Interaction between Mnk2 and CBCVHL ubiquitin ligase E3 complex

    Institute of Scientific and Technical Information of China (English)

    WANG Pingzhang; WANG Xin; WANG Feng; CAI Tianjing; LUO Ying

    2006-01-01

    MAP kinase-interacting kinase-2 (Mnk2) is one of the downstream kinases activated by MAP kinases. It phosphorylates the eukaryotic initiation factor 4E (eIF4E), although the role of eIF4E phosphorylation and the role of Mnk2 in the process of protein translation are not well understood. Except for eIF4E, other physiological substrates of Mnk2 are still unidentified. To look for these unidentified substrates and to reveal the physiological function of Mnk2, we performed a yeast two-hybrid screening with Mnk2 as the bait. The results demonstrated Mnk2 could interact with VHL (von Hippel-Lindau tumor suppressor), Rbx1 (ring-box 1) and Cul2 (Cullin2) proteins in yeast cells. Furthermore, we validated the interaction between Mnk2 and VHL proteins in mammalian cells by co-immunoprecipitation analysis. Because the three proteins VHL, Rbx1 and Cul2 are all components of the CBCVHL ubiquitin ligase E3 complex, it has been shown that Mnk2 can interact with CBCVHL complex, and is probably one of the new substrates of the CBCVHL complex. Furthermore, during the interaction of Mnk2 with von Hippel-Lindau (VHL) tumor suppressor- binding protein 1 (VBP1), it appears that Mnk2 also joins to modulate cell shape as VBP1 plays an important role in the process of the maturation of the cytoskeleton and in the process of morphogenesis.

  6. High Precision Topographic Mapping at Chang'E-3 Landing Site with Multi-Source Data

    Science.gov (United States)

    Liu, Y.; Liu, B.; Xu, B.; Liu, Z.; Di, K.; Zhou, J.

    2014-04-01

    Chang'e-3 (CE-3) is the first lander and rover of China following the success of Chang'e-1 and Chang'e-2 (CE-2) orbiters. High precision topographic mapping can provide detailed terrain information to ensure the safety of the rover as well as to support scientific investigations. In this research, multi-source data are co-registered into a uniform geographic framework for high precision topographic mapping at the CE-3 landing site. CE-2 CCD images with 7 m- and 1.5 m- resolutions are registered using selfcalibration bundle adjustment method with ground control points (GCPs) selected from LRO WAC mosaic map and LOLA DTM. The trajectory of CE-3 descent images are recovered using self-calibration free net bundle adjustment, and then the topographic data is rectified by absolute orientation with GCPs selected from the adjusted CE-2 DEM and DOM. Finally, these topographic data are integrated into the same geographic framework for unified, multi-scale, high precision mapping of the CE-3 landing site. Key technologies and the mapping products of this research have been used to support the surface operations of CE-3 mission.

  7. The E3 ubiquitin ligase activity of Trip12 is essential for mouse embryogenesis.

    Directory of Open Access Journals (Sweden)

    Masashi Kajiro

    Full Text Available Protein ubiquitination is a post-translational protein modification that regulates many biological conditions. Trip12 is a HECT-type E3 ubiquitin ligase that ubiquitinates ARF and APP-BP1. However, the significance of Trip12 in vivo is largely unknown. Here we show that the ubiquitin ligase activity of Trip12 is indispensable for mouse embryogenesis. A homozygous mutation in Trip12 (Trip12(mt/mt that disrupts the ubiquitin ligase activity resulted in embryonic lethality in the middle stage of development. Trip12(mt/mt embryos exhibited growth arrest and increased expression of the negative cell cycle regulator p16. In contrast, Trip12(mt/mt ES cells were viable. They had decreased proliferation, but maintained both the undifferentiated state and the ability to differentiate. Trip12(mt/mt ES cells had increased levels of the BAF57 protein (a component of the SWI/SNF chromatin remodeling complex and altered gene expression patterns. These data suggest that Trip12 is involved in global gene expression and plays an important role in mouse development.

  8. The evolutionarily conserved E3 ubiquitin ligase AtCHIP contributes to plant immunity

    Directory of Open Access Journals (Sweden)

    Xin eLi

    2016-03-01

    Full Text Available Plants possess a sophisticated immune system to recognize and respond to microbial threats in their environment. The level of immune signaling must be tightly regulated so that immune responses can be quickly activated in the presence of pathogens, while avoiding autoimmunity. HSP90s, along with their diverse array of co-chaperones, forms chaperone complexes that have been shown to play both positive and negative roles in regulating the accumulation of immune receptors and regulators. In this study, we examined the role of AtCHIP, an evolutionarily conserved E3 ligase that was known to interact with chaperones including HSP90s in multicellular organisms including fruit fly, C. elegans, plants and human. Atchip knockout mutants display enhanced disease susceptibility to a virulent oomycete pathogen, and overexpression of AtCHIP causes enhanced disease resistance at low temperature. Although CHIP was reported to target HSP90 for ubiquitination and degradation, accumulation of HSP90.3 was not affected in Atchip plants. In addition, protein accumulation of nucleotide-binding, leucine-rich repeat domain immune receptor (NLR SNC1 is not altered in Atchip mutant. Thus, while AtCHIP plays a role in immunity, it does not seem to regulate the turnover of HSP90 or SNC1. Further investigation is needed in order to determine the exact mechanism behind AtCHIP’s role in regulating plant immune responses.

  9. BICP0 and its RING finger domain act as ubiquitin E3 ligases in vitro

    Institute of Scientific and Technical Information of China (English)

    DIAO Lirong; QIAO Wentao; CHEN Qimin; WANG Chen; GENG Yunqi

    2005-01-01

    Bovine infected-cell protein 0 (BICP0) encoded by bovine herpes virus 1 (BHV-1) immediate early gene is necessary for efficient productive infection, in a large part because it activates all 3 classes of BHV-1 genes. It also has the ability to efficiently transactivate promoters that are not derived from BHV-1. To investigate the mechanism by which BICP0 achieves these effects, we expressed and purified BICP0 and its different mutants in E. coli. In vitro assays showed that both full-length BICP0 and its isolated RING finger domain induce the accumulation of polyubiquitin chains. Mutations within the RING finger region that abolish the in vitro ubiquitination activity also cause severe reductions in BICP0 activity in other assays. Based on these, we conclude that BICP0 has the potential to act as an E3 ubiquitin ligase during viral infection and its RING finger domain is necessary for this function. These strongly support the hypothesis that BICP0 might influence virus infection through its ability to interact with the ubiquitin-proteasome pathway.

  10. CRL4A(CRBN) E3 ubiquitin ligase restricts BK channel activity and prevents epileptogenesis.

    Science.gov (United States)

    Liu, Jiye; Ye, Jia; Zou, Xiaolong; Xu, Zhenghao; Feng, Yan; Zou, Xianxian; Chen, Zhong; Li, Yuezhou; Cang, Yong

    2014-05-21

    Ion channels regulate membrane excitation, and mutations of ion channels often cause serious neurological disorders including epilepsy. Compared with extensive analyses of channel protein structure and function, much less is known about the fine tuning of channel activity by post-translational modification. Here we report that the large conductance, Ca(2+)- and voltage-activated K(+) (BK) channels are targeted by the E3 ubiquitin ligase CRL4A(CRBN) for polyubiquitination and retained in the endoplasmic reticulum (ER). Inactivation of CRL4A(CRBN) releases deubiquitinated BK channels from the ER to the plasma membrane, leading to markedly enhanced channel activity. Mice with CRL4A(CRBN) mutation in the brain or treated with a CRL4A(CRBN) inhibitor are very sensitive to seizure induction, which can be attenuated by blocking BK channels. Finally, the mutant mice develop spontaneous epilepsy when aged. Therefore, ubiquitination of BK channels before their cell surface expression is an important step to prevent systemic neuronal excitability and epileptogenesis.

  11. Natural polymorphisms in C. elegans HECW-1 E3 ligase affect pathogen avoidance behaviour.

    Science.gov (United States)

    Chang, Howard C; Paek, Jennifer; Kim, Dennis H

    2011-11-16

    Heritable variation in behavioural traits generally has a complex genetic basis, and thus naturally occurring polymorphisms that influence behaviour have been defined only in rare instances. The isolation of wild strains of Caenorhabditis elegans has facilitated the study of natural genetic variation in this species and provided insights into its diverse microbial ecology. C. elegans responds to bacterial infection with conserved innate immune responses and, although lacking the immunological memory of vertebrate adaptive immunity, shows an aversive learning response to pathogenic bacteria. Here, we report the molecular characterization of naturally occurring coding polymorphisms in a C. elegans gene encoding a conserved HECT domain-containing E3 ubiquitin ligase, HECW-1. We show that two distinct polymorphisms in neighbouring residues of HECW-1 each affect C. elegans behavioural avoidance of a lawn of Pseudomonas aeruginosa. Neuron-specific rescue and ablation experiments and genetic interaction analysis indicate that HECW-1 functions in a pair of sensory neurons to inhibit P. aeruginosa lawn avoidance behaviour through inhibition of the neuropeptide receptor NPR-1 (ref. 10), which we have previously shown promotes P. aeruginosa lawn avoidance behaviour. Our data establish a molecular basis for natural variation in a C. elegans behaviour that may undergo adaptive changes in response to microbial pathogens.

  12. An Assessment of Japanese Carbon Tax Reform Using the E3MG Econometric Model

    Directory of Open Access Journals (Sweden)

    Soocheol Lee

    2012-01-01

    Full Text Available This paper analyses the potential economic and environmental effects of carbon taxation in Japan using the E3MG model, a global macroeconometric model constructed by the University of Cambridge and Cambridge Econometrics. The paper approaches the issues by considering first the impacts of the carbon tax in Japan introduced in 2012 and then the measures necessary to reduce Japan’s emissions in line with its Copenhagen pledge of −25% compared to 1990 levels. The results from the model suggest that FY2012 Tax Reform has only a small impact on emission levels and no significant impact on GDP and employment. The potential costs of reducing emissions to meet the 25% reduction target for 2020 are quite modest, but noticeable. GDP falls by around 1.2% compared to the baseline and employment by 0.4% compared to the baseline. But this could be offset, with some potential economic benefits, if revenues are recycled efficiently. This paper considers two revenue recycling scenarios. The most positive outcome is if revenues are used both to reduce income tax rates and to increase investment in energy efficiency. This paper shows there could be double dividend effects, if Carbon Tax Reform is properly designed.

  13. The E3 Ubiquitin Ligase TMEM129 Is a Tri-Spanning Transmembrane Protein

    Directory of Open Access Journals (Sweden)

    Michael L. van de Weijer

    2016-11-01

    Full Text Available Misfolded proteins from the endoplasmic reticulum (ER are transported back into the cytosol for degradation via the ubiquitin-proteasome system. The human cytomegalovirus protein US11 hijacks this ER-associated protein degradation (ERAD pathway to downregulate human leukocyte antigen (HLA class I molecules in virus-infected cells, thereby evading elimination by cytotoxic T-lymphocytes. Recently, we identified the E3 ubiquitin ligase transmembrane protein 129 (TMEM129 as a key player in this process, where interference with TMEM129 activity in human cells completely abrogates US11-mediated class I degradation. Here, we set out to further characterize TMEM129. We show that TMEM129 is a non-glycosylated protein containing a non-cleaved signal anchor sequence. By glycosylation scanning mutagenesis, we show that TMEM129 is a tri-spanning ER-membrane protein that adopts an Nexo–Ccyto orientation. This insertion in the ER membrane positions the C-terminal really interesting new gene (RING domain of TMEM129 in the cytosol, making it available to catalyze ubiquitination reactions that are required for cytosolic degradation of secretory proteins.

  14. Natural variation and dosage of the HEI10 meiotic E3 ligase control Arabidopsis crossover recombination

    Science.gov (United States)

    Ziolkowski, Piotr A.; Underwood, Charles J.; Lambing, Christophe; Martinez-Garcia, Marina; Lawrence, Emma J.; Ziolkowska, Liliana; Griffin, Catherine; Choi, Kyuha; Franklin, F. Chris H.; Martienssen, Robert A.; Henderson, Ian R.

    2017-01-01

    During meiosis, homologous chromosomes undergo crossover recombination, which creates genetic diversity and balances homolog segregation. Despite these critical functions, crossover frequency varies extensively within and between species. Although natural crossover recombination modifier loci have been detected in plants, causal genes have remained elusive. Using natural Arabidopsis thaliana accessions, we identified two major recombination quantitative trait loci (rQTLs) that explain 56.9% of crossover variation in Col×Ler F2 populations. We mapped rQTL1 to semidominant polymorphisms in HEI10, which encodes a conserved ubiquitin E3 ligase that regulates crossovers. Null hei10 mutants are haploinsufficient, and, using genome-wide mapping and immunocytology, we show that transformation of additional HEI10 copies is sufficient to more than double euchromatic crossovers. However, heterochromatic centromeres remained recombination-suppressed. The strongest HEI10-mediated crossover increases occur in subtelomeric euchromatin, which is reminiscent of sex differences in Arabidopsis recombination. Our work reveals that HEI10 naturally limits Arabidopsis crossovers and has the potential to influence the response to selection. PMID:28223312

  15. The HECTD3 E3 ubiquitin ligase suppresses cisplatin-induced apoptosis via stabilizing MALT1.

    Science.gov (United States)

    Li, Yi; Chen, Xi; Wang, Zehua; Zhao, Dong; Chen, Hui; Chen, Wenlin; Zhou, Zhongmei; Zhang, Junran; Zhang, Jing; Li, Hongmin; Chen, Ceshi

    2013-01-01

    Homologous to the E6-associated protein carboxyl terminus domain containing 3 (HECTD3) is an E3 ubiquitin ligase with unknown functions. Here, we show that HECTD3 confers cancer cell resistance to cisplatin. To understand the molecular mechanisms, we performed a yeast two-hybrid analysis and identified mucosa-associated lymphoid tissue 1 (MALT1) as an HECTD3-interacting protein. HECTD3 promotes MALT1 ubiquitination with nondegradative polyubiquitin chains by direct interacting with the MALT1 through its N-terminal destruction of cyclin domain. HECTD3 does not target MALT1 for degradation but stabilize it. HECTD3 depletion dramatically decreases the levels of MALT1 in MCF7 and HeLa cells treated with cisplatin, which is correlated to an increase in apoptosis. Knockdown of MALT1 likewise increases cisplatin-induced apoptosis in these cancer cells. However, HECTD3 over-expression leads to a decreased cisplatin-induced apoptosis, whereas overexpression of MALT1 partially rescues HECTD3 depletion-induced apoptosis. These findings suggest that HECTD3 promotes cell survival through stabilizing MALT1. Our data have important implications in cancer therapy by providing novel molecular targets.

  16. The HECTD3 E3 Ubiquitin Ligase Suppresses Cisplatin-Induced Apoptosis via Stabilizing MALT1

    Directory of Open Access Journals (Sweden)

    Yi Li

    2013-01-01

    Full Text Available Homologous to the E6-associated protein carboxyl terminus domain containing 3 (HECTD3 is an E3 ubiquitin ligase with unknown functions. Here, we show that HECTD3 confers cancer cell resistance to cisplatin. To understand the molecular mechanisms, we performed a yeast two-hybrid analysis and identified mucosa-associated lymphoid tissue 1 (MALT1 as an HECTD3-interacting protein. HECTD3 promotes MALT1 ubiquitination with non-degradative polyubiquitin chains by direct interacting with the MALT1 through its N-terminal destruction of cyclin domain. HECTD3 does not target MALT1 for degradation but stabilize it. HECTD3 depletion dramatically decreases the levels of MALT1 in MCF7 and HeLa cells treated with cisplatin, which is correlated to an increase in apoptosis. Knockdown of MALT1 likewise increases cisplatin-induced apoptosis in these cancer cells. However, HECTD3 overexpression leads to a decreased cisplatin-induced apoptosis, whereas overexpression of MALT1 partially rescues HECTD3 depletion–induced apoptosis. These findings suggest that HECTD3 promotes cell survival through stabilizing MALT1. Our data have important implications in cancer therapy by providing novel molecular targets.

  17. An Arabidopsis SUMO E3 Ligase, SIZ1, Negatively Regulates Photomorphogenesis by Promoting COP1 Activity

    KAUST Repository

    Lin, Xiao-Li

    2016-04-29

    COP1 (CONSTITUTIVE PHOTOMORPHOGENIC 1), a ubiquitin E3 ligase, is a central negative regulator of photomorphogenesis. However, how COP1 activity is regulated by post-translational modifications remains largely unknown. Here we show that SUMO (small ubiquitin-like modifier) modification enhances COP1 activity. Loss-of-function siz1 mutant seedlings exhibit a weak constitutive photomorphogenic phenotype. SIZ1 physically interacts with COP1 and mediates the sumoylation of COP1. A K193R substitution in COP1 blocks its SUMO modification and reduces COP1 activity in vitro and in planta. Consistently, COP1 activity is reduced in siz1 and the level of HY5, a COP1 target protein, is increased in siz1. Sumoylated COP1 may exhibits higher transubiquitination activity than does non-sumoylated COP1, but SIZ1-mediated SUMO modification does not affect COP1 dimerization, COP1-HY5 interaction, and nuclear accumulation of COP1. Interestingly, prolonged light exposure reduces the sumoylation level of COP1, and COP1 mediates the ubiquitination and degradation of SIZ1. These regulatory mechanisms may maintain the homeostasis of COP1 activity, ensuing proper photomorphogenic development in changing light environment. Our genetic and biochemical studies identify a function for SIZ1 in photomorphogenesis and reveal a novel SUMO-regulated ubiquitin ligase, COP1, in plants.

  18. Myc protein is stabilized by suppression of a novel E3 ligase complex in cancer cells

    Science.gov (United States)

    Choi, Seung H.; Wright, Jason B.; Gerber, Scott A.; Cole, Michael D.

    2010-01-01

    Rapid Myc protein turnover is critical for maintaining basal levels of Myc activity in normal cells and a prompt response to changing growth signals. We characterize a new Myc-interacting factor, TRPC4AP (transient receptor potential cation channel, subfamily C, member 4-associated protein)/TRUSS (tumor necrosis factor receptor-associated ubiquitous scaffolding and signaling protein), which is the receptor for a DDB1 (damage-specific DNA-binding protein 1)–CUL4 (Cullin 4) E3 ligase complex for selective Myc degradation through the proteasome. TRPC4AP/TRUSS binds specifically to the Myc C terminus and promotes its ubiquitination and destruction through the recognition of evolutionarily conserved domains in the Myc N terminus. TRPC4AP/TRUSS suppresses Myc-mediated transactivation and transformation in a dose-dependent manner. Finally, we found that TRPC4AP/TRUSS expression is strongly down-regulated in most cancer cell lines, leading to Myc protein stabilization. These studies identify a novel pathway targeting Myc degradation that is suppressed in cancer cells. PMID:20551172

  19. ATLs and BTLs, plant-specific and general eukaryotic structurally-related E3 ubiquitin ligases.

    Science.gov (United States)

    Guzmán, Plinio

    2014-02-01

    Major components of the ubiquitin proteasome system are the enzymes that operate on the transfer of ubiquitin to selected target substrate, known as ubiquitin ligases. The RING finger is a domain that is present in key classes of ubiquitin ligases. This domain coordinates the interaction with a suitable E2 conjugase and the transfer of ubiquitin from the E2 to protein targets. Additional domains coupled to the same polypeptide are important for modulating the function of these ubiquitin ligases. Plants contain several types of E3 ubiquitin ligases that in many cases have expanded as multigene families. Some families are specific to the plant lineage, whereas others may have a common ancestor among plants and other eukaryotic lineages. Arabidopsis Tóxicos en Levadura (ATLs) and BCA2 zinc finger ATLs (BTLs) are two families of ubiquitin ligases that share some common structural features. These are intronless genes that encode a highly related RING finger domain, and yet during evolutionary history, their mode of gene expansion and function is rather different. In each of these two families, the co-occurrence of transmembrane helices or C2/C2 (BZF finger) domains with a selected variation on the RING finger has been subjected to strong selection pressure in order to preserve their unique domain architectures during evolution.

  20. An assessment of Japanese carbon tax reform using the E3MG econometric model.

    Science.gov (United States)

    Lee, Soocheol; Pollitt, Hector; Ueta, Kazuhiro

    2012-01-01

    This paper analyses the potential economic and environmental effects of carbon taxation in Japan using the E3MG model, a global macroeconometric model constructed by the University of Cambridge and Cambridge Econometrics. The paper approaches the issues by considering first the impacts of the carbon tax in Japan introduced in 2012 and then the measures necessary to reduce Japan's emissions in line with its Copenhagen pledge of -25% compared to 1990 levels. The results from the model suggest that FY2012 Tax Reform has only a small impact on emission levels and no significant impact on GDP and employment. The potential costs of reducing emissions to meet the 25% reduction target for 2020 are quite modest, but noticeable. GDP falls by around 1.2% compared to the baseline and employment by 0.4% compared to the baseline. But this could be offset, with some potential economic benefits, if revenues are recycled efficiently. This paper considers two revenue recycling scenarios. The most positive outcome is if revenues are used both to reduce income tax rates and to increase investment in energy efficiency. This paper shows there could be double dividend effects, if Carbon Tax Reform is properly designed.

  1. Termination of single-crystal B i2S e3 surfaces prepared by various methods

    Science.gov (United States)

    Zhou, Weimin; Zhu, Haoshan; Yarmoff, Jory A.

    2016-11-01

    Bismuth Selenide (B i2S e3) is a topological insulator with a two-dimensional layered structure that enables clean and well-ordered surfaces to be prepared by cleaving. Although some studies have demonstrated that the cleaved surface is terminated with Se, as expected from the bulk crystal structure, other reports have indicated either a Bi- or mixed-termination. Low-energy ion scattering (LEIS), low energy electron diffraction (LEED) and x-ray photoelectron spectroscopy (XPS) are used here to compare surfaces prepared by ex situ cleaving, in situ cleaving, and ion bombardment and annealing (IBA) in ultrahigh vacuum (UHV). Surfaces prepared by in situ cleaving and IBA are well ordered and Se-terminated. Ex situ cleaved samples could be either Se-terminated or Bi-rich, are less well ordered and have adsorbed contaminants. This suggests that a chemical reaction involving atmospheric contaminants, which may preferentially adsorb at surface defects, could contribute to the nonreproducibility of the termination.

  2. RING finger E3 ligase PPP1R11 regulates TLR2 signaling and innate immunity

    Science.gov (United States)

    McKelvey, Alison C; Lear, Travis B; Dunn, Sarah R; Evankovich, John; Londino, James D; Bednash, Joseph S; Zhang, Yingze; McVerry, Bryan J; Liu, Yuan; Chen, Bill B

    2016-01-01

    Toll-like receptor 2 (TLR2) is a pattern recognition receptor that recognizes many types of PAMPs that originate from gram-positive bacteria. Here we describe a novel mechanism regulating TLR2 protein expression and subsequent cytokine release through the ubiquitination and degradation of the receptor in response to ligand stimulation. We show a new mechanism in which an uncharacterized RING finger E3 ligase, PPP1R11, directly ubiquitinates TLR2 both in vitro and in vivo, which leads to TLR2 degradation and disruption of the signaling cascade. Lentiviral gene transfer or knockdown of PPP1R11 in mouse lungs significantly affects lung inflammation and the clearance of Staphylococcus aureus. There is a negative correlation between PPP1R11 and TLR2 levels in white blood cell samples isolated from patients with Staphylococcus aureus infections. These results suggest that PPP1R11 plays an important role in regulating innate immunity and gram-positive bacterial clearance by functioning, in part, through the ubiquitination and degradation of TLR2. DOI: http://dx.doi.org/10.7554/eLife.18496.001 PMID:27805901

  3. Modulation of immune cell functions by the E3 ligase CBL-b

    Directory of Open Access Journals (Sweden)

    Christina eLutz-Nicoladoni

    2015-03-01

    Full Text Available Maintenance of immunological tolerance is a critical hallmark of the immune system. Several signaling checkpoints necessary to balance activating and inhibitory input to immune cells have been described so far, among which the E3 ligase Cbl-b appears to be a central player. Cbl-b is expressed in all leukocyte subsets and regulates several signaling pathways in T cells, NK cells, B cells and different types of myeloid cells. In most cases Cbl-b negatively regulates activation signals through antigen or pattern recognition receptors and co-stimulatory molecules. In line with this function, cblb-deficient immune cells display lower activation thresholds and cblb knockout mice spontaneously develop autoimmunity and are highly susceptible to experimental autoimmunity. Interestingly, genetic association studies link cblb-polymorphisms with autoimmunity also in humans. Vice versa, the increased activation potential of cblb-deficient cells renders them more potent to fight against malignancies or infections. Accordingly, several reports have shown that cblb knockout mice reject tumors, which mainly depends on cytotoxic T and NK cells. Thus targeting Cbl-b may be an interesting strategy to enhance anti-cancer immunity. In this review we summarize the findings on the molecular function of Cbl-b in different cell types and illustrate the potential of Cbl-b as target for immunomodulatory therapies.

  4. Mutation in SUMO E3 ligase, SIZ1, disrupts the mature female gametophyte in Arabidopsis

    KAUST Repository

    Ling, Yu

    2012-01-09

    Female gametophyte is the multicellular haploid structure that can produce embryo and endosperm after fertilization, which has become an attractive model system for investigating molecular mechanisms in nuclei migration, cell specification, cell-to-cell communication and many other processes. Previous reports found that the small ubiquitin-like modifier (SUMO) E3 ligase, SIZ1, participated in many processes depending on particular target substrates and suppression of salicylic acid (SA) accumulation. Here, we report that SIZ1 mediates the reproductive process. SIZ1 showed enhanced expression in female organs, but was not detected in the anther or pollen. A defect in the siz1-2 maternal source resulted in reduced seed-set regardless of high SA concentration within the plant. Moreover, aniline blue staining and scanning electron microscopy revealed that funicular and micropylar pollen tube guidance was arrested in siz1-2 plants. Some of the embryo sacs of ovules in siz1-2 were also disrupted quickly after stage FG7. There was no significant affects of the siz1-2 mutation on expression of genes involved in female gametophyte development- or pollen tube guidance in ovaries. Together, our results suggest that SIZ1 sustains the stability and normal function of the mature female gametophyte which is necessary for pollen tube guidance. © 2012 Ling et al.

  5. E3 ubiquitin ligases Pellinos as regulators of pattern recognition receptor signaling and immune responses.

    Science.gov (United States)

    Medvedev, Andrei E; Murphy, Michael; Zhou, Hao; Li, Xiaoxia

    2015-07-01

    Pellinos are a family of E3 ubiquitin ligases discovered for their role in catalyzing K63-linked polyubiquitination of Pelle, an interleukin-1 (IL-1) receptor-associated kinase homolog in the Drosophila Toll pathway. Subsequent studies have revealed the central and non-redundant roles of mammalian Pellino-1, Pellino-2, and Pelino-3 in signaling pathways emanating from IL-1 receptors, Toll-like receptors, NOD-like receptors, T- and B-cell receptors. While Pellinos ability to interact with many signaling intermediates suggested their scaffolding roles, recent findings in mice expressing ligase-inactive Pellinos demonstrated the importance of Pellino ubiquitin ligase activity. Cell-specific functions of Pellinos have emerged, e.g. Pellino-1 being a negative regulator in T lymphocytes and a positive regulator in myeloid cells, and details of molecular regulation of receptor signaling by various members of the Pellino family have been revealed. In this review, we summarize current information about Pellino-mediated regulation of signaling by pattern recognition receptors, T-cell and B-cell receptors and tumor necrosis factor receptors, and discuss Pellinos roles in sepsis and infectious diseases, as well as in autoimmune, inflammatory, and allergic disorders. We also provide our perspective on the potential of targeting Pellinos with peptide- or small molecule-based drug compounds as a new therapeutic approach for septic shock and autoimmune pathologies.

  6. MDM2 E3 ubiquitin ligase mediates UT-A1 urea transporter ubiquitination and degradation.

    Science.gov (United States)

    Chen, Guangping; Huang, Haidong; Fröhlich, Otto; Yang, Yuan; Klein, Janet D; Price, S Russ; Sands, Jeff M

    2008-11-01

    UT-A1 is the primary urea transporter in the apical plasma membrane responsible for urea reabsorption in the inner medullary collecting duct. Although the physiological function of UT-A1 has been well established, the molecular mechanisms that regulate its activity are less well understood. Analysis of the UT-A1 amino acid sequence revealed a potential MDM2 E3 ubiquitin ligase-binding motif in the large intracellular loop of UT-A1, suggesting that UT-A1 urea transporter protein may be regulated by the ubiquitin-proteasome pathway. Here, we report that UT-A1 is ubiquitinated and degraded by the proteasome but not the lysosome proteolytic pathway. Inhibition of proteasome activity causes UT-A1 cell surface accumulation and concomitantly increases urea transport activity. UT-A1 interacts directly with MDM2; the binding site is located in the NH2-terminal p53-binding region of MDM2. MDM2 mediates UT-A1 ubiquitination both in vivo and in vitro. Overexpression of MDM2 promotes UT-A1 degradation. The mechanism is likely to be physiologically important as UT-A1 ubiquitination was identified in kidney inner medullary tissue. The ubiquitin-proteasome degradation pathway provides an important novel mechanism for UT-A1 regulation.

  7. 某10万m3钢储罐罐体变形的修复措施%The Rectification Methodof 100,000 m3 Steel Oil Storage Tank Wall Deformation

    Institute of Scientific and Technical Information of China (English)

    应付钊; 丁伟

    2013-01-01

    The differential settlement of tank foundation or low quality tank erection will cause wall deformation of steel oil storage tank, the low quality tank erection will have greater effect on the lifting of floating roof than the differential settlement of tank foundation. In the paper, the reason causing wall deformation and rectification method were introduced, some questions that need considered during steel oil storage tank erection and high pressure filling method of cavity which is between tank bottom plate and tank foundation were pointed. Finally, some referable conclusions are obtained.%地基不均匀沉降和安装不当均会引起钢储罐罐体变形,安装不当引起的罐体变形比罐基础不均匀沉降造成的罐体变形对浮船升降影响可能更大.通过对某10万m3钢储罐产生罐壁变形的原因分析和纠偏措施介绍,提出了一些大型储罐在安装过程中应注意的问题,给出了罐体顶升后间隙采用高压吹填的处理措施,对同类工程设计有一定的借鉴意义.

  8. 基于nRF24L01和Cortex-M3的无线测控系统%Wireless measurement and control system based on nRF24L01 and Cortex-M3

    Institute of Scientific and Technical Information of China (English)

    袁正道; 董丽莎; 王家斌

    2012-01-01

      在井下抢险或其它搜救现场,通常都需要一种远程遥测系统来取代人工进入一些危险场所。文中提出了一种基于nRF24L01和Cortex的无线测控系统的开发方法,简要讨论了其结构和开发原理,并详细介绍了该测控系统的硬件构造和软件开发流程%  On the downhole resuce and other rescue spot, a remote-measuring system is used to enter into the dangerous areas instead of persons. A design scheme of wireless measurement and control system based on RF24L01 and Cortex-M3 is given in the paper. In the paper a brief discussion on the structure and development principles of the system is made and the hardware construction and software development process are introduced in detail.

  9. GABA(A) receptor M2-M3 loop secondary structure and changes in accessibility during channel gating.

    Science.gov (United States)

    Bera, Amal K; Chatav, Maya; Akabas, Myles H

    2002-11-08

    The gamma-aminobutyric acid type A (GABA(A)) receptor M2-M3 loop structure and its role in gating were investigated using the substituted cysteine accessibility method. Residues from alpha(1)Arg-273 to alpha(1)Ile-289 were mutated to cysteine, one at a time. MTSET(+) or MTSES(-) reacted with all mutants from alpha(1)R273C to alpha(1)Y281C, except alpha(1)P277C, in the absence and presence of GABA. The MTSET(+) closed-state reaction rate was >1000 liters/mol-s at alpha(1)N274C, alpha(1)S275C, alpha(1)K278C, and alpha(1)Y281C and was <300 liters/mol-s at alpha(1)R273C, alpha(1)L276C, alpha(1)V279C, alpha(1)A280C, and alpha(1)A284C. These two groups of residues lie on opposite sides of an alpha-helix. The fast reacting group lies on a continuation of the M2 segment channel-lining helix face. This suggests that the M2 segment alpha-helix extends about two helical turns beyond alpha(1)N274 (20'), aligned with the extracellular ring of charge. At alpha(1)S275C, alpha(1)V279C, alpha(1)A280C, and alpha(1)A284C the reaction rate was faster in the presence of GABA. The reagents had no functional effect on the mutants from alpha(1)A282C to alpha(1)I289C, except alpha(1)A284C. Access may be sterically hindered possibly by close interaction with the extracellular domain. We suggest that the M2 segment alpha-helix extends beyond the predicted extracellular end of the M2 segment and that gating induces a conformational change in and/or around the N-terminal half of the M2-M3 loop. Implications for coupling ligand-evoked conformational changes in the extracellular domain to channel gating in the membrane-spanning domain are discussed.

  10. Sustainable Transition

    DEFF Research Database (Denmark)

    2014-01-01

    What. The chapter addresses designing for sustainability as interventions in socio-technical systems and social practices of users and communities. It calls for reflexive design practices challenging dominant regimes and shaping alternative design spaces. The specific case is the reconfiguration...... of agendas/vision, technologies, actors and institutions in the emergent design of an urban mobility system based on an electric car sharing system. Why. Designing for sustainability is a fundamental challenge for future design practices; designers have to obtain an ability to contribute to sustainable...... transition processes. Where. Addresses design processes aimed at sustainable transition enacted in complex social settings, socio-technical systems involving many different actors and agendas. How. The chapter outlines a conceptual and analytic framework for a reflexive design practice for sustainability...

  11. Transition Operators

    CERN Document Server

    Alcock-Zeilinger, Judith

    2016-01-01

    In this paper, we give a generic algorithm of the transition operators between Hermitian Young projection operators corresponding to equivalent irreducible representations of SU(N), using the compact expressions of Hermitian Young projection operators derived in a companion paper. We show that the Hermitian Young projection operators together with their transition operators constitute a fully orthogonal basis for the algebra of invariants of $V^{\\otimes m}$ that exhibits a systematically simplified multiplication table. We discuss the full algebra of invariants over $V^{\\otimes 3}$ and $V^{\\otimes 4}$ as explicit examples. In our presentation we make use of various standard concepts such as Young projection operators, Clebsch-Gordan operators, and invariants (in birdtrack notation). We tie these perspectives together and use them to shed light on each other.

  12. Molecular organization of the complex between the muscarinic M3 receptor and the regulator of G protein signaling, Gbeta(5)-RGS7.

    Science.gov (United States)

    Sandiford, Simone L; Wang, Qiang; Levay, Konstantin; Buchwald, Peter; Slepak, Vladlen Z

    2010-06-22

    The complex of the regulator of G protein signaling (RGS), Gbeta(5)-RGS7, can inhibit signal transduction via the M3 muscarinic acetylcholine receptor (M3R). RGS7 consists of three distinct structural entities: the DEP domain and its extension DHEX, the Ggamma-like (GGL) domain, which is permanently bound to Gbeta subunit Gbeta(5), and the RGS domain responsible for the interaction with Galpha subunits. Inhibition of the M3R by Gbeta(5)-RGS7 is independent of the RGS domain but requires binding of the DEP domain to the third intracellular loop of the receptor. Recent studies identified the dynamic intramolecular interaction between the Gbeta(5) and DEP domains, which suggested that the Gbeta(5)-RGS7 dimer could alternate between the "open" and "closed" conformations. Here, we identified point mutations that weaken DEP-Gbeta(5) binding, presumably stabilizing the open state, and tested their effects on the interaction of Gbeta(5)-RGS7 with the M3R. We found that these mutations facilitated binding of Gbeta(5)-RGS7 to the recombinant third intracellular loop of the M3R but did not enhance its ability to inhibit M3R-mediated Ca(2+) mobilization. This led us to the idea that the M3R can effectively induce the Gbeta(5)-RGS7 dimer to open; such a mechanism would require a region of the receptor distinct from the third loop. Indeed, we found that the C-terminus of M3R interacts with Gbeta(5)-RGS7. Truncation of the C-terminus rendered the M3R insensitive to inhibition by wild-type Gbeta(5)-RGS7; however, the open mutant of Gbeta(5)-RGS7 was able to inhibit signaling by the truncated M3R. The GST fusion of the M3R C-tail could not bind to wild-type Gbeta(5)-RGS7 but could associate with its open mutant as well as with the separated recombinant DEP domain or Gbeta(5). Taken together, our data are consistent with the following model: interaction of the M3R with Gbeta(5)-RGS7 causes the DEP domain and Gbeta(5) to dissociate from each other and bind to the C-tail, and the DEP

  13. 基于Cortex-M3的电池内阻检测系统设计与实现%Design and implementation of battery internal resistance detection system based on Cortex-M3

    Institute of Scientific and Technical Information of China (English)

    张乐芳; 荆炳礼; 任志宏

    2015-01-01

    以电池为能源的各类电气设备,在工业生产、交通、军事、通信等领域广泛应用,电池性能对电子、电气设备的正常运行具有极其重要的作用。电池在使用过程中,其性能和容量会随充放电次数的增加而下降,所以,定期维护及检验电池性能,是保证电器设备可靠工作的重要内容。电池内阻是检验电池性能和容量的重要参数,通过内阻检测评估电池性能和容量参数,也是科学研究和工业应用的基本原理。电池内阻测量的常用方法一般采用电位差原理。但是,该测量方法对于大型设备的高容量电池存在测量误差大、发热、易损电池等弊端。本文采用基于Cortex-M3核32位微处理微计算机控制和电位差原理的智能内阻测量系统,实现了大容量电池的精确、快速、安全测量和高度智能化的故障诊断功能,具有重要的科学研究意义及实用价值。%All kinds of electrical equipment which use battery as energy sources, are widely used in the industrial production, transportation, military, communications and other fields. And the battery performance is of great importance to normal operation of electrical and electronic equipment. Because the performance and capacity of battery decreases with the increasing number of charge cycles and discharge, the regular maintenance and test of battery performance is the important to guarantee working reliability of electrical equipment. Evaluation battery performance and capacity by testing battery internal resistance, which is the vital parameter for battery performance and capacity, is the basic principles of scientific research and industrial application. Potential difference principle is common method to measure battery internal resistance, but in which the disadvantage is that causing large measurement error, producing heat and damaging battery easily for the large capacity battery of large equipment. In this

  14. Underground low flux neutron background measurements in LSM using a large volume (1m3) spherical proportional counter

    Science.gov (United States)

    Savvidis, I.; Giomataris, I.; Bougamont, E.; Irastorza, I.; Aune, S.; Chapelier, M.; Charvin, P. H.; Colas, P.; Derre, J.; Ferrer, E.; Gerbier, G.; Gros, M.; Mangier, P.; Navick, X. F.; Salin, P.; Vergados, J. D.; Zampalo, M.

    2010-01-01

    A large volume (1m3) spherical proportional counter has been developed at CEA/Saclay, for low flux neutron measurements. The high voltage is applied to a small sphere 15mm in diameter, located in the center of the counter and the wall of the counter is grounded. Neutrons can be measured successfully, with high sensitivity, using 3He gas in the detector. The proton and tritium energy deposition in the drift gaseous volume, from the reaction 3He(n,p)3H, can provide the neutron spectra from thermal neutrons up to several MeV. The detector has been installed in the underground laboratory in Modane (LSM) to measure the neutron background. The sphere has been has been filled with gas mixture of Ar + 2% CH4 +3gr He-3, at 275 mbar. The thermal neutron peak is well separated from the cosmic ray and gamma background, permitting of neutron flux calculation. Other potential applications requiring large volume of about 10 m in radius are described in detail in reference

  15. Tests of shielding effectiveness of Kevlar and Nextel onboard the International Space Station and the Foton-M3 capsule.

    Science.gov (United States)

    Pugliese, M; Bengin, V; Casolino, M; Roca, V; Zanini, A; Durante, M

    2010-08-01

    Radiation assessment and protection in space is the first step in planning future missions to the Moon and Mars, where mission and number of space travelers will increase and the protection of the geomagnetic shielding against the cosmic radiation will be absent. In this framework, the shielding effectiveness of two flexible materials, Kevlar and Nextel, were tested, which are largely used in the construction of spacecrafts. Accelerator-based tests clearly demonstrated that Kevlar is an excellent shield for heavy ions, close to polyethylene, whereas Nextel shows poor shielding characteristics. Measurements on flight performed onboard of the International Space Station and of the Foton-M3 capsule have been carried out with special attention to the neutron component; shielded and unshielded detectors (thermoluminescence dosemeters, bubble detectors) were exposed to a real radiation environment to test the shielding properties of the materials under study. The results indicate no significant effects of shielding, suggesting that thin shields in low-Earth Orbit have little effect on absorbed dose.

  16. [Morphofunctional state of hepatocytes nuclear apparatus in Mongolian herbils after the flight on space apparatus Foton-M3].

    Science.gov (United States)

    Atiakshin, D A; Il'in, E A; Pashkov, A N

    2010-01-01

    Morphofunctional state of hepatocytes nuclear apparatus was analyzed in the liver of Mongolian gerbils Meriones unguiculatus returned from 12-d space flight of Foton-M3 (SF) and their vivarium and ground synchronous controls. Volume, ploidy and number of hepatocyte nuclei, nucleolus dimensions and number as well as contacts with karyolemma were determined in the central, intermediate and peripheral areas of the liver classical lobe. Also, total number of mitoses and amitoses was determined in the liver parenchyma. The vivarium control animals displayed specifics of the nucleus apparatus structure that depended on intralobe topography. Based on the selected criteria, high functional activity was characteristic of cells in the intermediate area. According to the criteria, nuclear apparatus in the synchronous control tended to down the functional activity The adaptive adjustment of nuclei in SF seemed to have been initiated by changes in the hepatic blood flow: volumes of hepatocyte nuclei and nucleoli increased as did the number of nuclei in cell, whereas ploidy made a decrease, especially in the intermediate area. Under the SF conditions, particularly important compensatory mechanism for the liver function was intensification of amitosis and consequent increase of the population of dinuclear hepatocytes.

  17. The WA105-3x1x1 m3 dual phase LAr-TPC demonstrator

    CERN Document Server

    Murphy, Sebastien

    2016-11-15

    The dual phase Liquid Argon Time Projection Chamber (LAr TPC) is the state-of-art technology for neutrino detection thanks to its superb 3D tracking and calorimetry performance. Its main feature is the charge amplification in gas argon which provides excellent signal-to-noise ratio. Electrons produced in the liquid argon are extracted in the gas phase. Here, a readout plane based on Large Electron Multiplier detectors provides amplification of the charges before its collection onto an anode with strip readout. The charge amplification enables constructing fully homoge- nous giant LAr-TPCs with tuneable gain, excellent charge imaging performance and increased sensitivity to low energy events. Following a staged approach the WA105 collaboration is con- structing a dual phase LAr-TPC with an active volume of 3x1x1m3 that will soon be tested with cosmic rays. Its construction and operation aims to test scalable solutions for the crucial aspects of this technology: ultra high argon purity in non-evacuable tank, la...

  18. Full Stokes observations in the He I 1083 nm spectral region covering an M3.2 flare

    CERN Document Server

    Kuckein, C; Sainz, R Manso; Ramos, A Asensio

    2015-01-01

    We present an exceptional data set acquired with the Vacuum Tower Telescope (Tenerife, Spain) covering the pre-flare, flare, and post-flare stages of an M3.2 flare. The full Stokes spectropolarimetric observations were recorded with the Tenerife Infrared Polarimeter in the He I 1083.0 nm spectral region. The object under study was active region NOAA 11748 on 2013 May 17. During the flare the chomospheric He I 1083.0 nm intensity goes strongly into emission. However, the nearby photospheric Si I 1082.7 nm spectral line profile only gets shallower and stays in absorption. Linear polarization (Stokes Q and U) is detected in all lines of the He I triplet during the flare. Moreover, the circular polarization (Stokes V) is dominant during the flare, being the blue component of the He I triplet much stronger than the red component, and both are stronger than the Si I Stokes V profile. The Si I inversions reveal enormous changes of the photospheric magnetic field during the flare. Before the flare magnetic field conc...

  19. Reactor performance of a 750 m(3) anaerobic digestion plant: varied substrate input conditions impacting methanogenic community.

    Science.gov (United States)

    Wagner, Andreas Otto; Malin, Cornelia; Lins, Philipp; Gstraunthaler, Gudrun; Illmer, Paul

    2014-10-01

    A 750 m(3) anaerobic digester was studied over a half year period including a shift from good reactor performance to a reduced one. Various abiotic parameters like volatile fatty acids (VFA) (formic-, acetic-, propionic-, (iso-)butyric-, (iso-)valeric-, lactic acid), total C, total N, NH4 -N, and total proteins, as well as the organic matter content and dry mass were determined. In addition several process parameters such as temperature, pH, retention time and input of substrate and the concentrations of CH4, H2, CO2 and H2S within the reactor were monitored continuously. The present study aimed at the investigation of the abundance of acetogens and total cell numbers and the microbial methanogenic community as derived from PCR-dHPLC analysis in order to put it into context with the determined abiotic parameters. An influence of substrate quantity on the efficiency of the anaerobic digestion process was found as well as a shift from a hydrogenotrophic in times of good reactor performance towards an acetoclastic dominated methanogenic community in times of reduced reactor performance. After the change in substrate conditions it took the methano-archaeal community about 5-6 weeks to be affected but then changes occurred quickly.

  20. SUMO E3 Ligase AtMMS21 Regulates Drought Tolerance in Arabidopsis thaliana

    Institute of Scientific and Technical Information of China (English)

    Shengchun Zhang; Yanli Qi; Ming Liu; ChengweiYang

    2013-01-01

    Post-translational modifications of proteins by small ubiquitin-like modifiers (SUMOs) play crucial roles in plant growth and development,and in stress responses.The MMS21 is a newly-identified Arabidopsis thaliana L.SUMO E3 ligase gene aside from the SIZ1,and its function requires further elucidation.Here,we show that MMS21 deficient plants display improved drought tolerance,and constitutive expression of MMS21 reduces drought tolerance.The expression of MMS21 was reduced by abscisic acid (ABA),polyethylene glycol (PEG) or drought stress.Under drought conditions,mms21 mutants showed the highest survival rate and the slowest water loss,and accumulated a higher level of free proline compared to wild-type (WT) and MMS21 over-expression plants.Stomatal aperture,seed germination and cotyledon greening analysis indicated that mms21 was hypersensitive to ABA.Molecular genetic analysis revealed that MMS21 deficiency led to elevated expression of a series of ABA-mediated stress-responsive genes,including COR15A,RD22,and P5CS1 The ABA and drought-induced stress-responsive genes,including RAB18,RD29A and RD29B,were inhibited by constitutive expression of MMS21.Moreover,ABA-induced accumulation of SUMO-protein conjugates was blocked in the mms21 mutant.We thus conclude that MMS21 plays a role in the drought stress response,likely through regulation of gene expression in an ABA-dependent pathway.

  1. CHK2 stability is regulated by the E3 ubiquitin ligase SIAH2.

    Science.gov (United States)

    García-Limones, C; Lara-Chica, M; Jiménez-Jiménez, C; Pérez, M; Moreno, P; Muñoz, E; Calzado, M A

    2016-08-18

    The serine threonine checkpoint kinase 2 (CHK2) is a critical protein involved in the DNA damage-response pathway, which is activated by phosphorylation inducing cellular response such as DNA repair, cell-cycle regulation or apoptosis. Although CHK2 activation mechanisms have been amply described, very little is known about degradation control processes. In the present study, we identify the ubiquitin E3 ligase SIAH2 as an interaction partner of CHK2, which mediates its ubiquitination and proteasomal degradation. CHK2 degradation is independent of both its activation and its kinase activity, but also of the phosphorylation in S456. We show that SIAH2-deficient cells present CHK2 accumulation together with lower ubiquitination levels. Accordingly, SIAH2 depletion by siRNA increases CHK2 levels. In response to DNA damage induced by etoposide, interaction between both proteins is disrupted, thus avoiding CHK2 degradation and promoting its stabilization. We also found that CHK2 phosphorylates SIAH2 at three residues (Thr26, Ser28 and Thr119), modifying its ability to regulate certain substrates. Cellular arrest in the G2/M phase induced by DNA damage is reverted by SIAH2 expression through the control of CHK2 levels. We observed that hypoxia decreases CHK2 levels in parallel to SIAH2 induction. Similarly, we provide evidence suggesting that resistance to apoptosis induced by genotoxic agents in cells subjected to hypoxia could be partly explained by the mutual regulation between both proteins. These results indicate that SIAH2 regulates CHK2 basal turnover, with important consequences on cell-cycle control and on the ability of hypoxia to alter the DNA damage-response pathway in cancer cells.

  2. The role of the e3 ligase cbl-B in murine dendritic cells.

    Directory of Open Access Journals (Sweden)

    Stephanie Wallner

    Full Text Available Dendritic cells (DCs are potent antigen-presenting cells with a promising potential in cancer immunotherapy. Cbl proteins are E3 ubiquitin ligases and have been implicated in regulating the functional activity of various immune cells. As an example, c-Cbl negatively affects DC activation. We here describe that another member of the Cbl-protein family (i.e. Cbl-b is highly expressed in murine bone-marrow-derived DCs (BMDCs. Differentiation of cblb-/- bone marrow mononuclear cells into classical BMDCs is unaltered, except enhanced induction of DEC-205 (CD205 expression. When tested in mixed-lymphocyte reaction (MLR, cblb-/- BMDCs exhibit increased allo-stimulatory capacity in vitro. BMDCs were next in vitro stimulated by various toll like receptor (TLR-agonists (LPS, Poly(I:C, CpG and exposed to FITC-labeled dextran. Upon TLR-stimulation, cblb-/- BMDCs produce higher levels of proinflammatory cytokines (IL-1α, IL-6 and TNF-α and exhibit a slightly higher level of FITC-dextran uptake. To further characterize the functional significance of cblb-/- BMDCs we tested them in antigen-specific T cell responses against ovalbumin (OVA protein and peptides, activating either CD8(+ OT-I or CD4(+ OT-II transgenic T cells. However, cblb-/- BMDCs are equally effective in inducing antigen-specific T cell responses when compared to wildtype BMDCs both in vitro and in vivo. The migratory capacity into lymph nodes during inflammation was similarly not affected by the absence of Cbl-b. In line with these observations, cblb-/- peptide-pulsed BMDCs are equally effective vaccines against OVA-expressing B16 tumors in vivo when compared to wildtype BMDCs. We conclude that in contrast to c-Cbl, Cbl-b plays only a limited role in the induction of Ag-specific T cell responses by murine BMDCs in vitro and in vivo.

  3. Aβ-Induced Synaptic Alterations Require the E3 Ubiquitin Ligase Nedd4-1.

    Science.gov (United States)

    Rodrigues, Elizabeth M; Scudder, Samantha L; Goo, Marisa S; Patrick, Gentry N

    2016-02-03

    Alzheimer's disease (AD) is a neurodegenerative disease in which patients experience progressive cognitive decline. A wealth of evidence suggests that this cognitive impairment results from synaptic dysfunction in affected brain regions caused by cleavage of amyloid precursor protein into the pathogenic peptide amyloid-β (Aβ). Specifically, it has been shown that Aβ decreases surface AMPARs, dendritic spine density, and synaptic strength, and also alters synaptic plasticity. The precise molecular mechanisms by which this occurs remain unclear. Here we demonstrate a role for ubiquitination in Aβ-induced synaptic dysfunction in cultured rat neurons. We find that Aβ promotes the ubiquitination of AMPARs, as well as the redistribution and recruitment of Nedd4-1, a HECT E3 ubiquitin ligase we previously demonstrated to target AMPARs for ubiquitination and degradation. Strikingly, we show that Nedd4-1 is required for Aβ-induced reductions in surface AMPARs, synaptic strength, and dendritic spine density. Our findings, therefore, indicate an important role for Nedd4-1 and ubiquitin in the synaptic alterations induced by Aβ. Synaptic changes in Alzheimer's disease (AD) include surface AMPAR loss, which can weaken synapses. In a cell culture model of AD, we found that AMPAR loss correlates with increased AMPAR ubiquitination. In addition, the ubiquitin ligase Nedd4-1, known to ubiquitinate AMPARs, is recruited to synapses in response to Aβ. Strikingly, reducing Nedd4-1 levels in this model prevented surface AMPAR loss and synaptic weakening. These findings suggest that, in AD, Nedd4-1 may ubiquitinate AMPARs to promote their internalization and weaken synaptic strength, similar to what occurs in Nedd4-1's established role in homeostatic synaptic scaling. This is the first demonstration of Aβ-mediated control of a ubiquitin ligase to regulate surface AMPAR expression. Copyright © 2016 the authors 0270-6474/16/361590-06$15.00/0.

  4. Iduna is a poly(ADP-ribose) (PAR)-dependent E3 ubiquitin ligase that regulates DNA damage

    Science.gov (United States)

    Kang, Ho Chul; Lee, Yun-Il; Shin, Joo-Ho; Andrabi, Shaida A.; Chi, Zhikai; Gagné, Jean-Philippe; Lee, Yunjong; Ko, Han Seok; Lee, Byoung Dae; Poirier, Guy G.; Dawson, Valina L.; Dawson, Ted M.

    2011-01-01

    Ubiquitin mediated protein degradation is crucial for regulation of cell signaling and protein quality control. Poly(ADP-ribose) (PAR) is a cell-signaling molecule that mediates changes in protein function through binding at PAR binding sites. Here we characterize the PAR binding protein, Iduna, and show that it is a PAR-dependent ubiquitin E3 ligase. Iduna’s E3 ligase activity requires PAR binding because point mutations at Y156A and R157A eliminate Iduna’s PAR binding and Iduna’s E3 ligase activity. Iduna’s E3 ligase activity also requires an intact really interesting new gene (RING) domain because Iduna possessing point mutations at either H54A or C60A is devoid of ubiquitination activity. Tandem affinity purification reveals that Iduna binds to a number of proteins that are either PARsylated or bind PAR including PAR polymerase-1, 2 (PARP1, 2), nucleolin, DNA ligase III, KU70, KU86, XRCC1, and histones. PAR binding to Iduna activates its E3 ligase function, and PAR binding is required for Iduna ubiquitination of PARP1, XRCC1, DNA ligase III, and KU70. Iduna’s PAR-dependent ubiquitination of PARP1 targets it for proteasomal degradation. Via PAR binding and ubiquitin E3 ligase activity, Iduna protects against cell death induced by the DNA damaging agent N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and rescues cells from G1 arrest and promotes cell survival after γ-irradiation. Moreover, Iduna facilitates DNA repair by reducing apurinic/apyrimidinic (AP) sites after MNNG exposure and facilitates DNA repair following γ-irradiation as assessed by the comet assay. These results define Iduna as a PAR-dependent E3 ligase that regulates cell survival and DNA repair. PMID:21825151

  5. Association of NR2E3 but not NRL mutations with retinitis pigmentosa in the Chinese population.

    Science.gov (United States)

    Yang, Yaping; Zhang, Xin; Chen, Li Jia; Chiang, Sylvia W Y; Tam, Pancy O S; Lai, Timothy Y Y; Chan, Carmen K M; Wang, Ningli; Lam, Dennis S C; Pang, Chi Pui

    2010-04-01

    Purpose. Mutations in the NR2E3 and NRL genes have been implicated in both autosomal dominant and autosomal recessive retinitis pigmentosa (RP). In this study, the mutation profiles of these two genes were investigated in Chinese RP patients. Methods. In 172 RP patients and 360 normal control subjects (180 from Hong Kong and 180 from Beijing), the coding exons and the exon-intron boundaries of NR2E3 and NRL were screened by direct DNA sequencing after PCR. Association analysis was performed for common single-nucleotide polymorphisms (SNPs), whereas in silico programs were used for analysis of rare missense variants. Results. In NR2E3, 14 novel sequence changes have been identified. Two missense variants, p.G56R and p.V118M, were exclusively found in RP patients with frequencies at 1.2% (2/172) and 1.7% (3/172), respectively. All five patients were found to be heterozygous for these two mutations. Computational analysis suggested functional defects on the NR2E3 protein, indicating disease-causing roles. The p.E121K variant of NR2E3, which reportedly caused enhanced S-cone syndrome (ESCS) in Caucasians, was found concurrently in RP patients (13.4%) and control subjects from Hong Kong (10.5%) and Beijing (12.8%). In NRL, six novel sequence changes were identified, none of them associated with RP. Conclusions. In this study, NR2E3 mutations (p.G56R, p.V118M) were found to be responsible for approximately 2.9% of overall RP in Chinese patients, comparable to the contributions of RHO and RP1 mutations. The p.E121K in NR2E3 is a common SNP in the Chinese, suggesting another genetic or environmental factor is involved in its causative role in ESCS in Caucasians.

  6. Changing M3G/M6G ratios and pharmacodynamics in a cancer patient during long-term morphine treatment

    DEFF Research Database (Denmark)

    Andersen, Gertrud; Christrup, Lona Louring; Sjøgren, Per;

    2002-01-01

    A cancer patient receiving long-term oral sustained-release morphine treatment and periodically presenting with unusually high plasma M3G/M6G ratios is described. We found the patient's formation of M6G more unstable and perhaps delayed compared to the formation of M3G. There is no apparent...... explanation for this phenomenon and the high M3G/M6G ratios had no implications for the patient's pain experience or side effects from the morphine treatment....

  7. Progress in TMT M3 system%TMT 望远镜三镜系统的研究进展

    Institute of Scientific and Technical Information of China (English)

    王富国; 杨飞; 赵宏超; 苏燕芹; 陈宝刚

    2013-01-01

    介绍30 m望远镜(TMT)的相关背景以及我国在TMT项目中承担的任务。从TMT三镜系统的总体要求出发,论述了三镜系统的两个主要部分(M3CA和M3PA)的具体要求、技术难点以及初步方案。针对M3CA,介绍了底支撑方案和侧支撑方案,采用Kinematic的底支撑方案时其面形精度RMS可以达到109.7 nm,SlopeRMS为0.95μrad,采用Kinematic的侧支撑方案时其面形精度RMS<15 nm,一阶谐振频率等于17.7 Hz,均达到了设计要求。针对M3PA,介绍了Tilt轴系和Rotator轴系的方案。最后,简要介绍了三镜控制系统(M3CS)的要求和目标。%The background of Thirty Meter Telescope(TMT) and its mission that we should take in hand are introdced.The detailed specifications and the preliminary scheme for the M 3CA and M3PA in the 3 mirror (M3) system are presented according to the general specification .Then, the two parts,axial support and later-al support of M3CA, are designed in detail.Due to the kinematic concept design used in both of axial support and lateral support, the mirror surface error can be reduced in a acceptable level .When the kinematic axial support scheme is taken, its surface accuracy RMS is 109.7 nm and Slope RMS is 0.95μrad, while the kine-matic lateral support scheme is taken, its surface accuracy RMS is 15 nm,and the first natural frequency can reach to 17.7 Hz.The design proposal for M3PA is discussed and the control system for M3 system(M3CS) is introduced briefly.

  8. 基于MDK RTX的Cortex-M3多任务应用设计%Multi-task Application Design Based on MDK RTX

    Institute of Scientific and Technical Information of China (English)

    方安平; 武永谊

    2008-01-01

    MDK RL-RTX是ARM公司推出的最新实时多任务内核,Cortex-M3是ARM公司最新发布的嵌入式处理器.将RL-RTX实时多任务内核应用到Cortex-M3处理器上,可大大提高代码密度,减少系统内存,提升系统性能.本文介绍了RL-RTX在Cortex-M3上的移植以及多任务应用设计方法.

  9. Characterization of the Arabidopsis thaliana E3 ubiquitin-ligase AtSINAL7 and identification of the ubiquitination sites.

    Directory of Open Access Journals (Sweden)

    Diego A Peralta

    Full Text Available Protein ubiquitination leading to degradation by the proteasome is an important mechanism in regulating key cellular functions. Protein ubiquitination is carried out by a three step process involving ubiquitin (Ub activation by a E1 enzyme, the transfer of Ub to a protein E2, finally an ubiquitin ligase E3 catalyzes the transfer of the Ub peptide to an acceptor protein. The E3 component is responsible for the specific recognition of the target, making the unveiling of E3 components essential to understand the mechanisms regulating fundamental cell processes through the protein degradation pathways. The Arabidopsis thaliana seven in absentia-like 7 (AtSINAL7 gene encodes for a protein with characteristics from a C3HC4-type E3 ubiquitin ligase. We demonstrate here that AtSINAL7 protein is indeed an E3 protein ligase based on the self-ubiquitination in vitro assay. This activity is dependent of the presence of a Lys residue in position 124. We also found that higher AtSINAL7 transcript levels are present in tissues undergoing active cell division during floral development. An interesting observation is the circadian expression pattern of AtSINAL7 mRNA in floral buds. Furthermore, UV-B irradiation induces the expression of this transcript indicating that AtSINAL7 may be involved in a wide range of different cell processes.

  10. E3B1/ABI-1 Isoforms Are Down-Regulated in Cancers of Human Gastrointestinal Tract

    Directory of Open Access Journals (Sweden)

    Rafia A. Baba

    2012-01-01

    Full Text Available The expression of E3B1/ABI-1 protein and its role in cancer progression and prognosis are largely unknown in the majority of solid tumors. In this study, we examined the expression pattern of E3B1/ABI-1 protein in histologically confirmed cases of esophageal (squamous cell carcinoma and adenocarcinoma, gastro-esophageal junction, colorectal cancers and corresponding normal tissues freshly resected from a cohort of 135 patients, by Western Blotting and Immunofluorescence Staining. The protein is present in its phosphorylated form in cells and tissues. Depending on the extent of phosphorylation it is either present in hyper-phosphorylated (M. Wt. 72 kDa form or in hypo-phosphorylated form (M. Wt. 68 kDa and 65 kDa. A thorough analysis revealed that expression of E3B1/ABI-1 protein is significantly decreased in esophageal, gastro-esophageal junction and colorectal carcinomas irrespective of age, gender, dietary and smoking habits of the patients. The decrease in expression of E3B1/ABI-1 was consistently observed for all the three isoforms. However, the decrease in the expression of isoforms varied with different forms of cancers. Down-regulation of E3B1/ABI-1 expression in human carcinomas may play a critical role in tumor progression and in determining disease prognosis.

  11. Conformational Transitions

    Science.gov (United States)

    Czerminski, Ryszard; Roitberg, Adrian; Choi, Chyung; Ulitsky, Alexander; Elber, Ron

    1991-10-01

    Two computational approaches to study plausible conformations of biological molecules and the transitions between them are presented and discussed. The first approach is a new search algorithm which enhances the sampling of alternative conformers using a mean field approximation. It is argued and demonstrated that the mean field approximation has a small effect on the location of the minima. The method is a combination of the LES protocol (Locally Enhanced Sampling) and simulated annealing. The LES method was used in the past to study the diffusion pathways of ligands from buried active sites in myoglobin and leghemoglobin to the exterior of the protein. The present formulation of LES and its implementation in a Molecular Dynamics program is described. An application for side chain placement in a tetrapeptide is presented. The computational effort associated with conformational searches using LES grows only linearly with the number of degrees of freedom, whereas in the exact case the computational effort grows exponentially. Such saving is of course associated with a mean field approximation. The second branch of studies pertains to the calculation of reaction paths in large and flexible biological systems. An extensive mapping of minima and barriers for two different tetrapeptides is calculated from the known minima and barriers of alanine tetrapeptide which we calculated recently.1 The tetrapeptides are useful models for the formation of secondary structure elements since they are the shortest possible polymers of this type which can still form a complete helical turn. The tetrapeptides are isobutyryl-val(χ1=60)-ala-ala and isobutyryl-val(χ1=-60)-ala-ala. Properties of the hundreds of minima and of the hundreds intervening barriers are discussed. Estimates for thermal transition times between the many conformers (and times to explore the complete phase space) are calculated and compared. It is suggested that the most significant effect of the side chain size is

  12. Rapid transitions

    Energy Technology Data Exchange (ETDEWEB)

    Hamrin, J.G.

    1980-01-01

    Solar energy programs are entering a critical transitional period as we move from the initial marketing of solar technologies into a phase of widespread commercialization. We face the dual challenge of trying to get enough solar systems in place fast enough to prove solar is a viable alternative, while trying to ensure the systems are designed and installed properly, proving the energy savings as promised. This is a period of both great opportunity and high risk as the field becomes crowded with new solar cheerleaders and supporters but seldom enough competent players. The status of existing and proposed programs for the accelerated commercialization of solar energy in California is described.

  13. Transit space

    DEFF Research Database (Denmark)

    Raahauge, Kirsten Marie

    2008-01-01

    This article deals with representations of one specific city, Århus, Denmark, especially its central district. The analysis is based on anthropological fieldwork conducted in Skåde Bakker and Fedet, two well-off neighborhoods. The overall purpose of the project is to study perceptions of space...... and the interaction of cultural, social, and spatial organizations, as seen from the point of view of people living in Skåde Bakker and Fedet. The focus is on the city dwellers’ representations of the central district of Århus with specific reference to the concept of transit space. When applied to various Århusian...

  14. Using Predefined M3(μ3-O) Clusters as Building Blocks for an Isostructural Series of Metal-Organic Frameworks.

    Science.gov (United States)

    Peng, Li; Asgari, Mehrdad; Mieville, Pascal; Schouwink, Pascal; Bulut, Safak; Sun, Daniel T; Zhou, Zhongrui; Pattison, Philip; van Beek, Wouter; Queen, Wendy L

    2017-07-19

    Metal-organic frameworks (MOFs) have attracted much attention in the past decade owing to their unprecedented internal surface areas, tunable topologies, designable surfaces, and various potential applications. One bottleneck in the field regarding MOF synthesis is controlling the metal-containing secondary building unit (SBU) incorporated into the structure. In this work we report the synthesis and characterization of five trimeric [M3(μ3-O)(CH3CO2)6](x) clusters (where M = Fe(3+), Cr(3+), Fe(3+)/Cr(3+), Fe(3+)/Co(2+), or Fe(3+)/Ni(2+) and x = +1 or 0). The monocarboxylate capping ligand, acetate in this case, readily undergoes exchange with several difunctional counterparts, including 1,4-benzenedicarboxylic acid (H2-BDC) and biphenyl-4,4'-dicarboxylic acid (H2-BPDC), for the formation of an isostructural series of MOFs, several of which are newly reported (for M = Fe(3+)/Cr(3+), Fe(3+)/Co(2+), and Fe(3+)/Ni(2+)) and show excellent CO2 adsorption properties. In this report, a host of techniques including NMR, ICP, and ESI-MS are used to probe the ligand exchange process and composition of the SBUs, and XAS is used to monitor the Fe(3+) and Cr(3+) environment throughout the reactions, giving strong evidence that the clusters stay intact throughout the MOF synthesis. This work reveals that predefined SBUs is an effective means to create metal-substituted analogues of known frameworks. Further, CO adsorption and in situ IR are used to probe accessibility of the metals after solvent removal. We show for the first time that the incorporation of the neutral clusters, containing weaker Lewis acids like Ni(2+) and Co(2+), can promote the formation of open metal sites in the MOF frameworks, structural features known to enhance the binding energy of small guest molecules like CO2.

  15. A preliminary investigating the geomorphological characteristics of surrounding Chang'E-3 landing site

    Science.gov (United States)

    Li, C.; Mu, L.; Zuo, W.; Li, H.; Feng, J.

    2015-12-01

    On 2013 December 14, at 13:11:13(UTC), China's first lunar probe to make a soft landing, Chang'E-3(CE-3), touched down on the east edge of Mare Imbrium beside a crater with a diameter of 430m in the east part of Sinus Iridum. To better understand the environment of this region, We utilizes the available lunar topography, image and geology data with high resolution(in meters), as well as image data captured by the landing camera and topography camera on CE-3(in centimeters) to analyze the topography, landforms, geology and lunar dust from perspectives ranging from large spatial areas(hundreds of kilometers like Sinus Iridum and North Mare Imbrium, 45×75 km) to a smaller scale of kilometers near the landing site(4×4 km) and finally to the immediate area around the landing site in meters. We can find that:1)The probe landed on a flat lunar mare with an elevation of -2615m. The landing site is high titanium basalt stratum, and its geological age is young Eratoshenian. 10km to the north of the landing site is the older Mare Imbrium stratum, and the location of the landing site is in the area that is the intersection of these two strata; 2)The landing site lies on the edge of a plateau in a flat plain with a declining trend from west to east, and the topographic slope and waviness of the area are low, which is typical for terrain in lunar mare; 3)The adjacent area of the landing point is flat terrain, with landforms such as craters, domes, strata and rocks with different albedos, which are good targets for scientific exploration; 4)By comparing images captured before and after landing, we find that during the landing process of CE-3, lots of lunar dust was blown away by the engine plume, and the scope of influence is about 60m from east to west and 135m from south to north. Thus, this leads to a redistribution of lunar dust and changes in space weathering on the lunar surface.

  16. Association between melanocytic nevi and risk of breast diseases: The French E3N prospective cohort.

    Directory of Open Access Journals (Sweden)

    Marina Kvaskoff

    2014-06-01

    Full Text Available BACKGROUND: While melanocytic nevi have been associated with genetic factors and childhood sun exposure, several observations also suggest a potential hormonal influence on nevi. To test the hypothesis that nevi are associated with breast tumor risk, we explored the relationships between number of nevi and benign and malignant breast disease risk. METHODS AND FINDINGS: We prospectively analyzed data from E3N, a cohort of French women aged 40-65 y at inclusion in 1990. Number of nevi was collected at inclusion. Hazard ratios (HRs for breast cancer and 95% confidence intervals (CIs were calculated using Cox proportional hazards regression models. Associations of number of nevi with personal history of benign breast disease (BBD and family history of breast cancer were estimated using logistic regression. Over the period 15 June 1990-15 June 2008, 5,956 incident breast cancer cases (including 5,245 invasive tumors were ascertained among 89,902 women. In models adjusted for age, education, and known breast cancer risk factors, women with "very many" nevi had a significantly higher breast cancer risk (HR = 1.13, 95% CI = 1.01-1.27 versus "none"; ptrend = 0.04, although significance was lost after adjustment for personal history of BBD or family history of breast cancer. The 10-y absolute risk of invasive breast cancer increased from 3,749 per 100,000 women without nevi to 4,124 (95% CI = 3,674-4,649 per 100,000 women with "very many" nevi. The association was restricted to premenopausal women (HR = 1.40, ptrend = 0.01, even after full adjustment (HR = 1.34, ptrend = 0.03; phomogeneity = 0.04, but did not differ according to breast cancer type or hormone receptor status. In addition, we observed significantly positive dose-response relationships between number of nevi and history of biopsy-confirmed BBD (n = 5,169; ptrend<0.0001 and family history of breast cancer in first-degree relatives (n = 7,472; ptrend = 0.0003. The main limitations of our study

  17. A Very Fast Pulsed Electron Gun for (e, 2e) and (e, 3e) Studies

    Institute of Scientific and Technical Information of China (English)

    CaoShiping; MaXinwen; ShaShan; ZhuXiaolong; LiuHuipin

    2003-01-01

    Reaction microscope is a powerful tool for studying ion-atom/molecule dynamics, it can also be employed to investigate electron impact ionization processes. Traditionally these processes are studied by using the (e, 2e) or (e, 3e) techniques, most data are collected for single ionization and for very small scattering angles, i.e. (e, 2e), experimental data of double ionization (e, 3e)[1] and multiple ionization are scarce, because in most cases the efficiencies (mainly determined by solid angles) are extremely small for (e, 3e) processes, about 10-7~10-9. On the other hand, the new technique-reaction microscope can detect mutli-fragments in one collision with very

  18. A comparison between immunofluorescence staining on smears from Membrana nictitans (M3 test), immunohistopathology and routine pathology in cats with suspected feline infectious peritonitis (FIP).

    Science.gov (United States)

    Hök, K

    1991-01-01

    An indirect immunofluorescence method using smears from membrana nictitans (M3 test) to diagnose feline corona virus (FCV) infection was compared with immunohistopathology (using indirect immunofluorescence assay (IFFA) performed on organs (IFO], and routine pathology (RP) in cats with suspected feline infectious peritonitis (FIP). A close correlation between the 2 immunofluorescence methods (IFO and M3) was observed. Although the M3 test requires samples from only 1 organ per animal, both the sensitivity and specificity were high (80%), when compared to IFO (using samples from an average of 5 organs per animal). In 21% of the cats with suspected FIP typical pathological lesions were found. As the M3 test is relatively easy to perform, it could reduce work-load of pathology laboratories and provide valuable data for clinical and epidemiological use.

  19. The use of occupation isoboles for analysis of a response mediated by two receptors: M2 and M3 muscarinic receptor subtype-induced mouse stomach contractions.

    Science.gov (United States)

    Braverman, Alan S; Tallarida, Ronald J; Ruggieri, Michael R

    2008-06-01

    Smooth muscle contains multiple muscarinic receptor subtypes, including M2 and M3. M2 receptors outnumber M3 receptors. Based on the potency of subtype selective anticholinergics, contraction is mediated by the M3 subtype. However, results from knockout (KO) mice show that the M2 receptor mediates approximately 45% of the contractile response produced by the M3 receptor. The traditional theory of one receptor mediating a response does not allow assessment of interactions between receptors when more than one receptor participates in a response. Our study was performed using a novel analysis method based on dual receptor occupancy to determine how M2 and M3 receptor subtypes interact to mediate contraction in mouse stomach. Cumulative carbachol concentration contractile responses were determined for wild-type, M2-KO, and M3-KO stomach body smooth muscle. Using affinity constants for carbachol at M2 and M3 cholinergic receptors, the concentration values were converted to fractional receptor occupation. The resulting occupation-effect relations showed maximum effects for the M2 and M3 subtypes, respectively. These occupation-effect relations allow determination of the additive (expected) isobole based on this dual occupancy, thereby providing a curve (mathematically derived) for comparison against the experimentally derived value in wild type. The actual values determined experimentally in the wild type were not statistically significantly different from that predicted by the isobole. This confirms that the interaction between these mutually occupied receptors is additive. The new method of analysis also expands the traditional Schild theory that was based on a single receptor type to which the agonist and antagonist bind.

  20. σ-Aromatic cyclic M3(+) (M = Cu, Ag, Au) clusters and their complexation with dimethyl imidazol-2-ylidene, pyridine, isoxazole, furan, noble gases and carbon monoxide.

    Science.gov (United States)

    Pan, Sudip; Saha, Ranajit; Mandal, Subhajit; Chattaraj, Pratim K

    2016-04-28

    The σ-aromaticity of M3(+) (M = Cu, Ag, Au) is analyzed and compared with that of Li3(+) and a prototype σ-aromatic system, H3(+). Ligands (L) like dimethyl imidazol-2-ylidene, pyridine, isoxazole and furan are employed to stabilize these monocationic M3(+) clusters. They all bind M3(+) with favorable interaction energy. Dimethyl imidazol-2-ylidene forms the strongest bond with M3(+) followed by pyridine, isoxazole and furan. Electrostatic contribution is considerably more than that of orbital contribution in these M-L bonds. The orbital interaction arises from both L → M σ donation and L ← M back donation. M3(+) clusters also bind noble gas atoms and carbon monoxide effectively. In general, among the studied systems Au3(+) binds a given L most strongly followed by Cu3(+) and Ag3(+). Computation of the nucleus-independent chemical shift (NICS) and its different extensions like the NICS-rate and NICS in-plane component vs. NICS out-of-plane component shows that the σ-aromaticity in L bound M3(+) increases compared to that of bare clusters. The aromaticity in pyridine, isoxazole and furan bound Au3(+) complexes is quite comparable with that in the recently synthesized Zn3(C5(CH3)5)3(+). The energy gap between the highest occupied molecular orbital and the lowest unoccupied molecular orbital also increases upon binding with L. The blue-shift and red-shift in the C-O stretching frequency of M3(CO)3(+) and M3(OC)3(+), respectively, are analyzed through reverse polarization of the σ- and π-orbitals of CO as well as the relative amount of OC → M σ donation and M → CO π back donation. The electron density analysis is also performed to gain further insight into the nature of interaction.

  1. Mare Imbrium Regolith and Rock Information Retrieved from Imaging Spectrometer and Panorama Cameras onboard the Yutu Rover of Chang'E 3 Mission

    Science.gov (United States)

    Zhang, Hao; Jin, Weidong; Yuan, Ye; Yang, Yazhou; Wang, Ziwei; Xiao, Long

    2014-11-01

    The Chang’E 3 mission successfully landed on the Mare Imbrium region on December 14, 2013 and deployed the Yutu Rover to roam near the Chang’E A Crater. Although the rover roamed just over 100 meters before its premature failure, its onboard visible and near-infrared (VisNIR) imaging spectrometer was able to collect 4 spectra at 4 different sites which are the first in-situ lunar surface spectra ever taken. The onboard panorama cameras (PCAM) also photographed large amount of surface features since the Apollo era and some images have clearly shown the lunar opposition effect. The VisNIR spectrometer spans the wavelength from 450 to 2395 nm with a step of 5 nm. By performing radiometric and photometric calibrations, the absolute reflectance are obtained and it is found that the in-situ spectra are much bighter than that of the same area measured by the M3 instrument. The in-situ spectra also have a much deeper 1 μm absorption feature than that of the M3 spectra measured remotely. We conjecture that such differences are caused by the fact that the lander’s descent engines must have blown away the top-most layers which are much more mature than the exposed underlying layers. A comparison of the continuum-removed in-situ spectra with that of the mineral spectral library gives the concentrations of major lunar rock-forming minerals including olivine, pyroxenes and plagioclase at these 4 different sites. The phase curve retrieved from the PCAM shows a strong opposition surge below 10-deg phase angle and the phase reddening effect. We attempt to retrieve the regolith physical properties using both the Hapke and Shkuratov photometric models. At a close distance the PCAM also captured high resolution images of a 4-meter across boulder at the edge of the Chang’E A Crater. Centimeter-sized bright clasts on its surface may indicate its basaltic nature. By comparing the VisNIR spectra of its nearby regoliths with that of the Apollo samples, we believe this boulder

  2. The insect repellent N,N-diethyl-m-toluamide (DEET) induces angiogenesis via allosteric modulation of the M3 muscarinic receptor in endothelial cells.

    Science.gov (United States)

    Legeay, Samuel; Clere, Nicolas; Hilairet, Grégory; Do, Quoc-Tuan; Bernard, Philippe; Quignard, Jean-François; Apaire-Marchais, Véronique; Lapied, Bruno; Faure, Sébastien

    2016-06-27

    The insect repellent N,N-diethyl-m-toluamide (DEET) has been reported to inhibit AChE (acetylcholinesterase) and to possess potential carcinogenic properties with excessive vascularization. In the present paper, we demonstrate that DEET specifically stimulates endothelial cells that promote angiogenesis which increases tumor growth. DEET activates cellular processes that lead to angiogenesis including proliferation, migration and adhesion. This is associated with an enhancement of NO production and VEGF expression in endothelial cells. M3 silencing or the use of a pharmacological M3 inhibitor abrogates all of these effects which reveals that DEET-induced angiogenesis is M3 sensitive. The experiments involving calcium signals in both endothelial and HEK cells overexpressing M3 receptors, as well as binding and docking studies demonstrate that DEET acts as an allosteric modulator of the M3 receptor. In addition, DEET inhibited AChE which increased acetylcholine bioavailability and binding to M3 receptors and also strengthened proangiogenic effects by an allosteric modulation.

  3. Real-time monitoring of genetically modified Chlamydomonas reinhardtii during the Foton M3 space mission and ground irradiation experiment

    Science.gov (United States)

    Lambreva, Maya; Rea, Giuseppina; Antonacci, Amina; Serafini, Agnese; Damasso, Mario; Margonelli, Andrea; Johanningmeier, Udo; Bertalan, Ivo; Pezzotti, Gianni; Giardi, Maria Teresa

    Long-term space exploration, colonization or habitation requires biological life support systems capable to cope with the deleterious space environment. The use of oxygenic photosynthetic microrganisms is an intriguing possibility mainly for food, O2 and nutraceutical compounds production. The critical points of utilizing plantsor algae-based life support systems are the microgravity and the ionizing radiation, which can influence the performance of these organisms. The aim of the present study was to assess the effects of space environment on the photosynthetic activity of various microrganisms and to select space stress-tolerant strains. Site-directed and random mutants of the unicellular green alga Chlamydomonas reinhardtii of Photosystem II D1 protein were used as a model system to test and select the amino acid substitutions capable to account for space stress tolerance. We focussed our studies also on the accumulation of the Photosystem II photoprotective carotenoids (the xantophylls violaxanthin, anteraxanthin and zeaxanthin), powerful antioxidants that epidemiological studies demonstrated to be human vision protectors. Metabolite profiling by quantitative HPLC methods revealed the organisms and the stress conditions capable to accumulate the highest pigment levels. In order to develop a project for a rationale metabolic engineering of algal secondary metabolites overproduction, we are performing expression analyses on the carotenoid biosynthetic pathway under physiological and mimicked space conditions. To identify the consequences of the space environment on the photosynthetic apparatus the changes in the Photosystem II efficiency were monitored in real time during the ESA-Russian Foton-M3 mission in September 2007. For the space flight a high-tech, multicell fluorescence biosensor, Photo-II, was designed and built by the Centre for Advanced Research in Space Optics in collaboration with Kayser-Italy, Biosensor and DAS. Photo-II is an automatic device

  4. Structural and spectral investigations of the recently synthesized chalcone (E)-3-mesityl-1-(naphthalen-2-yl) prop-2-en-1-one, a potential chemotherapeutic agent.

    Science.gov (United States)

    Barakat, Assem; Al-Majid, Abdullah Mohammed; Soliman, Saied M; Mabkhot, Yahia Nasser; Ali, M; Ghabbour, Hazem A; Fun, Hoong-Kun; Wadood, Abdul

    2015-01-01

    Chalcones (1,3-diaryl-2-propen-1-ones, represent an important subgroup of the polyphenolic family, which have shown a wide spectrum of medical and industrial application. Due to their redundancy in plants and ease of preparation, this category of molecules has inspired considerable attention for potential therapeutic uses. They are also effective in vivo as anti-tumor promoting, cell proliferating inhibitors and chemo preventing agents. Synthesis and molecular structure investigation of (E)-3-mesityl-1-(naphthalen-2-yl) prop-2-en-1-one (3) is reported. The structure of the title compound 3 is confirmed by X-ray crystallography. The optimized molecular structure of the studied compound is calculated using DFT B3LYP/6-311G (d,p) method. The calculated geometric parameters are in good agreement with the experimental data obtained from our reported X-ay structure. The calculated IR fundamental bands were assigned and compared with the experimental data. The electronic spectra of the studied compound have been calculated using the time dependant density functional theory (TD-DFT). The longest wavelength band is due to H → L (79 %) electronic transition which belongs to π-π* excitation. The (1)H- and (13)C-NMR chemical shifts were calculated using gauge independent atomic orbitals (GIAO) method, which showed good correlations with the experimental data (R(2) = 0.9911-0.9965). The natural bond orbital (NBO) calculations were performed to predict the natural atomic charges at different atomic sites. The molecular electrostatic potential (MEP) was used to visualize the charge distribution on the molecule. Molecular docking results suggest that the compound might exhibit inhibitory activity against GPb and may act as potential anti-diabetic compound. (E)-3-Mesityl-1-(naphthalen-2-yl) prop-2-en-1-one single crystal is grown and characterized by single crystal X-ray diffraction, FT-IR, UV-vis, DFT and optimized geometrical parameters are close to the experimental

  5. The effect of whole grain wheat sourdough bread consumption on serum lipids in healthy normoglycemic/normoinsulinemic and hyperglycemic/hyperinsulinemic adults depends on presence of the APOE E3/E3 genotype: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Bakovic Marica

    2010-05-01

    Full Text Available Abstract Background Epidemiological studies associate consumption of whole grain foods, including breads, with reduced cardiovascular disease (CVD risk; however, few studies have compared wheat whole grains with wheat refined grains. Methods This study investigated effects of 6-week consumption of whole grain wheat sourdough bread in comparison to white bread on fasting serum lipids in normoglycemic/normoinsulinemic (NGI; n = 14 and hyperglycemic/hyperinsulinemic (HGI; n = 14 adults. The influence of single-nucleotide polymorphisms, 3 within the APOE gene (E2, E3, E4 and 2 within the hepatic lipase gene promoter (LIPC -514C>T, LIPC -250G>A were considered. Results At baseline, HGI participants had significantly higher body weight, waist circumference, body fat, and fasted glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR, glucagon, triacylglycerols (TAG and TAG:HDL-cholesterol, compared to NGI participants; however, none of these in addition to none of the other serum lipids, differed between bread treatments, within either participant group. For participants with the APOE E3/E3 genotype, LDL-cholesterol (P = 0.02 increased in the NGI group (n = 7, and TAG (P = 0.03 and TAG:HDL-cholesterol (P = 0.04 increased in the HGI group (n = 10, following consumption of whole grain wheat sourdough compared to white bread. Conclusions In summary, 6-week consumption of whole grain wheat sourdough bread did not significantly modulate serum lipids in NGI or HGI adults; however, it significantly increased LDL-cholesterol, TAG and TAG:HDL-cholesterol in participants with the APOE E3/E3 genotype. These data add to limited literature comparing wheat whole grains to wheat refined grains on CVD risk and highlight the need to consider genetic variation in relation to lipoprotein lipid content and CVD risk.

  6. Effects of dietary fish oil on serum lipids and VLDL kinetics in hyperlipidemic apolipoprotein E*3-Leiden transgenic mice

    NARCIS (Netherlands)

    Vlijmen, B.J.M. van; Mensink, R.P.; Hof, H.B. van 't; Offermans, R.F.G.; Hofker, M.H.; Havekes, L.M.

    1998-01-01

    Studying the effects of dietary fish oil on VLDL metabolism in humans is subject to both large intra- and interindividual variability. In the present study we therefore used hyperlipidentic apolipoprotein (APO) E*3-Leiden mice, which have impaired chylomicron and very low density lipoprotein (VDL) r

  7. Phosphorylation in vitro of eukaryotic initiation factors IF-E2 and IF-E3 by protein kinases

    DEFF Research Database (Denmark)

    Issinger, O G; Benne, R; Hershey, J W;

    1976-01-01

    is composed of 9 to 11 nonidentical polypeptides; only 2 of these, with molecular weights of 120,000 and 70,000, were phosphorylated. A lower level of phosphorylation of initiation factor IF-E3 was found with the cyclic AMP-dependent protein kinase; the polypeptide of molecular weight 140,000 was the major...

  8. Nr2e3 and Nrl can reprogram retinal precursors to the rod fate in Xenopus retina.

    Science.gov (United States)

    McIlvain, Vera A; Knox, Barry E

    2007-07-01

    Transformation of undifferentiated progenitors into specific cell types is largely dependent on temporal and spatial expression of a complex network of transcription factors. Here, we examined whether neural retina leucine zipper (Nrl) and photoreceptor-specific nuclear receptor Nr2e3 transcription factors contribute to cell fate determination. We cloned the Xenopus Nr2e3 gene and showed that its temporal and spatial expression is similar to its mammalian ortholog. We tested its in vivo function by misexpressing these transcription factors in Xenopus eye primordia, demonstrating that either human Nr2e3 or Nrl directed photoreceptor precursors to become rods at the expense of cones. Furthermore, overexpression of Xenopus Nrl dramatically increased the number of lens fibers, whereas human Nrl did not, suggesting evolutionary divergence of function of the Nrl gene family. Misexpression of Nrl and Nr2e3 together were more effective than either transcription factor alone in directing precursors to the rod fate. Copyright 2007 Wiley-Liss, Inc.

  9. Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors

    NARCIS (Netherlands)

    Koo, B.K.; Spit, M.; Jordens, I.; Low, T.Y.; Stange, D.E.; van de Wetering, M.; van Es, J.H.; Mohammed, S.; Heck, A.J.R.; Maurice, M.M.; Clevers, H.

    2012-01-01

    LGR5+ stem cells reside at crypt bottoms, intermingled with Paneth cells that provide Wnt, Notch and epidermal growth factor signals. Here we find that the related RNF43 and ZNRF3 transmembrane E3 ubiquitin ligases are uniquely expressed in LGR5+ stem cells. Simultaneous deletion of the two genes en

  10. Rosuvastatin reduces plasma lipids by inhibiting VLDL production and enhancing hepatobiliary lipid excretion in ApoE*3-Leiden mice

    NARCIS (Netherlands)

    Delsing, DJM; Post, SM; Groenendijk, M; Solaas, K; van der Boom, H; van Duyvenvoorde, W; de Wit, ECM; Bloks, VW; Kuipers, F; Havekes, LM; Princen, HMG

    The present study was designed to investigate the lipid-lowering properties and mechanisms of action of a new HMG-CoA reductase inhibitor, rosuvastatin, in female ApoE*3-Leiden transgenic mice. Mice received a high fat/cholesterol (HFC) diet containing either rosuvastatin (0 [control], 0.00125%,

  11. X-ray and Optical Study of Low Core Density Globular Clusters NGC6144 and E3

    CERN Document Server

    Lan, Shih Hao; Verbunt, Frank; Lewin, Walter H G; Bassa, Cees; Anderson, Scott F; Pooley, David

    2009-01-01

    We report on the Chandra X-ray Observatory and Hubble Space Telescope observation of two low core density globular clusters, NGC6144 and E3. By comparing the number of X-ray sources inside the half-mass radius to those outside, we found 6 X-ray sources within the half-mass radius of NGC6144, among which 4 are expected to be background sources; 3 X-ray sources are also found within the half-mass radius of E3, of which 3 is expected to be background source. Therefore, we cannot exclude that all our sources are background sources. However, combining the results from X-ray and optical observations, we found that 1-2 sources in NGC6144 and 1 source in E3 are likely to be cataclysmic variables and that 1 source in NGC6144 is an active binary, based on the X-ray and optical properties. The number of faint X-ray sources in NGC6144 and E3 found with Chandra and HST is higher than a prediction based on collision frequency, but is closer to that based on mass. Our observations strongly suggest that the compact binary sy...

  12. K48-linked KLF4 ubiquitination by E3 ligase Mule controls T-cell proliferation and cell cycle progression

    DEFF Research Database (Denmark)

    Hao, Zhenyue; Sheng, Yi; Duncan, Gordon S.

    2017-01-01

    T-cell proliferation is regulated by ubiquitination but the underlying molecular mechanism remains obscure. Here we report that Lys-48-linked ubiquitination of the transcription factor KLF4 mediated by the E3 ligase Mule promotes T-cell entry into S phase. Mule is elevated in T cells upon TCR...

  13. Dimension Changing Phase Transitions in Instanton Crystals

    CERN Document Server

    Kaplunovsky, Vadim

    2013-01-01

    We investigate lattices of instantons and the dimension-changing transitions between them. Our ultimate goal is the 3d->4D transition, which is holographically dual to the phase transition between the baryonic and the quarkyonic phases of cold nuclear matter. However, in this paper (just as in [1]) we focus on lower dimensions -- the 1D lattice of instantons in a harmonic potential V M_2^2x_2^2+M_3^2x_2^2+M_4^2x_4^2 and the zigzag-shaped lattice as a first stage of the 1D->2D transition. We prove that in the low- and moderate-density regimes, interactions between the instantons are dominated by two-body forces. This drastically simplifies finding the ground state of the instantons' orientations, so we made a numeric scan of the whole orientation space instead of assuming any particular ansatz. We find that depending on the M_2/M_3/M_4 ratios, the ground state of instanton orientations can follow a wide variety of patterns. For the straight 1D lattices, we found orientations periodically running over elements ...

  14. The M3 phosphorylation site is required for trafficking and biological roles of PIN-FORMED1, 2, and 7 in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Daeeun Ki

    2016-09-01

    Full Text Available Asymmetrically localized PIN-FORMED (PIN auxin efflux carriers play key roles in regulating directional intercellular auxin movement, generating local auxin gradients, and diverse auxin-mediated growth and development. The polar localization of PINs is controlled by phosphorylation in the central hydrophilic loop (HL of PINs. Although the M3 phosphorylation site, including phosphorylatable 5 Ser/Thr residues, is conserved among long HL-PINs, its native role has only been characterized in PIN3. In this study, we examined the role of M3 phosphorylation site of PIN1, PIN2, and PIN7 in intracellular trafficking, phosphorylation, and biological functions of those PINs in their native expressing tissues. Phosphorylation-defective mutations of the phosphorylatable residues in the M3 site of PIN1-HL led to alteration in subcellular polarity of PIN1 and caused defects in PIN1-mediated biological functions such as cotyledon development, phyllotaxy of vegetative leaves, and development of reproductive organs. The M3 mutations of PIN7 interfered with its polar recycling in the root columella cell in response to gravity stimulus and partially disrupted root gravitropism. On the other hand, the M3 site of PIN2 was shown to be necessary for its targeting to the plasma membrane. In vitro phosphorylation assay showed that the M3 phosphorylation residues of PIN1 are the partial targets by PINOID kinase. Our data suggest that the M3 phosphorylation site is functionally conserved among long HL-PINs by playing roles for their subcellular trafficking and auxin-mediated developmental processes.

  15. The M3 Phosphorylation Site Is Required for Trafficking and Biological Roles of PIN-FORMED1, 2, and 7 in Arabidopsis

    Science.gov (United States)

    Ki, Daeeun; Sasayama, Daisuke; Cho, Hyung-Taeg

    2016-01-01

    Asymmetrically localized PIN-FORMED (PIN) auxin efflux carriers play key roles in regulating directional intercellular auxin movement, generating local auxin gradients, and diverse auxin-mediated growth and development. The polar localization of PINs is controlled by phosphorylation in the central hydrophilic loop (HL) of PINs. Although the M3 phosphorylation site, including phosphorylatable 5 Ser/Thr residues, is conserved among long HL-PINs, its native role has only been characterized in PIN3. In this study, we examined the role of M3 phosphorylation site of PIN1, PIN2, and PIN7 in intracellular trafficking, phosphorylation, and biological functions of those PINs in their native expressing tissues. Phosphorylation-defective mutations of the phosphorylatable residues in the M3 site of PIN1-HL led to alteration in subcellular polarity of PIN1 and caused defects in PIN1-mediated biological functions such as cotyledon development, phyllotaxy of vegetative leaves, and development of reproductive organs. The M3 mutations of PIN7 interfered with its polar recycling in the root columella cell in response to gravity stimulus and partially disrupted root gravitropism. On the other hand, the M3 site of PIN2 was shown to be necessary for its targeting to the plasma membrane. In vitro phosphorylation assay showed that the M3 phosphorylation residues of PIN1 are the partial targets by PINOID kinase. Our data suggest that the M3 phosphorylation site is functionally conserved among long HL-PINs by playing roles for their subcellular trafficking and auxin-mediated developmental processes.

  16. Binding and repressive activities of apolipoprotein E3 and E4 isoforms on the human ApoD promoter.

    Science.gov (United States)

    Levros, Louis-Charles; Labrie, Marilyne; Charfi, Cyndia; Rassart, Eric

    2013-12-01

    Apolipoprotein D (ApoD) gene expression is increased in several neurological disorders such as Alzheimer's disease (AD) and multiple sclerosis. We previously showed that transgenic mice that overexpress human ApoD show a better resistance against paraquat or OC43 coronavirus-induced neurodegeneration. Here, we identified several nuclear factors from the cortex of control and OC43-infected mice which bind a fragment of the proximal ApoD promoter in vitro. Of interest, we detected apolipoprotein E (ApoE). Human ApoE consists of three isoforms (E2, E3, and E4) with the E4 and E2 alleles representing a greater and a lower risk for developping AD, respectively. Our results show that ApoE is located in the nucleus and on the ApoD promoter in human hepatic and glioblastoma cells lines. Furthermore, overexpression of ApoE3 and ApoE4 isoforms but not ApoE2 significantly inhibited the ApoD promoter activity in U87 cells (E3/E3 genotype) cultured under normal or different stress conditions while ApoE knock-down by siRNA had a converse effect. Consistent with these results, we also demonstrated by ChIP assay that E3 and E4 isoforms, but not E2, bind the ApoD promoter. Moreover, using the Allen Brain Atlas in situ hybridization database, we observed an inverse correlation between ApoD and ApoE mRNA expression during development and in several regions of the mouse brain, notably in the cortex, hippocampus, plexus choroid, and cerebellum. This negative correlation was also observed for cortex layers IV-VI based on a new Transcriptomic Atlas of the Mouse Neocortical Layers. These findings reveal a new function for ApoE by regulating ApoD gene expression.

  17. Quantitation of the Contractile Response Mediated by Two Receptors: M2 and M3 Muscarinic Receptor-Mediated Contractions of Human Gastroesophageal Smooth MuscleS⃞

    Science.gov (United States)

    Braverman, Alan S.; Miller, Larry S.; Vegesna, Anil K.; Tiwana, Mansoor I.; Tallarida, Ronald J.; Ruggieri, Michael R.

    2009-01-01

    Although muscarinic receptors are known to mediate tonic contraction of human gastrointestinal tract smooth muscle, the receptor subtypes that mediate the tonic contractions are not entirely clear. Whole human stomachs with attached esophagus were procured from organ transplant donors. Cholinergic contractile responses of clasp, sling, lower esophageal circular (LEC), midesophageal circular (MEC), and midesophageal longitudinal (MEL) muscle strips were determined. Sling fibers contracted greater than the other fibers. Total, M2 and M3 muscarinic receptor density was determined for each of these dissections by immunoprecipitation. M2 receptor density is greatest in the sling fibers, followed by clasp, LEC, MEC, and then MEL, whereas M3 density is greatest in LEC, followed by MEL, MEC, sling, and then clasp. The potency of subtype-selective antagonists to inhibit bethanechol-induced contraction was calculated by Schild analysis to determine which muscarinic receptor subtypes contribute to contraction. The results suggest both M2 and M3 receptors mediate contraction in clasp and sling fibers. Thus, this type of analysis in which multiple receptors mediate the contractile response is inappropriate, and an analysis method relating dual occupation of M2 and M3 receptors to contraction is presented. Using this new method of analysis, it was found that the M2 muscarinic receptor plays a greater role in mediating contraction of clasp and sling fibers than in LEC, MEC, and MEL muscles in which the M3 receptor predominantly mediates contraction. PMID:19126780

  18. Quantitation of the contractile response mediated by two receptors: M2 and M3 muscarinic receptor-mediated contractions of human gastroesophageal smooth muscle.

    Science.gov (United States)

    Braverman, Alan S; Miller, Larry S; Vegesna, Anil K; Tiwana, Mansoor I; Tallarida, Ronald J; Ruggieri, Michael R

    2009-04-01

    Although muscarinic receptors are known to mediate tonic contraction of human gastrointestinal tract smooth muscle, the receptor subtypes that mediate the tonic contractions are not entirely clear. Whole human stomachs with attached esophagus were procured from organ transplant donors. Cholinergic contractile responses of clasp, sling, lower esophageal circular (LEC), midesophageal circular (MEC), and midesophageal longitudinal (MEL) muscle strips were determined. Sling fibers contracted greater than the other fibers. Total, M(2) and M(3) muscarinic receptor density was determined for each of these dissections by immunoprecipitation. M(2) receptor density is greatest in the sling fibers, followed by clasp, LEC, MEC, and then MEL, whereas M(3) density is greatest in LEC, followed by MEL, MEC, sling, and then clasp. The potency of subtype-selective antagonists to inhibit bethanechol-induced contraction was calculated by Schild analysis to determine which muscarinic receptor subtypes contribute to contraction. The results suggest both M(2) and M(3) receptors mediate contraction in clasp and sling fibers. Thus, this type of analysis in which multiple receptors mediate the contractile response is inappropriate, and an analysis method relating dual occupation of M(2) and M(3) receptors to contraction is presented. Using this new method of analysis, it was found that the M(2) muscarinic receptor plays a greater role in mediating contraction of clasp and sling fibers than in LEC, MEC, and MEL muscles in which the M(3) receptor predominantly mediates contraction.

  19. Microwave irradiation induces neurite outgrowth in PC12m3 cells via the p38 mitogen-activated protein kinase pathway.

    Science.gov (United States)

    Inoue, Shigeki; Motoda, Hirotoshi; Koike, Yoshihisa; Kawamura, Kenji; Hiragami, Fukumi; Kano, Yoshio

    2008-02-13

    The increasing use of mobile phone communication has raised concerns about possible health hazard effects of microwave irradiation. We investigated damage and differentiation caused by microwave irradiation on drug-hypersensitive PC12 cell line (PC12m3). These cells showed enhancement of neurite outgrowth to various stimulants. The frequency of neurite outgrowth induced by 2.45 GHz (200 W) of microwave irradiation was approximately 10-fold greater than that of non-irradiated control cells. Incubation of PC12m3 cells with SB203580, a specific inhibitor of p38 MAPK, resulted in marked inhibition of the microwave radiation-induced neurite outgrowth. Also, activation of the transcription factor CREB induced by microwave irradiation was inhibited by SB203580. Heat shock treatment at 45 degrees C had a strong toxic effect on PC12m3 cells, whereas microwave treatment had no toxic effect on PC12m3 cells. These findings indicate that p38 MAPK is responsible for the survival of PC12m3 cells and might induce neurite outgrowth via a CREB signaling pathway when subjected to microwave irradiation.

  20. Virtual Screening of M3 Protein Antagonists for Finding a Model to Study the Gammaherpesvirus Damaged Immune System and Chemokine Related Diseases

    Directory of Open Access Journals (Sweden)

    Ibrahim Torktaz

    2013-12-01

    Full Text Available Introduction: M3 protein is a chemokine decoy receptor involved in pathogenesis of persistent infection with gammaherpesvirus and complications related to the latency of this pathogen. We proposed that antagonists of the M3 would provide a unique opportunity for studying new therapeutic strategies in disordered immune system, immune-deficient states and role of chemokines in pathogenesis development. Methods: Comparative modeling and fold recognition algorithms have been used for prediction of M3 protein 3-D model. Evaluation of the models using Q-mean and ProSA-web score, has led to choosing predicted model by fold recognition algorithm as the best model which was minimized regarding energy level using Molegro Virtual Docker 2011.4.3.0 (MVD software. Pockets and active sites of model were recognized using MVD cavity detection, and MetaPocket algorithms. Ten thousand compounds accessible on KEGG database were screened; MVD was used for computer simulated docking study; MolDock SE was selected as docking scoring function and final results were evaluated based on MolDock and Re-rank score. Results: Docking data suggested that prilocaine, which is generally applied as a topical anesthetic, binds strongly to 3-D model of M3 protein. Conclusion: This study proposes that prilocaine is a potential inhibitor of M3 protein and possibly has immune enhancing properties.

  1. Transition to Adulthood

    Science.gov (United States)

    ... Quick summary of transition IDEA’s definition of transition services Considering the definition Students at the heart of planning their transition ... fix that! Keep reading… Back to top IDEA’s Definition of Transition Services Any discussion of transition services must begin with ...

  2. Research on sub-surface damage and its stress deformation in the process of large aperture and high diameter-to-thickness ratio TMT M3MP

    Science.gov (United States)

    Hu, Hai-xiang; Qi, Erhui; Cole, Glen; Hu, Hai-fei; Luo, Xiao; Zhang, Xue-jun

    2016-10-01

    Large flat mirrors play important roles in large aperture telescopes. However, they also introduce unpredictable problems. The surface errors created during manufacturing, testing, and supporting are all combined during measurement, thus making understanding difficult for diagnosis and treatment. Examining a high diameter-to-thickness ratio flat mirror, TMT M3MP, and its unexpected deformation during processing, we proposed a strain model of subsurface damage to explain the observed phenomenon. We designed a set of experiment, and checked the validity of our diagnosis. On that basis, we theoretical predicted the trend of this strain and its scale effect on Zerodur®, and checked the validity on another piece experimentally. This work guided the grinding-polishing process of M3MP, and will be used as reference for M3M processing as well.

  3. The ARC1 E3 ligase gene is frequently deleted in self-compatible Brassicaceae species and has a conserved role in Arabidopsis lyrata self-pollen rejection.

    Science.gov (United States)

    Indriolo, Emily; Tharmapalan, Pirashaanthy; Wright, Stephen I; Goring, Daphne R

    2012-11-01

    Self-pollen rejection is an important reproductive regulator in flowering plants, and several different intercellular signaling systems have evolved to elicit this response. In the Brassicaceae, the self-incompatibility system is mediated by the pollen S-locus Cys-Rich/S-locus Protein11 (SCR/SP11) ligand and the pistil S Receptor Kinase (SRK). While the SCR/SP11-SRK recognition system has been identified in several species across the Brassicaceae, less is known about the conservation of the SRK-activated cellular responses in the stigma, following self-pollen contact. The ARM Repeat Containing1 (ARC1) E3 ubiquitin ligase functions downstream of SRK for the self-incompatibility response in Brassica, but it has been suggested that ARC1 is not required in Arabidopsis species. Here, we surveyed the presence of ARC1 orthologs in several recently sequenced genomes from Brassicaceae species that had diversified ∼20 to 40 million years ago. Surprisingly, the ARC1 gene was deleted in several species that had lost the self-incompatibility trait, suggesting that ARC1 may lose functionality in the transition to self-mating. To test the requirement of ARC1 in a self-incompatible Arabidopsis species, transgenic ARC1 RNA interference Arabidopsis lyrata plants were generated, and they exhibited reduced self-incompatibility responses resulting in successful fertilization. Thus, this study demonstrates a conserved role for ARC1 in the self-pollen rejection response within the Brassicaceae.

  4. Carbon-free D3d [E3ME3]2- (E=P,As;M=Ni,Pd,Pt):The smallest inorganic sandwich complexes with aromatic η3-P3- and η3-As3- ligands

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    A density functional theory and wave function theory investigation on the possibility of carbon-free phosphametallocenes [P3MP3]2-and arsenametallocenes [As3MAs3]2- (M=Ni, Pd, Pt) is presented in this work. Staggered singlet D3d [E3ME3]2- (E=P, As)-the smallest inorganic metallocenes possible to construct-proved to be the global minima of the heptaatomic sys- tems and may be targeted in future experiments. Cyclo-P3- and cyclo-As3- turned out to possess similar aromaticity to cyclo-P5- and cyclo-As5- and may serve as effective ligands to sandwich a wide range of transition metals. The first vertical electron detachment energies of Cs [E3ME3]Li+ monoanions with a staggered [E3ME3]2- sandwich core were predicted to be between 2.7 and 2.9 eV; the extent of stabilization by Li+ suggests that such materials be viable targets for experimental characterization.

  5. Comparison of Transport Calculation Between 2D/1D synthesis and RAPTOR-M3G at Core Barrel of Korea Standard Nuclear Plant(KSNP), OPR-1000

    Energy Technology Data Exchange (ETDEWEB)

    Maeng, Young Jae; Kim, Byoung Chul; Lim, Mi Joung; Kim, Kyung Sik; Jeon, Young Kyou [Korea Reactor Integrity Surveillance Technology, Daejeon (Korea, Republic of); Yoo, Chun Sung [Korea Atomic Energy Research Institutes, Daejeon (Korea, Republic of)

    2013-10-15

    The DORT code for 2D/1D synthesis has been actively applied to calculate the fast neutron (E>1.0MeV) fluence exposure of RPV. RAPTOR-M3G code is also applied for the comparison of 2D/1D synthesis, and it was found that 2D/1D synthesis method generally provided more conservative results than RAPTOR-M3G at both RPV and surveillance capsule locations. As a result, definitely RAPTOR-M3G for 3D calculation must apply for accurate evaluation of the integrity and ageing of RPV and internal structures. Therefore, the purpose of this paper is to compare the differences in terms of geometric aspect of KSNP model between 2D/1D synthesis and RAPTOR-M3G at core barrel area. 2D/1D synthesis method shows still higher results at the shortest distance of bypass water region. The reason is that 2D/1D synthesis method has excessive conservatism because of having just one model of R-θ and R-Z separately. Angles (5, 25, 45, 65 and 90 degrees) that RAPTOR-M3G results are higher than 2D/1D synthesis results seem to have almost regular interval. The reason can be that neutron flux to reach to barrel is affected by the nearest core definitely and all of near core areas including bypass water. RAPTOR-M3G performing 3D calculation can be applied to various reactor structures, because the code can simulate the model realistically and reasonably in geometric view points. Understanding the phenomenon that 45 degree shows downward peak, in spite of baffle corner location, remains.

  6. Length and amino acid sequence of peptides substituted for the 5-HT3A receptor M3M4 loop may affect channel expression and desensitization.

    Directory of Open Access Journals (Sweden)

    Nicole K McKinnon

    Full Text Available 5-HT3A receptors are pentameric neurotransmitter-gated ion channels in the Cys-loop receptor family. Each subunit contains an extracellular domain, four transmembrane segments (M1, M2, M3, M4 and a 115 residue intracellular loop between M3 and M4. In contrast, the M3M4 loop in prokaryotic homologues is <15 residues. To investigate the limits of M3M4 loop length and composition on channel function we replaced the 5-HT3A M3M4 loop with two to seven alanine residues (5-HT3A-A(n = 2-7. Mutants were expressed in Xenopus laevis oocytes and characterized using two electrode voltage clamp recording. All mutants were functional. The 5-HT EC(50's were at most 5-fold greater than wild-type (WT. The desensitization rate differed significantly among the mutants. Desensitization rates for 5-HT3A-A(2, 5-HT3A-A(4, 5-HT3A-A(6, and 5-HT3A-A(7 were similar to WT. In contrast, 5-HT3A-A(3 and 5-HT3A-A(5 had desensitization rates at least an order of magnitude faster than WT. The one Ala loop construct, 5-HT3A-A(1, entered a non-functional state from which it did not recover after the first 5-HT application. These results suggest that the large M3M4 loop of eukaryotic Cys-loop channels is not required for receptor assembly or function. However, loop length and amino acid composition can effect channel expression and desensitization. We infer that the cytoplasmic ends of the M3 and M4 segments may undergo conformational changes during channel gating and desensitization and/or the loop may influence the position and mobility of these segments as they undergo gating-induced conformational changes. Altering structure or conformational mobility of the cytoplasmic ends of M3 and M4 may be the basis by which phosphorylation or protein binding to the cytoplasmic loop alters channel function.

  7. Binding properties of nine 4-diphenyl-acetoxy-N-methyl-piperidine (4-DAMP) analogues to M1, M2, M3 and putative M4 muscarinic receptor subtypes.

    OpenAIRE

    Waelbroeck, M.; Camus, J.; Tastenoy, M.; Christophe, J.

    1992-01-01

    1. We compared the binding properties of 4-diphenyl-acetoxy-N-methyl-piperidine methiodide (4-DAMP) and nine analogues of this compound on muscarinic receptors of human neuroblastoma NB-OK1 cells (M1 subtype), rat heart (M2 subtype), rat pancreas (M3 subtype) and to the putative M4 subtype in striatum. 2. The requirements for high affinity binding were somewhat different for the four receptor subtypes. In general, the requirements of M3 receptors were more stringent than for M1, M2 or putativ...

  8. Cloning and Expression of Apolipoprotein E3 and Its Variant apoE2 and apoE4

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In order to obtain three isoforms of apolipoprotein E (apoE), the cDNA encoding apoE3 was obtained by RT-PCR from normal human liver tissue. Site-directed mutagenesis was used to obtain the cDNAs encoding apoE2 and apoE4 isoforms. The 3 cDNAs were subcloned into vector pGEM-3Z and verified by DNA sequencing. The expression recombinant which can express the target protein as a (His) 6-tagged fusion was constructed by subcloning apoE cDNA into vector pT7-PL. The purified proteins were gained by Ni-NTA column. The SDS-PAGE results revealed the 6 His fusion proteins (apoE2, apoE3 and apoE4) were correctly expressed and purified successfully.

  9. The activities of the E3 ubiquitin ligase COP1/SPA, a key repressor in light signaling.

    Science.gov (United States)

    Hoecker, Ute

    2017-06-01

    Light is a critical signal to integrate plant growth and development with the environment. Downstream of photoreceptors, the E3 ubiquitin ligase COP1/SPA is a key repressor of photomorphogenesis which targets many positive regulators of light signaling, mainly transcription factors, for degradation in darkness. In light-grown plants COP1/SPA activity is repressed, allowing light responses to occur. This review provides an overview on our current knowledge on COP1/SPA repressor function, focusing in particular on the roles of the respective protein domains and the mechanisms of light-induced inactivation of COP1/SPA. Moreover, we summarize how COP1 activity is regulated by other interacting proteins, such as a SUMO E3 ligase and Phytochrome-Interacting Factors (PIFs), as well as by hormones. At last, several novel functions of COP1 that were recently revealed are included. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Preliminary Report on Oak Ridge National Laboratory Testing of Drake/ACSS/MA2/E3X

    Energy Technology Data Exchange (ETDEWEB)

    Irminger, Philip [ORNL; Davis, Cody [General Cable Corporation; Temple, Bill [General Cable Corporation; Baker, Gord [General Cable Corporation; Starke, Michael R [ORNL

    2016-01-01

    A key to industry acceptance of a new technology is extensive validation in field trials. The Powerline Conductor Accelerated Test facility (PCAT) at Oak Ridge National Laboratory (ORNL) is specifically designed to evaluate the performance and reliability of a new conductor technology under real world conditions. The facility is set up to capture large amounts of data during testing. General Cable used the ORNL PCAT facility to validate the performance of TransPowr with E3X Technology a standard overhead conductor with an inorganic high emissivity, low absorptivity surface coating. Extensive testing has demonstrated a significant improvement in conductor performance across a wide range of operating temperatures, indicating that E3X Technology can provide a reduction in temperature, a reduction in sag, and an increase in ampacity when applied to the surface of any overhead conductor. This report provides initial results of that testing.

  11. Cyclin F: A component of an E3 ubiquitin ligase complex with roles in neurodegeneration and cancer.

    Science.gov (United States)

    Galper, Jasmin; Rayner, Stephanie L; Hogan, Alison L; Fifita, Jennifer A; Lee, Albert; Chung, Roger S; Blair, Ian P; Yang, Shu

    2017-08-01

    Cyclin F, encoded by CCNF, is the substrate recognition component of the Skp1-Cul1-F-box E3 ubiquitin ligase complex, SCF(cyclin F). E3 ubiquitin ligases play a key role in ubiquitin-proteasome mediated protein degradation, an essential component of protein homeostatic mechanisms within the cell. By recognising and regulating the availability of several protein substrates, SCF(cyclin F) plays a role in regulating various cellular processes including replication and repair of DNA and cell cycle checkpoint control. Cyclin F dysfunction has been implicated in various forms of cancer and CCNF mutations were recently linked to familial and sporadic amyotrophic lateral sclerosis and frontotemporal dementia, offering a new lead to understanding the pathogenic mechanisms underlying neurodegeneration. In this review, we evaluate the current literature on the function of cyclin F with an emphasis on its roles in cancer and neurodegeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Estimated dietary dioxin exposure and breast cancer risk among women from the French E3N prospective cohort.

    Science.gov (United States)

    Danjou, Aurélie M N; Fervers, Béatrice; Boutron-Ruault, Marie-Christine; Philip, Thierry; Clavel-Chapelon, Françoise; Dossus, Laure

    2015-03-17

    Dioxins are environmental and persistent pollutants mostly emitted from combustion facilities (e.g. waste incinerators, metal and cement industries). Known to be endocrine disrupting chemicals, dioxins are suspected to increase breast cancer (BC) risk. Although diet is considered the primary source of dioxin exposure, no previous study has been published on dietary dioxin exposure in relation to BC risk. We aimed to assess dietary dioxin exposure among women from the E3N cohort and estimate BC risk associated with this exposure. The study included 63,830 women from the E3N cohort who completed a diet history questionnaire (DHQ) in 1993 and were followed until 2008. Dietary dioxin exposure was estimated by combining consumption data from the E3N DHQ and food dioxin contamination data from a French national monitoring program. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox models adjusted for BC risk factors. Mean dietary dioxin exposure was estimated at 1.3 ± 0.4 pg/kg body weight (BW)/day. A 0.4 pg/kg BW/d increase in dioxin intake was not associated with overall BC risk (HR = 1.00; 95% CI: 0.96, 1.05). A significant decrease in risk of estrogen receptor negative (ER-)/progesterone receptor negative (PR-) tumors was observed among post-menopausal women in the upper quartile of estimated dioxin intake (HR for Q4 vs. Q1: 0.65; 95% CI: 0.45, 0.96; P for trend across quartiles = 0.0463). Overall, no association between estimated dietary dioxin exposure and BC risk was found among E3N women. Further studies should include both dietary and environmental exposures to determine whether low-dose dioxin exposure is associated with BC risk.

  13. Small, N-terminal tags activate Parkin E3 ubiquitin ligase activity by disrupting its autoinhibited conformation.

    Directory of Open Access Journals (Sweden)

    Lynn Burchell

    Full Text Available Parkin is an E3 ubiquitin ligase, mutations in which cause Autosomal Recessive Parkinson's Disease. Many studies aimed at understanding Parkin function, regulation and dysfunction are performed using N-terminal epitope tags. We report here that the use of small tags such as FLAG, cMyc and HA, influence the physical stability and activity of Parkin in and out of cells, perturbing the autoinhibited native state of Parkin, resulting in an active-for-autoubiquitination species.

  14. Inactivation of Sag/Rbx2/Roc2 E3 Ubiquitin Ligase Triggers Senescence and Inhibits Kras-Induced Immortalization

    Directory of Open Access Journals (Sweden)

    Mingjia Tan

    2015-01-01

    Full Text Available Our recent study showed that SAG/RBX2 E3 ubiquitin ligase regulates apoptosis and vasculogenesis by promoting degradation of NOXA and NF1, and co-operates with Kras to promote lung tumorigenesis by activating NFκB and mTOR pathways via targeted degradation of tumor suppressive substrates including IκB, DEPTOR, p21 and p27. Here we investigated the role of Sag/Rbx2 E3 ligase in cellular senescence and immortalization of mouse embryonic fibroblasts (MEFs and report that Sag is required for proper cell proliferation and KrasG12D-induced immortalization. Sag inactivation by genetic deletion remarkably suppresses cell proliferation by inducing senescence, which is associated with accumulation of p16, but not p53. Mechanistically, Sag deletion caused accumulation of Jun-B, a substrate of Sag-Fbxw7 E3 ligase and a transcription factor that drives p16 transcription. Importantly, senescence triggered by Sag deletion can be largely rescued by simultaneous deletion of Cdkn2a, the p16 encoding gene, indicating its causal role. Furthermore, KrasG12D-induced immortalization can also be abrogated by Sag deletion via senescence induction, which is again rescued by simultaneous deletion of Cdkn2a. Finally, we found that Sag deletion inactivates KrasG12D activity and block the MAPK signaling pathway, together with accumulated p16, to induce senescence. Taken together, our results demonstrated that Sag is a KrasG12D-cooperating oncogene required for KrasG12D-induced immortalization and transformation, and targeting SAG-SCF E3 ligase may, therefore, have therapeutic value for senescence-based cancer treatment.

  15. Non-vanishing $U_{e3}$ and $\\cos{2 \\theta_{23}}$ from a broken $Z_2$ symmetry

    CERN Document Server

    Grimus, Walter; Kaneko, S; Lavoura, L; Sawanaka, H; Tanimoto, M; Grimus, Walter; Joshipura, Anjan S.; Kaneko, Satoru; Lavoura, Lu\\'{i}s; Sawanaka, Hideyuki; Tanimoto, Morimitsu

    2004-01-01

    It is shown that the neutrino mass matrices in the flavour basis yielding a vanishing $U_{e3}$ are characterized by invariance under a class of effective $Z_2$ symmetries. A specific $Z_2$ in this class also leads to a maximal atmospheric mixing angle $\\theta_{23}$. The breaking of that $Z_2$ can be parameterized by two dimensionless quantities, $\\e$ and $\\e'$; the effects of $\\e, \\e' \

  16. Dietary factors, metabolic syndrome and risks of breast cancer and type II diabetes in the E3N cohort

    OpenAIRE

    Fagherazzi, Guy

    2011-01-01

    Breast cancer and type II diabetes are two of the main chronic diseases in women and are suspected to share common risk factors. But their etiologies are still partially unknown, in particular concerning some dietary factors and some parameters of the metabolic syndrome. If evidence is convincing that themetabolic syndrome is associated with an increased type II diabetes risk, questions remain unanswered regarding cholesterol level, anthropometric factors and breast cancer risk. The French E3...

  17. A family of Salmonella virulence factors functions as a distinct class of autoregulated E3 ubiquitin ligases

    Science.gov (United States)

    Quezada, Cindy M.; Hicks, Stuart W.; Galán, Jorge E.; Stebbins, C. Erec

    2009-01-01

    Processes as diverse as receptor binding and signaling, cytoskeletal dynamics, and programmed cell death are manipulated by mimics of host proteins encoded by pathogenic bacteria. We show here that the Salmonella virulence factor SspH2 belongs to a growing class of bacterial effector proteins that harness and subvert the eukaryotic ubiquitination pathway. This virulence protein possesses ubiquitination activity that depends on a conserved cysteine residue. A crystal structure of SspH2 reveals a canonical leucine-rich repeat (LRR) domain that interacts with a unique E3 ligase [which we have termed NEL for Novel E3 Ligase] C-terminal fold unrelated to previously observed HECT or RING-finger E3 ligases. Moreover, the LRR domain sequesters the catalytic cysteine residue contained in the NEL domain, and we suggest a mechanism for activation of the ligase requiring a substantial conformational change to release the catalytic domain for function. We also show that the N-terminal domain targets SspH2 to the apical plasma membrane of polarized epithelial cells and propose a model whereby binding of the LRR to proteins at the target site releases the ligase domain for site-specific function. PMID:19273841

  18. Allosteric Interactions by p53 mRNA Govern HDM2 E3 Ubiquitin Ligase Specificity under Different Conditions.

    Science.gov (United States)

    Medina-Medina, Ixaura; García-Beltrán, Paola; de la Mora-de la Mora, Ignacio; Oria-Hernández, Jesús; Millot, Guy; Fahraeus, Robin; Reyes-Vivas, Horacio; Sampedro, José G; Olivares-Illana, Vanesa

    2016-08-15

    HDM2 and HDMX are key negative regulatory factors of the p53 tumor suppressor under normal conditions by promoting its degradation or preventing its trans activity, respectively. It has more recently been shown that both proteins can also act as positive regulators of p53 after DNA damage. This involves phosphorylation by ATM on serine residues HDM2(S395) and HDMX(S403), promoting their respective interaction with the p53 mRNA. However, the underlying molecular mechanisms of how these phosphorylation events switch HDM2 and HDMX from negative to positive regulators of p53 is not known. Our results show that these phosphorylation events reside within intrinsically disordered domains and change the conformation of the proteins. The modifications promote the exposition of N-terminal interfaces that support the formation of a new HDMX-HDM2 heterodimer independent of the C-terminal RING-RING interaction. The E3 ubiquitin ligase activity of this complex toward p53 is prevented by the p53 mRNA ligand but, interestingly, does not affect the capacity to ubiquitinate HDMX and HDM2. These results show how ATM-mediated modifications of HDMX and HDM2 switch HDM2 E3 ubiquitin ligase activity away from p53 but toward HDMX and itself and illustrate how the substrate specificity of HDM2 E3 ligase activity is regulated.

  19. Lafora disease E3-ubiquitin ligase malin is related to TRIM32 at both the phylogenetic and functional level

    Directory of Open Access Journals (Sweden)

    Gentry Matthew S

    2011-07-01

    Full Text Available Abstract Background Malin is an E3-ubiquitin ligase that is mutated in Lafora disease, a fatal form of progressive myoclonus epilepsy. In order to perform its function, malin forms a functional complex with laforin, a glucan phosphatase that facilitates targeting of malin to its corresponding substrates. While laforin phylogeny has been studied, there are no data on the evolutionary lineage of malin. Results After an extensive search for malin orthologs, we found that malin is present in all vertebrate species and a cephalochordate, in contrast with the broader species distribution previously reported for laforin. These data suggest that in addition to forming a functional complex, laforin and perhaps malin may also have independent functions. In addition, we found that malin shares significant identity with the E3-ubiquitin ligase TRIM32, which belongs to the tripartite-motif containing family of proteins. We present experimental evidence that both malin and TRIM32 share some substrates for ubiquitination, although they produce ubiquitin chains with different topologies. However, TRIM32-specific substrates were not reciprocally ubiquitinated by the laforin-malin complex. Conclusions We found that malin and laforin are not conserved in the same genomes. In addition, we found that malin shares significant identity with the E3-ubiquitin ligase TRIM32. The latter result suggests a common origin for malin and TRIM32 and provides insights into possible functional relationships between both proteins.

  20. FERM-dependent E3 ligase recognition is a conserved mechanism for targeted degradation of lipoprotein receptors.

    Science.gov (United States)

    Calkin, Anna C; Goult, Benjamin T; Zhang, Li; Fairall, Louise; Hong, Cynthia; Schwabe, John W R; Tontonoz, Peter

    2011-12-13

    The E3 ubiquitin ligase IDOL (inducible degrader of the LDL receptor) regulates LDL receptor (LDLR)-dependent cholesterol uptake, but its mechanism of action, including the molecular basis for its stringent specificity, is poorly understood. Here we show that IDOL uses a singular strategy among E3 ligases for target recognition. The IDOL FERM domain binds directly to a recognition sequence in the cytoplasmic tails of lipoprotein receptors. This physical interaction is independent of IDOL's really interesting new gene (RING) domain E3 ligase activity and its capacity for autoubiquitination. Furthermore, IDOL controls its own stability through autoubiquitination of a unique FERM subdomain fold not present in other FERM proteins. Key residues defining the IDOL-LDLR interaction and IDOL autoubiquitination are functionally conserved in their insect homologs. Finally, we demonstrate that target recognition by IDOL involves a tripartite interaction between the FERM domain, membrane phospholipids, and the lipoprotein receptor tail. Our data identify the IDOL-LDLR interaction as an evolutionarily conserved mechanism for the regulation of lipid uptake and suggest that this interaction could potentially be exploited for the pharmacologic modulation of lipid metabolism.

  1. Association of APOE (E2, E3 and E4) gene variants and lipid levels in ischemic stroke, its subtypes and hemorrhagic stroke in a South Indian population.

    Science.gov (United States)

    Das, Satrupa; Kaul, Subhash; Jyothy, Akka; Munshi, Anjana

    2016-08-15

    In the present study we evaluated the association of APOE (E2/E3/E4) polymorphism with ischemic stroke (n=620), its subtypes and hemorrhagic stroke (n=250) in a South Indian population from Telangana. The genotypes were determined using PCR-RFLP while lipid levels were measured using commercially available kits. We found significant difference in the genotypic distribution between hemorrhagic stroke patients and controls for certain genetic models [E2/E2 vs. E2/E4; E3/E3 vs. E2/E3; E3/E3 vs. E2/E4; E4/E4 vs. E2/E3; E4/E4 vs.E2/E4 and E3 vs. E4]. However, no significant difference was observed in genotypic distribution between ischemic stroke patients and controls. On analysing the genotypic distribution between ischemic and hemorrhagic stroke patients, statistically significant difference was observed in specific genetic models [E2/E2 vs. E2/E4; E3/E3 vs. E2/E3; E3/E3 vs. E2/E4; E4/E4 vs. E2/E3 and E4/E4 vs. E2/E4]. In ischemic stroke subtypes analysing for alleles E3 vs. E2 and E3 vs. E4, we found significant association with intracranial large artery (p=0.01), cardioembolic stroke (p=0.001 and p=0.0004) and lacunar stroke (p=0.02). Analysing the association of various genotypes with different lipid levels significant association was observed for VLDL (P=0.000) and for triglyceride (P=0.000) levels with E2/E4 and E3/E4 genotypes in ischemic stroke but not in hemorrhagic stroke. In conclusion, our results suggest that APOE polymorphism does seem to play a role in hemorrhagic stroke and also in the development of specific subtypes of ischemic stroke. Further, in ischemic stroke VLDL and triglycerides levels were found to be significantly associated with E2/E4 and E3/E4 genotypes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Roles of the TRAF6 and Pellino E3 ligases in MyD88 and RANKL signaling.

    Science.gov (United States)

    Strickson, Sam; Emmerich, Christoph H; Goh, Eddy T H; Zhang, Jiazhen; Kelsall, Ian R; Macartney, Thomas; Hastie, C James; Knebel, Axel; Peggie, Mark; Marchesi, Francesco; Arthur, J Simon C; Cohen, Philip

    2017-04-25

    It is widely accepted that the essential role of TRAF6 in vivo is to generate the Lys63-linked ubiquitin (K63-Ub) chains needed to activate the "master" protein kinase TAK1. Here, we report that TRAF6 E3 ligase activity contributes to but is not essential for the IL-1-dependent formation of K63-Ub chains, TAK1 activation, or IL-8 production in human cells, because Pellino1 and Pellino2 generate the K63-Ub chains required for signaling in cells expressing E3 ligase-inactive TRAF6 mutants. The IL-1-induced formation of K63-Ub chains and ubiquitylation of IRAK1, IRAK4, and MyD88 was abolished in TRAF6/Pellino1/Pellino2 triple-knockout (KO) cells, but not in TRAF6 KO or Pellino1/2 double-KO cells. The reexpression of E3 ligase-inactive TRAF6 mutants partially restored IL-1 signaling in TRAF6 KO cells, but not in TRAF6/Pellino1/Pellino2 triple-KO cells. Pellino1-generated K63-Ub chains activated the TAK1 complex in vitro with similar efficiently to TRAF6-generated K63-Ub chains. The early phase of TLR signaling and the TLR-dependent secretion of IL-10 (controlled by IRAKs 1 and 2) was only reduced modestly in primary macrophages from knockin mice expressing the E3 ligase-inactive TRAF6[L74H] mutant, but the late-phase production of IL-6, IL-12, and TNFα (controlled only by the pseudokinase IRAK2) was abolished. RANKL-induced signaling in macrophages and the differentiation of bone marrow to osteoclasts was similar in TRAF6[L74H] and wild-type cells, explaining why the bone structure and teeth of the TRAF6[L74H] mice was normal, unlike TRAF6 KO mice. We identify two essential roles of TRAF6 that are independent of its E3 ligase activity.

  3. Oxylipin biosynthesis in spikemoss Selaginella moellendorffii: Molecular cloning and identification of divinyl ether synthases CYP74M1 and CYP74M3.

    Science.gov (United States)

    Gorina, Svetlana S; Toporkova, Yana Y; Mukhtarova, Lucia S; Smirnova, Elena O; Chechetkin, Ivan R; Khairutdinov, Bulat I; Gogolev, Yuri V; Grechkin, Alexander N

    2016-04-01

    Nonclassical P450s of CYP74 family control the secondary conversions of fatty acid hydroperoxides to bioactive oxylipins in plants. At least ten genes attributed to four novel CYP74 subfamilies have been revealed by the recent sequencing of the spikemoss Selaginella moellendorffii Hieron genome. Two of these genes CYP74M1 and CYP74M3 have been cloned in the present study. Both recombinant proteins CYP74M1 and CYP74M3 were active towards the 13(S)-hydroperoxides of α-linolenic and linoleic acids (13-HPOT and 13-HPOD, respectively) and exhibited the activity of divinyl ether synthase (DES). Products were analyzed by gas chromatography-mass spectrometry. Individual oxylipins were purified by HPLC and finally identified by their NMR data, including the (1)H NMR, 2D-COSY, HSQC and HMBC. CYP74M1 (SmDES1) specifically converted 13-HPOT to (11Z)-etherolenic acid and 13-HPOD to (11Z)-etheroleic acid. CYP74M3 (SmDES2) turned 13-HPOT and 13-HPOD mainly to etherolenic and etheroleic acids, respectively. CYP74M1 and CYP74M3 are the first DESs detected in non-flowering plants. The obtained results demonstrate the existence of the sophisticated oxylipin biosynthetic machinery in the oldest taxa of vascular plants.

  4. Maternal Malaria and Malnutrition (M3) initiative, a pooled birth cohort of 13 pregnancy studies in Africa and the Western Pacific

    DEFF Research Database (Denmark)

    Unger, Holger W; Cates, Jordan E; Gutman, Julie

    2016-01-01

    PURPOSE: The Maternal Malaria and Malnutrition (M3) initiative has pooled together 13 studies with the hope of improving understanding of malaria-nutrition interactions during pregnancy and to foster collaboration between nutritionists and malariologists. PARTICIPANTS: Data were pooled on 14 635...

  5. Muscarinic acetylcholine receptor M1 and M3 subtypes mediate acetylcholine-induced endothelium-independent vasodilatation in rat mesenteric arteries.

    Science.gov (United States)

    Tangsucharit, Panot; Takatori, Shingo; Zamami, Yoshito; Goda, Mitsuhiro; Pakdeechote, Poungrat; Kawasaki, Hiromu; Takayama, Fusako

    2016-01-01

    The present study investigated pharmacological characterizations of muscarinic acetylcholine receptor (AChR) subtypes involving ACh-induced endothelium-independent vasodilatation in rat mesenteric arteries. Changes in perfusion pressure to periarterial nerve stimulation and ACh were measured before and after the perfusion of Krebs solution containing muscarinic receptor antagonists. Distributions of muscarinic AChR subtypes in mesenteric arteries with an intact endothelium were studied using Western blotting. The expression level of M1 and M3 was significantly greater than that of M2. Endothelium removal significantly decreased expression levels of M2 and M3, but not M1. In perfused mesenteric vascular beds with intact endothelium and active tone, exogenous ACh (1, 10, and 100 nmol) produced concentration-dependent and long-lasting vasodilatations. In endothelium-denuded preparations, relaxation to ACh (1 nmol) disappeared, but ACh at 10 and 100 nmol caused long-lasting vasodilatations, which were markedly blocked by the treatment of pirenzepine (M1 antagonist) or 4-DAMP (M1 and M3 antagonist) plus hexamethonium (nicotinic AChR antagonist), but not methoctramine (M2 and M4 antagonist). These results suggest that muscarinic AChR subtypes, mainly M1, distribute throughout the rat mesenteric arteries, and that activation of M1 and/or M3 which may be located on CGRPergic nerves releases CGRP, causing an endothelium-independent vasodilatation. Copyright © 2015 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.

  6. Muscarinic acetylcholine receptor M1 and M3 subtypes mediate acetylcholine-induced endothelium-independent vasodilatation in rat mesenteric arteries

    Directory of Open Access Journals (Sweden)

    Panot Tangsucharit

    2016-01-01

    Full Text Available The present study investigated pharmacological characterizations of muscarinic acetylcholine receptor (AChR subtypes involving ACh-induced endothelium-independent vasodilatation in rat mesenteric arteries. Changes in perfusion pressure to periarterial nerve stimulation and ACh were measured before and after the perfusion of Krebs solution containing muscarinic receptor antagonists. Distributions of muscarinic AChR subtypes in mesenteric arteries with an intact endothelium were studied using Western blotting. The expression level of M1 and M3 was significantly greater than that of M2. Endothelium removal significantly decreased expression levels of M2 and M3, but not M1. In perfused mesenteric vascular beds with intact endothelium and active tone, exogenous ACh (1, 10, and 100 nmol produced concentration-dependent and long-lasting vasodilatations. In endothelium-denuded preparations, relaxation to ACh (1 nmol disappeared, but ACh at 10 and 100 nmol caused long-lasting vasodilatations, which were markedly blocked by the treatment of pirenzepine (M1 antagonist or 4-DAMP (M1 and M3 antagonist plus hexamethonium (nicotinic AChR antagonist, but not methoctramine (M2 and M4 antagonist. These results suggest that muscarinic AChR subtypes, mainly M1, distribute throughout the rat mesenteric arteries, and that activation of M1 and/or M3 which may be located on CGRPergic nerves releases CGRP, causing an endothelium-independent vasodilatation.

  7. Metal-organic Kagome lattices M3(2,3,6,7,10,11-hexaiminotriphenylene)2 (M = Ni and Cu): from semiconducting to metallic by metal substitution.

    Science.gov (United States)

    Chen, Shuang; Dai, Jun; Zeng, Xiao Cheng

    2015-02-28

    Motivated by recent experimental synthesis of a semiconducting metal-organic graphene analogue (J. Am. Chem. Soc., 2014, 136, 8859), i.e., Ni3(2,3,6,7,10,11-hexaiminotriphenylene)2 [Ni3(HITP)2], a new Kagome lattice, Cu3(HITP)2, is designed by substituting the coordination of Ni by Cu. Such substitution results in interesting changes in electronic properties of the M3(HITP)2 bulk and two-dimensional (2D) sheets. In Ni3(HITP)2, each Ni atom adopts the dsp(2) hybridization, forming a perfect 2D conjugation, whereas in Cu3(HITP)2, each Cu atom adopts the sp(3) hybridization, resulting in a distorted 2D sheet. The M3(HITP)2 bulks, assembled from M3(HITP)2 sheets via both strong π-π interaction and weak metal-metal interaction, are metallic. However, the 2D Ni3(HITP)2 sheet is a semiconductor with a narrow band gap whereas the 2D Cu3(HITP)2 sheet is a metal. Remarkably, both the 2D M3(HITP)2 Kagome lattices possess Dirac bands in the vicinity of the Fermi level. Additional ab initio molecular dynamics simulations show that both sheets exhibit high thermal stability at elevated temperatures. Our theoretical study offers new insights into tunability of electronic properties for the 2D metal-organic frameworks (MOFs).

  8. Maternal Malaria and Malnutrition (M3) initiative, a pooled birth cohort of 13 pregnancy studies in Africa and the Western Pacific

    DEFF Research Database (Denmark)

    Unger, Holger W; Cates, Jordan E; Gutman, Julie;

    2016-01-01

    PURPOSE: The Maternal Malaria and Malnutrition (M3) initiative has pooled together 13 studies with the hope of improving understanding of malaria-nutrition interactions during pregnancy and to foster collaboration between nutritionists and malariologists. PARTICIPANTS: Data were pooled on 14 635...... and alternative or intensified malaria prevention regimens, and the settings in which these interventions would be most effective....

  9. Comparison of the space radiation environment at Foton M3 satellite altitudes and on aircraft altitudes for minimum of solar activity

    Science.gov (United States)

    Ploc, Ondrej; Dachev, Tsvetan; Spurny, Frantisek; Tomov, Borislav; Dimitrov, Plamen; Matviichuk, Yury; Bankov, Nikolay

    The space radiation environments at Foton M3 and aircraft altitudes were measured by using of practically equal silicon detector based on a deposited energy spectrometers in the fall of 2007. The aircraft measurements were performed on commercial flights of CSA airlines, while the Foton M3 measurements were inside of the ESA Biopan 6 experiment. Foton M3 orbit was close to circular between 260 and 289 km altitude and about 63° inclination. The relatively high inclination and small shielding of the detector (0.81 g/cm2 ) allow us to observe doses by electrons in the outer radiation belt as high as 2.3 mGy/hour. The comparison of the total GCR deposited doses for the Foton M3 time interval, which coincides with the absolute cycle 23 minimum of the solar activity is about 15% higher than the measured during the Foton M2 satellite doses in 2005. Comparisons of the latitudinal profiles for ISS in 2001, Foton 2 and 3 satellites and aircrafts show that the ratio of doses is as 1:2:3. Aircraft measurements are characterised through average values of exposure during frequent, statistically well based measurements on the routes Prague - New York. Dose absorbed in Si-detector per flight on these routes was about 8% higher in 2007 than in 2005. Different comparisons with the existing models for the radiation environment on aircraft and spacecraft altitudes are presented in the paper also and discussed.

  10. The colon-selective spasmolytic otilonium bromide inhibits muscarinic M3 receptor-coupled calcium signals in isolated human colonic crypts

    Science.gov (United States)

    Lindqvist, Susanne; Hernon, James; Sharp, Paul; Johns, Neil; Addison, Sarah; Watson, Mark; Tighe, Richard; Greer, Shaun; Mackay, Jean; Rhodes, Michael; Lewis, Michael; Stebbings, William; Speakman, Chris; Evangelista, Stefano; Johnson, Ian; Williams, Mark

    2002-01-01

    Otilonium bromide (OB) is a smooth muscle relaxant used in the treatment of irritable bowel syndrome. Otilonium bromide has been shown to interfere with the mobilization of calcium in intestinal smooth muscle, but the effects on other intestinal tissues have not been investigated. We identified the muscarinic receptor subtype coupled to calcium signals in colonic crypt derived from the human colonic epithelium and evaluated the inhibitory effects of OB. Calcium signals were monitored by fluorescence imaging of isolated human colonic crypts and Chinese hamster ovary cells stably expressing the cloned human muscarinic M3 receptor subtype (CHO-M3). Colonic crypt receptor expression was investigated by pharmacological and immunohistochemical techniques. The secretagogue acetylcholine (ACh) stimulated calcium mobilization from intracellular calcium stores at the base of human colonic crypts with an EC50 of 14 μM. The muscarinic receptor antagonists 4-DAMP, AF-DX 384, pirenzepine and methroctamine inhibited the ACh-induced calcium signal with the following respective IC50 (pKb) values: 0.78 nM (9.1), 69 nM (7.2), 128 nM (7.1), and 2510 nM (5.8). Immunohistochemical analyses of muscarinic receptor expression demonstrated the presence of M3 receptor subtype expression at the crypt-base. Otilonium bromide inhibited the generation of ACh-induced calcium signals in a dose dependent manner (IC50=880 nM). In CHO-M3 cells, OB inhibited calcium signals induced by ACh, but not ATP. In addition, OB did not inhibit histamine-induced colonic crypt calcium signals. The present studies have demonstrated that OB inhibited M3 receptor-coupled calcium signals in human colonic crypts and CHO-M3 cells, but not those induced by stimulation of other endogenous receptor types. We propose that the M3 receptor-coupled calcium signalling pathway is directly targeted by OB at the level of the colonic epithelium, suggestive of an anti-secretory action in IBS patients suffering with diarrhoea. PMID

  11. The colon-selective spasmolytic otilonium bromide inhibits muscarinic M(3) receptor-coupled calcium signals in isolated human colonic crypts.

    Science.gov (United States)

    Lindqvist, Susanne; Hernon, James; Sharp, Paul; Johns, Neil; Addison, Sarah; Watson, Mark; Tighe, Richard; Greer, Shaun; Mackay, Jean; Rhodes, Michael; Lewis, Michael; Stebbings, William; Speakman, Chris; Evangelista, Stefano; Johnson, Ian; Williams, Mark

    2002-12-01

    1. Otilonium bromide (OB) is a smooth muscle relaxant used in the treatment of irritable bowel syndrome. Otilonium bromide has been shown to interfere with the mobilization of calcium in intestinal smooth muscle, but the effects on other intestinal tissues have not been investigated. We identified the muscarinic receptor subtype coupled to calcium signals in colonic crypt derived from the human colonic epithelium and evaluated the inhibitory effects of OB. 2. Calcium signals were monitored by fluorescence imaging of isolated human colonic crypts and Chinese hamster ovary cells stably expressing the cloned human muscarinic M(3) receptor subtype (CHO-M(3)). Colonic crypt receptor expression was investigated by pharmacological and immunohistochemical techniques. 3. The secretagogue acetylcholine (ACh) stimulated calcium mobilization from intracellular calcium stores at the base of human colonic crypts with an EC(50) of 14 micro M. The muscarinic receptor antagonists 4-DAMP, AF-DX 384, pirenzepine and methroctamine inhibited the ACh-induced calcium signal with the following respective IC(50) (pK(b)) values: 0.78 nM (9.1), 69 nM (7.2), 128 nM (7.1), and 2510 nM (5.8). 4. Immunohistochemical analyses of muscarinic receptor expression demonstrated the presence of M(3) receptor subtype expression at the crypt-base. 5. Otilonium bromide inhibited the generation of ACh-induced calcium signals in a dose dependent manner (IC(50)=880 nM). 6. In CHO-M(3) cells, OB inhibited calcium signals induced by ACh, but not ATP. In addition, OB did not inhibit histamine-induced colonic crypt calcium signals. 7. The present studies have demonstrated that OB inhibited M(3) receptor-coupled calcium signals in human colonic crypts and CHO-M(3) cells, but not those induced by stimulation of other endogenous receptor types. We propose that the M(3) receptor-coupled calcium signalling pathway is directly targeted by OB at the level of the colonic epithelium, suggestive of an anti-secretory action

  12. PyTransit: Transit light curve modeling

    Science.gov (United States)

    Parviainen, Hannu

    2015-05-01

    PyTransit implements optimized versions of the Giménez and Mandel & Agol transit models for exoplanet transit light-curves. The two models are implemented natively in Fortran with OpenMP parallelization, and are accessed by an object-oriented python interface. PyTransit facilitates the analysis of photometric time series of exoplanet transits consisting of hundreds of thousands of data points, and of multipassband transit light curves from spectrophotometric observations. It offers efficient model evaluation for multicolour observations and transmission spectroscopy, built-in supersampling to account for extended exposure times, and routines to calculate the projected planet-to-star distance for circular and eccentric orbits, transit durations, and more.

  13. Involvement of M3 Cholinergic Receptor Signal Transduction Pathway in Regulation of the Expression of Chemokine MOB-1, MCP-1 Genes in Pancreatic Acinar Cells

    Institute of Scientific and Technical Information of China (English)

    郑海; 陈道达; 张景輝; 田原

    2004-01-01

    Whether M3 cholinergic receptor signal transduction pathway is involved in regulation of the activation of NF-κB and the expression of chemokine MOB-1, MCP-1genes in pancreatic acinar cells was investigated. Rat pancreatic acinar cells were isolated, cultured and treated with carbachol, atropine and PDTC in vitro. The MOB-1 and MCP-1 mRNA expression was detected by using RT-PCR. The activation of NF-κB was monitored by using electrophoretic mobility shift assay.The results showed that as compared with control group, M3 cholinergic receptor agonist (103mol/L, 104-4ol/L carbachol) could induce a concentration-dependent and time-dependent increase in the expression of MOB-1, MCP-1 mRNA in pancreatic acinar cells. After treatment with 10 -3mol/L carbachol for 2 h, the expression of MOB-1, MCP-1 mRNA was strongest. The activity of NF-κB in pancreatic acinar cells was significantly increased (P<0.01) after treated with M3 cholinergic receptor agonist (10-3 mol/L carbachol) in vitro for 30 min. Either M3 cholinergic receptor antagonist (10-5 mol/L atropine) or NF-κB inhibitor (10-2 mol/L PDTC) could obviously inhibit the activation of NF-κB and the chemokine MOB-1, MCP-1 mRNA expression induced by carbachol (P <0.05). This inhibitory effect was significantly increased by atropine plus PDTC (P<0.01). The results of these studies indicated that M3 cholinergic receptor signal transduction pathway was likely involved in regulation of the expression of chemokine MOB-1 and MCP-1genes in pancreatic acinar cells in vitro through the activation of NF-κB.

  14. 天然产物(E)-3,5-二甲氧基二苯乙烯的合成%Synthesis of Natural Product (E) - 3, 5 - Dimethoxystilbene

    Institute of Scientific and Technical Information of China (English)

    杨金会; 刘海军

    2007-01-01

    以价廉易得的3,5-二羟基苯甲酸为原料,通过甲基化、还原、溴代、Arbuzor重排、Wittig-Horner缩合5步反应完成了目标化合物(E)-3,5-二甲氧基二苯乙烯的合成,总收率高达59.8%,各步反应所合成化合物结构均通过1H NMR及熔点进行了结构确证.

  15. Inactivation of SAG E3 ubiquitin ligase blocks embryonic stem cell differentiation and sensitizes leukemia cells to retinoid acid.

    Directory of Open Access Journals (Sweden)

    Mingjia Tan

    Full Text Available Sensitive to Apoptosis Gene (SAG, also known as RBX2 (RING box protein-2, is the RING component of SCF (SKP1, Cullin, and F-box protein E3 ubiquitin ligase. Our previous studies have demonstrated that SAG is an anti-apoptotic protein and an attractive anti-cancer target. We also found recently that Sag knockout sensitized mouse embryonic stem cells (mES to radiation and blocked mES cells to undergo endothelial differentiation. Here, we reported that compared to wild-type mES cells, the Sag(-/- mES cells were much more sensitive to all-trans retinoic acid (RA-induced suppression of cell proliferation and survival. While wild-type mES cells underwent differentiation upon exposure to RA, Sag(-/- mES cells were induced to death via apoptosis instead. The cell fate change, reflected by cellular stiffness, can be detected as early as 12 hrs post RA exposure by AFM (Atomic Force Microscopy. We then extended this novel finding to RA differentiation therapy of leukemia, in which the resistance often develops, by testing our hypothesis that SAG inhibition would sensitize leukemia to RA. Indeed, we found a direct correlation between SAG overexpression and RA resistance in multiple leukemia lines. By using MLN4924, a small molecule inhibitor of NEDD8-Activating Enzyme (NAE, that inactivates SAG-SCF E3 ligase by blocking cullin neddylation, we were able to sensitize two otherwise resistant leukemia cell lines, HL-60 and KG-1 to RA. Mechanistically, RA sensitization by MLN4924 was mediated via enhanced apoptosis, likely through accumulation of pro-apoptotic proteins NOXA and c-JUN, two well-known substrates of SAG-SCF E3 ligase. Taken together, our study provides the proof-of-concept evidence for effective treatment of leukemia patients by RA-MLN4924 combination.

  16. The Nedd4-like ubiquitin E3 ligases target angiomotin/p130 to ubiquitin-dependent degradation.

    Science.gov (United States)

    Wang, Chenji; An, Jian; Zhang, Pingzhao; Xu, Chen; Gao, Kun; Wu, Di; Wang, Dejie; Yu, Hongxiu; Liu, Jun O; Yu, Long

    2012-06-01

    AMOT (angiomotin) is a membrane-associated protein that is expressed in ECs (endothelial cells) and controls migration, TJ (tight junction) formation, cell polarity and angiogenesis. Recent studies have revealed that AMOT and two AMOT-like proteins, AMOTL1 and AMOTL2, play critical roles in the Hippo pathway by regulating the subcellular localization of the co-activators YAP (Yes-associated protein) and TAZ (transcriptional co-activator with PDZ-binding motif). However, it has been unclear how AMOT is regulated. In the present study, we report that AMOT undergoes proteasomal degradation. We identify three members of Nedd4 (neural-precursor-cell-expressed developmentally down-regulated)-like ubiquitin E3 ligases, Nedd4, Nedd4-2 and Itch, as the ubiquitin E3 ligases for the long isoform of AMOT, AMOT/p130. We demonstrate that Nedd4, Nedd4-2 and Itch mediate poly-ubiquitination of AMOT/p130 in vivo. Overexpression of Nedd4, Nedd4-2 or Itch leads to AMOT/p130 proteasomal degradation. Knockdown of Nedd4, Nedd4-2 and Itch causes an accumulation of steady-state level of AMOT/p130. We also show that three L/P-PXY motifs of AMOT/p130 and the WW domains of Nedd4 mediate their interaction. Furthermore, Nedd4-like ubiquitin E3 ligases might compete with YAP for the binding to AMOT/p130, and subsequently targeting AMOT/p130 for ubiquitin-dependent degradation. Together, these observations reveal a novel post-translational regulatory mechanism of AMOT/p130.

  17. The Blue Light-Dependent Polyubiquitination and Degradation of Arabidopsis Cryptochrome2 Requires Multiple E3 Ubiquitin Ligases.

    Science.gov (United States)

    Liu, Qing; Wang, Qin; Liu, Bin; Wang, Wei; Wang, Xu; Park, Joon; Yang, Zhenming; Du, Xinglin; Bian, Mingdi; Lin, Chentao

    2016-10-01

    Cryptochromes are blue light receptors regulated by light-dependent ubiquitination and degradation in both plant and animal lineages. The Arabidopsis genome encodes two cryptochromes, CRY1 and CRY2, of which CRY2 undergoes blue light-dependent ubiquitination and 26S proteasome-dependent degradation. The molecular mechanism regulating blue light-dependent proteolysis of CRY2 is still not fully understood. We found that the F-box proteins ZEITLUPE (ZTL) and Lov Kelch Protein2 (LKP2), which mediate blue light suppression of degradation of the CRY2 signaling partner CIB1, are not required for the blue light-dependent CRY2 degradation. We further showed that the previously reported function of the COP1-SPA1 protein complex in blue light-dependent CRY2 degradation is more likely to be attributable to its cullin 4 (CUL4)-based E3 ubiquitin ligase activity than its activity as the cryptochrome signaling partner. However, the blue light-dependent CRY2 degradation is only partially impaired in the cul4 mutant, the cop1-5 null mutant and the spa1234 quadruple mutant, suggesting a possible involvement of additional E3 ubiquitin ligases in the regulation of CRY2. Consistent with this hypothesis, we demonstrated that the blue light-dependent CRY2 degradation is significantly impaired in the temperature-sensitive cul1 mutant allele (axr6-3), especially under the non-permissive temperature. Based on these and other results presented, we propose that photoexcited CRY2 undergoes Lys48-linked polyubiquitination catalyzed by the CUL4- and CUL1-based E3 ubiquitin ligases.

  18. Recent development in thermally activated desalination methods: achieving an energy efficiency less than 2.5 kWhelec/m3

    KAUST Repository

    Shahzad, Muhammad Wakil

    2015-05-19

    Water-Energy-Environment nexus is a crucial consideration when designing seawater desalination processes, particularly for the water-stressed countries where the annual water availability is less than 250 m3 per capita. Despite the thermodynamics limit for seawater desalination at normal conditions is about 0.78 to 1.09 kWhelec/m3, the specific energy consumption of desalination of real plants is found to operate at several folds higher. Today’s technological advancement in membranes, namely the reverse osmosis processes, has set an energy consumption of around 3.5–5 kWhelec/m3, while the conventional perception of thermally activated processes such as MSF and MED tends to be higher. Although the higher energetic specific consumption of MED or MSF processes appeared to be higher at 60–100 kWhthermal/m3, their true electricity equivalent has been converted, hitherto, using the energetic analyses where the work potential of working steam of the processes cannot be captured adequately. Thermally activated processes, such as MED and MSF, form the bottoming cycle of a cogeneration plant where both electricity and desalination processes operate in tandem in a cascaded manner. Only the bled-steam at lower exergy is extracted for the desalination processes. In this presentation, we demonstrate that in a cogen plant with 30% bled-steam for MED processes, the exergy destruction ratio is found to be less than 7% of the total available exergy that emanated from the boilers. By the exergetic approach, the equivalent electricity consumption of an average 75 kWhthermal/m3 would result in an electrical equivalent of less than 2.5 kWhelec/m3. Also in this presentation, the authors will elaborate the latest developments in the use of hybridization concept where the MED and the AD cycles are thermodynamically integrated and enhancing the overall efficiency of desalination. © 2015 Balaban Desalination Publications. All rights reserved.

  19. A Sporadic Parkinson Disease Model via Silencing of the Ubiquitin-Proteasome/E3 Ligase Component SKP1A*

    OpenAIRE

    Fishman-Jacob, Tali; Reznichenko, Lydia; Youdim, Moussa B H; Mandel, Silvia A.

    2009-01-01

    The aim of this study was to develop a new model of sporadic Parkinson disease (PD) based on silencing of the SKP1A gene, a component of the ubiquitin-proteasome/E3 ligase complex, Skp1, Cullin 1, F-box protein, which was found to be highly decreased in the substantia nigra of sporadic PD patients. Initially, an embryonic mouse substantia nigra-derived cell line (SN4741 cells) was infected with short hairpin RNA lentiviruses encoding the murine transcript of the SKP1A gene or with scrambled v...

  20. Shigella IpaH7.8 E3 ubiquitin ligase targets glomulin and activates inflammasomes to demolish macrophages

    Science.gov (United States)

    Suzuki, Shiho; Mimuro, Hitomi; Kim, Minsoo; Ogawa, Michinaga; Ashida, Hiroshi; Toyotome, Takahito; Franchi, Luigi; Suzuki, Masato; Sanada, Takahito; Suzuki, Toshihiko; Tsutsui, Hiroko; Núñez, Gabriel; Sasakawa, Chihiro

    2014-01-01

    When nucleotide-binding oligomerization domain–like receptors (NLRs) sense cytosolic-invading bacteria, they induce the formation of inflammasomes and initiate an innate immune response. In quiescent cells, inflammasome activity is tightly regulated to prevent excess inflammation and cell death. Many bacterial pathogens provoke inflammasome activity and induce inflammatory responses, including cell death, by delivering type III secreted effectors, the rod component flagellin, and toxins. Recent studies indicated that Shigella deploy multiple mechanisms to stimulate NLR inflammasomes through type III secretion during infection. Here, we show that Shigella induces rapid macrophage cell death by delivering the invasion plasmid antigen H7.8 (IpaH7.8) enzyme 3 (E3) ubiquitin ligase effector via the type III secretion system, thereby activating the NLR family pyrin domain-containing 3 (NLRP3) and NLR family CARD domain-containing 4 (NLRC4) inflammasomes and caspase-1 and leading to macrophage cell death in an IpaH7.8 E3 ligase-dependent manner. Mice infected with Shigella possessing IpaH7.8, but not with Shigella possessing an IpaH7.8 E3 ligase-null mutant, exhibited enhanced bacterial multiplication. We defined glomulin/flagellar-associated protein 68 (GLMN) as an IpaH7.8 target involved in IpaH7.8 E3 ligase-dependent inflammasome activation. This protein originally was identified through its association with glomuvenous malformations and more recently was described as a member of a Cullin ring ligase inhibitor. Modifying GLMN levels through overexpression or knockdown led to reduced or augmented inflammasome activation, respectively. Macrophages stimulated with lipopolysaccharide/ATP induced GLMN puncta that localized with the active form of caspase-1. Macrophages from GLMN+/− mice were more responsive to inflammasome activation than those from GLMN+/+ mice. Together, these results highlight a unique bacterial adaptation that hijacks inflammasome activation via

  1. Overexpression of denticleless E3 ubiquitin protein ligase homolog (DTL) is related to poor outcome in gastric carcinoma

    OpenAIRE

    Kobayashi, Hiroki; Komatsu, Shuhei; Ichikawa, Daisuke; Kawaguchi, Tsutomu; Hirajima, Shoji; Miyamae, Mahito; Okajima, Wataru; Ohashi, Takuma; Kosuga, Toshiyuki; Konishi, Hirotaka; Shiozaki, Atsushi; FUJIWARA, Hitoshi; Okamoto, Kazuma; Tsuda, Hitoshi; Otsuji, Eigo

    2015-01-01

    Background Denticleless E3 ubiquitin protein ligase homolog (DTL) has been identified in amplified region (1q32) of several cancers and has an oncogenic function. In this study, we tested whether DTL acts as a cancer-promoting gene through its activation/overexpression in gastric cancer (GC). Methods We analyzed 7 GC cell lines and 100 primary tumors that were curatively resected in our hospital between 2001 and 2003. Results Overexpression of the DTL protein was detected in GC cell lines (4/...

  2. RING E3 mechanism for ubiquitin ligation to a disordered substrate visualized for human anaphase-promoting complex

    Science.gov (United States)

    Brown, Nicholas G.; VanderLinden, Ryan; Watson, Edmond R.; Qiao, Renping; Grace, Christy R. R.; Yamaguchi, Masaya; Weissmann, Florian; Frye, Jeremiah J.; Dube, Prakash; Ei Cho, Shein; Actis, Marcelo L.; Rodrigues, Patrick; Fujii, Naoaki; Peters, Jan-Michael; Stark, Holger; Schulman, Brenda A.

    2015-01-01

    For many E3 ligases, a mobile RING (Really Interesting New Gene) domain stimulates ubiquitin (Ub) transfer from a thioester-linked E2∼Ub intermediate to a lysine on a remotely bound disordered substrate. One such E3 is the gigantic, multisubunit 1.2-MDa anaphase-promoting complex/cyclosome (APC), which controls cell division by ubiquitinating cell cycle regulators to drive their timely degradation. Intrinsically disordered substrates are typically recruited via their KEN-box, D-box, and/or other motifs binding to APC and a coactivator such as CDH1. On the opposite side of the APC, the dynamic catalytic core contains the cullin-like subunit APC2 and its RING partner APC11, which collaborates with the E2 UBCH10 (UBE2C) to ubiquitinate substrates. However, how dynamic RING–E2∼Ub catalytic modules such as APC11–UBCH10∼Ub collide with distally tethered disordered substrates remains poorly understood. We report structural mechanisms of UBCH10 recruitment to APCCDH1 and substrate ubiquitination. Unexpectedly, in addition to binding APC11’s RING, UBCH10 is corecruited via interactions with APC2, which we visualized in a trapped complex representing an APCCDH1–UBCH10∼Ub–substrate intermediate by cryo-electron microscopy, and in isolation by X-ray crystallography. To our knowledge, this is the first structural view of APC, or any cullin–RING E3, with E2 and substrate juxtaposed, and it reveals how tripartite cullin–RING–E2 interactions establish APC’s specificity for UBCH10 and harness a flexible catalytic module to drive ubiquitination of lysines within an accessible zone. We propose that multisite interactions reduce the degrees of freedom available to dynamic RING E3–E2∼Ub catalytic modules, condense the search radius for target lysines, increase the chance of active-site collision with conformationally fluctuating substrates, and enable regulation. PMID:25825779

  3. E3 Charter Template

    Science.gov (United States)

    This is a charter template which includes decisions made during the project planning phase, as well as local project goals, a communication strategy, an outreach strategy, distribution of responsibilities and a schedule.

  4. Towards a liquid Argon TPC without evacuation filling of a 6$m^3$ vessel with argon gas from air to ppm impurities concentration through flushing

    CERN Document Server

    Curioni, A; Gendotti, A; Knecht, L; Lussi, D; Marchionni, A; Natterer, G; Resnati, F; Rubbia, A; Coleman, J; Lewis, M; Mavrokoridis, K; McCormick, K; Touramanis, C

    2010-01-01

    In this paper we present a successful experimental test of filling a volume of 6 $m^3$ with argon gas, starting from normal ambient air and reducing the impurities content down to few parts per million (ppm) oxygen equivalent. This level of contamination was directly monitored measuring the slow component of the scintillation light of the Ar gas, which is sensitive to $all$ sources of impurities affecting directly the argon scintillation.

  5. Sources and physical processes responsible for OH/H2O in the lunar soil as revealed by the Moon Mineralogy Mapper (M3)

    Science.gov (United States)

    McCord, T.B.; Taylor, L.A.; Combe, J.-P.; Kramer, G.; Pieters, C.M.; Sunshine, J.M.; Clark, R.N.

    2011-01-01

    Analysis of two absorption features near 3 m in the lunar reflectance spectrum, observed by the orbiting M3 spectrometer and interpreted as being due to OH and H2O, is presented, and the results are used to discuss the processes producing these molecules. This analysis focuses on the dependence of the absorptions on lunar physical properties, including composition, illumination, latitude, and temperature. Solar wind proton-induced hydroxylation is proposed as the creation process, and its products could be a source for other reported types of hydrogen-rich material and water. The irregular and damaged fine-grained lunar soil seems especially adapted for trapping solar wind protons and forming OH owing to abundant dangling oxygen bonds. The M3 data reveal that the strengths of the two absorptions are correlated and widespread, and both are correlated with lunar composition but in different ways. Feldspathic material seems richer in OH. These results seem to rule out water from the lunar interior and cometary infall as major sources. There appear to be correlations of apparent band strengths with time of day and lighting conditions. However, thermal emission from the Moon reduces the apparent strengths of the M3 absorptions, and its removal is not yet completely successful. Further, many of the lunar physical properties are themselves intercorrelated, and so separating these dependencies on the absorptions is difficult, due to the incomplete M3 data set. This process should also operate on other airless silicate surfaces, such as Mercury and Vesta, which will be visited by the Dawn spacecraft in mid-2011. Copyright 2011 by the American Geophysical Union.

  6. Virulence of two Streptococcus pyogenes strains (types M1 and M3) associated with toxic-shock-like syndrome depends on an intact mry-like gene.

    OpenAIRE

    Perez-Casal, J F; Dillon, H F; Husmann, L K; Graham, B.; Scott, J R

    1993-01-01

    The major virulence factor of Streptococcus pyogenes, the M protein, is positively regulated at the transcriptional level by mry in the M type 6 strain studied. We show here that in two S. pyogenes strains isolated from cases of toxic-shock-like syndrome, a type M1 strain and a type M3 strain, an mry-like gene is also required for resistance to phagocytosis.

  7. Comparison of Analysis Results Between 2D/1D Synthesis and RAPTOR-M3G in the Korea Standard Nuclear Plant (KSNP)

    Science.gov (United States)

    Joung Lim, Mi; Maeng, Young Jae; Fero, Arnold H.; Anderson, Stanwood L.

    2016-02-01

    The 2D/1D synthesis methodology has been used to calculate the fast neutron (E > 1.0 MeV) exposure to the beltline region of the reactor pressure vessel. This method uses the DORT 3.1 discrete ordinates code and the BUGLE-96 cross-section library based on ENDF/B-VI. RAPTOR-M3G (RApid Parallel Transport Of Radiation-Multiple 3D Geometries) which performs full 3D calculations was developed and is based on domain decomposition algorithms, where the spatial and angular domains are allocated and processed on multi-processor computer architecture. As compared to traditional single-processor applications, this approach reduces the computational load as well as the memory requirement per processor. Both methods are applied to surveillance test results for the Korea Standard Nuclear Plant (KSNP)-OPR (Optimized Power Reactor) 1000 MW. The objective of this paper is to compare the results of the KSNP surveillance program between 2D/1D synthesis and RAPTOR-M3G. Each operating KSNP has a reactor vessel surveillance program consisting of six surveillance capsules located between the core and the reactor vessel in the downcomer region near the reactor vessel wall. In addition to the In-Vessel surveillance program, an Ex-Vessel Neutron Dosimetry (EVND) program has been implemented. In order to estimate surveillance test results, cycle-specific forward transport calculations were performed by 2D/1D synthesis and by RAPTOR-M3G. The ratio between measured and calculated (M/C) reaction rates will be discussed. The current plan is to install an EVND system in all of the Korea PWRs including the new reactor type, APR (Advanced Power Reactor) 1400 MW. This work will play an important role in establishing a KSNP-specific database of surveillance test results and will employ RAPTOR-M3G for surveillance dosimetry location as well as positions in the KSNP reactor vessel.

  8. 肌肉白天使!——G—Power BMW M3(E92)GT2 R

    Institute of Scientific and Technical Information of China (English)

    斌志

    2013-01-01

    G-Power为德国老字号BMW改装商之一,推出了超暴力型的M3(E92)GT2R版本。雪白车漆配搭赛车拉花、20英寸黑色锻造轮毂、GT大尾翼以及全车碳纤宽体处理,横竖看都是暴力!!!

  9. RR Lyrae stars in the outer region of the globular cluster M3: a shortage of long periods at r ~ 3.5 to 6 arcmin ?

    CERN Document Server

    Butler, D J

    2004-01-01

    An analysis of the radial distribution of ab-type RR Lyrae star periods in the outer region of the globular cluster M3 at r >= 0.83 arcmin has been performed. That analysis points towards a real shortage of stars with long periods in the radial distance range 3.5 to 6 arcmin (or about 7 to 12 core radii). A brief discussion is presented. The origin of the phenomenon remains an open question.

  10. Real-space characterization of reactivity towards water at the B i2T e3 (111) surface

    Science.gov (United States)

    Zhang, Kai-Wen; Ding, Ding; Yang, Chao-Long; Gan, Yuan; Li, Shichao; Huang, Wen-Kai; Song, Ye-Heng; Jia, Zhen-Yu; Li, Xiang-Bing; Zhu, Zihua; Wen, Jinsheng; Chen, Mingshu; Li, Shao-Chun

    2016-06-01

    Surface reactivity is important in modifying the physical and chemical properties of surface-sensitive materials, such as the topological insulators. Even though many studies addressing the reactivity of topological insulators towards external gases have been reported, it is still under heavy debate whether and how the topological insulators react with H2O . Here, we employ scanning tunneling microscopy to directly probe the surface reaction of B i2T e3 towards H2O . Surprisingly, it is found that only the top quintuple layer is reactive to H2O , resulting in a hydrated Bi bilayer as well as some Bi islands, which passivate the surface and prevent subsequent reaction. A reaction mechanism is proposed with H2Te and hydrated Bi as the products. Unexpectedly, our study indicates that the reaction with water is intrinsic and not dependent on any surface defects. Since water inevitably exists, these findings provide key information when considering the reactions of B i2T e3 with residual gases or atmosphere.

  11. Sequence analysis of the E3 region and fiber gene of human adenovirus genome type 7h.

    Science.gov (United States)

    Kajon, A E; Wadell, G

    1996-01-15

    Adenovirus type 7h is currently the predominant virulent genome type of serotype 7 isolated in Argentina, Chile, and Uruguay in association with severe infantile pneumonia. In order to characterize possible molecular determinants of pathogenicity, the nucleotide sequence of a 5904-bp fragment (76 to 93 mu) containing the entire E3 region and the fiber gene of Ad7h was established. The organization of the ORFs within the E3 region was similar to that reported for the prototype strains of Ad7 and Ad3. A comparison of the nucleotide and amino acid sequences of all ORFs revealed a higher homology between Ad7h and Ad7p than between Ad7h and Ad3 for 12.0K and 16.1K, whereas the 15.3K ORF and the adjacent fiber gene were strikingly more homologous to those of Ad3 (99.5 vs 81.1% and 98.2 vs 66.6%, respectively). The equivalent to ORF 7.7K in Ad7p was missing in Ad7h due to a deletion and a mutation affecting the start codon (ATG-->ATT). Although the hemagglutinin of the Ad7h fiber could not be characterized due to its lack of activity on monkey erythrocytes, our results indicate that Ad7h is an intermediate strain 7-3.

  12. Iron-binding E3 ligase mediates iron response in plants by targeting basic helix-loop-helix transcription factors.

    Science.gov (United States)

    Selote, Devarshi; Samira, Rozalynne; Matthiadis, Anna; Gillikin, Jeffrey W; Long, Terri A

    2015-01-01

    Iron uptake and metabolism are tightly regulated in both plants and animals. In Arabidopsis (Arabidopsis thaliana), BRUTUS (BTS), which contains three hemerythrin (HHE) domains and a Really Interesting New Gene (RING) domain, interacts with basic helix-loop-helix transcription factors that are capable of forming heterodimers with POPEYE (PYE), a positive regulator of the iron deficiency response. BTS has been shown to have E3 ligase capacity and to play a role in root growth, rhizosphere acidification, and iron reductase activity in response to iron deprivation. To further characterize the function of this protein, we examined the expression pattern of recombinant ProBTS::β-GLUCURONIDASE and found that it is expressed in developing embryos and other reproductive tissues, corresponding with its apparent role in reproductive growth and development. Our findings also indicate that the interactions between BTS and PYE-like (PYEL) basic helix-loop-helix transcription factors occur within the nucleus and are dependent on the presence of the RING domain. We provide evidence that BTS facilitates 26S proteasome-mediated degradation of PYEL proteins in the absence of iron. We also determined that, upon binding iron at the HHE domains, BTS is destabilized and that this destabilization relies on specific residues within the HHE domains. This study reveals an important and unique mechanism for plant iron homeostasis whereby an E3 ubiquitin ligase may posttranslationally control components of the transcriptional regulatory network involved in the iron deficiency response.

  13. Ezrin ubiquitylation by the E3 ubiquitin ligase, WWP1, and consequent regulation of hepatocyte growth factor receptor activity.

    Directory of Open Access Journals (Sweden)

    Rania F Zaarour

    Full Text Available The membrane cytoskeleton linker ezrin participates in several functions downstream of the receptor Met in response to Hepatocyte Growth Factor (HGF stimulation. Here we report a novel interaction of ezrin with a HECT E3 ubiquitin ligase, WWP1/Aip5/Tiul1, a potential oncogene that undergoes genomic amplification and overexpression in human breast and prostate cancers. We show that ezrin binds to the WW domains of WWP1 via the consensus motif PPVY(477 present in ezrin's C-terminus. This association results in the ubiquitylation of ezrin, a process that requires an intact PPVY(477 motif. Interestingly ezrin ubiquitylation does not target the protein for degradation by the proteasome. We find that ezrin ubiquitylation by WWP1 in epithelial cells leads to the upregulation of Met level in absence of HGF stimulation and increases the response of Met to HGF stimulation as measured by the ability of the cells to heal a wound. Interestingly this effect requires ubiquitylated ezrin since it can be rescued, after depletion of endogenous ezrin, by wild type ezrin but not by a mutant of ezrin that cannot be ubiquitylated. Taken together our data reveal a new role for ezrin in Met receptor stability and activity through its association with the E3 ubiquitin ligase WWP1. Given the role of Met in cell proliferation and tumorigenesis, our results may provide a mechanistic basis for understanding the role of ezrin in tumor progression.

  14. The E3 Ubiquitin Ligase SCF(Cyclin F) Transmits AKT Signaling to the Cell-Cycle Machinery.

    Science.gov (United States)

    Choudhury, Rajarshi; Bonacci, Thomas; Wang, Xianxi; Truong, Andrew; Arceci, Anthony; Zhang, Yanqiong; Mills, Christine A; Kernan, Jennifer L; Liu, Pengda; Emanuele, Michael J

    2017-09-26

    The oncogenic AKT kinase is a key regulator of apoptosis, cell growth, and cell-cycle progression. Despite its important role in proliferation, it remains largely unknown how AKT is mechanistically linked to the cell cycle. We show here that cyclin F, a substrate receptor F-box protein for the SCF (Skp1/Cul1/F-box) family of E3 ubiquitin ligases, is a bona fide AKT substrate. Cyclin F expression oscillates throughout the cell cycle, a rare feature among the 69 human F-box proteins, and all of its known substrates are involved in proliferation. AKT phosphorylation of cyclin F enhances its stability and promotes assembly into productive E3 ligase complexes. Importantly, expression of mutant versions of cyclin F that cannot be phosphorylated by AKT impair cell-cycle entry. Our data suggest that cyclin F transmits mitogen signaling through AKT to the core cell-cycle machinery. This discovery has potential implications for proliferative control in malignancies where AKT is activated. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  15. The U-Box/ARM E3 ligase PUB13 regulates cell death, defense, and flowering time in Arabidopsis.

    Science.gov (United States)

    Li, Wei; Ahn, Il-Pyung; Ning, Yuese; Park, Chan-Ho; Zeng, Lirong; Whitehill, Justin G A; Lu, Haibin; Zhao, Qingzhen; Ding, Bo; Xie, Qi; Zhou, Jian-Min; Dai, Liangying; Wang, Guo-Liang

    2012-05-01

    The components in plant signal transduction pathways are intertwined and affect each other to coordinate plant growth, development, and defenses to stresses. The role of ubiquitination in connecting these pathways, particularly plant innate immunity and flowering, is largely unknown. Here, we report the dual roles for the Arabidopsis (Arabidopsis thaliana) Plant U-box protein13 (PUB13) in defense and flowering time control. In vitro ubiquitination assays indicated that PUB13 is an active E3 ubiquitin ligase and that the intact U-box domain is required for the E3 ligase activity. Disruption of the PUB13 gene by T-DNA insertion results in spontaneous cell death, the accumulation of hydrogen peroxide and salicylic acid (SA), and elevated resistance to biotrophic pathogens but increased susceptibility to necrotrophic pathogens. The cell death, hydrogen peroxide accumulation, and resistance to necrotrophic pathogens in pub13 are enhanced when plants are pretreated with high humidity. Importantly, pub13 also shows early flowering under middle- and long-day conditions, in which the expression of SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 and FLOWERING LOCUS T is induced while FLOWERING LOCUS C expression is suppressed. Finally, we found that two components involved in the SA-mediated signaling pathway, SID2 and PAD4, are required for the defense and flowering-time phenotypes caused by the loss of function of PUB13. Taken together, our data demonstrate that PUB13 acts as an important node connecting SA-dependent defense signaling and flowering time regulation in Arabidopsis.

  16. The Salmonella Effector Protein SopA Modulates Innate Immune Responses by Targeting TRIM E3 Ligase Family Members.

    Directory of Open Access Journals (Sweden)

    Jana Kamanova

    2016-04-01

    Full Text Available Salmonella Typhimurium stimulates inflammatory responses in the intestinal epithelium, which are essential for its ability to replicate within the intestinal tract. Stimulation of these responses is strictly dependent on the activity of a type III secretion system encoded within its pathogenicity island 1, which through the delivery of effector proteins, triggers signaling pathways leading to inflammation. One of these effectors is SopA, a HECT-type E3 ligase, which is required for the efficient stimulation of inflammation in an animal model of Salmonella Typhimurium infection. We show here that SopA contributes to the stimulation of innate immune responses by targeting two host E3 ubiquitin ligases, TRIM56 and TRIM65. We also found that TRIM65 interacts with the innate immune receptor MDA5 enhancing its ability to stimulate interferon-β signaling. Therefore, by targeting TRIM56 and TRIM65, SopA can stimulate signaling through two innate immune receptors, RIG-I and MDA5. These findings describe a Salmonella mechanism to modulate inflammatory responses by directly targeting innate immune signaling mechanisms.

  17. The putative E3 ubiquitin ligase ECERIFERUM9 regulates abscisic acid biosynthesis and response during seed germination and postgermination growth in arabidopsis

    KAUST Repository

    Zhao, Huayan

    2014-05-08

    The ECERIFERUM9 (CER9) gene encodes a putative E3 ubiquitin ligase that functions in cuticle biosynthesis and the maintenance of plant water status. Here, we found that CER9 is also involved in abscisic acid (ABA) signaling in seeds and young seedlings of Arabidopsis (Arabidopsis thaliana). The germinated embryos of the mutants exhibited enhanced sensitivity to ABA during the transition from reversible dormancy to determinate seedling growth. Expression of the CER9 gene is closely related to ABA levels and displays a similar pattern to that of ABSCISIC ACID-INSENSITIVE5 (ABI5), which encodes a positive regulator of ABA responses in seeds. cer9 mutant seeds exhibited delayed germination that is independent of seed coat permeability. Quantitative proteomic analyses showed that cer9 seeds had a protein profile similar to that of the wild type treated with ABA. Transcriptomics analyses revealed that genes involved in ABA biosynthesis or signaling pathways were differentially regulated in cer9 seeds. Consistent with this, high levels of ABA were detected in dry seeds of cer9. Blocking ABA biosynthesis by fluridone treatment or by combining an ABA-deficient mutation with cer9 attenuated the phenotypes of cer9. Whereas introduction of the abi1-1, abi3-1, or abi4-103 mutation could completely eliminate the ABA hypersensitivity of cer9, introduction of abi5 resulted only in partial suppression. These results indicate that CER9 is a novel negative regulator of ABA biosynthesis and the ABA signaling pathway during seed germination. © 2014 American Society of Plant Biologists. All Rights Reserved.

  18. Progressive Purkinje cell degeneration in tambaleante mutant mice is a consequence of a missense mutation in HERC1 E3 ubiquitin ligase.

    Directory of Open Access Journals (Sweden)

    Tomoji Mashimo

    2009-12-01

    Full Text Available The HERC gene family encodes proteins with two characteristic domains: HECT and RCC1-like. Proteins with HECT domains have been described to function as ubiquitin ligases, and those that contain RCC1-like domains have been reported to function as GTPases regulators. These two activities are essential in a number of important cellular processes such as cell cycle, cell signaling, and membrane trafficking. Mutations affecting these domains have been found associated with retinitis pigmentosa, amyotrophic lateral sclerosis, and cancer. In humans, six HERC genes have been reported which encode two subgroups of HERC proteins: large (HERC1-2 and small (HERC3-6. The giant HERC1 protein was the first to be identified. It has been involved in membrane trafficking and cell proliferation/growth through its interactions with clathrin, M2-pyruvate kinase, and TSC2 proteins. Mutations affecting other members of the HERC family have been found to be associated with sterility and growth retardation. Here, we report the characterization of a recessive mutation named tambaleante, which causes progressive Purkinje cell degeneration leading to severe ataxia with reduced growth and lifespan in homozygous mice aged over two months. We mapped this mutation in mouse chromosome 9 and then performed positional cloning. We found a GA transition at position 1448, causing a Gly to Glu substitution (Gly483Glu in the highly conserved N-terminal RCC1-like domain of the HERC1 protein. Successful transgenic rescue, with either a mouse BAC containing the normal copy of Herc1 or with the human HERC1 cDNA, validated our findings. Histological and biochemical studies revealed extensive autophagy associated with an increase of the mutant protein level and a decrease of mTOR activity. Our observations concerning this first mutation in the Herc1 gene contribute to the functional annotation of the encoded E3 ubiquitin ligase and underline the crucial and unexpected role of this protein

  19. Sleep as spatiotemporal integration of biological processes that evolved to periodically reinforce neurodynamic and metabolic homeostasis: The 2m3d paradigm of sleep.

    Science.gov (United States)

    Mader, Edward Claro; Mader, Annie Cielo Llave

    2016-08-15

    Sleep continues to perplex scientists and researchers. Despite decades of sleep research, we still lack a clear understanding of the biological functions and evolution of sleep. In this review, we will examine sleep from a functional and phylogenetic perspective and describe some important conceptual gaps in understanding sleep. Classical theories of the biology and evolution of sleep emphasize sensory activation, energy balance, and metabolic homeostasis. Advances in electrophysiology, functional neuroimaging, and neuroplasticity allow us to view sleep within the framework of neural dynamics. With this paradigm shift, we have come to realize the importance of neurodynamic homeostasis in shaping the biology of sleep. Evidently, animals sleep to achieve neurodynamic and metabolic homeostasis. We are not aware of any framework for understanding sleep where neurodynamic, metabolic, homeostatic, chronophasic, and afferent variables are all taken into account. This motivated us to propose the two-mode three-drive (2m3d) paradigm of sleep. In the 2m3d paradigm, local neurodynamic/metabolic (N/M) processes switch between two modes-m0 and m1-in response to three drives-afferent, chronophasic, and homeostatic. The spatiotemporal integration of local m0/m1 operations gives rise to the global states of sleep and wakefulness. As a framework of evolution, the 2m3d paradigm allows us to view sleep as a robust adaptive strategy that evolved so animals can periodically reinforce neurodynamic and metabolic homeostasis while remaining sensitive to their internal and external environment.

  20. Describing the heavy-ion above-barrier fusion using the bare potentials resulting from Migdal and M3Y double-folding approaches

    Science.gov (United States)

    Gontchar, I. I.; Chushnyakova, M. V.

    2016-08-01

    Systematic calculations of the Coulomb barrier parameters for collisions of spherical nuclei are performed within the framework of the double folding approach. The value of the parameter {B}Z={Z}P{Z}T/({A}P{1/3}+{A}T{1/3}) (which estimates the Coulomb barrier height) varies in these calculations from 10 MeV up to 150 MeV. The nuclear densities came from the Hartree-Fock calculations which reproduce the experimental charge densities with good accuracy. For the nucleon-nucleon effective interaction two analytical approximations known in the literature are used: the M3Y and Migdal forces. The calculations show that Migdal interaction always results in the higher Coulomb barrier. Moreover, as B Z increases the difference between the M3Y and Migdal barrier heights systematically increases as well. As the result, the above barrier fusion cross sections calculated dynamically with the M3Y forces and surface friction are in agreement with the data. The cross sections calculated with the Migdal forces are always below the experimental data even without accounting for the dissipation.

  1. Describing the heavy-ion above-barrier fusion using the bare potentials resulting from Migdal and M3Y double-folding approaches

    CERN Document Server

    Gontchar, Igor

    2015-01-01

    Systematic calculations of the Coulomb barrier parameters for collisions of spherical nuclei are performed within the framework of the double folding approach. The value of the parameter $B_Z=Z_PZ_T/(A^{1/3}_P+(A^{1/3}_P)$ (which estimates the Coulomb barrier height) varies in these calculations from 10 MeV up to 150 MeV. The nuclear densities came from the Hartree-Fock calculations which reproduce the experimental charge densities with good accuracy. For the nucleon-nucleon effective interaction two analytical approximations known in the literature are used: the M3Y and Migdal forces. The calculations show that Migdal interaction always results in the higher Coulomb barrier. Moreover, as $B_Z$ increases the difference between the M3Y and Migdal barrier heights systematically increases as well. As the result, the above barrier fusion cross sections calculated dynamically with the M3Y forces and surface friction are in agreement with the data. The cross sections calculated with the Migdal forces are always bel...

  2. K3M3 METAR

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — METAR is a routine scheduled observation and is the primary observation code used in the United States to satisfy requirements for reporting surface meteorological...

  3. 基于E^3-Value的服务供应链运作管理流程和方法%E^3-value based operation management process and method for service supply chain

    Institute of Scientific and Technical Information of China (English)

    何霆; 徐晓飞; 金铮

    2011-01-01

    目前尽管存在较多以产品为中心的供应链运作管理流程和方法,但在服务供应链领域,由于服务不同于产品的诸多特性局限了其进一步的应用。因此,采用结构化分析思想和方法,提出了基于E3-value的服务供应链运作管理逻辑流程和方法,该方法以价值为导向,不但可以解决现有供应链运作管理模式的一些适应性问题,而且能够解决"供应链运作管理模式为什么是这样,潜在盈利性如何量化"问题。%There were extensive product-centered supply chain operation management processes and methods at present.In Service Supply Chain(SSC) domain,these methods and processes did not have further application due to the differences between service and product.For above reasons,by using analytic technique of structuring,E3-value based operation management logistic process and method for SSC were proposed.This value oriented method could not only resolve the problems of applicability and effectiveness of the existing supply chain management models and methods,but answer the questions of "why the management model is like this?" and "how to quantify the potential profitability of the supply chains?"

  4. [Physiological and biochemical properties of the bacterial association of Klebsiella terrigena E6 and Bacillus firmus E3].

    Science.gov (United States)

    Zlotnikov, A K; Kazakov, M L; Zlotnikov, K M; Kazakov, A V; Umarov, M M

    2007-01-01

    Physiological and biochemical properties of the natural rhizospheric association of Klebsiella terrigena E6 and Bacillusfirmus E3 were studied. It was demonstrated that this association fixed actively molecular nitrogen at a rate of 110 nmol ethylene per 1 mg protein per h. The dynamics of bacterial population in the association and in pure cultures were studied. The properties of this association depended on the ratio of its components; the maximal nitrogen fixation was recorded at a content of B. firmus E310 amounting to 15% of the total cell number. It was demonstrated that the stability basis of this association was the specific interactions via its components via metabolites--phenol and para-hydroxybenzoic acid--as well as via nitrogen fixation, respiration, and pH of the medium. A scheme of the interactions between the components of association is shown.

  5. Crystal structure of the substrate-recognition domain of the Shigella E3 ligase IpaH9.8.

    Science.gov (United States)

    Takagi, Kenji; Kim, Minsoo; Sasakawa, Chihiro; Mizushima, Tsunehiro

    2016-04-01

    Infectious diseases caused by bacteria have significant impacts on global public health. During infection, pathogenic bacteria deliver a variety of virulence factors, called effectors, into host cells. The Shigella effector IpaH9.8 functions as an ubiquitin ligase, ubiquitinating the NF-κB essential modulator (NEMO)/IKK-γ to inhibit host inflammatory responses. IpaH9.8 contains leucine-rich repeats (LRRs) involved in substrate recognition and an E3 ligase domain. To elucidate the structural basis of the function of IpaH9.8, the crystal structure of the LRR domain of Shigella IpaH9.8 was determined and this structure was compared with the known structures of other IpaH family members. This model provides insights into the structural features involved in substrate specificity.

  6. Skeletal muscle atrophy and the E3 ubiquitin ligases MuRF1 and MAFbx/atrogin-1.

    Science.gov (United States)

    Bodine, Sue C; Baehr, Leslie M

    2014-09-15

    Muscle RING finger 1 (MuRF1) and muscle atrophy F-box (MAFbx)/atrogin-1 were identified more than 10 years ago as two muscle-specific E3 ubiquitin ligases that are increased transcriptionally in skeletal muscle under atrophy-inducing conditions, making them excellent markers of muscle atrophy. In the past 10 years much has been published about MuRF1 and MAFbx with respect to their mRNA expression patterns under atrophy-inducing conditions, their transcriptional regulation, and their putative substrates. However, much remains to be learned about the physiological role of both genes in the regulation of mass and other cellular functions in striated muscle. Although both MuRF1 and MAFbx are enriched in skeletal, cardiac, and smooth muscle, this review will focus on the current understanding of MuRF1 and MAFbx in skeletal muscle, highlighting the critical questions that remain to be answered.

  7. Structure of the Siz/PIAS SUMO E3 Ligase Siz1 and Determinants Required for SUMO Modification of PCNA

    Energy Technology Data Exchange (ETDEWEB)

    Yunus, Ali A.; Lima, Christopher D.; (SKI)

    2010-01-12

    Siz1 is a founding member of the Siz/PIAS RING family of SUMO E3 ligases. The X-ray structure of an active Siz1 ligase revealed an elongated tripartite architecture comprised of an N-terminal PINIT domain, a central zinc-containing RING-like SP-RING domain, and a C-terminal domain we term the SP-CTD. Structure-based mutational analysis and biochemical studies show that the SP-RING and SP-CTD are required for activation of the E2SUMO thioester, while the PINIT domain is essential for redirecting SUMO conjugation to the proliferating cell nuclear antigen (PCNA) at lysine 164, a nonconsensus lysine residue that is not modified by the SUMO E2 in the absence of Siz1. Mutational analysis of Siz1 and PCNA revealed surfaces on both proteins that are required for efficient SUMO modification of PCNA in vitro and in vivo.

  8. Search for heavy top quark partners with charge 5e/3 in the single lepton final state

    Science.gov (United States)

    Sagir, Sinan; CMS Collaboration

    2016-03-01

    A search is presented for a very heavy fermionic partner of the top quark with charge 5e/3 (X5 / 3), which is expected to decay into a top quark and a W boson. Events consistent with pair production of X5 / 3, where one of the four W bosons from the decays of X5 / 3 and top quarks decays leptonically, and all the other W bosons decay hadronically, are analyzed. The results from this semi-leptonic final state are then combined with same-sign dileptons signature to enhance the sensitivity. No excess of data above SM expectations is observed and 95 % CL upper limits on the X5 / 3 production cross section are set using the data corresponding to an integrated luminosity of 2.2 fb-1 collected by the CMS detector at center-of-mass energy of 13 TeV.

  9. Ubiquitylation of FACT by the cullin-E3 ligase Rtt101 connects FACT to DNA replication.

    Science.gov (United States)

    Han, Junhong; Li, Qing; McCullough, Laura; Kettelkamp, Charisse; Formosa, Tim; Zhang, Zhiguo

    2010-07-15

    FACT plays important roles in both gene transcription and DNA replication. However, how this protein complex is targeted to these two distinct cellular processes remains largely unknown. Here we show that ubiquitylation of the Spt16 subunit of FACT by Rtt101, the cullin subunit of an E3 ubiquitin ligase in Saccharomyces cerevisiae, links FACT to DNA replication. We find Rtt101 interacts with and ubiquitylates Spt16 in vitro and in vivo. Deletion of RTT101 leads to reduced association of both FACT and the replicative helicase MCM with replication origins. Loss of Rtt101 also reduces binding of FACT to MCM, but not the association of FACT with Leo1 and Spt5, two proteins involved in transcription. Origin function is compromised in cells lacking Rtt101 or with an Spt16 mutation. These findings identify Spt16 as an Rtt101 substrate, and suggest that Spt16 ubiquitylation is important for FACT to function during DNA replication.

  10. Sustainable energy development in Austria until 2020: Insights from applying the integrated model “e3.at”

    Science.gov (United States)

    Stocker, Andrea; Großmann, Anett; Madlener, Reinhard; Wolter, Marc Ingo

    2011-01-01

    This paper reports on the Austrian research project “Renewable energy in Austria: Modeling possible development trends until 2020”. The project investigated possible economic and ecological effects of a substantially increased use of renewable energy sources in Austria. Together with stakeholders and experts, three different scenarios were defined, specifying possible development trends for renewable energy in Austria. The scenarios were simulated for the period 2006–2020, using the integrated environment–energy–economy model “e3.at”. The modeling results indicate that increasing the share of renewable energy sources in total energy use is an important but insufficient step towards achieving a sustainable energy system in Austria. A substantial increase in energy efficiency and a reduction of residential energy consumption also form important cornerstones of a sustainable energy policy. PMID:21976785

  11. (E-3,4,5-Trimethoxy-N′-[(4-oxo-4H-chromen-3-ylmethylidene]benzohydrazide

    Directory of Open Access Journals (Sweden)

    Yoshinobu Ishikawa

    2014-04-01

    Full Text Available In the title chromone-tethered benzohydrazide derivative, C20H18N2O6, the atoms of the E-3-(hydrazonomethyl-4H-chromen-4-one segment are essentially coplanar, the largest deviation being 0.065 (6 Å. The dihedral angle between this segment and the benzene ring of the trimethoxybenzene unit is 40.18 (10 Å. In the crystal, the molecule is linked to its inverse-symmetry equivalent by pairs of N—H...O hydrogen bonds and C—H...π interactions. The –CH=N—NH– segment is stacked on the benzene ring of the chromone unit of a translation-related equivalent molecule [centroid–centroid distance = 3.413 (6 Å].

  12. Discovery of antibiotic (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one.

    Science.gov (United States)

    Bouley, Renee; Kumarasiri, Malika; Peng, Zhihong; Otero, Lisandro H; Song, Wei; Suckow, Mark A; Schroeder, Valerie A; Wolter, William R; Lastochkin, Elena; Antunes, Nuno T; Pi, Hualiang; Vakulenko, Sergei; Hermoso, Juan A; Chang, Mayland; Mobashery, Shahriar

    2015-02-11

    In the face of the clinical challenge posed by resistant bacteria, the present needs for novel classes of antibiotics are genuine. In silico docking and screening, followed by chemical synthesis of a library of quinazolinones, led to the discovery of (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one (compound 2) as an antibiotic effective in vivo against methicillin-resistant Staphylococcus aureus (MRSA). This antibiotic impairs cell-wall biosynthesis as documented by functional assays, showing binding of 2 to penicillin-binding protein (PBP) 2a. We document that the antibiotic also inhibits PBP1 of S. aureus, indicating a broad targeting of structurally similar PBPs by this antibiotic. This class of antibiotics holds promise in fighting MRSA infections.

  13. Skeletal muscle atrophy and the E3 ubiquitin ligases MuRF1 and MAFbx/atrogin-1

    Science.gov (United States)

    Baehr, Leslie M.

    2014-01-01

    Muscle RING finger 1 (MuRF1) and muscle atrophy F-box (MAFbx)/atrogin-1 were identified more than 10 years ago as two muscle-specific E3 ubiquitin ligases that are increased transcriptionally in skeletal muscle under atrophy-inducing conditions, making them excellent markers of muscle atrophy. In the past 10 years much has been published about MuRF1 and MAFbx with respect to their mRNA expression patterns under atrophy-inducing conditions, their transcriptional regulation, and their putative substrates. However, much remains to be learned about the physiological role of both genes in the regulation of mass and other cellular functions in striated muscle. Although both MuRF1 and MAFbx are enriched in skeletal, cardiac, and smooth muscle, this review will focus on the current understanding of MuRF1 and MAFbx in skeletal muscle, highlighting the critical questions that remain to be answered. PMID:25096180

  14. PUB13, a U-box/ARM E3 ligase, regulates plant defense, cell death, and flowering time.

    Science.gov (United States)

    Li, Wei; Dai, Liangying; Wang, Guo-Liang

    2012-08-01

    The ubiquitination pathway is involved in a variety of cellular processes in plant growth, development, and immune responses. However, the function of this pathway in connecting plant development and innate immunity is still largely unknown. Recently, we characterized the U-box/ARM E3 ubiquitin ligase PUB13, which regulates both immune responses and flowering time in Arabidopsis. Here, we show that the rice Spl11 gene can complement the cell death and flowering functions of PUB13 in the pub13 mutant. In addition, HFR1, which functions mainly in photomorphogenesis, was identified as one of the PUB13-interacting proteins through yeast two-hybrid screening and pull-down assays. Because the flowering phenotype of pub13 depends on photoperiod, we propose that PUB13 may regulate HFR1 to fine-tune photomorphogenesis and flowering time in Arabidopsis.

  15. A sporadic Parkinson disease model via silencing of the ubiquitin-proteasome/E3 ligase component SKP1A.

    Science.gov (United States)

    Fishman-Jacob, Tali; Reznichenko, Lydia; Youdim, Moussa B H; Mandel, Silvia A

    2009-11-20

    The aim of this study was to develop a new model of sporadic Parkinson disease (PD) based on silencing of the SKP1A gene, a component of the ubiquitin-proteasome/E3 ligase complex, Skp1, Cullin 1, F-box protein, which was found to be highly decreased in the substantia nigra of sporadic PD patients. Initially, an embryonic mouse substantia nigra-derived cell line (SN4741 cells) was infected with short hairpin RNA lentiviruses encoding the murine transcript of the SKP1A gene or with scrambled vector. SKP1A silencing resulted in increased susceptibility to neuronal damages induced by the parkinsonism-inducing neurotoxin 1-methyl-4-phenylpyridinium ion and serum starvation, in parallel with a decline in the expression of the dopaminergic markers, dopamine transporter and vesicular monoamine transporter-2. SKP1A-deficient cells presented a delay in completion of the cell cycle and the inability to arrest at the G(0)/G(1) phase when induced to differentiate. Instead, the cells progressed through S phase, developing rounded aggregates with characteristics of aggresomes including immunoreactivity for gamma-tubulin, alpha-synuclein, ubiquitin, tyrosine hydroxylase, Hsc-70 (70-kDa heat shock cognate protein), and proteasome subunit, and culminating in a lethal phenotype. Conversely, stably enforced expression of wild type SKP1A duplicated the survival index of naïve SN4741 cells under proteasomal inhibition injury, suggesting a new structural role of SKP1 in dopaminergic neuronal function, besides its E3 ligase activity. These results link, for the first time, SKP1 to dopamine neuronal function and survival, suggesting an essential role in sporadic PD. In summary, this new model has reproduced to a significant extent the molecular alterations described in sporadic PD at the cellular level, implicating Skp1 as a potential modifier in sporadic PD neurodegeneration.

  16. A Sporadic Parkinson Disease Model via Silencing of the Ubiquitin-Proteasome/E3 Ligase Component SKP1A*

    Science.gov (United States)

    Fishman-Jacob, Tali; Reznichenko, Lydia; Youdim, Moussa B. H.; Mandel, Silvia A.

    2009-01-01

    The aim of this study was to develop a new model of sporadic Parkinson disease (PD) based on silencing of the SKP1A gene, a component of the ubiquitin-proteasome/E3 ligase complex, Skp1, Cullin 1, F-box protein, which was found to be highly decreased in the substantia nigra of sporadic PD patients. Initially, an embryonic mouse substantia nigra-derived cell line (SN4741 cells) was infected with short hairpin RNA lentiviruses encoding the murine transcript of the SKP1A gene or with scrambled vector. SKP1A silencing resulted in increased susceptibility to neuronal damages induced by the parkinsonism-inducing neurotoxin 1-methyl-4-phenylpyridinium ion and serum starvation, in parallel with a decline in the expression of the dopaminergic markers, dopamine transporter and vesicular monoamine transporter-2. SKP1A-deficient cells presented a delay in completion of the cell cycle and the inability to arrest at the G0/G1 phase when induced to differentiate. Instead, the cells progressed through S phase, developing rounded aggregates with characteristics of aggresomes including immunoreactivity for γ-tubulin, α-synuclein, ubiquitin, tyrosine hydroxylase, Hsc-70 (70-kDa heat shock cognate protein), and proteasome subunit, and culminating in a lethal phenotype. Conversely, stably enforced expression of wild type SKP1A duplicated the survival index of naïve SN4741 cells under proteasomal inhibition injury, suggesting a new structural role of SKP1 in dopaminergic neuronal function, besides its E3 ligase activity. These results link, for the first time, SKP1 to dopamine neuronal function and survival, suggesting an essential role in sporadic PD. In summary, this new model has reproduced to a significant extent the molecular alterations described in sporadic PD at the cellular level, implicating Skp1 as a potential modifier in sporadic PD neurodegeneration. PMID:19748892

  17. HDAC7 Ubiquitination by the E3 Ligase CBX4 Is Involved in Contextual Fear Conditioning Memory Formation.

    Science.gov (United States)

    Jing, Xu; Sui, Wen-Hai; Wang, Shuai; Xu, Xu-Feng; Yuan, Rong-Rong; Chen, Xiao-Rong; Ma, Hui-Xian; Zhu, Ying-Xiao; Sun, Jin-Kai; Yi, Fan; Chen, Zhe-Yu; Wang, Yue

    2017-04-05

    Histone acetylation, an epigenetic modification, plays an important role in long-term memory formation. Recently, histone deacetylase (HDAC) inhibitors were demonstrated to promote memory formation, which raises the intriguing possibility that they may be used to rescue memory deficits. However, additional research is necessary to clarify the roles of individual HDACs in memory. In this study, we demonstrated that HDAC7, within the dorsal hippocampus of C57BL6J mice, had a late and persistent decrease after contextual fear conditioning (CFC) training (4-24 h), which was involved in long-term CFC memory formation. We also showed that HDAC7 decreased via ubiquitin-dependent degradation. CBX4 was one of the HDAC7 E3 ligases involved in this process. Nur77, as one of the target genes of HDAC7, increased 6-24 h after CFC training and, accordingly, modulated the formation of CFC memory. Finally, HDAC7 was involved in the formation of other hippocampal-dependent memories, including the Morris water maze and object location test. The current findings facilitate an understanding of the molecular and cellular mechanisms of HDAC7 in the regulation of hippocampal-dependent memory.SIGNIFICANCE STATEMENT The current findings demonstrated the effects of histone deacetylase 7 (HDAC7) on hippocampal-dependent memories. Moreover, we determined the mechanism of decreased HDAC7 in contextual fear conditioning (CFC) through ubiquitin-dependent protein degradation. We also verified that CBX4 was one of the HDAC7 E3 ligases. Finally, we demonstrated that Nur77, as one of the important targets for HDAC7, was involved in CFC memory formation. All of these proteins, including HDAC7, CBX4, and Nur77, could be potential therapeutic targets for preventing memory deficits in aging and neurological diseases. Copyright © 2017 the authors 0270-6474/17/373848-16$15.00/0.

  18. UBR-5, a Conserved HECT-Type E3 Ubiquitin Ligase, Negatively Regulates Notch-Type Signaling in Caenorhabditis elegans

    Science.gov (United States)

    Safdar, Komal; Gu, Anniya; Xu, Xia; Au, Vinci; Taylor, Jon; Flibotte, Stephane; Moerman, Donald G.; Maine, Eleanor M.

    2016-01-01

    Notch-type signaling mediates cell−cell interactions important for animal development. In humans, reduced or inappropriate Notch signaling activity is associated with various developmental defects and disease states, including cancers. Caenorhabditis elegans expresses two Notch-type receptors, GLP-1 and LIN-12. GLP-1 mediates several cell-signaling events in the embryo and promotes germline proliferation in the developing and adult gonad. LIN-12 acts redundantly with GLP-1 in certain inductive events in the embryo and mediates several cell−cell interactions during larval development. Recovery of genetic suppressors and enhancers of glp-1 or lin-12 loss- or gain-of-function mutations has identified numerous regulators of GLP-1 and LIN-12 signaling activity. Here, we report the molecular identification of sog-1, a gene identified in screens for recessive suppressors of conditional glp-1 loss-of-function mutations. The sog-1 gene encodes UBR-5, the sole C. elegans member of the UBR5/Hyd family of HECT-type E3 ubiquitin ligases. Molecular and genetic analyses indicate that the loss of ubr-5 function suppresses defects caused by reduced signaling via GLP-1 or LIN-12. In contrast, ubr-5 mutations do not suppress embryonic or larval lethality associated with mutations in a downstream transcription factor, LAG-1. In the gonad, ubr-5 acts in the receiving cells (germ cells) to limit GLP-1 signaling activity. SEL-10 is the F-box component of SCFSEL-10 E3 ubiquitin–ligase complex that promotes turnover of Notch intracellular domain. UBR-5 acts redundantly with SEL-10 to limit Notch signaling in certain tissues. We hypothesize that UBR-5 activity limits Notch-type signaling by promoting turnover of receptor or limiting its interaction with pathway components. PMID:27185398

  19. UBR-5, a Conserved HECT-Type E3 Ubiquitin Ligase, Negatively Regulates Notch-Type Signaling in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Komal Safdar

    2016-07-01

    Full Text Available Notch-type signaling mediates cell−cell interactions important for animal development. In humans, reduced or inappropriate Notch signaling activity is associated with various developmental defects and disease states, including cancers. Caenorhabditis elegans expresses two Notch-type receptors, GLP-1 and LIN-12. GLP-1 mediates several cell-signaling events in the embryo and promotes germline proliferation in the developing and adult gonad. LIN-12 acts redundantly with GLP-1 in certain inductive events in the embryo and mediates several cell−cell interactions during larval development. Recovery of genetic suppressors and enhancers of glp-1 or lin-12 loss- or gain-of-function mutations has identified numerous regulators of GLP-1 and LIN-12 signaling activity. Here, we report the molecular identification of sog-1, a gene identified in screens for recessive suppressors of conditional glp-1 loss-of-function mutations. The sog-1 gene encodes UBR-5, the sole C. elegans member of the UBR5/Hyd family of HECT-type E3 ubiquitin ligases. Molecular and genetic analyses indicate that the loss of ubr-5 function suppresses defects caused by reduced signaling via GLP-1 or LIN-12. In contrast, ubr-5 mutations do not suppress embryonic or larval lethality associated with mutations in a downstream transcription factor, LAG-1. In the gonad, ubr-5 acts in the receiving cells (germ cells to limit GLP-1 signaling activity. SEL-10 is the F-box component of SCFSEL-10 E3 ubiquitin–ligase complex that promotes turnover of Notch intracellular domain. UBR-5 acts redundantly with SEL-10 to limit Notch signaling in certain tissues. We hypothesize that UBR-5 activity limits Notch-type signaling by promoting turnover of receptor or limiting its interaction with pathway components.

  20. HIV-1 Vpr-mediated G2 arrest involves the DDB1-CUL4AVPRBP E3 ubiquitin ligase.

    Directory of Open Access Journals (Sweden)

    Jean-Philippe Belzile

    2007-07-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 viral protein R (Vpr has been shown to cause G2 cell cycle arrest in human cells by inducing ATR-mediated inactivation of p34cdc2, but factors directly engaged in this process remain unknown. We used tandem affinity purification to isolate native Vpr complexes. We found that damaged DNA binding protein 1 (DDB1, viral protein R binding protein (VPRBP, and cullin 4A (CUL4A--components of a CUL4A E3 ubiquitin ligase complex, DDB1-CUL4A(VPRBP--were able to associate with Vpr. Depletion of VPRBP by small interfering RNA impaired Vpr-mediated induction of G2 arrest. Importantly, VPRBP knockdown alone did not affect normal cell cycle progression or activation of ATR checkpoints, suggesting that the involvement of VPRBP in G2 arrest was specific to Vpr. Moreover, leucine/isoleucine-rich domain Vpr mutants impaired in their ability to interact with VPRBP and DDB1 also produced strongly attenuated G2 arrest. In contrast, G2 arrest-defective C-terminal Vpr mutants were found to maintain their ability to associate with these proteins, suggesting that the interaction of Vpr with the DDB1-VPRBP complex is necessary but not sufficient to block cell cycle progression. Overall, these results point toward a model in which Vpr could act as a connector between the DDB1-CUL4A(VPRBP E3 ubiquitin ligase complex and an unknown cellular factor whose proteolysis or modulation of activity through ubiquitination would activate ATR-mediated checkpoint signaling and induce G2 arrest.