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Sample records for atf torsatron

  1. Runaway studies in the ATF [Advanced Toroidal Facility] torsatron

    International Nuclear Information System (INIS)

    Pulsed torsatrons and heliotrons are susceptible to runaway electron formation and confinement resulting from the inherent good containment in the vacuum fields and the high loop voltages during the initiation and termination of the helical and vertical fields (''field ramping''). Because runaway electrons can cause an unacceptable level of hard X rays near the machine, a runaway suppression system was designed and included in the initial operation of the Advanced Toroidal Facility (ATF). The main component of the system is a rotating paddle that is normally left in the vacuum chamber during the field ramps. This device proved to be very effective in reducing the runaway population. Measurements of hard X rays from ATF have shown that the runaways are produced primarily during the field ramping but that usually a small steady-state runaway component is also present during the ''flat-top'' portion of the fields. The paddle is the main source of the hard X rays (thick-target bremsstrahlung), although other objects in the vacuum chamber also serve as targets for the runaways at various times. The maximum X-ray energy found by pulse height analysis is /approximately/12--15 MeV; the mean energy appears to be a few mega-electron-volts. A noticeable forward peaking of the bremsstrahlung from the paddle is evident. The limiters do not appear to be major sources of bremsstrahlung. 17 refs., 14 figs

  2. Experimental studies of radio frequency waves and confinement in the Auburn Torsatron

    International Nuclear Information System (INIS)

    The Auburn University Torsatron Group has been very active during the past year. The design of the new Compact Auburn Torsatron (CAT) was completed and construction is underway. Plasma experiments on the existing Auburn Torsatron in the areas of ICH and plasma microwave emission have also been carried out. Personnel from the Auburn Torsatron Group have also been involved in collaborative research with other research institutions, particularly the ATF Group at ORNL. Another significant development has been the Auburn Torsatron laboratory renovation project. Auburn University committed $75,000 to a laboratory upgrade in the Nuclear Science Center, the building which houses the Torsatron laboratory. The main result of this renovation is a doubling of the floor space in the Auburn Torsatron laboratory. This renovation work started on August 1, 1989 and is scheduled for completion on October 30, 1989

  3. Compact Torsatron configurations

    International Nuclear Information System (INIS)

    Low-aspect-ratio stellarator configurations can be realized by using torsatron winding. Plasmas with aspect ratios in the range of 3.5 to 5 can be confined by these Compact Torsatron configurations. Stable operation at high Β should be possible in these devices, if a vertical field coil system is adequately designed to avoid breaking of the magnetic surfaces at finite Β. 17 refs., 21 figs., 1 tab

  4. Divertor for a torsatron

    International Nuclear Information System (INIS)

    The divertor for a torsatron comprising a toroidal vacuum chamber embracing the toroidal chamber of torsatron trap and communicating with it through the gaps between helical conductors of the system for creation of the trap magnetic field is described. The divertor comprises also a collector realized in a form of plates crossing magnetic field force lines. With the purpose of decreasing the plasma contamination level the collector plates realized curvilinear and embrace conductors at full their length and have the curvature less than that of the magnetic field force lines in the plate mounting point. The invention permits to decrease the plasma contamination by decreasing the particles flux formed as a result of collector plates errosion and accordingly increase plasma temperature in the trap

  5. Compact torsatron reactors

    International Nuclear Information System (INIS)

    Low-aspect-ratio torsatron configurations could lead to compact stellarator reactors with R0 = 8--11m, roughly one-half to one-third the size of more conventional stellarator reactor designs. Minimum-size torsatron reactors are found using various assumptions. Their size is relatively insensitive to the choice of the conductor parameters and depends mostly on geometrical constraints. The smallest size is obtained by eliminating the tritium breeding blanket under the helical winding on the inboard side and by reducing the radial depth of the superconducting coil. Engineering design issues and reactor performance are examined for three examples to illustrate the feasibility of this approach for compact reactors and for a medium-size (R0 ≅ 4 m,/bar a/ /approx lt/ 1 m) copper-coil ignition experiment. 26 refs., 11 figs., 7 tabs

  6. MHD stability of torsatrons using the average method

    International Nuclear Information System (INIS)

    The stability of torsatrons is studied using the average method, or stellarator expansion. Attention is focused upon the Advanced Toroidal Fusion Device (ATF), an l = 2, 12 field period, moderate aspect ratio configuration which, through a combination of shear and toroidally induced magnetic well, is stable to ideal modes. Using the vertical field (VF) coil system of ATF it is possible to enhance this stability by shaping the plasma to control the rotational transform. The VF coils are also useful tools for exploring the stability boundaries of ATF. By shifting the plasma inward along the major radius, the magnetic well can be removed, leading to three types of long wavelength instabilities: (1) A free boundary ''edge mode'' occurs when the rotational transform at the plasma edge is just less than unity. This mode is stabilized by the placement of a conducting wall at 1.5 times the plasma radius. (2) A free boundary global kink mode is observed at high β. When either β is lowered or a conducting wall is placed at the plasma boundary, the global mode is suppressed, and (3) an interchange mode is observed instead. For this interchange mode, calculations of the second, third, etc., most unstable modes are used to understand the nature of the degeneracy breaking induced by toroidal effects. Thus, the ATF configuration is well chosen for the study of torsatron stability limits

  7. Torsatron equilibrium and stability studies

    International Nuclear Information System (INIS)

    Equilibrium and stability results are presented for the Advanced Toroidal Facility (ATF) device. The results of three-dimensional equilibrium calculations and free boundary average method calculations are shown to be in good agreement with previous fixed boundary average method results. These favorable comparisons serve as a valuable validation of the simple and computationally efficient fixed boundary average method. Stability calculations for the free boundary average method equilibria are also in good agreement with fixed boundary calculations, showing instability only when the plasma is shifted inward with an applied vertical field

  8. ATF [Advanced Toroidal Facility]-2 studies

    International Nuclear Information System (INIS)

    Design studies for a low-aspect-ratio, large next-generation stellarator, ATF-II, with high-current-density, high-field, stable NbTi/Cu helical windings are described. The design parameters are an average plasma radius of 0.52 m, a major radius of 2 m, and a field on axis of 4-5 T, with 10 to 15 MW of heating power. Such a device would be comparable in scope to other next-generation stellarators but would have roughly the same aspect ratio as the tokamaks without, however, the need for current drive to sustain steady-state operation. A number of low-aspect-ratio physics issues need to be addressed in the design of ATF-II, primarily compromises between high-beta capability and good confinement properties. A six-field-period Compact Torsatron is chosen as a reference design for ATF-II, and its main features and performance predictions are discussed. An integrated (beta capability and confinement) optimization approach and optimization of superconducting windings are also discussed. 36 refs., 13 figs., 2 tabs

  9. Wisconsin Torsatron/Stellarator Program, FY 1987

    International Nuclear Information System (INIS)

    The research of the Torsatron/Stellarator Laboratory during the present contract period has concentrated on several main areas. The confinement in IMS is being investigated under the conditions of an applied vertical magnetic field and with the insertion of a localized limiter. Excellent agreement between a simplified stochastic heating theory and the measured electron cyclotron breakdown and heating phases of the Proto-Cleo torsatron have been achieved. Measurements of the secondary currents and the ability to drive currents using Alfven waves are continuing on the Proto-Cleo stellarator. Theoretical efforts have concentrated on modelling the experimental devices, including 1-D transport modelling, particle-in-cell simulation and divertor field line following codes

  10. Wisconsin torsatron/stellarator program, FY 1989

    International Nuclear Information System (INIS)

    This proposal documents recent activities within the University of Wisconsin-Madison Torsatron/Stellarator Laboratory and presents plans for future research activities for a three year period. Research efforts have focused on fundamental stellarator physics issues through experimental investigations on the Interchangeable Module Stellarator (IMS) and the Proto-Cleo Stellarator. Theoretical activities and studies of new configurations are being undertaken to support and broaden the experimental program. Experimental research at the Torsatron Stellarator Laboratory has been primarily concerned with effects induced through electron-cyclotron resonant frequency plasma production and heating in the IMS device. Plasma electric fields have been shown to play a major role in particle transport and confinement in IMS. ECRF heating at 6 kG has produced electron tail populations in agreement with Monte-Carlo models. Electric and magnetic fields have been shown to alter the particle flows to the IMS modular divertors. 48 refs

  11. Design of the Compact Auburn Torsatron

    International Nuclear Information System (INIS)

    This paper describes the design and optimization procedure for the Compact Auburn Torsatron. Included in this is a description of the Cary-Hanson Optimization technique. In this paper the properties of the magnetic fields are presented and a description of the machine and the construction procedure. The experimental setup for the surface mapping is described and conclusions are presented. 10 refs., 9 figs., 1 tab

  12. ATF2 COMMISSIONING

    CERN Document Server

    Seryi, A; Parker, B; Schulte, D; Delahaye, J P; Tomas, R; Zimmermann, F; Wolski, A; Elsen, E; Sanuki, T; Gianfelice-Wendt, E; Ross, M; Wendt, M; Takahashi, T; Bai, S; Gao, J; Bolzon, B; Geffroy, N; Jeremie, A; Apsimon, R; Burrows, P; Constance, B; Perry, C; Resta-Lopez, J; Swinson, C; Araki, S; Aryshev, A; Hayano, H; Honda, Y; Kubo, K; Kume, T; Kuroda, S; Masuzawa, M; Naito, T; Okugi, T; Sugahara, R; Tauchi, T; Terunuma, N; Urakawa, J; Yokoya, K; Iwashita, Y; Sugimoto, T; Heo, A Y; Kim, E S; Kim, H S; Bambade, P; Renier, Y; Rimbault, C; Huang, J Y; Kim, S H; Park, Y J; Hwang, W H; Blair, G; Boogert, S; Karataev, P; Molloy, S; Amann, J; Bellomo, P; Lam, B; McCormick, D; Nelson, J; Paterson, E; Pivi, M; Raubenheimer, T; Spencer, C; Wang, M H; White, G; Wittmer, W; Woodley, M; Yan, Y; Zhou, F; Angal-Kalinin, D; Jones, J; Lyapin, A; Scarfe, A; Kamiya, Y; Komamiya, S; Oroku, M; Suehara, T; Yamanaka, T

    2010-01-01

    ATF2 is a final-focus test beam line that aims to focus the low-emittance beam from the ATF damping ring to a beam size of about 37 nm, and at the same time to demonstrate nm beam stability, using numerous advanced beam diagnostics and feedback tools. The construction has been finished at the end of 2008 and the beam commissioning of ATF2 has started in December of 2008. ATF2 is constructed and commissioned by ATF international collaborations with strong US, Asian and European participation.

  13. Perspectives on low-aspect-ratio torsatron/heliotron

    International Nuclear Information System (INIS)

    The advantages of the low-aspect-ratio torsatron/heliotron configuration is discussed from the point of view of plasma confinement. Recent numerical results on the configuration study and the experimental data base are reviewed. (author)

  14. [Wisconsin Torsatron/Stellarator Program: FY 1988

    International Nuclear Information System (INIS)

    The Torsatron/Stellarator Laboratory Program during the present period has concentrated on experimental investigations into ECR-produced plasmas in the IMS device. Significant progress has been made in understanding the role of convection in maintaining the hollow plasma density profiles under a wide range of operating conditions. Divertor studies have continued to show good agreement with predictions derived from simple field-line models and the ability to effect particle flows through biasing of divertor plates. Preliminary fluctuation studies showed a dependence of the amplitudes of the fluctuations and profile shapes as a function of the magnetic topology of the device. Theoretical support of the experimental program has provided models to help interpret the experimental results. New initiatives have begun in reduced-Q operation of the Proto-Cleo Stellarator, and in ion-Bernstein wave heating in IMS

  15. ATF2 Proposal

    Energy Technology Data Exchange (ETDEWEB)

    Grishanov, Boris Ivanovich; Logachev, Pavel; Podgorny, Fedor; Telnov, Valery; /Novosibirsk, IYF; Angal-Kalinin, Deepa; Appleby, Robert; Jones, James; Kalinin, Alexander; /Daresbury; Napoly, Olivier; Payet, Jacques; /DAPNIA, Saclay; Braun, Hans-Heinrich; Schulte, Daniel; Zimmermann, Frank; /CERN; Barlow, Roger; Bailey, Ian; Jenner, Leo; Jones, Roger; Kourevlev, German; /Daresbury; Walker, Nick; /DESY; Takahasi, Tohru; /Hiroshima U.; Gao, Jie; /Beijing, Inst. High Energy Phys. /Oxford U. /KEK, Tsukuba /Kyoto U., Inst. Chem. Res.

    2005-08-23

    This document is the first of two volumes describing the ATF2 project. The present volume discusses the technical justification for ATF2 and presents a design description. Since the International Committee for Future Accelerator (ICFA) decision on the choice of technology, a world-wide collaboration on the design of the International Linear Collider (ILC) has rapidly progressed [1]. The formation of the Global Design Effort (GDE) will accelerate the work towards a final design. An important technical challenge is obviously the high gradient acceleration but what is similarly challenging is the collision of extremely small beams of a few nanometer size. The latter challenge has three distinct issues: creating small emittance beams, preserving the emittance during acceleration and transport, and focusing the beams to nanometers. Most studies have been done using computer simulations but many issues still remain that require experimental verification. Accelerator Test Facility (ATF) at KEK was built to create small emittance beams, and succeeded in obtaining an emittance that almost satisfies the ILC requirements [2]. In this proposal we present a project, ATF2, which addresses the focusing of the beam into a nanometer spot. The ATF2 project will extend the extraction beamline of the ATF with an ILC-type final focus system to create a tightly focused, stable beam by making use of the small emittance of the ATF. The layout is shown in Figure 1.1. In the longer term, the ATF2 project would also provide invaluable input for the CLIC design of a future multi-TeV collider.

  16. TOREX-4: a torsatron proof of principle experiment

    International Nuclear Information System (INIS)

    TOREX-4 is a torsatron Proof of Principle experiment designed to simultaneously achieve ntau approx. = to 5 x 1013, n approx. = to 5 x 1014/cm3, and T greater than or equal to 1 keV. TOREX-4 is capable of operating without externally driven currents; sufficient neutral beam power to reach betas of 2 to 5% is provided. The unique 4(+2) constant pitch angle winding configuration allows the reliable design of large systems with far greater experimental flexibility than can be achieved in conventional stellarators of comparable size. This will allow investigation of the basic physics questions of the torsatron configuration over a wide range of plasma properties and field configurations without sacrifice of the Proof of Principle goals

  17. ATF2 Proposal Volume 2

    Energy Technology Data Exchange (ETDEWEB)

    Grishanov, B.I.; Logachev, P.; Podgorny, F.; Telnov, V.; /Novosibirsk, IYF; Angal-Kalinin, D.; Jones, J.; Kalinin, A.; /Daresbury; Napoly, O.; Payet, J.; /DAPNIA, Saclay; Braun, H.H.; Schulte, D.; Zimmermann, F.; /CERN; Appleby, R.; Barlow, R.; Bailey, I.; Jenner, L.; Jones, R.; Kourevlev, G.; /Cockcroft Inst.; Elsen, E.; Vogel, V.; Walker, N.; /DESY

    2006-02-27

    For achieving the high luminosity required at the International Linear Collider (ILC), it is critical to focus the beams to nanometer size with the ILC Beam Delivery System (BDS), and to maintain the beam collision with a nanometer-scale stability. To establish the technologies associated with this ultra-high precision beam handling, it has been proposed to implement an ILC-like final focus optics in an extension of the existing extraction beamline of ATF at KEK. The ATF is considered to be the best platform for this exercise, since it provides an adequate ultra-low emittance electron beam in a manner dedicated to the development of ILC. The two major goals for this facility, called ATF2, are: (A) Achievement of a 37 nm beam size, and (B) control of beam position down to 2 nm level. The scientific justification for the ATF2 project and its technical design have been described in Volume 1 of the ATF2 Proposal [1]. We present here Volume 2 of the ATF2 Proposal, in which we present specifics of the construction plans and the group organization to execute the research programs at ATF2. The sections in this report have been authored by relevant ATF2 subgroups within the International ATF Collaboration. The time line of the project is described in Section 2. Section 3 discuss the structure of the international collaboration. Sections 4 and 5 discuss budget considerations, which are presented as well as the design and construction tasks to be shared by the international collaboration at ATF2. Concluding remarks have been contributed by Dr. Ewan Paterson, Chair of the International Collaboration Board of the ATF collaboration.

  18. Observation of parallel viscosity in the CHS Heliotron/Torsatron

    International Nuclear Information System (INIS)

    Damping of the toroidal velocity owing to parallel viscosity is observed in the plasma with a tangential neutral beam injection in the CHS Heliotron/Torsatron device. Toroidal velocity profile is dominated by the perpendicular viscosity when magnetic field modulation is weak near axis. However, the parallel viscosity is found to be dominant when the modulation is strong enough and to increase in proportion to the square of the modulation of magnetic field. The absolute values of the viscosity agree with the neoclassical prediction within a factor of three. (author)

  19. ATF beam image monitor software

    International Nuclear Information System (INIS)

    We report about software for the beam image analysis at ATF. We developed image analysis software with a Linux computer. It acquire image data from a video and an IEEE1394 digital camera of the analog. (author)

  20. ATF2 Proposal v. 2

    CERN Document Server

    Grishanov, B I; Alabau-Pons, M; Angal-Kalinin, Deepa; Appleby, R; Araki, S; Bailey, I; Bambade, P; Bane, Karl Leopold Freitag; Barlow, R; Blair, G A; Bolzon, B; Boorman, G; Bosco, A; Brachmann, A; Braun, Hans Heinrich; Burrows, P N; Carter, J; Choi, J; Christian, Glenn B; Clarke, C; Dabiri-Khah, A; Dadoun, O; Danagulyan, S; Delerue, N; Dixit, S; Driouichi, C; Elsen E; Gao, J; Geffroy, N; Gronberg, J; Hartin, Anthony F; Hayano, H; Higashi, Y; Himel, T; Honda, Y; Howell, D; Huang, J Y; Iwashita, Y; Jenner, L; Jones, J; Jones, R; Jérémie, A; Kalinin, A; Kanazawa, K; Kang, H S; Karyotakis, Yu; Kim, E S; Kim, S; Komamiya, S; Kourevlev, German Yu; Kubo, K; Kumada, M; Kume, T; Kuriki, M; Kuroda, S; Liu, W; Logatchev, P V; Lyapin, A; Malton, S; Markiewicz, T W; Masuzawa, M; Mihara, T; Miller, D J; Molloy, S; Mtingwa, S; Naito, T; Nan-Phinney, Y; Napoly, O; Nelson, J; Okugi, T; Payet, J; Pei, G X; Pivi, M T F; Podgorny, F; Price, M; Raubenheimer, T O; Reichold, A; Ross, M; Sanuki, T; Schulte, Daniel; Seryi, R A; Solyak, N; Soo Ko In; Spencer, C M; Suehara, T; Sugahara, R; Takahashi, T; Takashi-Boogert, S; Tauchi, T; Telnov, Valery I; Tenenbaum, P G; Terunuma, N; Toge, N; Torrence, E; Urakawa, J; Urner, D; Vogel, V; Walker, N; Wang, J Q; Wendt, M; White, G; Wing, M; Wolski, A; Woodley, M; Yamaoka, H; Yokoya, K; Zimmermann, Frank

    2006-01-01

    For achieving the high luminosity required at the International Linear Collider (ILC), it is critical to focus the beams to nanometer size with the ILC Beam Delivery System (BDS), and to maintain the beam collision with a nanometer-scale stability. To establish the technologies associated with this ultra-high precision beam handling, it has been proposed to implement an ILC-like final focus optics in an extension of the existing extraction beamline of ATF at KEK. The ATF is considered to be the best platform for this exercise, since it provides an adequate ultra-low emittance electron beam in a manner dedicated to the development of ILC. The two major goals for this facility, called ATF2, are : (A) Achievement of a 37 nm beam size, and (B) control of beam position down to 2 nm level. The scientific justification for the ATF2 project and its technical design have been described in Volume 1 of the ATF2 Proposal [1]. We present here Volume 2 of the ATF2 Proposal, in which we present specifics of the construction...

  1. BNL ATF II beamlines design

    International Nuclear Information System (INIS)

    The Brookhaven National Laboratory. Accelerator Test Facility (BNL ATF) is currently undergoing a major upgrade (ATF-II). Together with a new location and much improved facilities, the ATF will see an upgrade in its major capabilities: electron beam energy and quality and CO2 laser power. The electron beam energy will be increased in stages, first to 100-150 MeV followed by a further increase to 500 MeV. Combined with the planned increase in CO2 laser power (from 1-100 TW), the ATF-II will be a powerful tool for Advanced Accelerator research. A high-brightness electron beam, produced by a photocathode gun, will be accelerated and optionally delivered to multiple beamlines. Besides the energy range (up to a possible 500 MeV in the final stage) the electron beam can be tailored to each experiment with options such as: small transverse beam size (<10 um), short bunch length (<100 fsec) and, combined short and small bunch options. This report gives a detailed overview of the ATFII capabilities and beamlines configuration.

  2. BNL ATF II beamlines design

    Energy Technology Data Exchange (ETDEWEB)

    Fedurin, M. [Brookhaven National Lab. (BNL), Upton, NY (United States); Jing, Y. [Brookhaven National Lab. (BNL), Upton, NY (United States); Stratakis, D. [Brookhaven National Lab. (BNL), Upton, NY (United States); Swinson, C. [Brookhaven National Lab. (BNL), Upton, NY (United States)

    2015-05-03

    The Brookhaven National Laboratory. Accelerator Test Facility (BNL ATF) is currently undergoing a major upgrade (ATF-II). Together with a new location and much improved facilities, the ATF will see an upgrade in its major capabilities: electron beam energy and quality and CO2 laser power. The electron beam energy will be increased in stages, first to 100-150 MeV followed by a further increase to 500 MeV. Combined with the planned increase in CO2 laser power (from 1-100 TW), the ATF-II will be a powerful tool for Advanced Accelerator research. A high-brightness electron beam, produced by a photocathode gun, will be accelerated and optionally delivered to multiple beamlines. Besides the energy range (up to a possible 500 MeV in the final stage) the electron beam can be tailored to each experiment with options such as: small transverse beam size (<10 um), short bunch length (<100 fsec) and, combined short and small bunch options. This report gives a detailed overview of the ATFII capabilities and beamlines configuration.

  3. Studies on magnetic surface structures and basic magnetic field properties in 'Ultimate' configurations of the L=1, m=13 torsatron and the 'Vint-20' torsatron

    International Nuclear Information System (INIS)

    The paper is concerned with numerical investigations of various magnetic configurations of a single-pole toroidal L=1, m=13 'ultimate' torsatron having a low aspect ratio Ah=4.345 and the modulation factors (-0.23) ≤ α ≤ 0.71 (K=1, β=0) of the helix law -mφ=Θ-αK SinΘ-βK sin2Θ. The extremums of the basic properties of closed magnetic surfaces as functions of the coefficient α in the neighborhood of α ∼ 0.4, as well as the structures of the edge magnetic field (substructures of virtual current) and the separatrix have been first determined for the L=1, m=13 'ultimate' torsatron and the 'Vint-20' torsatron. Unusual positions of the separatrix X-points in the cross sections for 1/4- and 3/4-magnetic field periods have been identified. The formula that takes into account the modulation factor α of the helix law was first derived to determine the average vertical magnetic field on the geometrical axis of the torus.

  4. On vacuum field properties of the URAGAN-2M Torsatron standard configuration

    International Nuclear Information System (INIS)

    Vacuum field properties of the URAGAN-2M Torsatron are investigated. In the 'Standard Case', within a certain range of field parameters, the size of the observed magnetic islands at τ = 2/3 can be reduced considerably. Some characteristic quantities for stellarator vacuum fields are reported. (orig.)

  5. Analytical estimation of ATF beam halo distribution

    CERN Document Server

    Wang, Dou; Yokoya, Kaoru; Gao, Jie

    2013-01-01

    In order to study the background status in the ATF2 beam line and the interaction point (IP), this paper developed an analytical method to give the estimation of ATF beam halo distribution based on K. Hirata and K. Yokoya's theory. The equilibrium particle distribution of beam tail in ATF damping ring, when each electron is being affected by, in addition to the synchrotron radiation damping effects, several stochastic processes, such as beam-gas scattring, beam-gas bremsstrahlung and intra-beam scattering, was presented. This method is common and can be applied on other electron rings.

  6. Chondrocytic Atf4 regulates osteoblast differentiation and function via Ihh

    OpenAIRE

    Wang, Weiguang; Lian, Na; Ma., Yun; LI, LINGZHEN; Gallant, Richard C.; Elefteriou, Florent; Yang, Xiangli

    2012-01-01

    Atf4 is a leucine zipper-containing transcription factor that activates osteocalcin (Ocn) in osteoblasts and indian hedgehog (Ihh) in chondrocytes. The relative contribution of Atf4 in chondrocytes and osteoblasts to the regulation of skeletal development and bone formation is poorly understood. Investigations of the Atf4–/–;Col2a1-Atf4 mouse model, in which Atf4 is selectively overexpressed in chondrocytes in an Atf4-null background, demonstrate that chondrocyte-derived Atf4 regulates osteog...

  7. The Straightness Monitor System at ATF2

    Energy Technology Data Exchange (ETDEWEB)

    Hildreth, Michael; /Notre Dame U.; Aryshev, Alexander; /Royal Holloway, U. of London; Boogert, Stewart; /Oxford U., JAI; Honda, Yosuke; /KEK, Tsukuba; Tauchi, Toshiaki; /KEK, Tsukuba; Terunuma, Nobuhiro; /KEK, Tsukuba; White, Glen; /SLAC

    2012-07-06

    The demonstration of absolute stability of the position of the focused beam is the primary goal of the ATF2 commissioning effort. We have installed a laser interferometer system that will eventually correct the measurement of high-precision Beam Position Monitors used in the ATF2Final Focus Steering Feedback for mechanical motion or vibrations. Here, we describe the installed system and present preliminary data on the short- and long-term mechanical stability of the BPM system.

  8. Beam halo study on ATF damping ring

    CERN Document Server

    Wang, Dou; Yokoya, Kaoru; Naito, Takashi; Gao, Jie

    2016-01-01

    Halo distribution is a key topic for background study. This paper has developed an analytical method to give an estimation of ATF beam halo distribution. The equilibrium particle distribution of the beam tail in the ATF damping ring is calculated analytically with different emittance and different vacuum degree. The analytical results agree the measurements very well. This is a general method which can be applied to any electron rings.

  9. Expression levels of the yeast alcohol acetyltransferase genes ATF1, Lg-ATF1, and ATF2 control the formation of a broad range of volatile esters.

    Science.gov (United States)

    Verstrepen, Kevin J; Van Laere, Stijn D M; Vanderhaegen, Bart M P; Derdelinckx, Guy; Dufour, Jean-Pierre; Pretorius, Isak S; Winderickx, Joris; Thevelein, Johan M; Delvaux, Freddy R

    2003-09-01

    Volatile aroma-active esters are responsible for the fruity character of fermented alcoholic beverages such as beer and wine. Esters are produced by fermenting yeast cells in an enzyme-catalyzed intracellular reaction. In order to investigate and compare the roles of the known Saccharomyces cerevisiae alcohol acetyltransferases, Atf1p, Atf2p and Lg-Atf1p, in volatile ester production, the respective genes were either deleted or overexpressed in a laboratory strain and a commercial brewing strain. Subsequently, the ester formation of the transformants was monitored by headspace gas chromatography and gas chromatography combined with mass spectroscopy (GC-MS). Analysis of the fermentation products confirmed that the expression levels of ATF1 and ATF2 greatly affect the production of ethyl acetate and isoamyl acetate. GC-MS analysis revealed that Atf1p and Atf2p are also responsible for the formation of a broad range of less volatile esters, such as propyl acetate, isobutyl acetate, pentyl acetate, hexyl acetate, heptyl acetate, octyl acetate, and phenyl ethyl acetate. With respect to the esters analyzed in this study, Atf2p seemed to play only a minor role compared to Atf1p. The atf1Delta atf2Delta double deletion strain did not form any isoamyl acetate, showing that together, Atf1p and Atf2p are responsible for the total cellular isoamyl alcohol acetyltransferase activity. However, the double deletion strain still produced considerable amounts of certain other esters, such as ethyl acetate (50% of the wild-type strain), propyl acetate (50%), and isobutyl acetate (40%), which provides evidence for the existence of additional, as-yet-unknown ester synthases in the yeast proteome. Interestingly, overexpression of different alleles of ATF1 and ATF2 led to different ester production rates, indicating that differences in the aroma profiles of yeast strains may be partially due to mutations in their ATF genes. PMID:12957907

  10. Stabilisation of ballooning modes in torsatrons with an externally applied toroidal current

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, W.A. [Ecole Polytechnique Federale, Lausanne (Switzerland). Centre de Recherche en Physique des Plasma (CRPP)

    1996-09-01

    It has been found that ideal ballooning modes can impose very restrictive volume average {beta} limits in torsatrons much below the typical values close to 5% that are required to be economically realisable as reactor systems and it has been shown that externally applied toroidal currents that are peaked can destabilise the Mercier criterion in this type of configuration. We will show here that if the applied currents are hollow, they can stabilise the ballooning modes without triggering Mercier instabilities and as a result raise the limiting {beta}* from 2% to 5%. (author) 3 figs., 10 refs.

  11. ATF3 inhibits PPARγ-stimulated transactivation in adipocyte cells

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Min-Kyung; Jung, Myeong Ho, E-mail: jung0603@pusan.ac.kr

    2015-01-02

    Highlights: • ATF3 inhibits PPARγ-stimulated transcriptional activation. • ATF3 interacts with PPARγ. • ATF3 suppresses p300-mediated transcriptional coactivation. • ATF3 decreases the binding of PPARγ and recruitment of p300 to PPRE. - Abstract: Previously, we reported that activating transcription factor 3 (ATF3) downregulates peroxisome proliferator activated receptor (PPARγ) gene expression and inhibits adipocyte differentiation in 3T3-L1 cells. Here, we investigated another role of ATF3 on the regulation of PPARγ activity. ATF3 inhibited PPARγ-stimulated transactivation of PPARγ responsive element (PPRE)-containing reporter or GAL4/PPARγ chimeric reporter. Thus, ATF3 effectively repressed rosiglitazone-stimulated expression of adipocyte fatty acid binding protein (aP2), PPARγ target gene, in 3T3-L1 cells. Coimmunoprecipitation and GST pulldown assay demonstrated that ATF3 interacted with PPARγ. Accordingly, ATF3 prevented PPARγ from binding to PPRE on the aP2 promoter. Furthermore, ATF3 suppressed p300-mediated transcriptional coactivation of PPRE-containing reporter. Chromatin immunoprecipitation assay showed that overexpression of ATF3 blocked both binding of PPARγ and recruitment of p300 to PPRE on aP2 promoter induced by rosiglitazone treatment in 3T3-L1 cells. Taken together, these results suggest that ATF3 interacts with PPARγ and represses PPARγ-mediated transactivation through suppression of p300-stimulated coactivation in 3T3-L1 cells, which may play a role in inhibition of adipocyte differentiation.

  12. ATF3 represses PPARγ expression and inhibits adipocyte differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Min-Kyung; Jung, Myeong Ho, E-mail: jung0603@pusan.ac.kr

    2014-11-07

    Highlights: • ATF3 decrease the expression of PPARγ and its target gene in 3T3-L1 adipocytes. • ATF3 represses the promoter activity of PPARγ2 gene. • ATF/CRE (−1537/−1530) is critical for ATF3-mediated downregulation of PPARγ. • ATF3 binds to the promoter region containing the ATF/CRE. • ER stress inhibits adipocyte differentiation through downregulation of PPARγ by ATF3. - Abstract: Activating transcription factor 3 (ATF3) is a stress-adaptive transcription factor that mediates cellular stress response signaling. We previously reported that ATF3 represses CCAAT/enhancer binding protein α (C/EBPα) expression and inhibits 3T3-L1 adipocyte differentiation. In this study, we explored potential role of ATF3 in negatively regulating peroxisome proliferator activated receptor-γ (PPARγ). ATF3 decreased the expression of PPARγ and its target gene in 3T3-L1 adipocytes. ATF3 also repressed the activity of −2.6 Kb promoter of mouse PPARγ2. Overexpression of PPARγ significantly prevented the ATF3-mediated inhibition of 3T3-L1 differentiation. Transfection studies with 5′ deleted-reporters showed that ATF3 repressed the activity of −2037 bp promoter, whereas it did not affect the activity of −1458 bp promoter, suggesting that ATF3 responsive element is located between the −2037 and −1458. An electrophoretic mobility shift assay and chromatin immunoprecipitation assay demonstrated that ATF3 binds to ATF/CRE site (5′-TGACGTTT-3′) between −1537 and −1530. Mutation of the ATF/CRE site abrogated ATF3-mediated transrepression of the PPARγ2 promoter. Treatment with thapsigargin, endoplasmic reticulum (ER) stress inducer, increased ATF3 expression, whereas it decreased PPARγ expression. ATF3 knockdown significantly blocked the thapsigargin-mediated downregulation of PPARγ expression. Furthermore, overexpression of PPARγ prevented inhibition of 3T3-L1 differentiation by thapsigargin. Collectively, these results suggest that ATF3-mediated

  13. Ripple transport in helical-axis advanced stellarators - a comparison with classical stellarator/torsatrons

    International Nuclear Information System (INIS)

    Calculations of the neoclassical transport rates due to particles trapped in the helical ripples of a stellarator's magnetic field are carried out, based on solutions of the bounce-averaged kinetic equation. These calculations employ a model for the magnetic field strength, B, which is an accurate approximation to the actual B for a wide variety of stellarator-type devices, among which are Helical-Axis Advanced Stellarators (Helias) as well as conventional stellarators and torsatrons. Comparisons are carried out in which it is shown that the Helias concept leads to significant reductions in neoclassical transport rates throughout the entire long-mean-free-path regime, with the reduction being particularly dramatic in the ν-1 regime. These findings are confirmed by numerical simulations. Further, it is shown that the behavior of deeply trapped particles in Helias can be fundamentally different from that in classical stellarator/torsatrons; as a consequence, the beneficial effects of a radial electric field on the transport make themselves felt at lower collision frequency than is usual. (orig.)

  14. Analysis list: ATF7IP [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ATF7IP Epidermis + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/ATF7IP....1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/ATF7IP.5.tsv http://dbarchive.biosciencedbc....jp/kyushu-u/hg19/target/ATF7IP.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/ATF7IP.Epidermis.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/Epidermis.gml ...

  15. Experimental studies of radio frequency waves and confinement in the Auburn Torsatron. Progress report

    International Nuclear Information System (INIS)

    The first year of operation of the Auburn Torsatron has resulted in the majority of the basic operating systems becoming operational or nearly operational. The diagnostic systems now include two microwave interferometers, a monochrometer, several probes and photodiodes. The plasma is produced by any of three sources: electron cyclotron heating with a cw power of 1 kW, low frequency rf heating with power soon to come up to 10 kW cw, and a pulsed washer-stack gun. The magnetic field studies have mapped the field surfaces and several corrections have been made to center the plasma. The ion-cyclotron source and antenna are nearly ready for experiments to begin

  16. A Superconducting Magnet Upgrade of the ATF2 Final Focus

    Energy Technology Data Exchange (ETDEWEB)

    Parker B.; Anerella M.; Escallier J.; He P.; Jain A.; Marone A.; Wanderer P.; Wu K.C.; Hauviller C.; Marin E.; Tomas R.; Zimmermann F.; Bolzon B.; Jeremie A.; Kimura N.; Kubo K.; Kume T.; Kuroda S.; Okugi T.; Tauchi T.; Terunuma N.; Tomaru T.; Tsuchiya K.; Urakawa J.; Yamamoto A.; Bambabe P.; Coe P.; Urner D.; Seryi A.; Spencer C.; White G.

    2010-05-23

    The ATF2 facility at KEK is a proving ground for linear collider technology with a well instrumented extracted beam line and Final Focus (FF). The primary ATF2 goal is to demonstrate the extreme beam demagnification and spot stability needed for a linear collider FF. But the ATF2 FF uses water cooled magnets and the ILC baseline has a superconducting (SC) FF. We plan to upgrade ATF2 and replace some of the warm FF magnets with SC FF magnets. The ATF2 SC magnets, like the ILC FF, will made via direct wind construction. ATF2 coil winding is in progress at BNL and warm magnetic measurements indicate we have achieved good field quality. Studies indicate that having ATF2 FF magnets with larger aperture and better field quality should allow reducing the ATF2 FF beta function for study of focusing regimes relevant to CLIC. The ATF2 magnet cryostat will have laser view ports for directly monitoring cold mass movement. We plan to make stability measurements at BNL and KEK to relate ATF2 FF magnet performance to that of a full length ILC QD0 R and D FF prototype under construction at BNL.

  17. A Superconducting Magnet Upgrade of the ATF2 Final Focus

    Energy Technology Data Exchange (ETDEWEB)

    Parker, Brett; /Brookhaven; Anerella, Michael; /Brookhaven; Escallier, John; /Brookhaven; He, Ping; /Brookhaven; Jain, Animesh; /Brookhaven; Marone, Andrew; /Brookhaven; Wanderer, Peter; /Brookhaven; Wu, Kuo-Chen; /Brookhaven; Bambade, Philip; /Orsay, LAL; Bolzon, Benoit; /Annecy, LAPP; Jeremie, Andrea; /Annecy, LAPP; Coe, Paul; /Oxford U.; Urner, David /Oxford U.; Hauviller, Claude; /CERN; Marin, Eduardo; /CERN; Tomas, Rogelio; /CERN; Zimmermann, Frank; /CERN; Kimura, Nobuhiro; /KEK, Tsukuba; Kubo, Kiyoshi; /KEK, Tsukuba; Kume, Tatsuya /KEK, Tsukuba; Kuroda, Shigeru; /KEK, Tsukuba /KEK, Tsukuba /KEK, Tsukuba /KEK, Tsukuba /KEK, Tsukuba /KEK, Tsukuba /KEK, Tsukuba /KEK, Tsukuba /SLAC /SLAC /SLAC

    2012-07-05

    The ATF2 facility at KEK is a proving ground for linear collider technology with a well instrumented extracted beam line and Final Focus (FF). The primary ATF2 goal is to demonstrate the extreme beam demagnification and spot stability needed for a linear collider FF. But the ATF2 FF uses water cooled magnets and the ILC baseline has a superconducting (SC) FF. We plan to upgrade ATF2 and replace some of the warm FF magnets with SC FF magnets. The ATF2 SC magnets, like the ILC FF, will made via direct wind construction. ATF2 coil winding is in progress at BNL and warm magnetic measurements indicate we have achieved good field quality. Studies indicate that having ATF2 FF magnets with larger aperture and better field quality should allow reducing the ATF2 FF beta function for study of focusing regimes relevant to CLIC. The ATF2 magnet cryostat will have laser view ports for directly monitoring cold mass movement. We plan to make stability measurements at BNL and KEK to relate ATF2 FF magnet performance to that of a full length ILC QD0 R&D FF prototype under construction at BNL.

  18. Solve: a non linear least-squares code and its application to the optimal placement of torsatron vertical field coils

    International Nuclear Information System (INIS)

    A computational method was developed which alleviates the need for lengthy parametric scans as part of a design process. The method makes use of a least squares algorithm to find the optimal value of a parameter vector. Optimal is defined in terms of a utility function prescribed by the user. The placement of the vertical field coils of a torsatron is such a non linear problem

  19. Analysis list: ATF4 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ATF4 Blood,Others + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/ATF4.1.tsv http:...//dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/ATF4.5.tsv http://dbarchive.biosciencedbc.jp/...kyushu-u/hg19/target/ATF4.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/ATF4.Blood.tsv,http://...dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/ATF4.Others.tsv http://dbarchive.bi...osciencedbc.jp/kyushu-u/hg19/colo/Blood.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/Others.gml ...

  20. Mineral trioxide aggregate induces osteoblastogenesis via Atf6

    Directory of Open Access Journals (Sweden)

    Toyonobu Maeda

    2015-06-01

    Full Text Available Mineral trioxide aggregate (MTA has been recommended for various uses in endodontics. To understand the effects of MTA on alveolar bone, we examined whether MTA induces osteoblastic differentiation using MC3T3-E1 cells. MTA enhanced mineralization concomitant with alkaline phosphatase activity in a dose- and time-dependent manner. MTA increased production of collagens (Type I and Type III and matrix metalloproteinases (MMP-9 and MMP-13, suggesting that MTA affects bone matrix remodeling. MTA also induced Bglap (osteocalcin but not Bmp2 (bone morphogenetic protein-2 mRNA expression. We observed induction of Atf6 (activating transcription factor 6, an endoplasmic reticulum (ER stress response transcription factor mRNA expression and activation of Atf6 by MTA treatment. Forced expression of p50Atf6 (active form of Atf6 markedly enhanced Bglap mRNA expression. Chromatin immunoprecipitation assay was performed to investigate the increase in p50Atf6 binding to the Bglap promoter region by MTA treatment. Furthermore, knockdown of Atf6 gene expression by introduction of Tet-on Atf6 shRNA expression vector abrogated MTA-induced mineralization. These results suggest that MTA induces in vitro osteoblastogenesis through the Atf6–osteocalcin axis as ER stress signaling. Therefore, MTA in endodontic treatment may affect alveolar bone healing in the resorbed region caused by pulpal infection.

  1. Shafranov shift in low-aspect-ratio heliotron/torsatron CHS

    International Nuclear Information System (INIS)

    The MHD equilibrium properties of neutral-beam-heated plasmas have been experimentally investigated in the Compact Helical System (CHS), a low-aspect-ratio (Ap ∼ 5) heliotron/torsatron. This configuration is characterized by a strong breaking of helical symmetry. The radial profiles measured by various diagnostics have shown significant Shafranov shift due to plasma pressure. The deviation of the magnetic axis from its vacuum position has reached 50% of the minor radius. When the three-dimensional equilibrium code VMEC is used to reconstruct the equilibrium from the experimental data, the result is in good agreement with the experimentally observed Shafranov shift as well as the diamagnetic pressure in plasmas with ≤ 1.2% and β0 ≤ 3.3%. This β value corresponds to half of the conventional equilibrium β limit defined by the Shafranov shift reaching a value of half the minor radius. Although tangential neutral beam injection has caused pressure anisotropies p parallel/p perpendicular ≤ 3, the description of the equilibrium assuming isotropic pressure is consistent with the experiment. (author)

  2. Proto-CIRCUS Tilted-Coil Tokamak-Torsatron Hybrid: Design and Construction

    CERN Document Server

    Clark, A W; Hammond, K C; Kornbluth, Y; Spong, D A; Sweeney, R; Volpe, F A

    2014-01-01

    We present the field-line modeling, design and construction of a prototype circular-coil tokamak-torsatron hybrid called Proto-CIRCUS. The device has a major radius R = 16 cm and minor radius a < 5 cm. The six "toroidal field" coils are planar as in a tokamak, but they are tilted. This, combined with induced or driven plasma current, is expected to generate rotational transform, as seen in field-line tracing and equilibrium calculations. The device is expected to operate at lower plasma current than a tokamak of comparable size and magnetic field, which might have interesting implications for disruptions and steady-state operation. Additionally, the toroidal magnetic ripple is less pronounced than in an equivalent tokamak in which the coils are not tilted. The tilted coils are interlocked, resulting in a relatively low aspect ratio, and can be moved, both radially and in tilt angle, between discharges. This capability will be exploited for detailed comparisons between calculations and field-line mapping me...

  3. Micron size laser-wire system at the ATF extraction line, recent results and ATF-II upgrade

    Energy Technology Data Exchange (ETDEWEB)

    Aryshev, A., E-mail: alar@post.kek.j [John Adams Institute at Royal Holloway, Egham, Surrey TW20 0EX (United Kingdom); Blair, G.A.; Boogert, S.T.; Boorman, G.; Bosco, A. [John Adams Institute at Royal Holloway, Egham, Surrey TW20 0EX (United Kingdom); Corner, L. [John Adams Institute at Oxford University, Nuclear and Astrophysics Laboratory, Keble Road, Oxford OX1 3RH (United Kingdom); Deacon, L. [John Adams Institute at Royal Holloway, Egham, Surrey TW20 0EX (United Kingdom); Delerue, N.; Foster, B.; Gannaway, F. [John Adams Institute at Oxford University, Nuclear and Astrophysics Laboratory, Keble Road, Oxford OX1 3RH (United Kingdom); Hayano, H. [KEK, 1-1 Oho, Tsukuba, Ibaraki 305-0801 (Japan); Howell, D. [John Adams Institute at Oxford University, Nuclear and Astrophysics Laboratory, Keble Road, Oxford OX1 3RH (United Kingdom); Karataev, P. [John Adams Institute at Royal Holloway, Egham, Surrey TW20 0EX (United Kingdom); Nevay, L.; Newman, M.; Senanayake, R. [John Adams Institute at Oxford University, Nuclear and Astrophysics Laboratory, Keble Road, Oxford OX1 3RH (United Kingdom); Terunuma, N.; Urakawa, J. [KEK, 1-1 Oho, Tsukuba, Ibaraki 305-0801 (Japan); Walczak, R. [John Adams Institute at Oxford University, Nuclear and Astrophysics Laboratory, Keble Road, Oxford OX1 3RH (United Kingdom)

    2010-11-01

    The KEK Accelerator test facility (ATF) extraction line laser-wire system has been upgraded last year allowing the measurement of micron scale transverse size electron beams. The last measurements using the upgraded system from recent operation at the ATF are presented, demonstrating raw measurements of order 3{mu}m RMS. The main component contributions to this measurement are also discussed.

  4. Micron size laser-wire system at the ATF extraction line, recent results and ATF-II upgrade

    Science.gov (United States)

    Aryshev, A.; Blair, G. A.; Boogert, S. T.; Boorman, G.; Bosco, A.; Corner, L.; Deacon, L.; Delerue, N.; Foster, B.; Gannaway, F.; Hayano, H.; Howell, D.; Karataev, P.; Nevay, L.; Newman, M.; Senanayake, R.; Terunuma, N.; Urakawa, J.; Walczak, R.

    2010-11-01

    The KEK Accelerator test facility (ATF) extraction line laser-wire system has been upgraded last year allowing the measurement of micron scale transverse size electron beams. The last measurements using the upgraded system from recent operation at the ATF are presented, demonstrating raw measurements of order 3 μm RMS. The main component contributions to this measurement are also discussed.

  5. Flavour formation in fungi: characterisation of KlAtf, the Kluyveromyces lactis orthologue of the Saccharomyces cerevisiae alcohol acetyltransferases Atf1 and Atf2.

    Science.gov (United States)

    Van Laere, Stijn D M; Saerens, Sofie M G; Verstrepen, Kevin J; Van Dijck, Patrick; Thevelein, Johan M; Delvaux, Freddy R

    2008-04-01

    Volatile aroma-active esters are responsible for the fruity character of fermented alcoholic beverages, such as beer and wine. In the brewers' yeast Saccharomyces cerevisiae, the major part of these esters is formed by two alcohol acetyltransferases, Atf1 and Atf2. In this paper, the existence of orthologues of these S. cerevisiae alcohol acetyltransferases in several ascomycetous fungi was investigated. Bioinformatic analysis of sequenced fungal genomes revealed the presence of multiple orthologues. The Saccharomyces sensu stricto yeasts all have two genes coding for orthologues. More distantly related fungi like Saccharomyces castelii, Candida glabrata, Kluyveromyces waltii and Kluyveromyces lactis have only one orthologue in their genome. The homology between the identified proteins and the S. cerevisiae alcohol acetyltransferases suggests a role for these orthologues in the aroma-active ester formation. To verify this, the K. lactis orthologue KlAtf was cloned and expressed in S. cerevisiae. Gas chromatographic analysis of small-scale fermentations with the transformant strains showed that, while S. cerevisiae ATF1 overexpression resulted in a substantial increase in acetate ester levels, S. cerevisiae ATF2 and K. lactis ATF overexpression only caused a moderate increase in acetate esters. This study is the first report of the presence of an ester synthesis gene in K. lactis.

  6. ATF3 suppresses ESCC via downregulation of ID1

    Science.gov (United States)

    Li, Jian; Yang, Zishan; Chen, Zhiuguo; Bao, Yonghua; Zhang, Huijuan; Fang, Xinhui; Yang, Wancai

    2016-01-01

    Esophageal cancer is one of the most prevalent forms of cancer and has a particularly high mortality rate due to early metastasis; however, the underlying mechanisms of its formation and progression remain unclear. The present study performed immunohistochemical analysis and observed that the expression of activating transcription factor 3 (ATF3) was reduced in esophageal squamous cell carcinoma (ESCC) in comparison with non-tumor adjacent tissues. By contrast, inhibitor of DNA binding 1 (ID1) was overexpressed in ESCC tissues, demonstrating an inverse correlation with ATF3 (PESCC EC109 and KYSE450 cells lines, transfection with an ATF3-overexpression plasmid resulted in the inhibition of cell proliferation, motility and migration, which was associated with the induction of E-cadherin expression and inhibition of cyclin D1 and Twist. Notably, ATF3 exerted an inverse regulatory interaction with ID1. The results of the present study provide additional evidence of the tumor suppressive features of ATF3 and demonstrate a novel mechanism of ATF3-mediated inhibition of cancer metastasis in esophageal cancer. PMID:27602100

  7. Micron Size Laser-Wire System at the ATF Extraction Line, Recent Results and ATF-II Upgrade

    CERN Document Server

    Blair, G A; Boorman, G; Bosco, A; Deacon, L; Karataev, P; Howell, D; Nevay, L J; Corner, L; Delerue, N; Foster, B; Gannaway, F; Newman, M; Senanayake, R; Walczak, R; Hayano, H; Aryshev, A; Terunuma, N; Urakawa, J

    2010-01-01

    The KEK Accelerator test facility (ATF) extraction line laser-wire system has been upgraded last year allowing the measurement of micron scale transverse size electron beams. The most recent measurements using the upgraded system are presented. The ATF-II extraction line design call for the major upgrade of the existing laser-wire system. We report on the hardware upgrades, including the major hardware upgrades to the laser transport, the laser beam diagnostics line, and the mechanical control systems.

  8. Characteristics of the three-half-turn-antenna-driven RF discharge in the Uragan-3M torsatron

    Energy Technology Data Exchange (ETDEWEB)

    Grigor’eva, L. I.; Chechkin, V. V., E-mail: chechkin@ipp.kharkov.ua; Moiseenko, V. E.; Grekov, D. L.; Pavlichenko, R. O.; Lozin, A. V.; Tarasov, I. K.; Kulaga, A. Ye.; Zamanov, N. V.; Tretiak, K. K.; Kozulya, M. M.; Beletskii, A. A.; Kasilov, A. A.; Mironov, Yu. K.; Romanov, V. S.; Voitsenya, V. S. [National Science Center Kharkiv Institute of Physics and Technology, Institute of Plasma Physics (Ukraine)

    2015-12-15

    In the ℓ = 3 Uragan-3M torsatron hydrogen plasma is produced by RF fields in the Alfvén range of frequencies (ω ≤ ω{sub ci}). The initial (target) plasma with the line-averaged density of units 10{sup 12} cm{sup −3} is produced by a frame antenna with a broad spectrum of generated parallel wavenumbers. After this, to heat the plasma and bring its density to ∼10{sup 13} cm{sup –3}, another, shorter wavelength three-half-turn antenna with large transverse currents is used. The behavior of the density, electron temperature, and loss of the plasma supported by the three-half-turn antenna is studied depending on the RF power fed to the antenna and initial values of the density and electron temperature supplied by the frame antenna.

  9. Determination of 2-dimensional temperature and density profiles of a plasma in the Auburn torsatron via computer control

    International Nuclear Information System (INIS)

    Early studies of the magnetic surfaces of the Auburn Torsatron indicated the presence of an X-point in the magnetic surfaces. Both theoretical calculations and experimental verification were performed in these studies. The plasma density distribution is believed to be determined by these magnetic surfaces. The 2-dimensional relative plasma density and electron temperature profiles over a cross-section of the plasma will verify that the X-point does have an influence on the distribution of the plasma. An electric double probe is used to measure the electron temperature and relative density at pre-defined points inside the plasma. The probe is on a moveable platform which is motor driven and positioned by a computer

  10. Transforming growth factor-beta1 regulation of ATF-3 and identification of ATF-3 target genes in breast cancer cells.

    Science.gov (United States)

    Kwok, Sukyee; Rittling, Susan R; Partridge, Nicola C; Benson, Chellakkan S; Thiyagaraj, Mayuranathan; Srinivasan, Narasimhan; Selvamurugan, Nagarajan

    2009-10-01

    Transforming growth factor-beta1 (TGF-beta1) is a crucial molecule for stimulation of breast cancer invasion and formation of bone metastases. The molecular mechanisms of how TGF-beta1 mediates these effects have yet to be completely determined. We have found that activating transcription factor-3 (ATF-3) is strongly stimulated and its level is sustained by TGF-beta1 in highly invasive and metastatic human breast cancer (MDA-MB231) and in mouse mammary pad tumor cells (r3T). ATF-3 is also overexpressed in human primary breast cancer tissue. Overexpression of ATF-3 increased normal human mammary epithelial cell number and DNA synthesis suggesting a role for ATF-3 in cell proliferation. The functional role of ATF-3 in breast cancer progression was determined by the RNA interference technique. Knockdown of ATF-3 by ATF-3 shRNA in MDA-MB231 cells decreased expression of cell cycle gene, cyclin A1 in MDA-MB231 cells. ATF-3 shRNA also decreased expression of an invasive and metastatic gene, matrix metalloproteinase-13 (MMP-13; collagenase-3) in these cells. Chromatin immunoprecipitation experiments identified the direct physical interaction of ATF-3 protein on the human MMP-13 promoter. Thus, the dysregulation of ATF-3 by TGF-beta1 is likely to activate cyclin A1 and MMP-13 genes in breast cancer cells and that would be key to the subsequent cancer cell invasion and metastasis.

  11. Initial results from model independent analysis of the KEK ATF

    International Nuclear Information System (INIS)

    Model Independent Analysis (MIA) has shown the potential to be a useful tool for diagnostics and optics verification. The Accelerator Test Facility (ATF) prototype damping ring at KEK has a diagnostic system with the ability to collect data allowing the application of MIA for analysis of the injection stability, and the storage ring optics and diagnostics. Understanding of all these issues will be important for improving the operational performance of a damping ring. We report here the results of a first attempt to apply MIA to the ATF

  12. Ceapins inhibit ATF6α signaling by selectively preventing transport of ATF6α to the Golgi apparatus during ER stress

    Science.gov (United States)

    Gallagher, Ciara M; Walter, Peter

    2016-01-01

    The membrane-bound transcription factor ATF6α is activated by proteolysis during endoplasmic reticulum (ER) stress. ATF6α target genes encode foldases, chaperones, and lipid biosynthesis enzymes that increase protein-folding capacity in response to demand. The off-state of ATF6α is maintained by its spatial separation in the ER from Golgi-resident proteases that activate it. ER stress induces trafficking of ATF6α. We discovered Ceapins, a class of pyrazole amides, as selective inhibitors of ATF6α signaling that do not inhibit the Golgi proteases or other UPR branches. We show that Ceapins block ATF6α signaling by trapping it in ER-resident foci that are excluded from ER exit sites. Removing the requirement for trafficking by pharmacological elimination of the spatial separation of the ER and Golgi apparatus restored cleavage of ATF6α in the presence of Ceapins. Washout of Ceapins resensitized ATF6α to ER stress. These results suggest that trafficking of ATF6α is regulated by its oligomeric state. DOI: http://dx.doi.org/10.7554/eLife.11880.001

  13. Mutation of ATF6 causes autosomal recessive achromatopsia.

    Science.gov (United States)

    Ansar, Muhammad; Santos-Cortez, Regie Lyn P; Saqib, Muhammad Arif Nadeem; Zulfiqar, Fareeha; Lee, Kwanghyuk; Ashraf, Naeem Mahmood; Ullah, Ehsan; Wang, Xin; Sajid, Sundus; Khan, Falak Sher; Amin-ud-Din, Muhammad; Smith, Joshua D; Shendure, Jay; Bamshad, Michael J; Nickerson, Deborah A; Hameed, Abdul; Riazuddin, Saima; Ahmed, Zubair M; Ahmad, Wasim; Leal, Suzanne M

    2015-09-01

    Achromatopsia (ACHM) is an early-onset retinal dystrophy characterized by photophobia, nystagmus, color blindness and severely reduced visual acuity. Currently mutations in five genes CNGA3, CNGB3, GNAT2, PDE6C and PDE6H have been implicated in ACHM. We performed homozygosity mapping and linkage analysis in a consanguineous Pakistani ACHM family and mapped the locus to a 15.12-Mb region on chromosome 1q23.1-q24.3 with a maximum LOD score of 3.6. A DNA sample from an affected family member underwent exome sequencing. Within the ATF6 gene, a single-base insertion variant c.355_356dupG (p.Glu119Glyfs*8) was identified, which completely segregates with the ACHM phenotype within the family. The frameshift variant was absent in public variant databases, in 130 exomes from unrelated Pakistani individuals, and in 235 ethnically matched controls. The variant is predicted to result in a truncated protein that lacks the DNA binding and transmembrane domains and therefore affects the function of ATF6 as a transcription factor that initiates the unfolded protein response during endoplasmic reticulum (ER) stress. Immunolabeling with anti-ATF6 antibodies showed localization throughout the mouse neuronal retina, including retinal pigment epithelium, photoreceptor cells, inner nuclear layer, inner and outer plexiform layers, with a more prominent signal in retinal ganglion cells. In contrast to cytoplasmic expression of wild-type protein, in heterologous cells ATF6 protein with the p.Glu119Glyfs*8 variant is mainly confined to the nucleus. Our results imply that response to ER stress as mediated by the ATF6 pathway is essential for color vision in humans. PMID:26063662

  14. A role for ATF2 in regulating MITF and melanoma development.

    Directory of Open Access Journals (Sweden)

    Meera Shah

    Full Text Available The transcription factor ATF2 has been shown to attenuate melanoma susceptibility to apoptosis and to promote its ability to form tumors in xenograft models. To directly assess ATF2's role in melanoma development, we crossed a mouse melanoma model (Nras(Q61K::Ink4a⁻/⁻ with mice expressing a transcriptionally inactive form of ATF2 in melanocytes. In contrast to 7/21 of the Nras(Q61K::Ink4a⁻/⁻ mice, only 1/21 mice expressing mutant ATF2 in melanocytes developed melanoma. Gene expression profiling identified higher MITF expression in primary melanocytes expressing transcriptionally inactive ATF2. MITF downregulation by ATF2 was confirmed in the skin of Atf2⁻/⁻ mice, in primary human melanocytes, and in 50% of human melanoma cell lines. Inhibition of MITF transcription by MITF was shown to be mediated by ATF2-JunB-dependent suppression of SOX10 transcription. Remarkably, oncogenic BRAF (V600E-dependent focus formation of melanocytes on soft agar was inhibited by ATF2 knockdown and partially rescued upon shMITF co-expression. On melanoma tissue microarrays, a high nuclear ATF2 to MITF ratio in primary specimens was associated with metastatic disease and poor prognosis. Our findings establish the importance of transcriptionally active ATF2 in melanoma development through fine-tuning of MITF expression.

  15. Identification of ATF2 as a transcriptional regulator of renin gene.

    Science.gov (United States)

    Desch, Michael; Hackmayer, Gerit; Todorov, Vladimir T

    2012-01-01

    The cAMP response element (enhCRE) in the distal enhancer regulatory region of renin gene is believed to play a major role in the control of renin transcription. enhCRE binds the CRE-binding protein (CREB), which is the main transcription factor target of cAMP signaling. Using the mouse renin-producing cell line As4.1 we found that activating transcription factor-2 (ATF2) also binds to enhCRE. N-terminal phosphorylation of ATF2, which controls its transactivation, is associated with downregulation of renin gene expression by the cytokine tumor necrosis factor-α (TNFα). The ubiquitin proteasome inhibitor MG132 also phosphorylates ATF2 and inhibits renin expression. Knockdown of ATF2 attenuated the suppression of renin gene expression by MG132, thus demonstrating that ATF2 mediates the inhibitory effect of MG132. In addition, MG132 increased the DNA-binding of ATF2 as well as the ratio of bound ATF2 to CREB. Using ATF2- and CREB-Gal4 fusion protein constructs coupled with luciferase reporter system we showed that ATF2 has a weaker transactivating capacity than CREB. These data suggest that ATF2 represses renin expression by drifting the transcriptional control of renin gene away from CREB. Accordingly, TNFα completely abrogated the cAMP-dependent stimulation of renin gene expression.

  16. Design of multichord Hα detector arrays for the U-3M torsatron and identification of rotating plasma perturbations

    Science.gov (United States)

    Dreval, M. B.; Shapoval, A. M.; Ozherelyev, F. I.; Makhov, M. M.

    2016-07-01

    An Hα camera has been designed and installed in the U-3M torsatron for spatially and temporally resolved measurements. This device provides fast measurements of the emission brightness profile in the noisy environment of the radio frequency (RF) heated plasma. Unusual topology of diagnostics and the data acquisition system are applied. All the system components, including digitizers, are assembled in a single unit. It allows the suppression of a low-frequency electromagnetic interference by eliminating the ground loops. And the suppression of RF noises is achieved by eliminating the signal interface cables and digital interface cables in the design. The Wi-Fi interface is used to prevent a ground loop in the data transfer stage. The achieved sensitivity of our diagnostics is high enough for measuring the Hα emission from the low-density (ne ≈ (1-2)ṡ1010 cm-3) plasma with a temporal resolution of about 20 μs in the noisy environment. Different types of Hα emission fluctuations within the frequency range of 1-5 kHz and poloidal mode numbers m = 0 and m = 5 have been observed in U-3M. A simple technique of the line-of-sight data analysis, based on the U-3M magnetic surface asymmetry, is proposed and used for the spatial localization of the rotating mode and for the determination of mode numbers and its poloidal rotation direction using a single Hα array.

  17. Testing of a pulsed He supersonic beam for plasma edge diagnostic in the TJ-IU torsatron

    Science.gov (United States)

    Tabarés, F. L.; Tafalla, D.; Herrero, V.; Tanarro, I.

    1997-02-01

    A new, compact atomic beam source based on the supersonic expansion of He has been developed for application as a plasma edge diagnostic. The beam is produced from a pulsed valve with a duration between 0.2 to 2 ms and a nominal repetition rate 10 and a divergence of ± 1° have been achieved at stagnation pressures below 2 bar. The diagnostic has been tested in ECRH plasmas on the TJ-IU torsatron, representing the first application of a supersonic beam to plasma characterization, to our knowledge. Operational conditions which minimized the total amount of He injected into the plasma were chosen. Non-perturbative injection conditions in the low density plasmas could be obtained at local He densities of ⋍ 1 × 10 11 cm -3 and a beam diameter < 1 cm. Due to the relatively low electron density of the ECRH plasmas, and to the good penetration characteristics of the supersonic He beam, the diagnostic could be used up to fairly low values of the normalized plasma minor radius, {r}/{a} (a = 12 cm) . Details of the optimization of the atomic beam diagnostics and typical results for steady state conditions in the TJ-IU plasmas are presented.

  18. Testing of a pulsed He supersonic beam for plasma edge diagnostic in the TJ-IU torsatron

    Energy Technology Data Exchange (ETDEWEB)

    Tabares, F.L. [Association EURATOM/CIEMAT, Madrid (Spain); Tafalla, D. [Association EURATOM/CIEMAT, Madrid (Spain); Herrero, V. [Instituto de Estructura de la Materia, CSIC, 28006 Madrid (Spain); Tanarro, I. [Instituto de Estructura de la Materia, CSIC, 28006 Madrid (Spain)

    1997-02-01

    A new, compact atomic beam source based on the supersonic expansion of He has been developed for application as a plasma edge diagnostic. The beam is produced from a pulsed valve with a duration between 0.2 to 2 ms and a nominal repetition rate <500 Hz. A terminal speed ratio >10 and a divergence of {+-}1 have been achieved at stagnation pressures below 2 bar. The diagnostic has been tested in ECRH plasmas on the TJ-IU torsatron, representing the first application of a supersonic beam to plasma characterization, to our knowledge. Operational conditions which minimized the total amount of He injected into the plasma were chosen. Non-perturbative injection conditions in the low density plasmas could be obtained at local He densities of {approx_equal}1 x 10{sup 11} cm{sup -3} and a beam diameter <1 cm. Due to the relatively low electron density of the ECRH plasmas, and to the good penetration characteristics of the supersonic He beam, the diagnostic could be used up to fairly low values of the normalized plasma minor radius, r/a (a=12 cm). Details of the optimization of the atomic beam diagnostics and typical results for steady state conditions in the TJ-IU plasmas are presented. (orig.).

  19. Detect ground motion effects on the trajectory at ATF2

    CERN Document Server

    Rénier, Yves; Garcia, Rogelio

    2011-01-01

    The Accelerator Test Facility 2 (ATF2) commissioning group aims to demonstrate the feasibility of the Beam Delivery System (BDS) of the next linear colliders (ILC and CLIC) as well as to define and to test the tunning methods. As the design vertical beam sizes of the linear colliders are about few nanometers, the stability of the trajectory as well as the control of the aberrations are very critical. The magnet displacements induced by ground motion are large enough for CLIC to perturb the beam stability above requirements. It is planned to measure the displacement of the magnets and implement a feed-forward correcting the effects on the beam trajectory with correctors (dipoles). This article studies the possibility to detect ground motion effects on the beam trajectory at ATF2. Characteristics of the ground motion at ATF2 are presented, the effects of the magnet displacements on the beam trajectory are simulated and an algorithm predicting the induced trajectory fluctuations is evaluated. After the estimated...

  20. Cavity Beam Position Monitor System for ATF2

    Energy Technology Data Exchange (ETDEWEB)

    Boogert, Stewart; /Oxford U., JAI; Boorman, Gary; /Oxford U., JAI; Swinson, Christina; /Oxford U., JAI; Ainsworth, Robert; /Royal Holloway, U. of London; Molloy, Stephen; /Royal Holloway, U. of London; Aryshev, Alexander; /KEK, Tsukuba; Honda, Yosuke; /KEK, Tsukuba; Tauchi, Toshiaki; /KEK, Tsukuba; Terunuma, Nobuhiro; /KEK, Tsukuba; Urakawa, Junji; /KEK, Tsukuba; Frisch, Josef; /SLAC; May, Justin; /SLAC; McCormick, Douglas; /SLAC; Nelson, Janice; /SLAC; Smith, Tonee; /SLAC; White, Glen; /SLAC; Woodley, Mark; /SLAC; Heo, Ae-young; /Kyungpook Natl. U.; Kim, Eun-San; /Kyungpook Natl. U.; Kim, Hyoung-Suk; /Kyungpook Natl. U.; Kim, Youngim; /Kyungpook Natl. U. /University Coll. London /Kyungpook Natl. U. /Fermilab /Pohang Accelerator Lab.

    2012-07-09

    The Accelerator Test Facility 2 (ATF2) in KEK, Japan, is a prototype scaled demonstrator system for the final focus required for a future high energy lepton linear collider. The ATF2 beam-line is instrumented with a total of 38 C and S band resonant cavity beam position monitors (CBPM) with associated mixer electronics and digitizers. The current status of the BPM system is described, with a focus on operational techniques and performance. The ATF2 C-band system is performing well, with individual CBPM resolution approaching or at the design resolution of 50 nm. The changes in the CBPM calibration observed over three weeks can probably be attributed to thermal effects on the mixer electronics systems. The CW calibration tone power will be upgraded to monitor changes in the electronics gain and phase. The four S-band CBPMs are still to be investigated, the main problem associated with these cavities is a large cross coupling between the x and y ports. This combined with the large design dispersion in that degion makes the digital signal processing difficult, although various techniques exist to determine the cavity parameters and use these coupled signals for beam position determination.

  1. ATF4 is involved in the regulation of simulated microgravity induced integrated stress response

    Science.gov (United States)

    Li, Yingxian; Li, Qi; Wang, Xiaogang; Sun, Qiao; Wan, Yumin; Li, Yinghui; Bai, Yanqiang

    Objective: Many important metabolic and signaling pathways have been identified as being affected by microgravity, thereby altering cellular functions such as proliferation, differentiation, maturation and cell survival. It has been demonstrated that microgravity could induce all kinds of stress response such as endoplasmic reticulum stress and oxidative stress et al. ATF4 belongs to the ATF/CREB family of basic region leucine zipper transcription factors. ATF4 is induced by stress signals including anoxia/hypoxia, ER stress, amino acid deprivation and oxidative stress. ATF4 regulates the expression of genes involved in oxidative stress, amino acid synthesis, differentiation, metastasis and angiogenesis. The aim of this study was to examine the changes of ATF4 under microgravity, and to investigate the role of ATF4 in microgravity induced stress. MethodsMEF cells were cultured in clinostat to simulate microgravity. Reverse transcription polymerase chain reaction (RT-PCR) and western blotting were used to examine mRNA and protein levels of ATF4 expression under simulated microgravity in MEF cells. ROS levels were measured with the use of the fluorescent signal H2DCF-DA. GFP-XBP1 stably transfected cell lines was used to detect the extent of ER stress under microgravity by the intensity of GFP. Dual luciferase reporter assay was used to detect the activity of ATF4. Co-immunoprecipitation was performed to analyze protein interaction. Results: ATF4 protein levels in MEF cells increased under simulated microgravity. However, ATF4 mRNA levels were consistent. XBP1 splicing can be induced due to ER stress caused by simulated microgravity. At the same time, ROS levels were also increased. Increased ATF4 could promote the expression of CHOP, which is responsible for cell apoptosis. ATF4 also play an important role in cellular anti-oxidant stress. In ATF4 -/-MEF cells, the ROS levels after H2O2 treatment were obviously higher than that of wild type cells. HDAC4 was

  2. A key role for ATF3 in regulating mast cell survival and mediator release

    OpenAIRE

    Gilchrist, Mark; Henderson, William R.; Morotti, Andrew; Carrie D. Johnson; Nachman, Alex; Schmitz, Frank; Smith, Kelly D.; Aderem, Alan

    2010-01-01

    Activating transcription factor 3 (ATF3) is a basic leucine zipper transcription factor that plays a regulatory role in inflammation, cell division, and apoptosis. Mast cells (MCs) initiate many inflammatory responses and have a central role in allergy and allergic diseases. We report here that ATF3 has a central role in MC development and function. Bone marrow–derived MC populations from ATF3-deficient mice are unresponsive to interleukin-3 (IL-3)–induced maturation signals, and this correla...

  3. Glucose deprivation induces chemoresistance in colorectal cancer cells by increasing ATF4 expression

    Science.gov (United States)

    Hu, Ya-Ling; Yin, Yuan; Liu, He-Yong; Feng, Yu-Yang; Bian, Ze-Hua; Zhou, Le-Yuan; Zhang, Ji-Wei; Fei, Bo-Jian; Wang, Yu-Gang; Huang, Zhao-Hui

    2016-01-01

    AIM: To investigate the role of activating transcription factor 4 (ATF4) in glucose deprivation (GD) induced colorectal cancer (CRC) drug resistance and the mechanism involved. METHODS: Chemosensitivity and apoptosis were measured under the GD condition. Inhibition of ATF4 using short hairpin RNA in CRC cells under the GD condition and in ATF4-overexpressing CRC cells was performed to identify the role of ATF4 in the GD induced chemoresistance. Quantitative real-time RT-PCR and Western blot were used to detect the mRNA and protein expression of drug resistance gene 1 (MDR1), respectively. RESULTS: GD protected CRC cells from drug-induced apoptosis (oxaliplatin and 5-fluorouracil) and induced the expression of ATF4, a key gene of the unfolded protein response. Depletion of ATF4 in CRC cells under the GD condition can induce apoptosis and drug re-sensitization. Similarly, inhibition of ATF4 in the ATF4-overexpressing CRC cells reintroduced therapeutic sensitivity and apoptosis. In addition, increased MDR1 expression was observed in GD-treated CRC cells. CONCLUSION: These data indicate that GD promotes chemoresistance in CRC cells through up-regulating ATF4 expression. PMID:27468213

  4. Improved antibody production in Chinese hamster ovary cells by ATF4 overexpression

    OpenAIRE

    Haredy, Ahmad M.; Nishizawa, Akitoshi; Honda, Kohsuke; Ohya, Tomoshi; Ohtake, Hisao; Omasa, Takeshi

    2013-01-01

    To improve antibody production in Chinese hamster ovary (CHO) cells, the humanized antibody-producing CHO DP-12-SF cell line was transfected with the gene encoding activating transcription factor 4 (ATF4), a central factor in the unfolded protein response. Overexpression of ATF4 significantly enhanced the production of antibody in the CHO DP-12-SF cell line. The specific IgG production rate of in the ATF4-overexpressing CHO-ATF4-16 cells was approximately 2.4 times that of the parental host c...

  5. Cadmium interferes with the degradation of ATF5 via a post-ubiquitination step of the proteasome degradation pathway

    International Nuclear Information System (INIS)

    ATF5 is a member of the CREB/ATF family of transcription factors. In the current study, using a transient transfection system to express FLAG epitope fusion proteins of ATF5, we have shown that CdCl2 or NaAsO3 increases the protein levels of ATF5 in cells, and that cadmium stabilizes the ATF5 protein. Proteasome inhibitors had a similar effect to cadmium on the cellular accumulation of ATF5. Proteasome inhibition led to an increase in ubiquitinated ATF5, while cadmium did not appear to reduce the extent of ATF5 ubiquitination. ATF5 contains a putative nuclear export signal within its N-terminus. We demonstrated that whereas deletion of N-terminal region resulted in a increase of ATF5 levels, this region does not appear to be involved in the ubiquitination of ATF5. These results indicate that ATF5 is targeted for degradation by the ubiquitin-proteasome pathway, and that cadmium slows the rate of ATF5 degradation via a post-ubiquitination mechanism.

  6. Turn by Turn Measurements at the KEK-ATF

    CERN Document Server

    Renier, Y; Tomas, R; Wendt, M; Eddy, N; Kubo, K; Kuroda, S; Naito, T; Okugi, T; Terunuma, N; Urakawa, J

    2013-01-01

    The ATF damping ring has been upgraded with new read-out electronics for the beam position monitors (BPM), capable to acquire the beam orbits on a turn-by-turn basis, as well as in a high resolution averaging mode. The new BPM system allows to improve optic corrections and to achieve an even smaller vertical emittance (<2pm). Experimental results are presented based on turn-by-turn beam orbit measurements in the ring, for estimating the β functions and dispersion along the lattice. A fast method to measure spectral line amplitude in a few turns is also presented, including the evaluation of chromaticity.

  7. Antenna Test Facility (ATF): User Test Planning Guide

    Science.gov (United States)

    Lin, Greg

    2011-01-01

    Test process, milestones and inputs are unknowns to first-time users of the ATF. The User Test Planning Guide aids in establishing expectations for both NASA and non-NASA facility customers. The potential audience for this guide includes both internal and commercial spaceflight hardware/software developers. It is intended to assist their test engineering personnel in test planning and execution. Material covered includes a roadmap of the test process, roles and responsibilities of facility and user, major milestones, facility capabilities, and inputs required by the facility. Samples of deliverables, test article interfaces, and inputs necessary to define test scope, cost, and schedule are included as an appendix to the guide.

  8. The ATF6-Met[67]Val Substitution Is Associated With Increased Plasma Cholesterol Levels

    NARCIS (Netherlands)

    Meex, Steven J. R.; Weissglas-Volkov, Daphna; van der Kallen, Carla J. H.; Thuerauf, Donna J.; van Greevenbroek, Marleen M. J.; Schalkwijk, Casper G.; Stehouwer, Coen D. A.; Feskens, Edith J. M.; Heldens, Lonneke; Ayoubi, Torik A.; Hofker, Marten H.; Wouters, Bradly G.; Vlietinck, Robert; Sinsheimer, Janet S.; Taskinen, Marja-Riitta; Kuusisto, Johanna; Laakso, Markku; de Bruin, Tjerk W. A.; Pajukanta, Paivi; Glembotski, Christopher C.

    2009-01-01

    Objective-Activating transcription factor 6 (ATF6) is a sensor of the endoplasmic reticulum stress response and regulates expression of several key lipogenic genes. We used a 2-stage design to investigate whether ATF6 polymorphisms are associated with lipids in subjects at increased risk for cardiov

  9. 斑马鱼基因ATF4多克隆抗体的制备%Preparation of Polyclonal Antibody of ATF4 in Zebrafish

    Institute of Scientific and Technical Information of China (English)

    李发祥; 杨荣; 陈婷芳; 唐雄卓; 赵碧峰; 江志钢; 张义; 李永青; 吴秀山

    2012-01-01

    ATF4 , a member of the ATF/CREB transcription factor family which contains a bZIP domain, plays a important role in the embryonic development, cell proliferation and differentiation. Therefore, it is advisable to prepare an antibody for the heart development research in Zerbrafish. In this research, a ATF4-specific, hydrophilic nucleotide sequence (about 1 017 bp) was selected by using bioinformatics methods, and the sequence was amplified by PCR, the PCR product was inserted into the prokaryotic expression vector pET-28a and then transformed into Rosetta cells. After the sequence result of the recombinant plasmid pET-28a-ATF4 is verified to be right, the fusion protein was induced to express in Rosetta cells by IPTG. The mouse was immunized by injecting appropriate amount of fusion protein, and the ATF4 polyclonal antibody was obtained. The antibody' s titer and specification was identified. Our results showed that the ATF4 polyclonal antibody was practical and available for western-blotting analysis and immunohisto-chemistry.%ATF4是含有bZIP结构域的ATF/CREB转录因子家族成员,对胚胎的发育以及细胞的增殖、分化有重要的调节作用.制备ATF4的多克隆抗体对于研究其在斑马鱼心脏发育过程中的作用有重要的意义.研究首先通过生物信息学方法,选择ATF4基因中特异性强、具亲水性的一段核苷酸序列(1 017 bp),通过PCR扩增,将片段重组到原核表达载体pET-28a,然后转化人Rosetta菌株中.经测序鉴定正确后,用IPTG诱导表达融合蛋白,以该融合蛋白免疫小鼠,获得ATF4多克隆抗鼠血清.对该多抗血清抗体进行验证,具有很好特异性和较高效价,可以用作Western-blotting、免疫印迹等试验分析.

  10. Atf3 mutant mice show reduced axon regeneration and impaired regeneration-associated gene induction after peripheral nerve injury

    Science.gov (United States)

    Gey, Manuel; Wanner, Renate; Schilling, Corinna; Pedro, Maria T.; Sinske, Daniela

    2016-01-01

    Axon injury in the peripheral nervous system (PNS) induces a regeneration-associated gene (RAG) response. Atf3 (activating transcription factor 3) is such a RAG and ATF3's transcriptional activity might induce ‘effector’ RAGs (e.g. small proline rich protein 1a (Sprr1a), Galanin (Gal), growth-associated protein 43 (Gap43)) facilitating peripheral axon regeneration. We provide a first analysis of Atf3 mouse mutants in peripheral nerve regeneration. In Atf3 mutant mice, facial nerve regeneration and neurite outgrowth of adult ATF3-deficient primary dorsal root ganglia neurons was decreased. Using genome-wide transcriptomics, we identified a neuropeptide-encoding RAG cluster (vasoactive intestinal peptide (Vip), Ngf, Grp, Gal, Pacap) regulated by ATF3. Exogenous administration of neuropeptides enhanced neurite growth of Atf3 mutant mice suggesting that these molecules might be effector RAGs of ATF3's pro-regenerative function. In addition to the induction of growth-promoting molecules, we present data that ATF3 suppresses growth-inhibiting molecules such as chemokine (C-C motif) ligand 2. In summary, we show a pro-regenerative ATF3 function during PNS nerve regeneration involving transcriptional activation of a neuropeptide-encoding RAG cluster. ATF3 is a general injury-inducible factor, therefore ATF3-mediated mechanisms identified herein might apply to other cell and injury types. PMID:27581653

  11. 75 FR 47254 - Elimination of Firearms Transaction Record, ATF Form 4473 (Low Volume) (2008R-21P)

    Science.gov (United States)

    2010-08-05

    ... Transaction Record, ATF Form 4473 (Low Volume) (2008R-21P) AGENCY: Bureau of Alcohol, Tobacco, Firearms, and... (ATF) by eliminating the Firearms Transaction Record, ATF Form 4473 (Low Volume (LV)), Parts I and II...) Part I, Firearms Transaction Record Part I--Low Volume--Over-The-Counter, or Form 4473 (LV) Part...

  12. Atf3 mutant mice show reduced axon regeneration and impaired regeneration-associated gene induction after peripheral nerve injury.

    Science.gov (United States)

    Gey, Manuel; Wanner, Renate; Schilling, Corinna; Pedro, Maria T; Sinske, Daniela; Knöll, Bernd

    2016-08-01

    Axon injury in the peripheral nervous system (PNS) induces a regeneration-associated gene (RAG) response. Atf3 (activating transcription factor 3) is such a RAG and ATF3's transcriptional activity might induce 'effector' RAGs (e.g. small proline rich protein 1a (Sprr1a), Galanin (Gal), growth-associated protein 43 (Gap43)) facilitating peripheral axon regeneration. We provide a first analysis of Atf3 mouse mutants in peripheral nerve regeneration. In Atf3 mutant mice, facial nerve regeneration and neurite outgrowth of adult ATF3-deficient primary dorsal root ganglia neurons was decreased. Using genome-wide transcriptomics, we identified a neuropeptide-encoding RAG cluster (vasoactive intestinal peptide (Vip), Ngf, Grp, Gal, Pacap) regulated by ATF3. Exogenous administration of neuropeptides enhanced neurite growth of Atf3 mutant mice suggesting that these molecules might be effector RAGs of ATF3's pro-regenerative function. In addition to the induction of growth-promoting molecules, we present data that ATF3 suppresses growth-inhibiting molecules such as chemokine (C-C motif) ligand 2. In summary, we show a pro-regenerative ATF3 function during PNS nerve regeneration involving transcriptional activation of a neuropeptide-encoding RAG cluster. ATF3 is a general injury-inducible factor, therefore ATF3-mediated mechanisms identified herein might apply to other cell and injury types. PMID:27581653

  13. The transcription factor ATF3 acts as an oncogene in mouse mammary tumorigenesis

    International Nuclear Information System (INIS)

    Overexpression of the bZip transcription factor, ATF3, in basal epithelial cells of transgenic mice under the control of the bovine cytokeratin-5 (CK5) promoter has previously been shown to induce epidermal hyperplasia, hair follicle anomalies and neoplastic lesions of the oral mucosa including squamous cell carcinomas. CK5 is known to be expressed in myoepithelial cells of the mammary gland, suggesting the possibility that transgenic BK5.ATF3 mice may exhibit mammary gland phenotypes. Mammary glands from nulliparous mice in our BK5.ATF3 colony, both non-transgenic and transgenic, were examined for anomalies by histopathology and immunohistochemistry. Nulliparous and biparous female mice were observed for possible mammary tumor development, and suspicious masses were analyzed by histopathology and immunohistochemistry. Human breast tumor samples, as well as normal breast tissue, were similarly analyzed for ATF3 expression. Transgenic BK5.ATF3 mice expressed nuclear ATF3 in the basal layer of the mammary ductal epithelium, and often developed squamous metaplastic lesions in one or more mammary glands by 25 weeks of age. No progression to malignancy was seen in nulliparous BK5.ATF3 or non-transgenic mice held for 16 months. However, biparous BK5.ATF3 mice developed mammary carcinomas with squamous metaplasia between 6 months and one year of age, reaching an incidence of 67%. Cytokeratin expression in the tumors was profoundly disturbed, including expression of CK5 and CK8 (characteristic of basal and luminal cells, respectively) throughout the epithelial component of the tumors, CK6 (potentially a stem cell marker), CK10 (a marker of interfollicular epidermal differentiation), and mIRSa2 and mIRSa3.1 (markers of the inner root sheath of hair follicles). Immunohistochemical studies indicated that a subset of human breast tumors exhibit high levels of nuclear ATF3 expression. Overexpression of ATF3 in CK5-expressing cells of the murine mammary gland results in the

  14. Loss of ATF2 function leads to cranial motoneuron degeneration during embryonic mouse development.

    Directory of Open Access Journals (Sweden)

    Julien Ackermann

    Full Text Available The AP-1 family transcription factor ATF2 is essential for development and tissue maintenance in mammals. In particular, ATF2 is highly expressed and activated in the brain and previous studies using mouse knockouts have confirmed its requirement in the cerebellum as well as in vestibular sense organs. Here we present the analysis of the requirement for ATF2 in CNS development in mouse embryos, specifically in the brainstem. We discovered that neuron-specific inactivation of ATF2 leads to significant loss of motoneurons of the hypoglossal, abducens and facial nuclei. While the generation of ATF2 mutant motoneurons appears normal during early development, they undergo caspase-dependent and independent cell death during later embryonic and foetal stages. The loss of these motoneurons correlates with increased levels of stress activated MAP kinases, JNK and p38, as well as aberrant accumulation of phosphorylated neurofilament proteins, NF-H and NF-M, known substrates for these kinases. This, together with other neuropathological phenotypes, including aberrant vacuolisation and lipid accumulation, indicates that deficiency in ATF2 leads to neurodegeneration of subsets of somatic and visceral motoneurons of the brainstem. It also confirms that ATF2 has a critical role in limiting the activities of stress kinases JNK and p38 which are potent inducers of cell death in the CNS.

  15. Functional interaction of TCF4 with ATF5 to regulate the Wnt signaling pathway

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Wnt signaling directs cell-fate choices during embryonic development and tissue tumorigenesis. T cell factor 4 (TCF4) plays a pivotal role in the Wnt signaling pathway. We demonstrate that a specific protein-protein interaction occurs between TCF4 and ATF5 (activating transcription factor 5) -- a new member of cAMP response element binding protein (CREB) with the yeast two-hybrid system. The N-terminal and DNA binding domain of TCF4 (TCF4ND, 1-495 aa) and the C-terminal spanning bZIP domain of ATF5 (162-282 aa) were found to be responsible for the interaction, and the C-terminal of ATF5 (ATF5/C) showed a much stronger interaction with TCF4ND than the full-length of ATF5 by detecting the ?-gal activity. Furthermore, overexpression of ATF5/C enhanced transcriptional activation by TCF4 proteins in luciferase assay by transient transfection. Taken together, these data suggest that ATF5 may function as a co-activator to potentiate the ability of TCF4 to activate transcription.

  16. Integrative decomposition procedure and Kappa statistics set up ATF2 ion binding module in malignant pleural mesothelioma (MPM)

    Institute of Scientific and Technical Information of China (English)

    Ying SUN; Lin WANG; Lei LIU

    2008-01-01

    Activating transcription factor 2 (ATF2) is a member of the ATF/cyclic AMP-responsive element bind-ing protein family of transcription factors. However, the information concerning ATF2 ion-mediated DNA binding module and function of ATF2 in malignant pleural mesothelioma (MPM) has never been addressed. In this study, by using GRNInfer and GVedit based on linear pro-gramming and a decomposition procedure, with integrated analysis of the function cluster using Kappa statistics and fuzzy heuristic clustering in MPM, we identified one ATF2 ion-mediated DNA binding module involved in invasive function including ATF2 inhibition to target genes FALZ, C20orf31, NME2, PLOD2, RNF10, and RNASEH1, upstream RNF10 and PLOD2 activation to ATF2, upstream RNASEH1 and FALZ inhibition to ATF2 from 40 MPM tumors and 5 normal pleural tissues. Remarkably, our results showed that the predominant effect of ATF2 occupancy is to suppress the activation of target genes on MPM. Importantly, the ATF2 ion-mediated DNA binding module reflects 'mutual' positive and negative feedback regulation mechanism of ATF2 with up-and down-stream genes. It may be useful for developing novel prognostic markers and therapeutic targets in MPM.

  17. Construction and Activity Assay of the Activating Transcription Factor 3 Reporter Vector pATF/CRE-luc

    Institute of Scientific and Technical Information of China (English)

    Jun-Qing XU; Jing-Lan DENG; You-Sheng WU; Han-Yan FU; Rui-Hua WANG; Jian ZHANG; Fan LU; Zhong-Liang ZHAO

    2006-01-01

    Activating transcription factor 3 (ATF3), a member of the activating transcription factor/cAMP responsive element binding protein (ATF/CREB) family of transcription factors, is induced by many physiological stresses. To investigate the activity of ATF/CREB in cells with physiological stresses, we developed a practical reporter vector, the plasmid pATF/CRE-luc, bearing activating transcription factor/cAMP responsive element (ATF/CRE) binding sites. This plasmid was constructed by inserting three repeats of the ATF/CRE binding element into the plasmid pG51uc, replacing the GAL-4 binding sites. The plasmids pACT/ATF3 and pATF/CRE-luc were transfected into HeLa and NIH3T3 cells, respectively, and the results showed that the expression of luciferase was increased in a dose-dependent manner on plasmid pACT/ATF3. The data suggested that the plasmid pATF/CRE-luc could be used as a sensitive and convenient reporter system of ATF3 activity.

  18. The loss of activating transcription factor 4 (ATF4) reduces bone toughness and fracture toughness.

    Science.gov (United States)

    Makowski, Alexander J; Uppuganti, Sasidhar; Wadeer, Sandra A; Whitehead, Jack M; Rowland, Barbara J; Granke, Mathilde; Mahadevan-Jansen, Anita; Yang, Xiangli; Nyman, Jeffry S

    2014-05-01

    Even though age-related changes to bone tissue affecting fracture risk are well characterized, only a few matrix-related factors have been identified as important to maintaining fracture resistance. As a gene critical to osteoblast differentiation, activating transcription factor 4 (ATF4) is possibly one of these important factors. To test the hypothesis that the loss of ATF4 affects the fracture resistance of bone beyond bone mass and structure, we harvested bones from Atf4+/+ and Atf4-/- littermates at 8 and 20 weeks of age (n≥9 per group) for bone assessment across several length scales. From whole bone mechanical tests in bending, femurs from Atf4-/- mice were found to be brittle with reduced toughness and fracture toughness compared to femurs from Atf4+/+ mice. However, there were no differences in material strength and in tissue hardness, as determined by nanoindentation, between the genotypes, irrespective of age. Tissue mineral density of the cortex at the point of loading as determined by micro-computed tomography was also not significantly different. However, by analyzing local composition by Raman Spectroscopy (RS), bone tissue of Atf4-/- mice was found to have higher mineral to collagen ratio compared to wild-type tissue, primarily at 20 weeks of age. From RS analysis of intact femurs at 2 orthogonal orientations relative to the polarization axis of the laser, we also found that the organizational-sensitive peak ratio, ν1Phosphate per Amide I, changed to a greater extent upon bone rotation for Atf4-deficient tissue, implying bone matrix organization may contribute to the brittleness phenotype. Target genes of ATF4 activity are not only important to osteoblast differentiation but also in maintaining bone toughness and fracture toughness.

  19. Scenarios for the ATF2 Ultra-Low Betas Proposal

    Energy Technology Data Exchange (ETDEWEB)

    Marin, Eduardo; /CERN; Tomas, Rogelio; /CERN; Bambade, Philip; /Orsay, LAL; Kuroda, Shigeru; /KEK, Tsukuba; Okugi, Toshiyuki; /KEK, Tsukuba; Tauchi, Toshiaki; /KEK, Tsukuba; Terunuma, Nobuhiro; /KEK, Tsukuba; Urakawa, Junji; /KEK, Tsukuba; Parker, Brett; /Brookhaven; Seryi, Andrei; /SLAC; White, Glen; /SLAC; Woodley, Mark; /SLAC

    2012-06-29

    The current ATF2 Ultra-Low beta proposal was designed to achieve 20nm vertical IP beam size without considering the multipolar components of the FD magnets. In this paper we describe different scenarios that avoid the detrimental effect of these multipolar errors to the beam size at the interaction point (IP). The simplest approach consists in modifying the optics, but other solutions are studied as the introduction of super-conducting wigglers to reduce the emittance or the replacement of the normal-conducting focusing quadrupole in the Final Doublet (NC-QF1FF) with a super-conducting quadrupole one (SC-QF1FF). These are fully addressed in the paper.

  20. Reconstruction of local emissivity profile from chord-integrated soft x-ray data in heliotron/torsatron plasmas by singular-value decomposition

    International Nuclear Information System (INIS)

    A reconstruction method for a local soft X-ray (SX) emissivity profile based on singular-value decomposition (SVD) was applied to the chord-integrated SX data obtained in the compact helical system (CHS) heliotron/torsatron. The numerical procedure for this method was simplified by introducing the data of equilibrium magnetic surfaces to analyze the experimental data efficiently. The applicability of the Akaide information criterion (AIC) was investigated for the determination of the optimal number of parameters characterizing a local emissivity profile. This method was applied to SX data for sawtoothing plasmas of the CHS. For these CHS data, the optimal number of parameters is determined from the spatial resolution of an SX detector array rather than the AIC. A characteristic feature of the off-axis or annular sawtooth crash was clearly derived with this technique. (author)

  1. Behaviour of the radiation of the suprathermal electrons at the Uragan-3M torsatron after rf heating off from ECE measurements

    International Nuclear Information System (INIS)

    The microwave radiometry is a well-known diagnostics to obtain the information on temporal evolution and radial profile of the electron temperature at U-3M torsatron plasma experiments. However, under low plasma density with this diagnostics we report on the large production of runaway electrons after RF heating pulse off. We notice a gradually increasing of the radiometer signal at the frequencies that match the second and third harmonics of electron cyclotron emission of the extraordinary mode. This effect could be explained with the existence of the ''runaway'' electrons in U-3M discharge. A phenomenological description of this process is presented, where the time evolution of the ECE radiation signal is compared to the electron density evolution

  2. Specifications of the octupole magnets required for the ATF2 ultra-low ß* lattice

    Energy Technology Data Exchange (ETDEWEB)

    Marin, E.; /SLAC; Modena, M.; /CERN; Tauchi, T.; Terunuma, N.; /KEK, Tsukuba; Tomas, R.; /CERN; White, G.R.; /SLAC

    2014-05-28

    The Accelerator Test Facility 2 (ATF2) aims to test the novel chromaticity correction for higher chromaticity lattices as the one of CLIC. To this end the ATF2 ultra-low ß* lattice is designed to vertically focus the beam at the focal point or usually referred to as interaction point (IP), down to 23 nm. However when the measured multipole components of the ATF2 magnets are considered in the simulations, the evaluated spot sizes at the IP are well above the design value. The designed spot size is effectively recovered by inserting a pair of octupole magnets. In this note we address the technical specifications required for these octupole magnets.

  3. ATF CO{sub 2} laser system upgrade to terawatt peak power

    Energy Technology Data Exchange (ETDEWEB)

    Pogorelsky, I.V.

    1995-05-01

    This document describes the proposed upgrade of the 10-GW peak power 50-ps CO{sub 2} laser presently operational at the ATF to the 1 TW level at a shorter, 3--10 ps, pulse duration. The approach adopted is based on state of the art CO{sub 2} laser technology and an experience gained in the course of the ATF laser design and application for the laser accelerator experiment. The proposed upgrade is an economical way for the ATF to become in a short time among leading users facilities available for next generation ({ge} 100 MeV) laser accelerator studies.

  4. Pancreatic β-cells activate a JunB/ATF3-dependent survival pathway during inflammation

    DEFF Research Database (Denmark)

    Gurzov, E N; Barthson, J; Marhfour, I;

    2012-01-01

    Destruction of insulin-producing pancreatic β-cells by local autoimmune inflammation is a hallmark of type 1 diabetes. Histochemical analysis of pancreases from non-obese diabetic mice indicated activation of the transcription factor JunB/AP-1 (activator protein-1) after autoimmune infiltration...... nearly 20% of the cytokine-modified β-cell genes, including the transcription factor ATF3. Direct transcriptional induction of ATF3 by JunB is a key event for β-cell survival after TNF-α+IFN-γ treatment. Moreover, pharmacological upregulation of JunB/ATF3 via increased cAMP protected rodent primary β...

  5. ATF6α/β-mediated adjustment of ER chaperone levels is essential for development of the notochord in medaka fish.

    OpenAIRE

    Ishikawa, Tokiro; Okada, Tetsuya; Ishikawa-Fujiwara, Tomoko; Todo, Takeshi; Kamei, Yasuhiro; Shigenobu, Shuji; Tanaka, Minoru; Saito, Taro L; Yoshimura, Jun; Morishita, Shinichi; Toyoda, Atsushi; Sakaki, Yoshiyuki; Taniguchi, Yoshihito; Takeda, Shunichi; Mori, Kazutoshi

    2013-01-01

    ATF6α and ATF6β are membrane-bound transcription factors activated by regulated intramembrane proteolysis in response to endoplasmic reticulum (ER) stress to induce various ER quality control proteins. ATF6α- and ATF6β single-knockout mice develop normally, but ATF6α/β double knockout causes embryonic lethality, the reason for which is unknown. Here we show in medaka fish that ATF6α is primarily responsible for transcriptional induction of the major ER chaperone BiP and that ATF6α/β double kn...

  6. ATF6α/β-mediated adjustment of ER chaperone levels is essential for development of the notochord in medaka fish

    OpenAIRE

    Ishikawa, Tokiro; Okada, Tetsuya; Ishikawa-Fujiwara, Tomoko; Todo, Takeshi; Kamei, Yasuhiro; Shigenobu, Shuji; Tanaka, Minoru; Saito, Taro L; Yoshimura, Jun; Morishita, Shinichi; Toyoda, Atsushi; Sakaki, Yoshiyuki; Taniguchi, Yoshihito; Takeda, Shunichi; Mori, Kazutoshi

    2013-01-01

    ATF6α and ATF6β are membrane-bound transcription factors activated by regulated intramembrane proteolysis in response to endoplasmic reticulum (ER) stress to induce various ER quality control proteins. ATF6α- and ATF6β single-knockout mice develop normally, but ATF6α/β double knockout causes embryonic lethality, the reason for which is unknown. Here we show in medaka fish that ATF6α is primarily responsible for transcriptional induction of the major ER chaperone BiP and that ATF6α/β double kn...

  7. ATF3 expression is induced by low glucose in pancreatic α and β cells and regulates glucagon but not insulin gene transcription.

    Science.gov (United States)

    Lee, Yong-Soo; Kobayashi, Masaki; Kikuchi, Osamu; Sasaki, Tsutomu; Yokota-Hashimoto, Hiromi; Susanti, Vina Yanti; Ido Kitamura, Yukari; Kitamura, Tadahiro

    2014-01-01

    The pancreas is critical for maintaining glucose homeostasis. Activating transcription factor 3 (ATF3) is an adaptive response transcription factor. There are major discrepancies in previous reports on pancreatic ATF3; therefore, its role in the pancreas is unclear. To better elucidate the role of ATF3 in the pancreas, we conducted in vitro studies using pancreatic α and β cell lines, and also evaluated the use of ATF3 antibodies for immunohistochemistry. We determined ATF3 expression was increased by low glucose and decreased by high glucose in both αTC-1.6 and βTC3 cells. We also showed that adenovirus-mediated ATF3 overexpression increased glucagon promoter activity and glucagon mRNA levels in αTC-1.6 cells; whereas, it had no effect on insulin promoter activity and insulin mRNA levels in βTC3 cells. Although immunostaining with the C-19 ATF3 antibody demonstrated predominant expression in α cells rather than β cells, ATF3 staining was still detected in ATF3 knockout mice as clearly as in control mice. On the other hand, another ATF3 antibody (H-90) detected ATF3 in both α cells and β cells, and was clearly diminished in ATF3 knockout mice. These results indicate that previous discrepancies in ATF3 expression patterns in the pancreas were caused by the varying specificities of the ATF3 antibodies used, and that ATF3 is actually expressed in both α cells and β cells.

  8. Atf6 plays protective and pathologic roles in fatty liver disease due to endoplasmic reticulum stress

    Science.gov (United States)

    Cinaroglu, Ayca; Gao, Chuan; Imrie, Dru; Sadler, Kirsten C.

    2011-01-01

    Many etiologies of fatty liver disease (FLD) are associated with hyper-activation of one of the three pathways that comprise the unfolded protein response (UPR), a harbinger of endoplasmic reticulum (ER) stress. The UPR is mediated by pathways initiated by PERK, IRE1a/XBP1and ATF6, and each of these pathways have been implicated as either protective or pathological in FLD. We use zebrafish with FLD and hepatic ER stress to explore the relationship between Atf6 and steatosis. Mutation of the foie gras (foigr) gene causes FLD and hepatic ER stress. Prolonged treatment of wild-type larvae with a dose of tunicamycin that causes chronic ER stress phenocopies foigr. In contrast, acute exposure to a high dose of tunicamycin robustly activates the UPR but is less effective at inducing steatosis. The Srebp transcription factors are not required for steatosis in any of these models. Instead, depleting larvae of active Atf6 either through mbtps1 mutation or atf6 morpholino injection protects against steatosis caused by chronic ER stress whereas it exacerbates steatosis caused by acute tunicamycin treatment. Conclusion ER stress causes FLD. Loss of Atf6 prevents steatosis caused by chronic ER stress but can also potentiate steatosis caused by acute ER stress. This demonstrates that Atf6 can play both protective and pathological roles in FLD. PMID:21538441

  9. Proceedings of the 2nd ATF international collaboration meeting

    International Nuclear Information System (INIS)

    Following the first one at SLAC in November 1996, the second ATF international collaboration meeting was held at KEK from June 12 and 13, 1997. In total 65 persons attended and 23 among them were from abroad as the first one held at SLAC November, 1996. While the main topic at the first meeting had been on the injection linac commissioning started in November 1995, this time its was on the damping ring which almost on schedule was put into operation in January 1997, after its 5 year long construction. Worldwide contributions, especially that of SLAC, were of vital importance in the design and construction of the ring. In the ring commissioning, however, ever more people from abroad have much enthusiastically taken part in various studies to achieve lower emittances. Thus it was the first task in the meeting to summarize the activities in these 6 months. Since a full system to measure the low emittances is to be completed in the shutdown of this summer, the other important task of the meeting for all attendants was to think very carefully about the work in the shutdown and study programs after it. (J.P.N.)

  10. Berberine, a natural isoquinoline alkaloid, induces NAG-1 and ATF3 expression in human colorectal cancer cells

    OpenAIRE

    Piyanuch, Rojsanga; SUKHTHANKAR, MUGDHA; Baek, Seung Joon

    2007-01-01

    Berberine is known to possess a wide variety of pharmacological activities, including pro-apoptotic activity. However, its molecular targets are not elucidated at present. NAG-1 and ATF3 are induced by several dietary compounds associated with pro-apoptotic activity. Berberine induces cell growth arrest, apoptosis, NAG-1, and ATF3 in human colorectal cancer cells. ATF3 induction by berberine is mediated in a p53-dependent manner, whereas NAG-1 induction by berberine is mediated by multiple si...

  11. ATF7 is stabilized during mitosis in a CDK1-dependent manner and contributes to cyclin D1 expression.

    Science.gov (United States)

    Schaeffer, Etienne; Vigneron, Marc; Sibler, Annie-Paule; Oulad-Abdelghani, Mustapha; Chatton, Bruno; Donzeau, Mariel

    2015-01-01

    The transcription factor ATF7 undergoes multiple post-translational modifications, each of which has distinct effects upon ATF7 function. Here, we show that ATF7 phosphorylation on residue Thr112 exclusively occurs during mitosis, and that ATF7 is excluded from the condensed chromatin. Both processes are CDK1/cyclin B dependent. Using a transduced neutralizing monoclonal antibody directed against the Thr112 epitope in living cells, we could demonstrate that Thr112 phosphorylation protects endogenous ATF7 protein from degradation, while it has no effect on the displacement of ATF7 from the condensed chromatin. The crucial role of Thr112 phosphorylation in stabilizing ATF7 protein during mitosis was confirmed using phospho-mimetic and phospho-deficient mutants. Finally, silencing ATF7 by CRISPR/Cas9 technology leads to a decrease of cyclin D1 protein expression levels. We propose that mitotic stabilized ATF7 protein re-localizes onto chromatin at the end of telophase and contributes to induce the cyclin D1 gene expression.

  12. Mutations in the unfolded protein response regulator ATF6 cause the cone dysfunction disorder achromatopsia.

    Science.gov (United States)

    Kohl, Susanne; Zobor, Ditta; Chiang, Wei-Chieh; Weisschuh, Nicole; Staller, Jennifer; Gonzalez Menendez, Irene; Chang, Stanley; Beck, Susanne C; Garcia Garrido, Marina; Sothilingam, Vithiyanjali; Seeliger, Mathias W; Stanzial, Franco; Benedicenti, Francesco; Inzana, Francesca; Héon, Elise; Vincent, Ajoy; Beis, Jill; Strom, Tim M; Rudolph, Günther; Roosing, Susanne; Hollander, Anneke I den; Cremers, Frans P M; Lopez, Irma; Ren, Huanan; Moore, Anthony T; Webster, Andrew R; Michaelides, Michel; Koenekoop, Robert K; Zrenner, Eberhart; Kaufman, Randal J; Tsang, Stephen H; Wissinger, Bernd; Lin, Jonathan H

    2015-07-01

    Achromatopsia (ACHM) is an autosomal recessive disorder characterized by color blindness, photophobia, nystagmus and severely reduced visual acuity. Using homozygosity mapping and whole-exome and candidate gene sequencing, we identified ten families carrying six homozygous and two compound-heterozygous mutations in the ATF6 gene (encoding activating transcription factor 6A), a key regulator of the unfolded protein response (UPR) and cellular endoplasmic reticulum (ER) homeostasis. Patients had evidence of foveal hypoplasia and disruption of the cone photoreceptor layer. The ACHM-associated ATF6 mutations attenuate ATF6 transcriptional activity in response to ER stress. Atf6(-/-) mice have normal retinal morphology and function at a young age but develop rod and cone dysfunction with increasing age. This new ACHM-related gene suggests a crucial and unexpected role for ATF6A in human foveal development and cone function and adds to the list of genes that, despite ubiquitous expression, when mutated can result in an isolated retinal photoreceptor phenotype. PMID:26029869

  13. Peripheral and central neuronal ATF3 precedes CD4+ T-cell infiltration in EAE.

    Science.gov (United States)

    Frezel, Noémie; Sohet, Fabien; Daneman, Richard; Basbaum, Allan I; Braz, Joao M

    2016-09-01

    Experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis produced by immunization with myelin oligodendrocyte glycoprotein (MOG) and adjuvants, results from profound T-cell mediated CNS demyelination. EAE is characterized by progressive, ascending motor dysfunction and symptoms of ongoing pain and hypersensitivity, in some cases preceding or concomitant with the motor deficits. In this regard, the EAE model mimics major features of multiple sclerosis, where a central neuropathic pain state is common. Although the latter condition is presumed to arise from a CNS loss of inhibitory controls secondary to the demyelination, dysfunction of sensory neurons may also contribute. Based on our previous studies that demonstrated the utility of monitoring expression of activating transcription factor 3 (ATF3), a sensitive marker of injured sensory neurons, here we followed both ATF3 and CD4+ T cells invasion of sensory ganglia (as well as the CNS) at different stages of the EAE model. We found that ATF3 is induced in peripheral sensory ganglia and brainstem well before the appearance of motor deficits. Unexpectedly, the ATF3 induction always preceded T cell infiltration, typically in adjacent, but non-overlapping regions. Surprisingly, control administration of the pertussis toxin and/or Complete Freund's adjuvants, without MOG, induced ATF3 in sensory neurons. In contrast, T cell infiltration only occurred with MOG. Taken together, our results suggest that the clinical manifestations in the EAE result not only from central demyelination but also from neuronal stress and subsequent pathophysiology of sensory neurons. PMID:27343802

  14. THE FONT5 PROTOTYPE ILC INTRA-TRAIN FEEDBACK SYSTEM AT ATF2

    CERN Document Server

    Apsimon, R J; Burrows, P N; Christian, G B; Constance, B; Perry, C; Resta-Lopez, J

    2011-01-01

    We present the design and beam test results of a prototype beam-based digital feedback system for the Interaction Point of the International Linear Collider. A custom analogue front-end signal processor, FPGA-based digital signal processing boards, and kicker drive amplifier have been designed, built, deployed and tested with beam in the extraction line of the KEK Accelerator Test Facility (ATF2). The system was used to provide orbit correction to the train of bunches extracted from the ATF damping ring. The latency was measured to be approximately 140 ns.

  15. Design of bunch compressing system with suppression of coherent synchrotron radiation for ATF upgrade

    Energy Technology Data Exchange (ETDEWEB)

    Jing, Yichao [Brookhaven National Lab. (BNL), Upton, NY (United States); Fedurin, Mikhail [Brookhaven National Lab. (BNL), Upton, NY (United States); Stratakis, Diktys [Brookhaven National Lab. (BNL), Upton, NY (United States)

    2015-05-03

    One of the operation modes for Accelerator Test Facility (ATF) upgrade is to provide high peak current, high quality electron beam for users. Such operation requires a bunch compressing system with a very large compression ratio. The CSR originating from the strong compressors generally could greatly degrade the quality of the electron beam. In this paper, we present our design for the entire bunch compressing system that will limit the effect of CSR on the e-beam’s quality. We discuss and detail the performance from the start to end simulation of such a compressor for ATF.

  16. Phosphorylation of the conserved transcription factor ATF-7 by PMK-1 p38 MAPK regulates innate immunity in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Robert P Shivers

    2010-04-01

    Full Text Available Innate immunity in Caenorhabditis elegans requires a conserved PMK-1 p38 mitogen-activated protein kinase (MAPK pathway that regulates the basal and pathogen-induced expression of immune effectors. The mechanisms by which PMK-1 p38 MAPK regulates the transcriptional activation of the C. elegans immune response have not been identified. Furthermore, in mammalian systems the genetic analysis of physiological targets of p38 MAPK in immunity has been limited. Here, we show that C. elegans ATF-7, a member of the conserved cyclic AMP-responsive element binding (CREB/activating transcription factor (ATF family of basic-region leucine zipper (bZIP transcription factors and an ortholog of mammalian ATF2/ATF7, has a pivotal role in the regulation of PMK-1-mediated innate immunity. Genetic analysis of loss-of-function alleles and a gain-of-function allele of atf-7, combined with expression analysis of PMK-1-regulated genes and biochemical characterization of the interaction between ATF-7 and PMK-1, suggest that ATF-7 functions as a repressor of PMK-1-regulated genes that undergoes a switch to an activator upon phosphorylation by PMK-1. Whereas loss-of-function mutations in atf-7 can restore basal expression of PMK-1-regulated genes observed in the pmk-1 null mutant, the induction of PMK-1-regulated genes by pathogenic Pseudomonas aeruginosa PA14 is abrogated. The switching modes of ATF-7 activity, from repressor to activator in response to activated PMK-1 p38 MAPK, are reminiscent of the mechanism of regulation mediated by the corresponding ancestral Sko1p and Hog1p proteins in the yeast response to osmotic stress. Our data point to the regulation of the ATF2/ATF7/CREB5 family of transcriptional regulators by p38 MAPK as an ancient conserved mechanism for the control of innate immunity in metazoans, and suggest that ATF2/ATF7 may function in a similar manner in the regulation of mammalian innate immunity.

  17. Measured Thermal and Fast Neutron Fluence Rates for ATF-1 Holders During ATR Cycle 157D

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Larry Don [Idaho National Lab. (INL), Idaho Falls, ID (United States); Miller, David Torbet [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2016-03-01

    This report contains the thermal (2200 m/s) and fast (E>1MeV) neutron fluence rate data for the ATF-1 holders located in core for ATR Cycle 157D which were measured by the Radiation Measurements Laboratory (RML) as requested by the Power Reactor Programs (ATR Experiments) Radiation Measurements Work Order.

  18. Mechanical Property and Oxidation Behavior of ATF cladding developed in KAERI

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun-Gil; Kim, Il-Hyun; Jung, Yang-Il; Park, Dong-Jun; Park, Jung-Hwan; Park, Jeong-Yong; Koo, Yang-Hyun [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-10-15

    To realize the coating cladding, coating material (Cr-based alloy) as well as coating technology (3D laser coating and arc ion plating combined with vacuum annealing) can be developed to meet the fuel cladding criteria. The coated Zr cladding can be produced after the optimization of coating technologies. The coated cladding sample showed the good oxidation/corrosion and adhesion properties without the spalling and/or severe interaction with the Zr alloy cladding from the various tests. Thus, it is known that the mechanical property and oxidation behavior of coated cladding concept developed in KAERI is reasonable for applying the ATF cladding in LWRs. At the present time various ATF concepts have been proposed and developing in many countries. The ATF concepts with potentially improved accident performance can be summarized to the coating cladding, Mo-Zr cladding, FeCrAl cladding, and SiCf/SiC cladding. Regarding the cladding performance, ATF cladding concepts will be evaluated with respect to the accident scenarios and normal operations of LWRs as well as to the fuel cladding fabrication.

  19. An FPGA-based Bunch-by-Bunch Position and Angle Feedback System at ATF2

    CERN Document Server

    Christian, G B; Bett, D R; Burrows, P N; Constance, B; Davis, M R; Gerbershagen, A; Perry, C; Resta Lopez, J

    2011-01-01

    The FONT5 intra-train feedback system serves as a prototype for an interaction point beam-based feedback system for future electron-positron colliders, such as the International Linear Collider. The system has been tested on the KEK Accelerator Test Facility (ATF) and is deployed to stabilise the beam orbit at the ATF2. The goal of this system is to correct both position and angle jitter in the vertical plane, providing stability of ~1 micron at the entrance to the ATF2 final-focus system. The system comprises three stripline beam position monitors (BPMs) and two stripline kickers, custom low-latency analogue front-end BPM processors, a custom FPGA-based digital processing board with fast ADCs, and custom kicker-drive amplifiers. An overview of the hardware, and the latest results from beam tests at ATF2, will be presented. The total latency of the system with coupled position and angle feedback loops operating simultaneously was measured to be approximately 140 ns. The greatest degree of correction observed ...

  20. C/EBPγ Is a Critical Regulator of Cellular Stress Response Networks through Heterodimerization with ATF4.

    Science.gov (United States)

    Huggins, Christopher J; Mayekar, Manasi K; Martin, Nancy; Saylor, Karen L; Gonit, Mesfin; Jailwala, Parthav; Kasoji, Manjula; Haines, Diana C; Quiñones, Octavio A; Johnson, Peter F

    2015-12-14

    The integrated stress response (ISR) controls cellular adaptations to nutrient deprivation, redox imbalances, and endoplasmic reticulum (ER) stress. ISR genes are upregulated in stressed cells, primarily by the bZIP transcription factor ATF4 through its recruitment to cis-regulatory C/EBP:ATF response elements (CAREs) together with a dimeric partner of uncertain identity. Here, we show that C/EBPγ:ATF4 heterodimers, but not C/EBPβ:ATF4 dimers, are the predominant CARE-binding species in stressed cells. C/EBPγ and ATF4 associate with genomic CAREs in a mutually dependent manner and coregulate many ISR genes. In contrast, the C/EBP family members C/EBPβ and C/EBP homologous protein (CHOP) were largely dispensable for induction of stress genes. Cebpg(-/-) mouse embryonic fibroblasts (MEFs) proliferate poorly and exhibit oxidative stress due to reduced glutathione levels and impaired expression of several glutathione biosynthesis pathway genes. Cebpg(-/-) mice (C57BL/6 background) display reduced body size and microphthalmia, similar to ATF4-null animals. In addition, C/EBPγ-deficient newborns die from atelectasis and respiratory failure, which can be mitigated by in utero exposure to the antioxidant, N-acetyl-cysteine. Cebpg(-/-) mice on a mixed strain background showed improved viability but, upon aging, developed significantly fewer malignant solid tumors than WT animals. Our findings identify C/EBPγ as a novel antioxidant regulator and an obligatory ATF4 partner that controls redox homeostasis in normal and cancerous cells.

  1. ATF7IP-Mediated Stabilization of the Histone Methyltransferase SETDB1 Is Essential for Heterochromatin Formation by the HUSH Complex

    Directory of Open Access Journals (Sweden)

    Richard T. Timms

    2016-10-01

    Full Text Available The histone methyltransferase SETDB1 plays a central role in repressive chromatin processes, but the functional requirement for its binding partner ATF7IP has remained enigmatic. Here, we show that ATF7IP is essential for SETDB1 stability: nuclear SETDB1 protein is degraded by the proteasome upon ablation of ATF7IP. As a result, ATF7IP is critical for repression that requires H3K9 trimethylation by SETDB1, including transgene silencing by the HUSH complex. Furthermore, we show that loss of ATF7IP phenocopies loss of SETDB1 in genome-wide assays. ATF7IP and SETDB1 knockout cells exhibit near-identical defects in the global deposition of H3K9me3, which results in similar dysregulation of the transcriptome. Overall, these data identify a critical functional role for ATF7IP in heterochromatin formation by regulating SETDB1 abundance in the nucleus.

  2. ATF3 upregulation in glia during Wallerian degeneration: differential expression in peripheral nerves and CNS white matter

    Directory of Open Access Journals (Sweden)

    Coffin Robert S

    2004-03-01

    Full Text Available Abstract Background Many changes in gene expression occur in distal stumps of injured nerves but the transcriptional control of these events is poorly understood. We have examined the expression of the transcription factors ATF3 and c-Jun by non-neuronal cells during Wallerian degeneration following injury to sciatic nerves, dorsal roots and optic nerves of rats and mice, using immunohistochemistry and in situ hybridization. Results Following sciatic nerve injury – transection or transection and reanastomosis – ATF3 was strongly upregulated by endoneurial, but not perineurial cells, of the distal stumps of the nerves by 1 day post operation (dpo and remained strongly expressed in the endoneurium at 30 dpo when axonal regeneration was prevented. Most ATF3+ cells were immunoreactive for the Schwann cell marker, S100. When the nerve was transected and reanastomosed, allowing regeneration of axons, most ATF3 expression had been downregulated by 30 dpo. ATF3 expression was weaker in the proximal stumps of the injured nerves than in the distal stumps and present in fewer cells at all times after injury. ATF3 was upregulated by endoneurial cells in the distal stumps of injured neonatal rat sciatic nerves, but more weakly than in adult animals. ATF3 expression in transected sciatic nerves of mice was similar to that in rats. Following dorsal root injury in adult rats, ATF3 was upregulated in the part of the root between the lesion and the spinal cord (containing Schwann cells, beginning at 1 dpo, but not in the dorsal root entry zone or in the degenerating dorsal column of the spinal cord. Following optic nerve crush in adult rats, ATF3 was found in some cells at the injury site and small numbers of cells within the optic nerve displayed weak immunoreactivity. The pattern of expression of c-Jun in all types of nerve injury was similar to that of ATF3. Conclusion These findings raise the possibility that ATF3/c-Jun heterodimers may play a role in

  3. ATF3 Mediates Anti-Cancer Activity of Trans-10, cis-12-Conjugated Linoleic Acid in Human Colon Cancer Cells

    OpenAIRE

    Kim, Kui-Jin; Lee, Jihye; Park, Yeonhwa; Lee, Seong-Ho

    2015-01-01

    Conjugated linoleic acids (CLA) are a family of isomers of linoleic acid. CLA increases growth arrest and apoptosis of human colorectal cancer cells through an isomer-specific manner. ATF3 belongs to the ATF/CREB family of transcription factors and is associated with apoptosis in colorectal cancer. The present study was performed to investigate the molecular mechanism by which t10, c12-CLA stimulates ATF3 expression and apoptosis in human colorectal cancer cells. t10, c12-CLA increased an apo...

  4. Analysis of Turn-by-Turn Orbit Data and Dynamic Aperture Considerations for the ATF Damping Ring

    CERN Document Server

    Schmidt, F; Hayano, H; Kubo, K; Terunuma, N; Urakawa, J

    1999-01-01

    We describe an attempt to deduce the tune shift with amplitude and resonance driving terms for the ATF Damping Ring from turn-by-turn orbit data, and to compare measurement results with tracking simulations. Our analysis reveals a significant tune ripple, but no evidence for low-order nonlinearities. We thus conjecture that the ATF dynamic aperture is caused by a conspiracy of tune ripple and as yet unidentified higher-order nonlinear fields.

  5. Parameters Optimization for a Novel Vacuum Laser Acceleration Test at BNL-ATF

    CERN Document Server

    Shao, Lei; Zhou, Feng

    2005-01-01

    This paper presents a new VLA theory model which has revealed that the injection electrons with low energy and small incident angle relative to the laser beam are captured and significantly accelerated in a strong laser field. For the further step for verifying the novel-VLA mechanics, we propose to use the BNL-ATF Terawatt CO2 laser and a high-brightness electron beam to carry out a proof-of-principle beam experiment. Experiment setup including the laser injection optics and electron extraction system and beam diagnostics is presented. Extensive optimized simulation results with ATF practical parameters are also presented, which shows that even when the laser intensity is not very high, the net energy gain still can be seen obviously. This could be prospect for a new revolution of vacuum laser acceleration.

  6. Nutrient shortage triggers the hexosamine biosynthetic pathway via the GCN2-ATF4 signalling pathway.

    Science.gov (United States)

    Chaveroux, Cédric; Sarcinelli, Carmen; Barbet, Virginie; Belfeki, Sofiane; Barthelaix, Audrey; Ferraro-Peyret, Carole; Lebecque, Serge; Renno, Toufic; Bruhat, Alain; Fafournoux, Pierre; Manié, Serge N

    2016-06-03

    The hexosamine biosynthetic pathway (HBP) is a nutrient-sensing metabolic pathway that produces the activated amino sugar UDP-N-acetylglucosamine, a critical substrate for protein glycosylation. Despite its biological significance, little is known about the regulation of HBP flux during nutrient limitation. Here, we report that amino acid or glucose shortage increase GFAT1 production, the first and rate-limiting enzyme of the HBP. GFAT1 is a transcriptional target of the activating transcription factor 4 (ATF4) induced by the GCN2-eIF2α signalling pathway. The increased production of GFAT1 stimulates HBP flux and results in an increase in O-linked β-N-acetylglucosamine protein modifications. Taken together, these findings demonstrate that ATF4 provides a link between nutritional stress and the HBP for the regulation of the O-GlcNAcylation-dependent cellular signalling.

  7. Beam-based alignment at the KEK-ATF damping ring

    Energy Technology Data Exchange (ETDEWEB)

    Woodley, Mark D.; Nelson, Janice; Ross, Marc; Turner, James; Wolski, A.; Kubo, Kiyoshi

    2004-06-30

    The damping rings of a future linear collider will have demanding alignment and stability requirements in order to achieve the low vertical emittance necessary for high luminosity. The Accelerator Test Facility (ATF) at KEK has successfully demonstrated the vertical emittance below 5 pm that is specified for the GLC/NLC Main Damping Rings. One contribution to this accomplishment has been the use of Beam Based Alignment (BBA) techniques. The mode of operation of the ATF presents particular challenges for BBA, and we describe here how we have deduced the offsets of the BPMs with respect to the quadrupoles. We also discuss a technique that allows for direct measurements of the beam-to-quad offsets.

  8. Transcription Factor ATF4 Induces NLRP1 Inflammasome Expression during Endoplasmic Reticulum Stress.

    Directory of Open Access Journals (Sweden)

    Andrea D'Osualdo

    Full Text Available Perturbation of endoplasmic reticulum (ER homeostasis triggers the ER stress response (also known as Unfolded Protein Response, a hallmark of many pathological disorders. However the connection between ER stress and inflammation remains largely unexplored. Recent data suggest that ER stress controls the activity of inflammasomes, key signaling platforms that mediate innate immune responses. Here we report that expression of NLRP1, a core inflammasome component, is specifically up-regulated during severe ER stress conditions in human cell lines. Both IRE1α and PERK, but not the ATF6 pathway, modulate NLRP1 gene expression. Furthermore, using mutagenesis, chromatin immunoprecipitation and CRISPR-Cas9-mediated genome editing technology, we demonstrate that ATF4 transcription factor directly binds to NLRP1 promoter during ER stress. Although involved in different types of inflammatory responses, XBP-1 splicing was not required for NLRP1 induction. This study provides further evidence that links ER stress with innate.

  9. Signaling dynamics of palmitate-induced ER stress responses mediated by ATF4 in HepG2 cells

    Directory of Open Access Journals (Sweden)

    Cho Hyunju

    2013-01-01

    Full Text Available Abstract Background Palmitic acid, the most common saturated free fatty acid, has been implicated in ER (endoplasmic reticulum stress-mediated apoptosis. This lipoapotosis is dependent, in part, on the upregulation of the activating transcription factor-4 (ATF4. To better understand the mechanisms by which palmitate upregulates the expression level of ATF4, we integrated literature information on palmitate-induced ER stress signaling into a discrete dynamic model. The model provides an in silico framework that enables simulations and predictions. The model predictions were confirmed through further experiments in human hepatocellular carcinoma (HepG2 cells and the results were used to update the model and our current understanding of the signaling induced by palmitate. Results The three key things from the in silico simulation and experimental results are: 1 palmitate induces different signaling pathways (PKR (double-stranded RNA-activated protein kinase, PERK (PKR-like ER kinase, PKA (cyclic AMP (cAMP-dependent protein kinase A in a time dependent-manner, 2 both ATF4 and CREB1 (cAMP-responsive element-binding protein 1 interact with the Atf4 promoter to contribute to a prolonged accumulation of ATF4, and 3 CREB1 is involved in ER-stress induced apoptosis upon palmitate treatment, by regulating ATF4 expression and possibly Ca2+ dependent-CaM (calmodulin signaling pathway. Conclusion The in silico model helped to delineate the essential signaling pathways in palmitate-mediated apoptosis.

  10. ATF4- and CHOP-Dependent Induction of FGF21 through Endoplasmic Reticulum Stress

    Directory of Open Access Journals (Sweden)

    Xiao-shan Wan

    2014-01-01

    Full Text Available Fibroblast growth factor 21 (FGF21 is an important endogenous regulator involved in the regulation of glucose and lipid metabolism. FGF21 expression is strongly induced in animal and human subjects with metabolic diseases, but little is known about the molecular mechanism. Endoplasmic reticulum (ER stress plays an essential role in metabolic homeostasis and is observed in numerous pathological processes, including type 2 diabetes, overweight, nonalcoholic fatty liver disease (NAFLD. In this study, we investigate the correlation between the expression of FGF21 and ER stress. We demonstrated that TG-induced ER stress directly regulated the expression and secretion of FGF21 in a dose- and time-dependent manner. FGF21 is the target gene for activating transcription factor 4 (ATF4 and CCAAT enhancer binding protein homologous protein (CHOP. Suppression of CHOP impaired the transcriptional activation of FGF21 by TG-induced ER stress in CHOP−/− mouse primary hepatocytes (MPH, and overexpression of ATF4 and CHOP resulted in FGF21 promoter activation to initiate the transcriptional programme. In mRNA stability assay, we indicated that ER stress increased the half-life of mRNA of FGF21 significantly. In conclusion, FGF21 expression is regulated by ER stress via ATF- and CHOP-dependent transcriptional mechanism and posttranscriptional mechanism, respectively.

  11. Functional analysis of atfA gene to stress response in pathogenic thermal dimorphic fungus Penicillium marneffei.

    Science.gov (United States)

    Nimmanee, Panjaphorn; Woo, Patrick C Y; Vanittanakom, Pramote; Youngchim, Sirida; Vanittanakom, Nongnuch

    2014-01-01

    Penicillium marneffei, the pathogenic thermal dimorphic fungus is a causative agent of a fatal systemic disease, penicilliosis marneffei, in immunocompromised patients especially HIV patients. For growth and survival, this fungus has to adapt to environmental stresses outside and inside host cells and this adaptation requires stress signaling pathways and regulation of gene expression under various kinds of stresses. In this report, P. marneffei activating transcription factor (atfA) gene encoding bZip-type transcription factor was characterized. To determine functions of this gene, atfA isogenic mutant strain was constructed using the modified split marker recombination method. The phenotypes and susceptibility to varieties of stresses including osmotic, oxidative, heat, UV, cell wall and cell membrane stresses of the mutant strain were compared with the wild type and the atfA complemented strains. Results demonstrated that the mRNA expression level of P. marneffei atfA gene increased under heat stress at 42°C. The atfA mutant was more sensitive to sodium dodecyl sulphate, amphotericin B and tert-butyl hydroperoxide than the wild type and complemented strains but not hydrogen peroxide, menadione, NaCl, sorbitol, calcofluor white, itraconazole, UV stresses and heat stress at 39°C. In addition, recovery of atfA mutant conidia after mouse and human macrophage infections was significantly decreased compared to those of wild type and complemented strains. These results indicated that the atfA gene was required by P. marneffei under specific stress conditions and might be necessary for fighting against host immune cells during the initiation of infection.

  12. Construction and initial operation of the Advanced Toroidal Facility

    International Nuclear Information System (INIS)

    The Advanced Toroidal Facility (ATF) torsatron was designed on a physics basis for access to the second stability regime and on an engineering basis for independent fabrication of high-accuracy components. The actual construction, assembly, and initial operation of ATF are compared with the characteristics expected during the design of ATF. 31 refs., 19 figs., 2 tabs

  13. Tests of the FONT3 Linear Collider Intra-Train Beam Feedback System at the ATF

    International Nuclear Information System (INIS)

    We report preliminary results of beam tests of the FONT3 Linear Collider intra-train position feedback system prototype at the Accelerator Test Facility at KEK. The feedback system incorporates a novel beam position monitor (BPM) processor with a latency below 5 nanoseconds, and a kicker driver amplifier with similar low latency. The 56 nanosecond-long bunchtrain in the ATF extraction line was used to test the prototype BPM processor. The achieved latency will allow a demonstration of intra-train feedback on timescales relevant even for the CLIC Linear Collider design

  14. Observations on Tune and $\\beta$ Functions at the ATF Damping Ring

    CERN Document Server

    Potier, J P; Terunuma, N; Mimashi, T; Kubo, K; Korhonen, T T; Hayano, H; Okugi, T; Kashiwagi, S; Zimmermann, Frank

    1998-01-01

    The precise measurement of the transverse tunes and their spectra is a basic demand in accelerator commissioning. It provides a simple access to lattice characterisation and validation of the optical model. This contribution describes recent improvements of the tune monitor system at the Accelerator Test Facility Damping Ring (ATF-DR) and the performance achieved. We present preliminary measurement results of beta functions, chromaticity, and dispersion on a relaxed optics with 90 degree horizontal phase advance per cell and compare these with the theoretical predictions.

  15. Development and quality assessments of commercial heat production of ATF FeCrAl tubes

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Yukinori [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-09-01

    Development and quality assessment of the 2nd generation ATF FeCrAl tube production with commercial manufacturers were conducted. The manufacturing partners include Sophisticated Alloys, Inc. (SAI), Butler, PA for FeCrAl alloy casting via vacuum induction melting, Oak Ridge National Laboratory (ORNL) for extrusion process to prepare the master bars/tubes to be tube-drawn, and Rhenium Alloys, Inc. (RAI), North Ridgeville, OH, for tube-drawing process. The masters bars have also been provided to Los Alamos National Laboratory (LANL) who works with Century Tubes, Inc., (CTI), San Diego, CA, as parallel tube production effort under the current program.

  16. Latest Performance Results from the FONT5 Intra-train Beam Position and Angle Feedback System at ATF2

    CERN Document Server

    Christian, G B; Bett, D R; Blaskovic Kraljevic, N; Burrows, P N; Davis, M R; Gerbershagen, A; Perry, C; Constance, B; Resta-Lopez, J

    2012-01-01

    A prototype Interaction Point beam-based feedback system for future electron-positron colliders, such as the International Linear Collider, has been designed and tested on the extraction line of the KEK Accelerator Test Facility (ATF). The FONT5 intra-train feedback system aims to stabilize the beam orbit by correcting both the position and angle jitter in the vertical plane on bunch-tobunch time scales, providing micron-level stability at the entrance to the ATF2 final-focus system. The system comprises three stripline beam position monitors (BPMs) and two stripline kickers, custom low-latency analogue front-end BPM processors, a custom FPGA-based digital processing board with fast ADCs, and custom kickerdrive amplifiers. The latest results from beam tests at ATF2 will be presented, including the system latency and correction performance.

  17. Fabrication Control Plan for ORNL RH-LOCA ATF Test Specimens to be Irradiated in the ATR

    Energy Technology Data Exchange (ETDEWEB)

    Kevin G. Field; Richard Howard; Michael Teague

    2014-06-01

    The purpose of this fabrication plan is (1) to summarize the design of a set of rodlets that will be fabricated and then irradiated in the Advanced Test Reactor (ATR) and (2) provide requirements for fabrication and acceptance criteria for inspections of the Light Water Reactor (LWR) – Accident Tolerant Fuels (ATF) rodlet components. The functional and operational (F&OR) requirements for the ATF program are identified in the ATF Test Plan. The scope of this document only covers fabrication and inspections of rodlet components detailed in drawings 604496 and 604497. It does not cover the assembly of these items to form a completed test irradiation assembly or the inspection of the final assembly, which will be included in a separate INL final test assembly specification/inspection document. The controls support the requirements that the test irradiations must be performed safely and that subsequent examinations must provide valid results.

  18. Performance of the FONT3 Fast Analogue Intra-Train Beam-Based Feedback System at ATF

    Energy Technology Data Exchange (ETDEWEB)

    Burrows, P.; /Queen Mary, U. of London; Christian, G.B.; Hartin, A.F.; Dabiri Khah, H.; White, G.R.; /Oxford U.; Clarke, C.C.; Perry, C.; /Oxford Instruments; Kalinin, A.; /Daresbury; McCormick, D.J.; Molloy, S.; Ross, M.C.; /SLAC

    2007-04-16

    We report results of beam tests of the FONT3 intra-train position feedback system prototype at the Accelerator Test Facility (ATF) at KEK. The feedback system incorporates a novel beam position monitor (BPM) processor with latency below 5 nanoseconds, and a kicker driver amplifier with similar low latency. The 56 nanosecond-long bunchtrain in the ATF extraction line was used to test the prototype feedback system. The achieved latency of 23ns provides a demonstration of intra-train feedback on very short timescales relevant even for the CLIC Linear Collider design.

  19. Performance of the FONT3 Fast Analogue Intra-Train Beam-Based Feedback System at ATF

    International Nuclear Information System (INIS)

    We report results of beam tests of the FONT3 intra-train position feedback system prototype at the Accelerator Test Facility (ATF) at KEK. The feedback system incorporates a novel beam position monitor (BPM) processor with latency below 5 nanoseconds, and a kicker driver amplifier with similar low latency. The 56 nanosecond-long bunchtrain in the ATF extraction line was used to test the prototype feedback system. The achieved latency of 23ns provides a demonstration of intra-train feedback on very short timescales relevant even for the CLIC Linear Collider design

  20. Coffee Polyphenols Change the Expression of STAT5B and ATF-2 Modifying Cyclin D1 Levels in Cancer Cells

    Directory of Open Access Journals (Sweden)

    Carlota Oleaga

    2012-01-01

    Full Text Available Background. Epidemiological studies suggest that coffee consumption reduces the risk of cancer, but the molecular mechanisms of its chemopreventive effects remain unknown. Objective. To identify differentially expressed genes upon incubation of HT29 colon cancer cells with instant caffeinated coffee (ICC or caffeic acid (CA using whole-genome microarrays. Results. ICC incubation of HT29 cells caused the overexpression of 57 genes and the underexpression of 161, while CA incubation induced the overexpression of 12 genes and the underexpression of 32. Using Venn-Diagrams, we built a list of five overexpressed genes and twelve underexpressed genes in common between the two experimental conditions. This list was used to generate a biological association network in which STAT5B and ATF-2 appeared as highly interconnected nodes. STAT5B overexpression was confirmed at the mRNA and protein levels. For ATF-2, the changes in mRNA levels were confirmed for both ICC and CA, whereas the decrease in protein levels was only observed in CA-treated cells. The levels of cyclin D1, a target gene for both STAT5B and ATF-2, were downregulated by CA in colon cancer cells and by ICC and CA in breast cancer cells. Conclusions. Coffee polyphenols are able to affect cyclin D1 expression in cancer cells through the modulation of STAT5B and ATF-2.

  1. Finding ATF4/p75NTR/IL-8 Signal Pathway in Endothelial–Mesenchymal Transition by Safrole Oxide

    Science.gov (United States)

    Zhao, Wenbo; Yue, Hongwei; Su, Le; Zhang, ShangLi; Zhao, Jing

    2014-01-01

    Targeting the endothelial-to-mesenchymal transition (EndoMT) may be a novel therapeutic strategy for cancer and various diseases induced by fibrosis. We aimed to identify a small chemical molecule as an inducer of EndoMT and find a new signal pathway by using the inducer. Safrole oxide (SFO), 50 µg/ml, could most effectively induce EndoMT within 12 h. To understand the underlying molecular mechanism, we performed microarray, quantitative real-time PCR and western blot analysis to find key factors involved in SFO-induced EndoMT and demonstrated the involvement of the factors by RNAi. The expression of activating transcription factor 4 (ATF4), p75 neurotrophin receptor (p75NTR), and interleukin 8 (IL-8) was greatly increased in SFO-induced EndoMT. Knockdown of ATF4 inhibited the SFO-induced EndoMT completely, and knockdown of p75NTR or IL-8 partially inhibited the EndoMT, which suggests that all three factors were involved in the process. Furthermore, knockdown of p75NTR inhibited the SFO-increased IL-8 expression and secretion, and knockdown of ATF4 inhibited SFO-increased p75NTR level significantly. The ATF4/p75NTR/IL-8 signal pathway may have an important role in EndoMT induced by SFO. Our findings support potential novel targets for the therapeutics of cancer and fibrosis disease. PMID:24905361

  2. Finding ATF4/p75NTR/IL-8 signal pathway in endothelial-mesenchymal transition by safrole oxide.

    Directory of Open Access Journals (Sweden)

    Di Ge

    Full Text Available Targeting the endothelial-to-mesenchymal transition (EndoMT may be a novel therapeutic strategy for cancer and various diseases induced by fibrosis. We aimed to identify a small chemical molecule as an inducer of EndoMT and find a new signal pathway by using the inducer. Safrole oxide (SFO, 50 µg/ml, could most effectively induce EndoMT within 12 h. To understand the underlying molecular mechanism, we performed microarray, quantitative real-time PCR and western blot analysis to find key factors involved in SFO-induced EndoMT and demonstrated the involvement of the factors by RNAi. The expression of activating transcription factor 4 (ATF4, p75 neurotrophin receptor (p75NTR, and interleukin 8 (IL-8 was greatly increased in SFO-induced EndoMT. Knockdown of ATF4 inhibited the SFO-induced EndoMT completely, and knockdown of p75NTR or IL-8 partially inhibited the EndoMT, which suggests that all three factors were involved in the process. Furthermore, knockdown of p75NTR inhibited the SFO-increased IL-8 expression and secretion, and knockdown of ATF4 inhibited SFO-increased p75NTR level significantly. The ATF4/p75NTR/IL-8 signal pathway may have an important role in EndoMT induced by SFO. Our findings support potential novel targets for the therapeutics of cancer and fibrosis disease.

  3. Finding ATF4/p75NTR/IL-8 signal pathway in endothelial-mesenchymal transition by safrole oxide.

    Science.gov (United States)

    Ge, Di; Jing, Qingchuan; Zhao, Wenbo; Yue, Hongwei; Su, Le; Zhang, ShangLi; Zhao, Jing

    2014-01-01

    Targeting the endothelial-to-mesenchymal transition (EndoMT) may be a novel therapeutic strategy for cancer and various diseases induced by fibrosis. We aimed to identify a small chemical molecule as an inducer of EndoMT and find a new signal pathway by using the inducer. Safrole oxide (SFO), 50 µg/ml, could most effectively induce EndoMT within 12 h. To understand the underlying molecular mechanism, we performed microarray, quantitative real-time PCR and western blot analysis to find key factors involved in SFO-induced EndoMT and demonstrated the involvement of the factors by RNAi. The expression of activating transcription factor 4 (ATF4), p75 neurotrophin receptor (p75NTR), and interleukin 8 (IL-8) was greatly increased in SFO-induced EndoMT. Knockdown of ATF4 inhibited the SFO-induced EndoMT completely, and knockdown of p75NTR or IL-8 partially inhibited the EndoMT, which suggests that all three factors were involved in the process. Furthermore, knockdown of p75NTR inhibited the SFO-increased IL-8 expression and secretion, and knockdown of ATF4 inhibited SFO-increased p75NTR level significantly. The ATF4/p75NTR/IL-8 signal pathway may have an important role in EndoMT induced by SFO. Our findings support potential novel targets for the therapeutics of cancer and fibrosis disease.

  4. MiR-214 regulates the function of osteoblast under simulated microgravity by targeting ATF4

    Science.gov (United States)

    Li, Yingxian; Wang, Xiaogang; Li, Qi; Lv, Ke; Wan, Yumin; Li, Yinghui; Bai, Yanqiang

    Background: MicroRNAs (miRNAs) are small fragments of single-stranded RNA containing 18-24 nucleotides, and are generated from endogenous transcripts. MicroRNAs function in post-transcriptional gene silencing by targeting the 3'-untranslated region (UTR) of mRNAs, resulting in translational repression. Growing evidence shows that microRNAs (miRNAs) regu-late various developmental and homeostatic events in vertebrates and invertebrates. Osteoblast differentiation is a key step in proper skeletal development and acquisition of bone mass; How-ever, the physiological role of non-coding small RNAs, especially miRNAs, in osteoblast dif-ferentiation remains elusive. Methods: To study the potential involvement of miRNAs in osteoblast differentiation under stimulated microgravity, we analyzed the expression of 20 bone relative miRNAs using real time PCR platform to find particularly miRNAs whose expression is altered during osteoblast differentiation. TargetScan, miRBase and Miranda were used to predict the target gene of candidate miRNA. To investigate whether ATF4 can be directly targeted by miR-214, we engineered luciferase reporters that have either the wild-type 3'UTRs of these genes, or the mutant UTRs with a 6 base pair (bp) deletion in the target sites. Lastly, to address the in vivo role of miR-214 in bone formation, tail suspension mice model was used to simulate the change of osteoblast function and bone loss. Results: Recent studies have sug-gested that miRNAs might play a role in osteoblast differentiation and bone formation. Here, we identify miR-214 in MC3T3-E1 cells, which is a primary mouse osteoblasts cell line, to promote osteoblast differentiation by repressing Activating Transcription Factor4 (ATF4) ex-pression at the posttranscriptional level. What is more, miR-214 was found to be transcribed in C2C12 cells during bone morphogenetic protein 2-induced (BMP2-induced) osteogenesis, and overexpression of miR-214 attenuated BMP2-induced osteoblastogenesis

  5. Plant lectin, ATF1011, on the tumor cell surface augments tumor-specific immunity through activation of T cells specific for the lectin.

    Science.gov (United States)

    Yoshimoto, R; Kondoh, N; Isawa, M; Hamuro, J

    1987-01-01

    The possibility that a plant lectin as a carrier protein would specifically activate T cells, resulting in the augmentation of antitumor immunity was investigated. ATF1011, a nonmitogenic lectin for T cells purified from Aloe arborescens Mill, bound equally to normal and tumor cells. ATF1011 binding on the MM102 tumor cell surfaces augmented anti-trinitrophenyl (TNP) antibody production of murine splenocytes when the mice were primarily immunized with TNP-conjugated MM102 tumor cells. The alloreactive cytotoxic T cell response was also augmented by allostimulator cells binding ATF1011 on the cell surfaces. These augmented responses may be assumed to be mediated by the activation of helper T cells recognizing ATF1011 as a carrier protein. Killer T cells were induced against ATF1011 antigen in the H-2 restricted manner using syngeneic stimulator cells bearing ATF1011 on the cell surfaces. When this lectin was administered intralesionally into the tumors, induction of cytotoxic effector cells was demonstrated. These results suggest that intralesionally administered ATF1011 binds to the tumor cell membrane and activates T cells specific for this carrier lectin in situ, which results in the augmented induction of systemic antitumor immunity. PMID:3496156

  6. Analysis of the autoantibody repertoire in Burkitt's lymphoma patients: frequent response against the transcription factor ATF-2.

    Science.gov (United States)

    Kersten, Christian; Delabie, Jan; Gaudernack, Gustav; Smeland, Erlend B; Fosså, Alexander

    2004-12-01

    In the last few years, serological identification of tumour-associated antigens (TAAs) by recombinant cDNA expression cloning (SEREX) has enabled the mapping of humoral immune responses against TAAs in various types of cancer. The present paper describes the application of SEREX to Burkitt's lymphoma (BL), a malignancy not previously characterized by SEREX. By using a cDNA library from a BL cell line that does not express IgG, technical difficulties related to background immunoglobulin clones were overcome. Screening with sera from three BL patients revealed immunoreactivity against seven different gene products, six of which represent known human genes. Five proteins had previously been characterized by SEREX in other malignancies or identified as targets of autoantibodies in autoimmune disease. Seroreactivity against ATF-2, a member of the AP-1 transcription factor family, was validated by enzyme-linked immunosorbent assay (ELISA) and Western blot analysis using recombinant ATF-2 protein. Autoantibody responses against ATF-2 were detected by ELISA in 6 of 8 BL patients, compared with 6 of 13 patients with T-cell non-Hodgkin's lymphoma (T-NHL), 5 of 23 patients with follicular lymphoma and 2 of 27 diffuse large B-cell lymphoma patients. In contrast, reactivity was found in only 1 of 50 healthy volunteers. Next, we showed by immunohistochemistry that the activated form of ATF2 (ATF-2pp) was highly expressed in six different BL samples. We conclude that the SEREX approach with a B-cell cDNA source is applicable in NHL. Furthermore, we identified genes with possible involvement in the pathogenesis of BL using this technique.

  7. Emittance reconstruction from measured beam sizes in ATF2 and perspectives for ILC

    Science.gov (United States)

    Faus-Golfe, A.; Navarro, J.; Fuster Martinez, N.; Resta Lopez, J.; Giner Navarro, J.

    2016-05-01

    The projected emittance (2D) and the intrinsic emittance (4D) reconstruction method by using the beam size measurements at different locations is analyzed in order to study analytically the conditions of solvability of the systems of equations involved in this process. Some conditions are deduced and discussed, and general guidelines about the locations of the measurement stations have been obtained to avoid unphysical results. The special case of the multi-Optical Transition Radiation system (m-OTR), made of four measurement stations, in the Extraction Line (EXT) of Accelerator Test Facility 2 (ATF2) has been simulated in much detail and compared with measurements. Finally a feasibility study of a multi-station system for fast transverse beam size measurement, emittance reconstruction and coupling correction in the Ring to Main Linac (RTML) of International Linear Collider (ILC) Diagnostic sections of the RTML has been discussed in detail.

  8. Measured Thermal and Fast Neutron Fluence Rates for ATF-1 Holders During ATR Cycle 157D

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Larry Don [Idaho National Lab. (INL), Idaho Falls, ID (United States); Miller, David Torbet [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2016-03-01

    This report contains the thermal (2200 m/s) and fast (E>1MeV) neutron fluence rate data for the ATF-1 holders located in core for ATR Cycle 157D which were measured by the Radiation Measurements Laboratory (RML) as requested by the Power Reactor Programs (ATR Experiments) Radiation Measurements Work Order. This report contains measurements of the fluence rates corresponding to the particular elevations relative to the 80-ft. core elevation. The data in this report consist of (1) a table of the ATR power history and distribution, (2) a hard copy listing of all thermal and fast neutron fluence rates, and (3) plots of both the thermal and fast neutron fluence rates. The fluence rates reported are for the average power levels given in the table of power history and distribution.

  9. Experiment studies on the polarized gamma-rays generation at KEK-ATF

    Institute of Scientific and Technical Information of China (English)

    LI Xiao-Ping; PEI Guo-Xi

    2009-01-01

    Polarized positrons can be created through electron-positron pair creation from circularly polarized gamma-rays. Laser-Compton scattering is an efficient method to generate circularly polarized gamma-rays. A high finesse 2-mirror optical stacking cavity had been installed on the straight section of the electron storage ring at KEK-ATF. A 1064 nm circularly polarized pulsed laser beam was stacked in the cavity. Polarized gamma-rays with a maximum energy of 28.3 MeV were produced via inverse Compton scattering of the enhanced laser pulse off an electron beam of 1.28 GeV. The number of generated gamma photons per collision was estimated by a photon detector. It was found that the experimental result was in agreement with the simulated value.

  10. Amino Acid Deprivation Promotes Tumor Angiogenesis through the GCN2/ATF4 Pathway

    Directory of Open Access Journals (Sweden)

    Yugang Wang

    2013-08-01

    Full Text Available As tumors continue to grow and exceed their blood supply, nutrients become limited leading to deficiencies in amino acids (AAD, glucose (GD, and oxygen (hypoxia. These alterations result in significant changes in gene expression. While tumors have been shown to overcome the stress associated with GD or hypoxia by stimulating vascular endothelial growth factor (VEGF-mediated angiogenesis, the role of AAD in tumor angiogenesis remains to be elucidated. We found that in human tumors, the expression of the general control non-derepressible 2 (GCN2, an AAD sensor kinase is elevated at both protein and mRNA levels. In vitro studies revealed that VEGF expression is universally induced by AAD treatment in all five cell lines tested (five of five. This is in contrast to two other angiogenesis mediators interleukin-6 (two of five and fibroblast growth factor 2 (two of five that have a more restricted expression. Suppressing GCN2 expression significantly decreased AAD-induced VEGF expression. Silencing activating transcription factor 4 (ATF4, a downstream transcription factor of the GCN2 signaling pathway, is also associated with strong inhibition of AAD-induced VEGF expression. PKR-like kinase, the key player in GD-induced unfolded protein response is not involved in this process. In vivo xenograft tumor studies in nonobese diabetic/severe combined immunodeficient mice confirmed that knockdown of GCN2 in tumor cells retards tumor growth and decreases tumor blood vessel density. Our results reveal that the GCN2/ATF4 pathway promotes tumor growth and angiogenesis through AAD-mediated VEGF expression and, thus, is a potential target in cancer therapy.

  11. Wake-field and space charge effects on high brightness beams calculations and measured results for the laser driven photoelectrons at BNL-ATF

    International Nuclear Information System (INIS)

    We discuss the formalism used to study the effects of the interactions between the highly charged particles and the fields in the accelerating structure, including space charge and wake fields. Some of our calculations and numerical simulation results obtained for the Brookhaven National Laboratory (BNL) high-brightness photoelectron beam at the Accelerator Test Facility (ATF) and the measured data at ATF are also included

  12. Inhibin beta E is upregulated by drug-induced endoplasmic reticulum stress as a transcriptional target gene of ATF4

    International Nuclear Information System (INIS)

    Inhibins and activins are gonadal peptide hormones of the transforming growth factor-β super family with important functions in the reproductive system. By contrast, the recently identified inhibin βE subunit, primarily expressed in liver cells, appears to exert functions unrelated to the reproductive system. Previously shown downregulation of inhibin βE in hepatoma cells and anti-proliferative effects of ectopic inhibin βE overexpression indicated growth-regulatory effects of inhibin βE. We observed a selective re-expression of the inhibin βE subunit in HepG2 hepatoblastoma cells, MCF7 breast cancer cells, and HeLa cervical cancer cells under endoplasmic reticulum stress conditions induced by tunicamycin, thapsigargin, and nelfinavir. Analysis of XPB1 splicing and ATF4 activation revealed that inhibin βE re-expression was associated with induction of the endoplasmic reticulum stress reaction by these drugs. Transfection of an ATF4 expression plasmid specifically induced inhibin βE expression in HeLa cells and indicates inhibin βE as a hitherto unidentified target gene of ATF4, a key transcription factor of the endoplasmic reticulum stress response. Therefore, the inhibin βE subunit defines not only a new player but also a possible new marker for drug-induced endoplasmic reticulum stress. -- Highlights: ► Endoplasmic reticulum stress induces inhibin beta E expression. ► Inhibin beta E is regulated by the transcription factor ATF4. ► Inhibin beta E expression can be used as a marker for drug-induced ER stress.

  13. Inhibin beta E is upregulated by drug-induced endoplasmic reticulum stress as a transcriptional target gene of ATF4

    Energy Technology Data Exchange (ETDEWEB)

    Brüning, Ansgar, E-mail: ansgar.bruening@med.uni-muenchen.de; Matsingou, Christina; Brem, German Johannes; Rahmeh, Martina; Mylonas, Ioannis

    2012-10-15

    Inhibins and activins are gonadal peptide hormones of the transforming growth factor-β super family with important functions in the reproductive system. By contrast, the recently identified inhibin βE subunit, primarily expressed in liver cells, appears to exert functions unrelated to the reproductive system. Previously shown downregulation of inhibin βE in hepatoma cells and anti-proliferative effects of ectopic inhibin βE overexpression indicated growth-regulatory effects of inhibin βE. We observed a selective re-expression of the inhibin βE subunit in HepG2 hepatoblastoma cells, MCF7 breast cancer cells, and HeLa cervical cancer cells under endoplasmic reticulum stress conditions induced by tunicamycin, thapsigargin, and nelfinavir. Analysis of XPB1 splicing and ATF4 activation revealed that inhibin βE re-expression was associated with induction of the endoplasmic reticulum stress reaction by these drugs. Transfection of an ATF4 expression plasmid specifically induced inhibin βE expression in HeLa cells and indicates inhibin βE as a hitherto unidentified target gene of ATF4, a key transcription factor of the endoplasmic reticulum stress response. Therefore, the inhibin βE subunit defines not only a new player but also a possible new marker for drug-induced endoplasmic reticulum stress. -- Highlights: ► Endoplasmic reticulum stress induces inhibin beta E expression. ► Inhibin beta E is regulated by the transcription factor ATF4. ► Inhibin beta E expression can be used as a marker for drug-induced ER stress.

  14. Letter Report Documenting Progress of Second Generation ATF FeCrAl Alloy Fabrication

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Y. [ORNL; Yang, Y. [ORNL; Field, K. G. [ORNL; Terrani, K. [ORNL; Pint, B. A. [ORNL; Snead, L. L. [ORNL

    2014-06-10

    Development of the 2nd generation ATF FeCrAl alloy has been initiated, and a candidate alloy was selected for trial tube fabrication through hot-extrusion and gun-drilling processes. Four alloys based on Fe-13Cr-4.5Al-0.15Y in weight percent were newly cast with minor alloying additions of Mo, Si, Nb, and C to promote solid-solution and second-phase precipitate strengthening. The alloy compositions were selected with guidance from computational thermodynamic tools. The lab-scale heats of ~ 600g were arc-melted and drop-cast, homogenized, hot-forged and -rolled, and then annealed producing plate shape samples. An alloy with Mo and Nb additions (C35MN) processed at 800°C exhibits very fine sub-grain structure with the sub-grain size of 1-3μm which exhibited more than 25% better yield and tensile strengths together with decent ductility compared to the other FeCrAl alloys at room temperature. It was found that the Nb addition was key to improving thermal stability of the fine sub-grain structure. Optimally, grains of less than 30 microns are desired, with grains up to and order of magnitude in desired produced through Nb addition. Scale-up effort of the C35MN alloy was made in collaboration with a commercial cast company who has a capability of vacuum induction melting. A 39lb columnar ingot with ~81mm diameter and ~305mm height (with hot-top) was commercially cast, homogenized, hot-extruded, and annealed providing 10mm-diameter bar-shape samples with the fine sub-grain structure. This commercial heat proved consistent with materials produced at ORNL at the lab-scale. Tubes and end caps were machined from the bar sample and provided to another work package for the ATF-1 irradiation campaign in the milestone M3FT-14OR0202251.

  15. Mmu-miR-702 functions as an anti-apoptotic mirtron by mediating ATF6 inhibition in mice.

    Science.gov (United States)

    Zhang, Wei-Guang; Chen, Lin; Dong, Qin; He, Juan; Zhao, Han-Dong; Li, Feng-Lan; Li, Hui

    2013-12-01

    MicroRNAs (miRNAs) are a group of endogenous, small, noncoding RNAs that function as key post-transcriptional regulators. miRNAs are involved in many biological processes including apoptosis. In this study, mouse miR-702 (mmu-miR-702), a mirtron derived from the 13th intron of the Plod3 gene, was identified as a regulator of anti-apoptosis. mmu-miR-702 was down-regulated after treatment with the apoptosis-inducer isoproterenol both in vivo and in vitro. According to over-expression experiments, mmu-miR-702 inhibited apoptosis as well as the expression levels of a subset of apoptosis-related genes including activating transcription factor 6 (ATF6). An interaction between mmu-miR-702 and the ATF6 3'-UTR binding site was confirmed using luciferase reporter and western blot assays. This is the first report of ATF6 interaction with miRNA. Although the possible existence of miR-702 in the human genome is low, our results indicate that mirtrons also participate in the process of apoptosis and may provide a novel study strategy for apoptosis. PMID:24035931

  16. Beam-Based Alignment, Tuning and Beam Dynamics Studies for the ATF2 Extraction Line and Final Focus System

    International Nuclear Information System (INIS)

    Using a new extraction line currently under construction, the ATF2 experiment plans to test the novel compact final focus optics design with local chromaticity correction intended for use in future linear colliders. With a 1.3 GeV design beam of 30nm normalized vertical emittance extracted from the ATF damping ring, the primary goal is to achieve a vertical spot-size at the IP waist of 37nm. We discuss our planned strategy for tuning the ATF2 beam to meet the primary goal. Simulation studies have been performed to asses the effectiveness of the strategy, including 'static' (installation) errors and dynamical effects (ground-motion, mechanical vibration, ring extraction jitter etc.). We have simulated all steps in the tuning procedure, from initial orbit establishment to final IP spot-size tuning. Through a Monte Carlo study of 100's of simulation seeds we find we can achieve a spot-size within ∼10% of the design optics value in at least 75% of cases. We also ran a simulation to study the long-term performance with the use of beam-based feedbacks

  17. Viability of thin wall tube forming of ATF FeCrAl

    Energy Technology Data Exchange (ETDEWEB)

    Maloy, Stuart Andrew [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Aydogan, Eda [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Anderoglu, Osman [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Lavender, Curt [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Yamamoto, Yukinori [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2016-09-16

    Fabrication of thin walled tubing of FeCrAl alloys is critical to its success as a candidate enhanced accident tolerant fuel cladding material. Alloys that are being investigated are Generation I and Generation II FeCrAl alloys produced at ORNL and an ODS FeCrAl alloy, MA-956 produced by Special Metals. Gen I and Gen II FeCrAl alloys were provided by ORNL and MA-956 was provided by LANL (initially produced by Special Metals). Three tube development efforts were undertaken. ORNL led the FeCrAl Gen I and Gen II alloy development and tube processing studies through drawing tubes at Rhenium Corporation. LANL received alloys from ORNL and led tube processing studies through drawing tubes at Century Tubing. PNNL led the development of tube processing studies on MA-956 through pilger processing working with Sandvik Corporation. A summary of the recent progress on tube development is provided in the following report and a separate ORNL report: ORNL/TM-2015/478, “Development and Quality Assessments of Commercial Heat Production of ATF FeCrAl Tubes”.

  18. Analysis of Performance of Selected AFC, ATF Fuels, and Lanthanide Transport

    Energy Technology Data Exchange (ETDEWEB)

    Unal, Cetin [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Galloway, Jack D. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-09-29

    We started to look at the performance of ATF concept in LWRs late in FY14 and finish our studies in FY15. The work has been presented in AFC review meetings, ICAPP and TOPFUEL conferences. The final version of the work is accepted for publication in Nuclear Engineering and Science Journal (NES). The copy of ICAPP and NES papers are attached separately to this document as our milestone deliverables. We made an important progress in the modeling of lanthanide transport in FY15. This work produced an ANS Winter Meeting paper and GLOBAL 2015 paper. GLOBAL 2015 paper is also attached as deliverable of FY15. The work on the lanthanide transport is preliminary. We are exploring other potential mechanisms, in addition to “liquid-like” diffusion mechanisms, proposed by Robert Mariani [1] before we analyze data that will be taken by Ohio State University. This year, we concentrate on developing diffusion kernels and principles of modeling. Next year, this work will continue and analyze the Ohio State data and develop approaches to solve multicomponent diffusion. In addition to three papers we attached to this report, we have done some research on coupling and the development of gas release model for metallic fuels in FY15. They are also preliminary in nature; therefore, we give the summary of what we found rather than an extended report that will be done in FY16.

  19. Metformin-induced inhibition of the mitochondrial respiratory chain increases FGF21 expression via ATF4 activation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kook Hwan [Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong Gangnam-gu, Seoul 135-710 (Korea, Republic of); Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University School of Medicine, 50 Irwon-dong Gangnam-gu, Seoul 135-710 (Korea, Republic of); Jeong, Yeon Taek [Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong Gangnam-gu, Seoul 135-710 (Korea, Republic of); Kim, Seong Hun [Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University School of Medicine, 50 Irwon-dong Gangnam-gu, Seoul 135-710 (Korea, Republic of); Jung, Hye Seung; Park, Kyong Soo [Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-dong Chongno-gu, Seoul 110-744 (Korea, Republic of); Lee, Hae-Youn [Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong Gangnam-gu, Seoul 135-710 (Korea, Republic of); Lee, Myung-Shik, E-mail: mslee0923@skku.edu [Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong Gangnam-gu, Seoul 135-710 (Korea, Republic of); Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University School of Medicine, 50 Irwon-dong Gangnam-gu, Seoul 135-710 (Korea, Republic of)

    2013-10-11

    Highlights: •Metformin induces FGF21 expression in an AMPK independent manner. •Metformin enhances FGF21 expression by inhibiting mitochondrial complex I activity. •The PERK-eIF2α-ATF4 axis is required for metformin-induced FGF21 expression. •Metformin activates the ATF4-FGF21 axis in the liver of mouse. •Metformin increases serum FGF21 level in diabetic human subjects. -- Abstract: Fibroblast growth factor 21 (FGF21) is an endocrine hormone that exhibits anti-obesity and anti-diabetes effects. Because metformin is widely used as a glucose-lowering agent in patients with type 2 diabetes (T2D), we investigated whether metformin modulates FGF21 expression in cell lines, and in mice or human subjects. We found that metformin increased the expression and release of FGF21 in a diverse set of cell types, including rat hepatoma FaO, primary mouse hepatocytes, and mouse embryonic fibroblasts (MEFs). Intriguingly, AMP-activated protein kinase (AMPK) was dispensable for the induction of FGF21 by metformin. Mammalian target of rapamycin complex 1 (mTORC1) and peroxisome proliferator-activated receptor α (PPARα), which are additional targets of metformin, were not involved in metformin-induced FGF21 expression. Importantly, inhibition of mitochondrial complex I activity by metformin resulted in FGF21 induction through PKR-like ER kinase (PERK)-eukaryotic translation factor 2α (eIF2α)-activating transcription factor 4 (ATF4). We showed that metformin activated ATF4 and increased FGF21 expression in the livers of mice, which led to increased serum levels of FGF21. We also found that serum FGF21 level was increased in human subjects with T2D after metformin therapy for 6 months. In conclusion, our results indicate that metformin induced expression of FGF21 through an ATF4-dependent mechanism by inhibiting mitochondrial respiration independently of AMPK. Therefore, FGF21 induction by metformin might explain a portion of the beneficial metabolic effects of metformin.

  20. Expression and purification of recombinant ATF-mellitin, a new type fusion protein targeting ovarian cancer cells, in P. pastoris.

    Science.gov (United States)

    Su, Manman; Chang, Weiqin; Zhang, Kun; Cui, Manhua; Wu, Shuying; Xu, Tianmin

    2016-02-01

    Melittin is well known to possess cytolytic activity with wide-spectrum lytic properties and its potential use as an agent to treat several types of cancer has been tested. Due to the non-specific toxicity, melittin can impair not only cancer cells but also normal tissue. Thus, tumor-targeted toxins may be helpful for developing novel anticancer therapeutics. The urokinase-type plasminogen activator (uPA) plays a central role in tissue remodelling events occurring in normal physiology and in pathophysiology, including cancer invasion and metastasis. Heartening findings showed that uPA receptor is predominantly expressed on many types of cancer. Therefore, the amino-terminal fragment (ATF) of uPA which was able to identify and bond with cancer cells was used as the cell-targeting domain to make up tumor-targeted toxin in this study. In the present study, pPICZαC-ATF-melittin eukaryotic expression vector was successfully constructed. After transformed into P. pastoris and induced by methanol, rATF-mellitin was detected by SDS-PAGE and western blot analysis. After induction with methanol, the expression level of rATF-mellitin was 312 mg/l in 80-l fermentor. rATF‑mellitin was purified to >95% purity using SP Sepharose ion exchange chromatography and source™ 30 RPC with 67.2% recovery. Cell proliferation assay showed that rATF-melittin inhibited growth of SKOV3 cells and had no cytotoxicity effect on normal cells. For the first time, we established a stable and effective rATF-mellitin P. pastoris expression system to obtain a high level of expression of secreted rATF-mellitin which was purified by a highly efficient purification procedure. PMID:26718643

  1. Overexpression of eIF5 or its protein mimic 5MP perturbs eIF2 function and induces ATF4 translation through delayed re-initiation

    Science.gov (United States)

    Kozel, Caitlin; Thompson, Brytteny; Hustak, Samantha; Moore, Chelsea; Nakashima, Akio; Singh, Chingakham Ranjit; Reid, Megan; Cox, Christian; Papadopoulos, Evangelos; Luna, Rafael E.; Anderson, Abbey; Tagami, Hideaki; Hiraishi, Hiroyuki; Slone, Emily Archer; Yoshino, Ken-ichi; Asano, Masayo; Gillaspie, Sarah; Nietfeld, Jerome; Perchellet, Jean-Pierre; Rothenburg, Stefan; Masai, Hisao; Wagner, Gerhard; Beeser, Alexander; Kikkawa, Ushio; Fleming, Sherry D.; Asano, Katsura

    2016-01-01

    ATF4 is a pro-oncogenic transcription factor whose translation is activated by eIF2 phosphorylation through delayed re-initiation involving two uORFs in the mRNA leader. However, in yeast, the effect of eIF2 phosphorylation can be mimicked by eIF5 overexpression, which turns eIF5 into translational inhibitor, thereby promoting translation of GCN4, the yeast ATF4 equivalent. Furthermore, regulatory protein termed eIF5-mimic protein (5MP) can bind eIF2 and inhibit general translation. Here, we show that 5MP1 overexpression in human cells leads to strong formation of 5MP1:eIF2 complex, nearly comparable to that of eIF5:eIF2 complex produced by eIF5 overexpression. Overexpression of eIF5, 5MP1 and 5MP2, the second human paralog, promotes ATF4 expression in certain types of human cells including fibrosarcoma. 5MP overexpression also induces ATF4 expression in Drosophila. The knockdown of 5MP1 in fibrosarcoma attenuates ATF4 expression and its tumor formation on nude mice. Since 5MP2 is overproduced in salivary mucoepidermoid carcinoma, we propose that overexpression of eIF5 and 5MP induces translation of ATF4 and potentially other genes with uORFs in their mRNA leaders through delayed re-initiation, thereby enhancing the survival of normal and cancer cells under stress conditions. PMID:27325740

  2. Parkin is transcriptionally regulated by ATF4: evidence for an interconnection between mitochondrial stress and ER stress.

    Science.gov (United States)

    Bouman, L; Schlierf, A; Lutz, A K; Shan, J; Deinlein, A; Kast, J; Galehdar, Z; Palmisano, V; Patenge, N; Berg, D; Gasser, T; Augustin, R; Trümbach, D; Irrcher, I; Park, D S; Wurst, W; Kilberg, M S; Tatzelt, J; Winklhofer, K F

    2011-05-01

    Loss of parkin function is responsible for the majority of autosomal recessive parkinsonism. Here, we show that parkin is not only a stress-protective, but also a stress-inducible protein. Both mitochondrial and endoplasmic reticulum (ER) stress induce an increase in parkin-specific mRNA and protein levels. The stress-induced upregulation of parkin is mediated by ATF4, a transcription factor of the unfolded protein response (UPR) that binds to a specific CREB/ATF site within the parkin promoter. Interestingly, c-Jun can bind to the same site, but acts as a transcriptional repressor of parkin gene expression. We also present evidence that mitochondrial damage can induce ER stress, leading to the activation of the UPR, and thereby to an upregulation of parkin expression. Vice versa, ER stress results in mitochondrial damage, which can be prevented by parkin. Notably, the activity of parkin to protect cells from stress-induced cell death is independent of the proteasome, indicating that proteasomal degradation of parkin substrates cannot explain the cytoprotective activity of parkin. Our study supports the notion that parkin has a role in the interorganellar crosstalk between the ER and mitochondria to promote cell survival under stress, suggesting that both ER and mitochondrial stress can contribute to the pathogenesis of Parkinson's disease.

  3. Amino acid availability controls TRB3 transcription in liver through the GCN2/eIF2α/ATF4 pathway.

    Directory of Open Access Journals (Sweden)

    Valérie Carraro

    Full Text Available In mammals, plasma amino acid concentrations are markedly affected by dietary or pathological conditions. It has been well established that amino acids are involved in the control of gene expression. Up to now, all the information concerning the molecular mechanisms involved in the regulation of gene transcription by amino acid availability has been obtained in cultured cell lines. The present study aims to investigate the mechanisms involved in transcriptional activation of the TRB3 gene following amino acid limitation in mice liver. The results show that TRB3 is up-regulated in the liver of mice fed a leucine-deficient diet and that this induction is quickly reversible. Using transient transfection and chromatin immunoprecipitation approaches in hepatoma cells, we report the characterization of a functional Amino Acid Response Element (AARE in the TRB3 promoter and the binding of ATF4, ATF2 and C/EBPβ to this AARE sequence. We also provide evidence that only the binding of ATF4 to the AARE plays a crucial role in the amino acid-regulated transcription of TRB3. In mouse liver, we demonstrate that the GCN2/eIF2α/ATF4 pathway is essential for the induction of the TRB3 gene transcription in response to a leucine-deficient diet. Therefore, this work establishes for the first time that the molecular mechanisms involved in the regulation of gene transcription by amino acid availability are functional in mouse liver.

  4. The PERK/ATF4/LAMP3-arm of the unfolded protein response affects radioresistance by interfering with the DNA damage response

    NARCIS (Netherlands)

    Nagelkerke, A.; Bussink, J.; Kogel, A.J. van der; Sweep, F.C.; Span, P.N.

    2013-01-01

    BACKGROUND AND PURPOSE: Lysosome-associated membrane protein 3 (LAMP3) is induced by the PKR-like ER kinase (PERK)/activating transcription factor 4 (ATF4)-arm of the unfolded protein response (UPR) during hypoxia. LAMP3 has prognostic value in breast cancer patients treated with radiotherapy. Here,

  5. Taxol-induced unfolded protein response activation in breast cancer cells exposed to hypoxia: ATF4 activation regulates autophagy and inhibits apoptosis.

    Science.gov (United States)

    Notte, Annick; Rebucci, Magali; Fransolet, Maude; Roegiers, Edith; Genin, Marie; Tellier, Celine; Watillon, Kassandra; Fattaccioli, Antoine; Arnould, Thierry; Michiels, Carine

    2015-05-01

    Understanding the mechanisms responsible for the resistance against chemotherapy-induced cell death is still of great interest since the number of patients with cancer increases and relapse is commonly observed. Indeed, the development of hypoxic regions as well as UPR (unfolded protein response) activation is known to promote cancer cell adaptive responses to the stressful tumor microenvironment and resistance against anticancer therapies. Therefore, the impact of UPR combined to hypoxia on autophagy and apoptosis activation during taxol exposure was investigated in MDA-MB-231 and T47D breast cancer cells. The results showed that taxol rapidly induced UPR activation and that hypoxia modulated taxol-induced UPR activation differently according to the different UPR pathways (PERK, ATF6, and IRE1α). The putative involvement of these signaling pathways in autophagy or in apoptosis regulation in response to taxol exposure was investigated. However, while no link between the activation of these three ER stress sensors and autophagy or apoptosis regulation could be evidenced, results showed that ATF4 activation, which occurs independently of UPR activation, was involved in taxol-induced autophagy completion. In addition, an ATF4-dependent mechanism leading to cancer cell adaptation and resistance against taxol-induced cell death was evidenced. Finally, our results demonstrate that expression of ATF4, in association with hypoxia-induced genes, can be used as a biomarker of a poor prognosis for human breast cancer patients supporting the conclusion that ATF4 might play an important role in adaptation and resistance of breast cancer cells to chemotherapy in hypoxic tumors.

  6. Zinc regulates expression of IL-23 p19 mRNA via activation of eIF2α/ATF4 axis in HAPI cells.

    Science.gov (United States)

    Doi, Takuya; Hara, Hirokazu; Kajita, Miho; Kamiya, Tetsuro; Adachi, Tetsuo

    2015-10-01

    Zinc (Zn(2+)) is considered to be one of the factors aggravating brain damage after cerebral ischemia. Since Zn(2+) activates microglia, immune cells in the brain, this metal is proposed to modulate neuroinflammatory responses in the post-ischemic brain. Interleukin (IL)-23 is a heterodimeric cytokine composed of the p19 subunit unique to IL-23 and the p40 subunit common to IL-12. IL-23 has been shown to play a critical role in the progression of ischemic brain injury. However, whether Zn(2+) participates in the expression of IL-23 in microglia remains unknown. In this study, we examined the effect of Zn(2+) on IL-23 p19 mRNA expression using rat immortalized microglia HAPI cells. Exposure to Zn(2+) dose- and time-dependently induced the expression of IL-23 p19 mRNA in HAPI cells. Inhibitors of MAPK and NF-κB pathways failed to suppress this induction. Interestingly, we found that Zn(2+) stimulated the phosphorylation of eIF2α and promoted the nuclear accumulation of activating transcription factor 4 (ATF4). Treatment with salubrinal, an eIF2α dephosphorylation inhibitor, enhanced Zn(2+)-induced ATF4 accumulation and IL-23 p19 mRNA expression. In addition, reporter assay using the IL-23 p19 promoter region revealed that ATF4 directly transactivated IL-23 p19 promoter and that dominant-negative ATF4 suppressed Zn(2+)-induced activation of IL-23 p19 promoter. Taken together, these findings suggest that Zn(2+) up-regulates expression of the IL-23 p19 gene via the eIF2α/ATF4 axis in HAPI cells. PMID:26174742

  7. ATF6 pathway of unfolded protein response mediates advanced oxidation protein product-induced hypertrophy and epithelial-to-mesenchymal transition in HK-2 cells.

    Science.gov (United States)

    Tang, Xun; Liang, Xiujie; Li, Minhui; Guo, Tingting; Duan, Na; Wang, Yue; Rong, Guang; Yang, Lei; Zhang, Shaojie; Zhang, Jun

    2015-09-01

    Advanced oxidation protein products (AOPPs) accelerate the progression of chronic kidney disease. We previously demonstrated that AOPPs induce hypertrophy and epithelial-to-mesenchymal transition (EMT) in human proximal tubular cells (HK-2 cells) through induction of endoplasmic reticulum (ER) stress. However, which pathway of unfolded protein response (UPR) induced by ER stress plays crucial roles in this process remains unclear. In this study, we investigated the roles of the protein kinase RNA-like ER kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring enzyme 1 (IRE1) pathways of UPR in this process in HK-2 cells. AOPP treatment induced the overexpression of cleaved ATF6 and spliced form of X-box binding protein-1, and induced the phosphorylation of PERK, eukaryotic translation initiation factor 2α and IRE1. Furthermore, silencing of ATF6 increased E-cadherin and zonula occludens-1 expression, lowered the expression of vimentin, and downregulated total protein content, whereas knockdown of PERK or IRE1 resulted in no difference compared with the scramble siRNA-transfected cells. AOPP-induced phosphorylation of Src, which was reproduced by thapsigargin, an inducer of ER stress, was partly reversed by salubrinal, an inhibitor of ER stress. Furthermore, the Src inhibitor saracatinib effectively blocked AOPP-induced phosphorylation of Src, activation of ER stress, hypertrophy, and EMT in HK-2 cells. Collectively, our results indicate that AOPPs induce the PERK, ATF6, and IRE1 pathways of UPR, and the ATF6 pathway rather than the other two pathways mediates AOPP-induced HK-2-cell hypertrophy and EMT. We also suggest that the ER stress involved in this process is likely mediated by the activation of Src kinase. PMID:26045172

  8. Development of a Turn-by-Turn Beam Position Monitoring System for Multiple Bunch Operation of the ATF Damping Ring

    CERN Document Server

    Burrows, P N; Kraljevic, N Blaskovic; Christian, G B; Davis, M R; Perry, C; Apsimon, R J; Constance, B; Gerbershagen, A; Resta-Lopez, J

    2012-01-01

    An FPGA-based monitoring system has been developed to study multi-bunch beam instabilities in the damping ring (DR) of the KEK Accelerator Test Facility (ATF). The system utilises a stripline beam position monitor (BPM) and single-stage down-mixing BPM processor. The system is designed to record the horizontal and/or vertical positions of up to three bunches in the DR with c. 150ns bunch spacing, or the head bunch of up to three trains in a multi-bunch mode with a bunch spacing of 5.6 ns. The FPGA firmware and data acquisition software allow the recording of turnby-turn data. An overview of the system and performance results will be presented.

  9. The operation of the BNL/ATF gun-IV photocathode RF gun at the Advanced Photon Source

    International Nuclear Information System (INIS)

    At the Advanced Photon Source (APS) at Argonne National Laboratory (ANL), a free-electron laser (FEL) based on the self-amplified spontaneous emission (SASE) process is nearing completion. Recently, an rf photoinjector gun system was made available to the APS by Brookhaven National Laboratory/Accelerator Test Facility (BNL/ATF). It will be used to provide the high-brightness, low-emittance, and low-energy spread electron beam required by the SASE FEL theory. A Nd:Glass laser system, capable of producing a maximum of 500 microJ of UV in a 1-10 ps pulse at up to a 10-Hz repetition rate, serves as the photoinjector's drive laser. Here, the design, commissioning, and integration of this gun with the APS is discussed

  10. Over-expression of ATF3 Inhibits the Proliferation of Esophageal Squamous Carcinoma Cells%激活转录因子3的过表达对食管癌细胞生长的抑制作用

    Institute of Scientific and Technical Information of China (English)

    谢仰民; 谢剑君; 周飞; 侯健; 曹君君; 许丽艳; 李恩民

    2009-01-01

    背景与目的:激活转录因子3(activating transcription factor 3,ATF3)在食管癌中表达异常下调,但其功能仍不清楚.本研究拟探讨ATF3在食管癌细胞过表达对癌细胞生长及裸鼠成瘤的影响. 材料与方法:利用分子克隆技术将ATF3基因完整编码区克隆至真核细胞表达载体pcDNA3中,获得重组表达质粒;将该表达质粒转染食管癌EC109细胞并用G418筛选稳定表达的细胞克隆;用Western blot检测ATF3的过表达效果;对ATF3过表达的细胞与相应对照细胞进行细胞克隆形成实验和裸鼠体内成瘤实验,以分析ATF3过表达对食管癌细胞生长的影响. 结果:ATF3的过表达在体外可以降低食管癌细胞的克隆形成能力;在体内可以抑制食管癌细胞在雌鼠中的成瘤能力,但对雄鼠中的成瘤能力没有明显影响.结论:ATF3的过表达可以抑制食管癌细胞的生长,ATF3可能在食管癌的发生发展中发挥重要作用.%BACKGROUND AND AIM: ATF3 was down-regulated in esophageal squamous cell carcinoma (ESCC), but the roles of ATF3 in ESCC cells still remained unclear. The purpose of this study was to explore the effect of ATF3 on the proliferation of ESCC cells. MATERIALS AND METHODS: The recombinant expressing plasmid was constructed by inserting the full coding sequence of ATF3 gene into the eukaryotic expressing vector pcDNA3. Then, the expressing plasmid was stably transfected into EC 109 cells, an ESCC cell line, and the over-expressing ATF3 cell clones were obtained. Colony formation assay and tumor formation assay in nude mice were used to explore the effect of ATF3 over-expression on the proliferation of ESCC cells. RESULTS: With the over-expression of ATF3, the colony formation ability of EC109 cells was decreased and the tumor formation of EC109 cells in female mice was inhibited. CONCLUSION: Over-expression of ATF3 could inhibit the proliferation of ESCC cells and ATF3 may play important roles in the progression of ESCC.

  11. Urotensin II inhibits doxorubicin-induced human umbilical vein endothelial cell death by modulating ATF expression and via the ERK and Akt pathway.

    Directory of Open Access Journals (Sweden)

    Yen-Ling Chen

    Full Text Available BACKGROUND AND PURPOSE: Regulation of the homeostasis of vascular endothelium is critical for the processes of vascular remodeling and angiogenesis under physiological and pathological conditions. Urotensin II (U-II, a potent vasoactive peptide, participates in vascular and myocardial remodeling after injury. We investigated the protective effect of U-II on doxorubicin (DOX-induced apoptosis in cultured human umbilical vein endothelial cells (HUVECs and the potential mechanisms involved in this process. EXPERIMENTAL APPROACH: Cultured HUVECs were treated with vehicle, DOX (1 µM, U-II, or U-II plus DOX. Apoptosis was evaluated by DNA strand break level with TdT-mediated dUTP nick-end labeling (TUNEL staining. Western blot analysis was employed to determine the related protein expression and flow cytometry assay was used to determine the TUNEL positive cells. KEY RESULTS: U-II reduced the quantity of cleaved caspase-3 and cytosol cytochrome c and increased Bcl-2 expression, which results in protecting HUVECs from DOX-induced apoptosis. U-II induced Activating transcription factor 3 (ATF3 at both mRNA and protein levels in U-II-treated cells. Knockdown of ATF3 with ATF3 siRNA significantly reduced ATF3 protein levels and U-II protective effect under DOX-treated condition. U-II downregulated p53 expression in DOX-induced HUVECs apoptosis, and it rapidly activated extracellular signal-regulated protein kinase (ERK and Akt. The DOX induced change of p53 was not affected by U-II antagonist (urantide under ATF-3 knockdown. The inhibitory effect of U-II on DOX-increased apoptosis was attenuated by inhibitors of ERK (U0126 and PI3K/Akt (LY294002. CONCLUSION AND IMPLICATIONS: Our observations provide evidence that U-II protects HUVECs from DOX-induced apoptosis. ERK-Akt phosphorylation, ATF3 activation, and p53 downregulation may play a signal-transduction role in this process.

  12. Activating Transcription Factor 4 (ATF4)-ATF3-C/EBP Homologous Protein (CHOP) Cascade Shows an Essential Role in the ER Stress-Induced Sensitization of Tetrachlorobenzoquinone-Challenged PC12 Cells to ROS-Mediated Apoptosis via Death Receptor 5 (DR5) Signaling.

    Science.gov (United States)

    Liu, Zixuan; Shi, Qiong; Song, Xiufang; Wang, Yuxin; Wang, Yawen; Song, Erqun; Song, Yang

    2016-09-19

    Tetrachlorobenzoquinone (TCBQ) is a downstream metabolite of pentachlorophenol (PCP). Previously, we demonstrated that TCBQ caused cytotoxicity due to mitochondrial-related apoptosis. Here, we confirmed the upregulation of death receptor 5 (DR5) followed by the construction of the death-inducing signaling complex (DISC). We also detected the activation of the caspase cascade, which was correlated with TCBQ-induced apoptotic cell death in PC12 cells. The upregulation of DR5 included transcriptional activation and de novo protein synthesis in response to TCBQ. We also identified the endoplasmic reticulum (ER) as a new target for the TCBQ challenge in PC12 cells. The protein kinase R-like ER kinase/eukaryotic translation initiation factor 2α (PERK/eIF2α)-mediated activating transcription factor 4 (ATF4)-ATF3-C/EBP homologous protein (CHOP) signaling pathway contributed to the process of TCBQ-induced ER stress. Blocking ATF4, ATF3, or CHOP signaling by gene silencing technology resulted in decreased cell apoptosis after exposure to TCBQ. Finally, NAC ameliorated TCBQ-induced apoptosis and ER stress, which illustrated that TCBQ-induced apoptosis is somehow ROS-dependent. In summary, this study provided important mechanistic insight into how TCBQ utilizes ER stress-related signaling to exhibit pro-apoptotic activity in PC12 cells. PMID:27484784

  13. Role of areca nut induced JNK/ATF2/Jun axis in the activation of TGF-β pathway in precancerous Oral Submucous Fibrosis

    Science.gov (United States)

    Pant, Ila; Rao, S. Girish; Kondaiah, Paturu

    2016-01-01

    Oral submucous fibrosis (OSF) is potentially premalignant with progressive and irreversible extracellular matrix deposition accompanied by epithelial atrophy and like other fibrotic disorders, is primarily a TGF-β driven disease. OSF is caused by prolonged chewing of areca nut. Our previous studies reported a pivotal role for TGF-β activation and its effects contributing to OSF. However, the mechanism for activation of TGF-β signaling in OSF is still unknown. In this study we demonstrate activation of TGF-β signaling with sub-cytotoxic dose of areca nut in epithelial cells and discovered a key role for pJNK in this process. In good correlation; pJNK was detected in OSF tissues but not in normal tissues. Moreover, activation of JNK was found to be dependent on muscarinic acid receptor induced Ca2+/CAMKII as well as ROS. JNK dependent phosphorylation of ATF2/c-Jun transcription factors resulted in TGF-β transcription and its signaling. pATF2/p-c-Jun were enriched on TGF-β promoter and co-localized in nuclei of epithelial cells upon areca nut treatment. In corroboration, OSF tissue sections also had nuclear pATF2 and p-c-Jun. Our results provide comprehensive mechanistic details of TGF-β signaling induced by etiological agent areca nut in the manifestation of fibrosis which can lead to new therapeutic modalities for OSF. PMID:27708346

  14. Linear Collider Test Facility: Twiss Parameter Analysis at the IP/Post-IP Location of the ATF2 Beam Line

    Energy Technology Data Exchange (ETDEWEB)

    Bolzon, Benoit; /Annecy, LAPP; Jeremie, Andrea; /Annecy, LAPP; Bai, Sha; /Beijing, Inst. High Energy Phys.; Bambade, Philip; /KEK, Tsukuba; White, Glen; /SLAC

    2012-07-02

    At the first stage of the ATF2 beam tuning, vertical beam size is usually bigger than 3 {micro}m at the IP. Beam waist measurements using wire scanners and a laser wire are usually performed to check the initial matching of the beam through to the IP. These measurements are described in this paper for the optics currently used ({beta}{sub x} = 4cm and {beta}{sub y} = 1mm). Software implemented in the control room to automate these measurements with integrated analysis is also described. Measurements showed that {beta} functions and emittances were within errors of measurements when no rematching and coupling corrections were done. However, it was observed that the waist in the horizontal (X) and vertical (Y) plane was abnormally shifted and simulations were performed to try to understand these shifts. They also showed that multiknobs are needed in the current optics to correct simultaneously {alpha}{sub x}, {alpha}{sub y} and the horizontal dispersion (D{sub x}). Such multiknobs were found and their linearity and orthogonality were successfully checked using MAD optics code. The software for these multiknobs was implemented in the control room and waist scan measurements using the {alpha}{sub y} knob were successfully performed.

  15. Scoping assessments of ATF impact on late-stage accident progression including molten core-concrete interaction

    Science.gov (United States)

    Farmer, M. T.; Leibowitz, L.; Terrani, K. A.; Robb, K. R.

    2014-05-01

    Simple scoping models that can be used to evaluate ATF performance under severe accident conditions have been developed. The methodology provides a fundamental technical basis (a.k.a. metric) based on the thermodynamic boundary for evaluating performance relative to that of traditional Zr-based claddings. The initial focus in this study was on UO2 fuel with the advanced claddings 310 SS, D9, FeCrAl, and SiC. The evaluation considered only energy release with concurrent combustible gas production from fuel-cladding-coolant interactions and, separately, molten core-concrete interactions at high temperatures. Other important phenomenological effects that can influence the rate and extent of cladding decomposition (e.g., eutectic interactions, degradation of other core constituents) were not addressed. For the cladding types addressed, potential combustible gas production under both in-vessel and ex-vessel conditions was similar to that for Zr. However, exothermic energy release from cladding oxidation was substantially less for iron-based alloys (by at least a factor of 4), and modestly less (by ∼20%) for SiC. Data on SiC-clad UO2 fuel performance under severe accident conditions are sparse in the literature; thus, assumptions on the nature of the cladding decomposition process were made in order to perform this initial screening evaluation. Experimental data for this system under severe accident conditions is needed for a proper evaluation and comparison to iron-based claddings.

  16. PERK-eIF2α-ATF4 pathway mediated by endoplasmic reticulum stress response is involved in osteodifferentiation of human periodontal ligament cells under cyclic mechanical force.

    Science.gov (United States)

    Yang, Shuang-Yan; Wei, Fu-Lan; Hu, Li-Hua; Wang, Chun-Ling

    2016-08-01

    To prevent excess accumulation of unfolded proteins in endoplasmic reticulum (ER), eukaryotic cells have signaling pathways from the ER to the cytosol or nucleus. These processes are known as the endoplasmic reticulum stress (ERS) response. Protein kinase R like endoplasmic reticulum kinase (PERK) is a major transducer of the ERS response and it directly phosphorylate α-subunit of eukaryotic initiation factor 2 (eIF2α), resulting in translational attenuation. Phosphorylated eIF2α specifically promoted the translation of the activating transcription factor 4 (ATF4). ATF4 is a known important transcription factor which plays a pivotal role in osteoblast differentiation and bone formation. Furthermore, ATF4 is a downstream target of PERK. Studies have shown that PERK-eIF2α-ATF4 signal pathway mediated by ERS was involved in osteoblastic differentiation of osteoblasts. We have known that orthodontic tooth movement is a process of periodontal ligament cells (PDLCs) osteodifferentiation and alveolar bone remodeling under mechanical force. However, the involvement of PERK-eIF2α-ATF4 signal pathway mediated by ERS in osteogenic differentiation of PDLCs under mechanical force has not been unclear. In our study, we applied the cyclic mechanical force at 10% elongation with 0.5Hz to mimic occlusal force, and explored whether PERK-eIF2α-ATF4 signaling pathway mediated by ERS involved in osteogenic differentiation of PDLCs under mechanical force. Firstly, cyclic mechanical force will induce ERS and intensify several osteoblast marker genes (ATF4, OCN, and BSP). Next, we found that PERK overexpression increased eIF2α phosphorylation and expression of ATF4, furthermore induced BSP, OCN expression, thus it will promote osteodifferentiation of hPDLCs; mechanical force could promote this effect. However, PERK(-/-) cells showed the opposite changes, which will inhibit osteodifferentiation of hPDLCs. Taken together, our study proved that PERK-eIF2α-ATF4 signaling pathway

  17. PERK-eIF2α-ATF4 pathway mediated by endoplasmic reticulum stress response is involved in osteodifferentiation of human periodontal ligament cells under cyclic mechanical force.

    Science.gov (United States)

    Yang, Shuang-Yan; Wei, Fu-Lan; Hu, Li-Hua; Wang, Chun-Ling

    2016-08-01

    To prevent excess accumulation of unfolded proteins in endoplasmic reticulum (ER), eukaryotic cells have signaling pathways from the ER to the cytosol or nucleus. These processes are known as the endoplasmic reticulum stress (ERS) response. Protein kinase R like endoplasmic reticulum kinase (PERK) is a major transducer of the ERS response and it directly phosphorylate α-subunit of eukaryotic initiation factor 2 (eIF2α), resulting in translational attenuation. Phosphorylated eIF2α specifically promoted the translation of the activating transcription factor 4 (ATF4). ATF4 is a known important transcription factor which plays a pivotal role in osteoblast differentiation and bone formation. Furthermore, ATF4 is a downstream target of PERK. Studies have shown that PERK-eIF2α-ATF4 signal pathway mediated by ERS was involved in osteoblastic differentiation of osteoblasts. We have known that orthodontic tooth movement is a process of periodontal ligament cells (PDLCs) osteodifferentiation and alveolar bone remodeling under mechanical force. However, the involvement of PERK-eIF2α-ATF4 signal pathway mediated by ERS in osteogenic differentiation of PDLCs under mechanical force has not been unclear. In our study, we applied the cyclic mechanical force at 10% elongation with 0.5Hz to mimic occlusal force, and explored whether PERK-eIF2α-ATF4 signaling pathway mediated by ERS involved in osteogenic differentiation of PDLCs under mechanical force. Firstly, cyclic mechanical force will induce ERS and intensify several osteoblast marker genes (ATF4, OCN, and BSP). Next, we found that PERK overexpression increased eIF2α phosphorylation and expression of ATF4, furthermore induced BSP, OCN expression, thus it will promote osteodifferentiation of hPDLCs; mechanical force could promote this effect. However, PERK(-/-) cells showed the opposite changes, which will inhibit osteodifferentiation of hPDLCs. Taken together, our study proved that PERK-eIF2α-ATF4 signaling pathway

  18. Non-destructive Preirradiation Assessment of UN / U-Si “LANL1” ATF formulation

    Energy Technology Data Exchange (ETDEWEB)

    Vogel, Sven C. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Losko, Adrian Simon [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Pokharel, Reeju [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Ickes, Timothy Lee [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Hunter, James F. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Brown, Donald William [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Voit, Stewart Lancaster [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Tremsin, Anton S. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Bourke, Mark Andrew [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); McClellan, Kenneth James [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-09-15

    The goal of the Advanced Non-destructive Fuel Examination (ANDE) work package is the development and application of non-destructive neutron imaging and scattering techniques to ceramic and metallic nuclear fuels, ultimately also to irradiated fuels. The results of these characterizations provide complete pre- and post-irradiation on length scales ranging from mm to nm, guide destructive examination, and inform modelling efforts. Besides technique development and application to samples to be irradiated, the ANDE work package also examines possible technologies to provide these characterization techniques pool-side, e.g. at the Advanced Test Reactor (ATR) at Idaho National Laboratory (INL) using laser-driven intense pulsed neutron and gamma sources. Neutron tomography and neutron diffraction characterizations were performed on nine pellets; four UN/ U-Si composite formulations (two enrichment levels), three pure U3Si5 reference formulations (two enrichment levels), and two reject pellets with visible flaws (to qualify the technique). The 235U enrichments ranged from 0.2 to 8.8 wt. %. The nitride/silicide composites are candidate compositions for use as Accident Tolerant Fuel (ATF). The monophase U3Si5 material was included as a reference. Pellets from the same fabrication batches will be inserted in the Advanced Test Reactor at Idaho during 2016. We have also proposed a data format to build a database for characterization results of individual pellets. Neutron data reported in this report were collected in the LANSCE run cycle that started in September 2015 and ended in March 2016. This report provides the results for the characterized samples and discussion in the context of ANDE and APIE. We quantified the gamma spectra of several samples in their received state as well as after neutron irradiation to ensure that the neutron irradiation does not add significant activation that would complicate shipment and

  19. Influence of the valine zipper region on the structure and aggregation of the basic leucine zipper (bZIP) domain of activating transcription factor 5 (ATF5).

    Science.gov (United States)

    Ciaccio, Natalie A; Reynolds, T Steele; Middaugh, C Russell; Laurence, Jennifer S

    2012-11-01

    Protein aggregation is a major problem for biopharmaceuticals. While the control of aggregation is critically important for the future of protein pharmaceuticals, mechanisms of aggregate assembly, particularly the role that structure plays, are still poorly understood. Increasing evidence indicates that partially folded intermediates critically influence the aggregation pathway. We have previously reported the use of the basic leucine zipper (bZIP) domain of activating transcription factor 5 (ATF5) as a partially folded model system to investigate protein aggregation. This domain contains three regions with differing structural propensity: a N-terminal polybasic region, a central helical leucine zipper region, and a C-terminal extended valine zipper region. Additionally, a centrally positioned cysteine residue readily forms an intermolecular disulfide bond that reduces aggregation. Computational analysis of ATF5 predicts that the valine zipper region facilitates self-association. Here we test this hypothesis using a truncated mutant lacking the C-terminal valine zipper region. We compare the structure and aggregation of this mutant to the wild-type (WT) form under both reducing and nonreducing conditions. Our data indicate that removal of this region results in a loss of α-helical structure in the leucine zipper and a change in the mechanism of self-association. The mutant form displays increased association at low temperature but improved resistance to thermally induced aggregation. PMID:23067245

  20. Influence of the valine zipper region on the structure and aggregation of the basic leucine zipper (bZIP) domain of activating transcription factor 5 (ATF5).

    Science.gov (United States)

    Ciaccio, Natalie A; Reynolds, T Steele; Middaugh, C Russell; Laurence, Jennifer S

    2012-11-01

    Protein aggregation is a major problem for biopharmaceuticals. While the control of aggregation is critically important for the future of protein pharmaceuticals, mechanisms of aggregate assembly, particularly the role that structure plays, are still poorly understood. Increasing evidence indicates that partially folded intermediates critically influence the aggregation pathway. We have previously reported the use of the basic leucine zipper (bZIP) domain of activating transcription factor 5 (ATF5) as a partially folded model system to investigate protein aggregation. This domain contains three regions with differing structural propensity: a N-terminal polybasic region, a central helical leucine zipper region, and a C-terminal extended valine zipper region. Additionally, a centrally positioned cysteine residue readily forms an intermolecular disulfide bond that reduces aggregation. Computational analysis of ATF5 predicts that the valine zipper region facilitates self-association. Here we test this hypothesis using a truncated mutant lacking the C-terminal valine zipper region. We compare the structure and aggregation of this mutant to the wild-type (WT) form under both reducing and nonreducing conditions. Our data indicate that removal of this region results in a loss of α-helical structure in the leucine zipper and a change in the mechanism of self-association. The mutant form displays increased association at low temperature but improved resistance to thermally induced aggregation.

  1. Armament Technology Facility (ATF)

    Data.gov (United States)

    Federal Laboratory Consortium — The Armament Technology Facility is a 52,000 square foot, secure and environmentally-safe, integrated small arms and cannon caliber design and evaluation facility....

  2. DESIGN AND INITIAL RESULTS OF A TURN-BY-TURN BEAM POSITION MONITORING SYSTEM FOR MULTIPLE BUNCH OPERATION OF THE ATF DAMPING RING

    CERN Document Server

    Christian, G B; Bett, D R; Burrows, P N; Davis, M R; Gerbershagen, A; Perry, C; Constance, B; Resta-Lopez, J

    2011-01-01

    An FPGA-based monitoring system has been developed to study multi-bunch beam instabilities in the damping ring (DR) of the KEK Accelerator Test Facility (ATF), utilising a stripline beam position monitor (BPM) and existing BPM processor hardware. The system is designed to record the horizontal and/or vertical positions of up to three bunches in the DR in single-bunch multi-train mode or the head bunch of up to three trains in multi-bunch mode, with a bunch spacing of 5.6 ns. The FPGA firmware and data acquisition software were modified to record turn-by-turn data for up to six channels and 1–3 bunches in the DR. An overview of the system and initial results will be presented.

  3. The Role of the PERK/eIF2α/ATF4/CHOP Signaling Pathway in Tumor Progression During Endoplasmic Reticulum Stress

    Science.gov (United States)

    Rozpędek, W.; Pytel, D.; Mucha, B.; Leszczyńska, H.; Diehl, J. Alan; Majsterek, I.

    2016-01-01

    Hypoxia is a major hallmark of the tumor microenvironment that is strictly associated with rapid cancer progression and induction of metastasis. Hypoxia inhibits disulfide bond formation and impairs protein folding in the Endoplasmic Reticulum (ER). The stress in the ER induces the activation of Unfolded Protein Response (UPR) pathways via the induction of protein kinase RNA-like endoplasmic reticulum kinase (PERK). As a result, the level of phosphorylated Eukaryotic Initiation Factor 2 alpha (eIF2α) is markedly elevated, resulting in the promotion of a pro-adaptive signaling pathway by the inhibition of global protein synthesis and selective translation of Activating Transcription Factor 4 (ATF4). On the contrary, during conditions of prolonged ER stress, pro-adaptive responses fail and apoptotic cell death ensues. Interestingly, similar to the activity of the mitochondria, the ER may also directly activate the apoptotic pathway through ER stress-mediated leakage of calcium into the cytoplasm that leads to the activation of death effectors. Apoptotic cell death also ensues by ATF4-CHOP- mediated induction of several pro-apoptotic genes and suppression of the synthesis of anti-apoptotic Bcl-2 proteins. Advancing molecular insight into the transition of tumor cells from adaptation to apoptosis under hypoxia-induced ER stress may provide answers on how to overcome the limitations of current anti-tumor therapies. Targeting components of the UPR pathways may provide more effective elimination of tumor cells and as a result, contribute to the development of more promising anti-tumor therapeutic agents. PMID:27211800

  4. The Role of the PERK/eIF2α/ATF4/CHOP Signaling Pathway in Tumor Progression During Endoplasmic Reticulum Stress.

    Science.gov (United States)

    Rozpedek, W; Pytel, D; Mucha, B; Leszczynska, H; Diehl, J A; Majsterek, I

    2016-01-01

    Hypoxia is a major hallmark of the tumor microenvironment that is strictly associated with rapid cancer progression and induction of metastasis. Hypoxia inhibits disulfide bond formation and impairs protein folding in the Endoplasmic Reticulum (ER). The stress in the ER induces the activation of Unfolded Protein Response (UPR) pathways via the induction of protein kinase RNA-like endoplasmic reticulum kinase (PERK). As a result, the level of phosphorylated Eukaryotic Initiation Factor 2 alpha (eIF2α) is markedly elevated, resulting in the promotion of a pro-adaptive signaling pathway by the inhibition of global protein synthesis and selective translation of Activating Transcription Factor 4 (ATF4). On the contrary, during conditions of prolonged ER stress, pro-adaptive responses fail and apoptotic cell death ensues. Interestingly, similar to the activity of the mitochondria, the ER may also directly activate the apoptotic pathway through ER stress-mediated leakage of calcium into the cytoplasm that leads to the activation of death effectors. Apoptotic cell death also ensues by ATF4-CHOP- mediated induction of several pro-apoptotic genes and suppression of the synthesis of anti-apoptotic Bcl-2 proteins. Advancing molecular insight into the transition of tumor cells from adaptation to apoptosis under hypoxia-induced ER stress may provide answers on how to overcome the limitations of current anti-tumor therapies. Targeting components of the UPR pathways may provide more effective elimination of tumor cells and as a result, contribute to the development of more promising anti-tumor therapeutic agents.

  5. Sinulariolide Induced Hepatocellular Carcinoma Apoptosis through Activation of Mitochondrial-Related Apoptotic and PERK/eIF2α/ATF4/CHOP Pathway

    Directory of Open Access Journals (Sweden)

    Yu-Jen Wu

    2013-08-01

    Full Text Available Sinulariolide, an active compound isolated from the cultured soft coral Sinularia flexibilis, has potent anti-microbial and anti-tumorigenesis effects towards melanoma and bladder cancer cells. In this study, we investigated the effects of sinulariolide on hepatocellular carcinoma (HCC cell growth and protein expression. Sinulariolide suppressed the proliferation and colony formation of HCC HA22T cells in a dose-dependent manner and induced both early and late apoptosis according to flow cytometry, Annexin V/PI stain and TUNEL/DAPI stain analyses. A mechanistic analysis demonstrated that sinulariolide-induced apoptosis was activated through a mitochondria-related pathway, showing up-regulation of Bax, Bad and AIF, and down- regulation of Bcl-2, Bcl-xL, MCl-1 and p-Bad. Sinulariolide treatment led to loss of the mitochondrial membrane potential, release of mitochondrial cytochrome c to the cytosol, and activation of both caspase-9 and caspase-3. Sinulariolide-induced apoptosis was significantly blocked by the caspase inhibitors Z-VAD-FMK and Z-DEVD-FMK. The increased expression of cleaved PARP also suggested that caspase-independent apoptotic pathway was involved. In the western blotting; the elevation of ER chaperones GRP78; GRP94; and CALR; as well as up-regulations of PERK/eIF2α/ATF4/CHOP; and diminished cell death with pre-treatment of eIF2α phosphatase inhibitor; salubrinal; implicated the involvement of ER stress-mediated PERK/eIF2α/ATF4/CHOP apoptotic pathway following sinulariolide treatment in hepatoma cells. The current study suggested sinulariolide-induced hepatoma cell cytotoxicity involved multiple apoptotic signal pathways. This may implicate that sinulariolide is a potential compound for the treatment of hepatocellular carcinoma.

  6. SB203580 Modulates p38 MAPK Signaling and Dengue Virus-Induced Liver Injury by Reducing MAPKAPK2, HSP27, and ATF2 Phosphorylation.

    Directory of Open Access Journals (Sweden)

    Gopinathan Pillai Sreekanth

    Full Text Available Dengue virus (DENV infection causes organ injuries, and the liver is one of the most important sites of DENV infection, where viral replication generates a high viral load. The molecular mechanism of DENV-induced liver injury is still under investigation. The mitogen activated protein kinases (MAPKs, including p38 MAPK, have roles in the hepatic cell apoptosis induced by DENV. However, the in vivo role of p38 MAPK in DENV-induced liver injury is not fully understood. In this study, we investigated the role of SB203580, a p38 MAPK inhibitor, in a mouse model of DENV infection. Both the hematological parameters, leucopenia and thrombocytopenia, were improved by SB203580 treatment and liver transaminases and histopathology were also improved. We used a real-time PCR microarray to profile the expression of apoptosis-related genes. Tumor necrosis factor α, caspase 9, caspase 8, and caspase 3 proteins were significantly lower in the SB203580-treated DENV-infected mice than that in the infected control mice. Increased expressions of cytokines including TNF-α, IL-6 and IL-10, and chemokines including RANTES and IP-10 in DENV infection were reduced by SB203580 treatment. DENV infection induced the phosphorylation of p38MAPK, and its downstream signals including MAPKAPK2, HSP27 and ATF-2. SB203580 treatment did not decrease the phosphorylation of p38 MAPK, but it significantly reduced the phosphorylation of MAPKAPK2, HSP27, and ATF2. Therefore, SB203580 modulates the downstream signals to p38 MAPK and reduces DENV-induced liver injury.

  7. THAP and ATF-2 regulated sterol carrier protein-2 promoter activities in the larval midgut of the yellow fever mosquito, Aedes aegypti.

    Science.gov (United States)

    Peng, Rong; Fu, Qiang; Hong, Huazhu; Schwaegler, Tyler; Lan, Que

    2012-01-01

    Expression of sterol carrier protein-2 (SCP-2) in Aedes aegypti shows a distinct temporal/spatial pattern throughout the life cycle. In order to identify the transcription factors responsible for the larval temporal/spatial regulation of AeSCP-2 transcription, AeSCP-2 promoter activities were studied in vivo via transient transfection of promoter/reporter gene assays. Regulatory sequences upstream -1.3 kb of the transcription start site of AeSCP-2 were found to be critical for the in vivo temporal/spatial promoter activity. Interestingly, the -1.6 kb promoter sequence efficiently drove the larval midgut-specific siRNA expression, indicating that the -1.6 kb upstream sequence is sufficient for temporal/spatial AeSCP-2 transcriptional activity. Four transcription factors were identified in the midgut nuclear extract from feeding larvae via labeled -1.6/-1.3 kb DNA probe pull-down and proteomic analysis. Co-transfection of the promoter/reporter gene with inducible siRNA expression of each transcription factor was performed to confirm the regulatory function of individual transcription factor on AeSCP-2 transcriptional activities in the larval midgut. The results indicate that two of the identified transcription factors, Thanatos-associated protein (THAP) and activating transcription factor-2 (ATF-2), antagonistically control AeSCP-2 transcriptional activity in the midgut of feeding larvae via the regulatory sequences between -1.6 to -1.3 kb 5' upstream of the transcription start site. In vivo expression knockdown of THAP and ATF-2 resulted in significant changes in developmental progression, which may be partially due to their effects on AeSCP-2 expression. PMID:23056538

  8. THAP and ATF-2 regulated sterol carrier protein-2 promoter activities in the larval midgut of the yellow fever mosquito, Aedes aegypti.

    Directory of Open Access Journals (Sweden)

    Rong Peng

    Full Text Available Expression of sterol carrier protein-2 (SCP-2 in Aedes aegypti shows a distinct temporal/spatial pattern throughout the life cycle. In order to identify the transcription factors responsible for the larval temporal/spatial regulation of AeSCP-2 transcription, AeSCP-2 promoter activities were studied in vivo via transient transfection of promoter/reporter gene assays. Regulatory sequences upstream -1.3 kb of the transcription start site of AeSCP-2 were found to be critical for the in vivo temporal/spatial promoter activity. Interestingly, the -1.6 kb promoter sequence efficiently drove the larval midgut-specific siRNA expression, indicating that the -1.6 kb upstream sequence is sufficient for temporal/spatial AeSCP-2 transcriptional activity. Four transcription factors were identified in the midgut nuclear extract from feeding larvae via labeled -1.6/-1.3 kb DNA probe pull-down and proteomic analysis. Co-transfection of the promoter/reporter gene with inducible siRNA expression of each transcription factor was performed to confirm the regulatory function of individual transcription factor on AeSCP-2 transcriptional activities in the larval midgut. The results indicate that two of the identified transcription factors, Thanatos-associated protein (THAP and activating transcription factor-2 (ATF-2, antagonistically control AeSCP-2 transcriptional activity in the midgut of feeding larvae via the regulatory sequences between -1.6 to -1.3 kb 5' upstream of the transcription start site. In vivo expression knockdown of THAP and ATF-2 resulted in significant changes in developmental progression, which may be partially due to their effects on AeSCP-2 expression.

  9. Afatinib down-regulates MCL-1 expression through the PERK-eIF2α-ATF4 axis and leads to apoptosis in head and neck squamous cell carcinoma.

    Science.gov (United States)

    Liu, Xianfang; Lv, Zhenghua; Zou, Jidong; Liu, Xiuxiu; Ma, Juke; Wang, Jinhua; Sa, Na; Jing, Peihang; Xu, Wei

    2016-01-01

    Afatinib is the second generation of irreversible inhibitor of EGFR, HER2 and HER4, which has shown encouraging phase II and III clinical outcomes in the treatment of head and neck squamous cell carcinoma (HNSCC). However, the molecular mechanism of afatinib-induced apoptosis in HNSCC is poorly understood. In the present investigation, we discovered that down-regulation of MCL-1, an anti-apoptotic member of BCL-2 family, was responsible for afatinib-triggered apoptosis. And the inactivation of AKT-mTOR signaling caused by afatinib lead to translational inhibition of MCL-1 expression. As a crucial branch of ER stress, PERK-eIF2α-ATF4 axis was also stimulated in HNSCC cells after afatinib incubation. Silencing either eIF2α or ATF4 by siRNA transfection relieved afatinib-caused suppression of AKT-mTOR activity, attenuating MCL-1 down-regulation as well as subsequent apoptosis. Collectively, the results show that afatinib hampers AKT-mTOR activation by stimulating PERK-eIF2α-ATF4 signaling pathway, giving rise to MCL-1 down-regulation mediated apoptosis in HNSCC cells. Therefore, our findings reveal the elaborate molecular network of afatinib-induced apoptosis in HNSCC, which would provide substantial theoretical underpinnings for afatinib clinical application and highlight its promising prospect in HNSCC treatment. PMID:27648360

  10. Myxoma virus attenuates expression of activating transcription factor 4 (ATF4 which has implications for the treatment of proteasome inhibitor–resistant multiple myeloma

    Directory of Open Access Journals (Sweden)

    Dunlap KM

    2015-01-01

    Full Text Available Katherine M Dunlap, Mee Y Bartee, Eric Bartee Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA Abstract: The recent development of chemotherapeutic proteasome inhibitors, such as bortezomib, has improved the outcomes of patients suffering from the plasma cell malignancy multiple myeloma. Unfortunately, many patients treated with these drugs still suffer relapsing disease due to treatment-induced upregulation of the antiapoptotic protein Mcl1. We have recently demonstrated that an oncolytic poxvirus, known as myxoma, can rapidly eliminate primary myeloma cells by inducing cellular apoptosis. The efficacy of myxoma treatment on proteasome inhibitor–relapsed or –refractory myeloma, however, remains unknown. We now demonstrate that myxoma-based elimination of myeloma is not affected by cellular resistance to proteasome inhibitors. Additionally, myxoma virus infection specifically prevents expression of Mcl1 following induction of the unfolded protein response, by blocking translation of the unfolded protein response activating transcription factor (ATF4. These results suggest that myxoma-based oncolytic therapy represents an attractive option for myeloma patients whose disease is refractory to chemotherapeutic proteasome inhibitors due to upregulation of Mcl1. Keywords: drug resistance, oncolytic

  11. NEAMS-ATF M3 Milestone Report: Literature Review of Modeling of Radiation-Induced Swelling in Fe-Cr-Al Steels

    Energy Technology Data Exchange (ETDEWEB)

    Bai, Xianming [Idaho National Lab. (INL), Idaho Falls, ID (United States). Fuel Modeling and Simulation Dept.; Biner, Suleyman Bulent [Idaho National Lab. (INL), Idaho Falls, ID (United States). Fuel Modeling and Simulation Dept.; Jiang, Chao [Idaho National Lab. (INL), Idaho Falls, ID (United States). Fuel Modeling and Simulation Dept.

    2015-12-01

    Fe-Cr-Al steels are proposed as accident-tolerant-fuel (ATF) cladding materials in light water reactors due to their excellent oxidation resistance at high temperatures. Currently, the understanding of their performance in reactor environment is still limited. In this review, firstly we reviewed the experimental studies of Fe-Cr-Al based alloys with particular focus on the radiation effects in these alloys. Although limited data are available in literature, several previous and recent experimental studies have shown that Fe-Cr-Al based alloys have very good void swelling resistance at low and moderate irradiation doses but the growth of dislocation loops is very active. Overall, the behavior of radiation damage evolution is similar to that in Fe-Cr ferritic/martensitic alloys. Secondly, we reviewed the rate theory-based modeling methods for modeling the coevolution of voids and dislocation loops in materials under irradiation such as Frenkel pair three-dimensional diffusion model (FP3DM) and cluster dynamics. Finally, we summarized and discussed our review and proposed our future plans for modeling radiation damage in Fe-Cr-Al based alloys.

  12. Translational and posttranslational regulation of XIAP by eIF2α and ATF4 promotes ER stress-induced cell death during the unfolded protein response.

    Science.gov (United States)

    Hiramatsu, Nobuhiko; Messah, Carissa; Han, Jaeseok; LaVail, Matthew M; Kaufman, Randal J; Lin, Jonathan H

    2014-05-01

    Endoplasmic reticulum (ER) protein misfolding activates the unfolded protein response (UPR) to help cells cope with ER stress. If ER homeostasis is not restored, UPR promotes cell death. The mechanisms of UPR-mediated cell death are poorly understood. The PKR-like endoplasmic reticulum kinase (PERK) arm of the UPR is implicated in ER stress-induced cell death, in part through up-regulation of proapoptotic CCAAT/enhancer binding protein homologous protein (CHOP). Chop((-)/(-)) cells are partially resistant to ER stress-induced cell death, and CHOP overexpression alone does not induce cell death. These findings suggest that additional mechanisms regulate cell death downstream of PERK. Here we find dramatic suppression of antiapoptosis XIAP proteins in response to chronic ER stress. We find that PERK down-regulates XIAP synthesis through eIF2α and promotes XIAP degradation through ATF4. Of interest, PERK's down-regulation of XIAP occurs independently of CHOP activity. Loss of XIAP leads to increased cell death, whereas XIAP overexpression significantly enhances resistance to ER stress-induced cell death, even in the absence of CHOP. Our findings define a novel signaling circuit between PERK and XIAP that operates in parallel with PERK to CHOP induction to influence cell survival during ER stress. We propose a "two-hit" model of ER stress-induced cell death involving concomitant CHOP up-regulation and XIAP down-regulation both induced by PERK.

  13. The ATF/CREB site is the key element for transcription of the human RNA methyltransferase like 1 (RNMTL1) gene, a newly discovered 17p13.3 gene

    Institute of Scientific and Technical Information of China (English)

    JIAN; XU; JING; DE; ZHU; MIN; NI; DA; FANG; WAN; JIAN; REN; GU

    2002-01-01

    The human RNA methyltransferase like i gene (RNMTL1) is one of thirteen newly discovered geneswithin a 116 Kb segment of the chromosome 17p13.3 that suffers from a high frequent loss of heterozygosityin human hepatocellular carcinoma in China[1-5]. To understand the molecular mechanisms underlyingtranscription control of the RNMTL1 gene in human cancers, we decline using of the conventional approachwhere the cis-elements bound by the known transcription factors are primary targets, and carried out thesystematic analyses to dissect the promoter structure and identify/characterize the key cis-elements thatare responsible for its strong expression in cell. The molecular approaches applied included 1, the primerextension for mapping of the transcription starts; 2, the transient transfection/reporter assays on a largenumber of deletion and site-specific mutants of the promoter segment for defining the minimal promoterand the crucial elements within; and 3, the electrophoresis mobility shift assay with specific antibodies forreconfirming the nature of the transcription factors and their cognate cis-elements. We have shown that theinteraction of an ATF/CREB element (-38 to -31) and its cognate transcription factors play a predominantrole in the promoter activity of the RNMTL1 gene. The secondary DNA structures of the ATF/CREBelement play a more vital role in the protein-DNA interaction. Finally, we reported a novel mechanismunderlying the YY1 mediated transcription repression, namely, the ATF/CREB dependent transcription-repression by YY1 is executed in absence of its own sequence-specific binding.

  14. INHIBITION OF ERN1 SIGNALING ENZYME AFFECTS HYPOXIC REGULATION OF THE EXPRESSION OF E2F8, EPAS1, HOXC6, ATF3, TBX3 AND FOXF1 GENES IN U87 GLIOMA CELLS.

    Science.gov (United States)

    Minchenko, O H; Tsymbal, D O; Minchenko, D O; Kovalevska, O V; Karbovskyi, L L; Bikfalvi, A

    2015-01-01

    Hypoxia as well as the endoplasmic reticulum stress are important factors of malignant tumor growth and control of the expression of genes, which regulate numerous metabolic processes and cell proliferation. Furthermore, blockade of ERN1 (endoplasmic reticulum to nucleus 1) suppresses cell proliferation and tumor growth. We studied the effect of hypoxia on the expression of genes encoding the transcription factors such as E2F8 (E2F transcription factor 8), EPAS1 (endothelial PAS domain protein 1), TBX3 (T-box 3), ATF3 (activating transcription factor 3), FOXF1 (forkhead box F), and HOXC6 (homeobox C6) in U87 glioma cells with and without ERN1 signaling enzyme function. We have established that hypoxia enhances the expression of HOXC6, E2F8, ATF3, and EPAS1 genes but does not change TBX3 and FOXF1 gene expression in glioma cells with ERNI function. At the same time, the expression level of all studied genes is strongly decreased, except for TBX3 gene, in glioma cells without ERN1 function. Moreover, the inhibition of ERN1 signaling enzyme function significantly modifies the effect of hypoxia on the expression of these transcription factor genes. removes or introduces this regulation as well as changes a direction or magnitude of hypoxic regulation. Present study demonstrates that fine-tuning of the expression of proliferation related genes depends upon hypoxia and ERN1-mediated endoplasmic reticulum stress signaling and correlates with slower proliferation rate of glioma cells without ERN1 function. PMID:26255341

  15. 异相睡眠剥夺对大鼠脑内质网应激相关蛋白ATF4表达的影响%Effects of rapid eye movement sleep deprivation on expression of activating transcription factor 4 in rat brain

    Institute of Scientific and Technical Information of China (English)

    江波; 赵忠新

    2008-01-01

    目的 研究异相睡眠(REM 睡眠)剥夺对大鼠海马及额叶内质网应激相关蛋白转录活化因子4(ATF4)表达的影响.方法 大鼠采用完全随机数字表法分为6组:空白对照组(CC组)、环境对照组(TC)、睡眠剥夺(SD)6h、12 h、1 d、3 d组,每组10只.采用改良多平台睡眠剥夺法建立REM 睡眠剥夺大鼠模型,免疫组织化学及Westemblot方法测定不同时间点大鼠额叶及海马ATF4蛋白的表达.结果 CC组大鼠海鸟及额叶均未检测出ATF4.TC组海马、额叶均有ATF4表达,SD组海马、额叶6 h时开始表达ATF4,12 h后达到高峰,1 d、3 d呈逐渐下降趋势.结论 REM睡眠剥夺可诱发内质网应激,睡眠剥夺后大鼠海马与额叶发生内质网应激的时间及发展趋势基本相同.%Objective To investigate the expression of endoplasmic reticulum stress-related protein activating transcription factor 4 (ATF4, also known as CAMP-response element protein 2) in rat brain after rapid eye movement (REM) sleep deprivation. Methods Using a modified multiple platform method, REM sleep deprivation for different time lengths was induced in 4 groups of rats (n=10, for 6, 12, 24, and 72 h, respectively), with 10 normal rats as the cage control and another 10 as the tank control groups. Immunohistochemistry and Western blotting were performed to detect ATF4 protein expression in the hippocampus and frontal lobe of the rats. Results No ATF4 was detected in the cage control group. ATF4 expression was detected in the brain tissues of the rats in the tank control group, and the expression peaked after REM sleep deprivation for 12 h, followed by gradual declination as the sleep deprivation was prolonged to 24 and 72 h. Conclusion REM sleep deprivation can induce endoplasmic reticulum stress. The timing of endoplasmic reticulum stress onset and the course of its development following sleep deprivation are almost identical in the frontal lobe and hippocampus of rats.

  16. Bee Venom Accelerates Wound Healing in Diabetic Mice by Suppressing Activating Transcription Factor-3 (ATF-3) and Inducible Nitric Oxide Synthase (iNOS)-Mediated Oxidative Stress and Recruiting Bone Marrow-Derived Endothelial Progenitor Cells.

    Science.gov (United States)

    Badr, Gamal; Hozzein, Wael N; Badr, Badr M; Al Ghamdi, Ahmad; Saad Eldien, Heba M; Garraud, Olivier

    2016-10-01

    Multiple mechanisms contribute to impaired diabetic wound healing including impaired neovascularization and deficient endothelial progenitor cell (EPC) recruitment. Bee venom (BV) has been used as an anti-inflammatory agent for the treatment of several diseases. Nevertheless, the effect of BV on the healing of diabetic wounds has not been studied. Therefore, in this study, we investigated the impact of BV on diabetic wound closure in a type I diabetic mouse model. Three experimental groups were used: group 1, non-diabetic control mice; group 2, diabetic mice; and group 3, diabetic mice treated with BV. We found that the diabetic mice exhibited delayed wound closure characterized by a significant decrease in collagen production and prolonged elevation of inflammatory cytokines levels in wounded tissue compared to control non-diabetic mice. Additionally, wounded tissue in diabetic mice revealed aberrantly up-regulated expression of ATF-3 and iNOS followed by a marked elevation in free radical levels. Impaired diabetic wound healing was also characterized by a significant elevation in caspase-3, -8, and -9 activity and a marked reduction in the expression of TGF-β and VEGF, which led to decreased neovascularization and angiogenesis of the injured tissue by impairing EPC mobilization. Interestingly, BV treatment significantly enhanced wound closure in diabetic mice by increasing collagen production and restoring the levels of inflammatory cytokines, free radical, TGF-β, and VEGF. Most importantly, BV-treated diabetic mice exhibited mobilized long-lived EPCs by inhibiting caspase activity in the wounded tissue. Our findings reveal the molecular mechanisms underlying improved diabetic wound healing and closure following BV treatment. J. Cell. Physiol. 231: 2159-2171, 2016. © 2016 Wiley Periodicals, Inc. PMID:26825453

  17. ATF Neutron Irradiation Program Technical Plan

    Energy Technology Data Exchange (ETDEWEB)

    Geringer, J. W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Materials Science and Technology Division; Katoh, Yutai [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Materials Science and Technology Division

    2016-03-01

    The Japan Atomic Energy Agency (JAEA) under the Civil Nuclear Energy Working Group (CNWG) is engaged in a cooperative research effort with the U.S. Department of Energy (DOE) to explore issues related to nuclear energy, including research on accident-tolerant fuels and materials for use in light water reactors. This work develops a draft technical plan for a neutron irradiation program on the candidate accident-tolerant fuel cladding materials and elements using the High Flux Isotope Reactor (HFIR). The research program requires the design of a detailed experiment, development of test vehicles, irradiation of test specimens, possible post irradiation examination and characterization of irradiated materials and the shipment of irradiated materials to JAEA in Japan. This report discusses the technical plan of the experimental study.

  18. Mechanism of the induction of endoplasmic reticulum stress by the anti-cancer agent, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT): Activation of PERK/eIF2α, IRE1α, ATF6 and calmodulin kinase.

    Science.gov (United States)

    Merlot, Angelica M; Shafie, Nurul H; Yu, Yu; Richardson, Vera; Jansson, Patric J; Sahni, Sumit; Lane, Darius J R; Kovacevic, Zaklina; Kalinowski, Danuta S; Richardson, Des R

    2016-06-01

    The endoplasmic reticulum (ER) plays a major role in the synthesis, maturation and folding of proteins and is a critical calcium (Ca(2+)) reservoir. Cellular stresses lead to an overwhelming accumulation of misfolded proteins in the ER, leading to ER stress and the activation of the unfolded protein response (UPR). In the stressful tumor microenvironment, the UPR maintains ER homeostasis and enables tumor survival. Thus, a novel strategy for cancer therapeutics is to overcome chronically activated ER stress by triggering pro-apoptotic pathways of the UPR. Considering this, the mechanisms by which the novel anti-cancer agent, Dp44mT, can target the ER stress response pathways were investigated in multiple cell-types. Our results demonstrate that the cytotoxic chelator, Dp44mT, which forms redox-active metal complexes, significantly: (1) increased ER stress-associated pro-apoptotic signaling molecules (i.e., p-eIF2α, ATF4, CHOP); (2) increased IRE1α phosphorylation (p-IRE1α) and XBP1 mRNA splicing; (3) reduced expression of ER stress-associated cell survival signaling molecules (e.g., XBP1s and p58(IPK)); (4) increased cleavage of the transcription factor, ATF6, which enhances expression of its downstream targets (i.e., CHOP and BiP); and (5) increased phosphorylation of CaMKII that induces apoptosis. In contrast to Dp44mT, the iron chelator, DFO, which forms redox-inactive iron complexes, did not affect BiP, p-IRE1α, XBP1 or p58(IPK) levels. This study highlights the ability of a novel cancer therapeutic (i.e., Dp44mT) to target the pro-apoptotic functions of the UPR via cellular metal sequestration and redox stress. Assessment of ER stress-mediated apoptosis is fundamental to the understanding of the pharmacology of chelation for cancer treatment. PMID:27059255

  19. Mechanism of the induction of endoplasmic reticulum stress by the anti-cancer agent, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT): Activation of PERK/eIF2α, IRE1α, ATF6 and calmodulin kinase.

    Science.gov (United States)

    Merlot, Angelica M; Shafie, Nurul H; Yu, Yu; Richardson, Vera; Jansson, Patric J; Sahni, Sumit; Lane, Darius J R; Kovacevic, Zaklina; Kalinowski, Danuta S; Richardson, Des R

    2016-06-01

    The endoplasmic reticulum (ER) plays a major role in the synthesis, maturation and folding of proteins and is a critical calcium (Ca(2+)) reservoir. Cellular stresses lead to an overwhelming accumulation of misfolded proteins in the ER, leading to ER stress and the activation of the unfolded protein response (UPR). In the stressful tumor microenvironment, the UPR maintains ER homeostasis and enables tumor survival. Thus, a novel strategy for cancer therapeutics is to overcome chronically activated ER stress by triggering pro-apoptotic pathways of the UPR. Considering this, the mechanisms by which the novel anti-cancer agent, Dp44mT, can target the ER stress response pathways were investigated in multiple cell-types. Our results demonstrate that the cytotoxic chelator, Dp44mT, which forms redox-active metal complexes, significantly: (1) increased ER stress-associated pro-apoptotic signaling molecules (i.e., p-eIF2α, ATF4, CHOP); (2) increased IRE1α phosphorylation (p-IRE1α) and XBP1 mRNA splicing; (3) reduced expression of ER stress-associated cell survival signaling molecules (e.g., XBP1s and p58(IPK)); (4) increased cleavage of the transcription factor, ATF6, which enhances expression of its downstream targets (i.e., CHOP and BiP); and (5) increased phosphorylation of CaMKII that induces apoptosis. In contrast to Dp44mT, the iron chelator, DFO, which forms redox-inactive iron complexes, did not affect BiP, p-IRE1α, XBP1 or p58(IPK) levels. This study highlights the ability of a novel cancer therapeutic (i.e., Dp44mT) to target the pro-apoptotic functions of the UPR via cellular metal sequestration and redox stress. Assessment of ER stress-mediated apoptosis is fundamental to the understanding of the pharmacology of chelation for cancer treatment.

  20. University of Wisconsin torsatron/stellarator laboratory program final report, January 1, 1986--January 31, 1994

    International Nuclear Information System (INIS)

    This document reports work performed in the final period of the referenced grant number, from January 1992 through January 1994. Prior work under this grant number has been reported in previous reports of this series. Measurements of the radial electric field, flow velocity, and momentum decay times were made in the IMS stellarator to examine the effects of in-neutral collisions and viscosity showing the importance of the collision effects. A new neoclassical model including these effects has been developed and applied to this analysis. Fluctuation-induced transport studies have also been performed with a full 2-D poloidal cross-section analysis. Electrode biasing was used to induce rotation into the plasma. The data shows the fluctuation-induced transport to be poloidally asymmetric and dependent upon the location of the electron cyclotron resonance layer and the electrode biasing. The induced plasma ploidal flow changes the nominally outward fluctuation-induced transport to be inward by changing the phase relationship of the density and potential oscillations. The amplitude of the fluctuations is, in general, not reduced by the sheared poloidal flows. Computed Reynolds stress flows are comparable to those measured, but uncertainties in the data and its analysis on this drive mechanism for poloidal flow does not permit the authors to make definitive conclusions

  1. 直连式高空台试验中真空度与次流作用力校准的一种新方法%A New Measurement Method for the Action of the Secondary Flow and Vacuum in Direct-Connect ATF

    Institute of Scientific and Technical Information of China (English)

    刘志友; 吴锋; 仇钎

    2013-01-01

    Regarding the problems of measuring or calibrating both the vacuum-acting force and secondary flow-acting force coefficients with the accustomed method for a specific engine ATF test, through the analy⁃sis of the action on engine thrust measurement system of both air flow for cell-cooling and differential pres⁃sure between outdoor-cell and indoor-cell, a new measurement method is put forward which derived from their action mechanisms and the dependence relation between both acting force and engine gross thrust. Moreover, the new method can be used under lesser restricted condition and less cost in contrast to the rou⁃tine way. So there is certain reference value for engineering application.%  针对某发动机高空台试验难以用加装堵板的常规方法测定真空度与次流作用力系数的情况,通过高空舱内冷却空气流动与高空舱内外压差对发动机测力系统作用的分析,介绍了高空舱内真空度和次流对发动机台架测量推力影响的作用机理,并从真空度作用力和次流作用力与发动机总推力的关系出发,经理论推导提出了一种确定真空度与次流作用力系数的新方法。该方法使用限制条件少,试验经济性好,具有较强的工程应用参考价值。

  2. Optical alignment and diagnostics for the ATF microundulator FEL oscillator

    International Nuclear Information System (INIS)

    The microundulator FEL oscillator has a wiggler period of 8.8 mm, and is designed for initial lasing at 0.5 microns with a 50 MeV electron beam. The design and performance of the optical diagnostics and alignment are discussed. A HeNe coalignment laser is mode-matched to the resonator cavity for transverse alignment. Interference fringes are observed in the cavity with a pellicle, allowing an alignment tolerance of +/- 10 micro-radians. The same pellicle is used to produce transition radiation by the electron beam. This enables precise transverse alignment of the electron beam to the resonator axis. The HeNe laser is also used to align the wiggler by backlighting its bore. This method aligns the wiggler to the optic axis to a tolerance of +/- 50 microns. A frequency-doubled,pulsed Nd:YAG laser that produces the electron bunch train is also mode-matched to the FEL cavity. The cavity length is adjusted to resonate with this pulse train. Light from the FEL is transported to the diagnostic room using two separate paths: one for the single pass spontaneous emission, and the second for the multipass cavity output. Several diagnostics (CCD camera, photodiode, photomultiplier tube, joulemeter, spectrometer, and streak camera) are used to characterize the light. These instruments measure light energy per micropulse ranging from 10 femto-Joules to 10 micro-Joules

  3. Fast ion behavior during neutral beam injection in ATF

    Energy Technology Data Exchange (ETDEWEB)

    Wade, M.R.; Thomas, C.E.; Colchin, R.J.; Rome, J.A.; England, A.C.; Fowler, R.H. [Oak Ridge National Lab., TN (United States); Aceto, S.C. [Rensselaer Polytechnic Inst., Troy, NY (United States)

    1993-09-01

    In stellarators, single-particle confinement properties can be more complex than in their tokamak counterparts. Fast-ion behavior in tokamaks has been well characterized through an abundance of measurements on various devices and in general has been shown to be consistent with classical slowing-down theory, although anomalous ion behavior has been observed during intense beam injection in ISX-B, during fishbone instabilities in PDX, and in experiments on TFR. In contrast, fast ion behavior in stellarators is not as wel established experimentally with the primary experiments to date focusing o near-perpendicular or perpendicular neutral beam injection (NBI) on the Wendelstein 7-A stellarator (91 and Heliotron-E. This paper addresses fast-ion confinement properties in a large-aspect-ratio, moderate-shear stellarator, the Advanced Toroidal Facility, during tangential NBI. The primary data used in this study are the experimentally measured energy spectra of charge-exchange neutrals escaping from the plasma, using a two-dimensional scanning neutral particle analyzer. This diagnostic method is well established, having been used on several devices since the early 1970`s. Various aspects of fast-ion behavior are investigated by comparing these data with computed theoretical spectra based on energeticion distributions derived from the fastion Fokker-Planck equation. Ion orbits are studied by computer orbit following, by the computation of J* surfaces, and by Monte Carlo calculations.

  4. Design of a Nanometer Beam Size Monitor for ATF2

    CERN Document Server

    Suehara, Taikan; Yamanaka, Takashi; Yoda, Hakutaro; Nakamura, Tomoya; Kamiya, Yoshio; Honda, Yosuke; Kume, Tatsuya; Tauchi, Toshiaki; Sanuki, Tomoyuki; Komamiya, Sachio

    2008-01-01

    We developed an electron beam size monitor for extremely small beam sizes. It uses a laser interference fringe for a scattering target with the electron beam. Our target performance is < 2 nm systematic error for 37 nm beam size and < 10% statistical error in a measurement using 90 electron bunches for 25 - 6000 nm beam size. A precise laser interference fringe control system using an active feedback function is incorporated to the monitor to achieve the target performance. We describe an overall design, implementations, and performance estimations of the monitor.

  5. Staged electron laser accelerator (STELLA) experiment at brookhaven ATF

    Energy Technology Data Exchange (ETDEWEB)

    Pogorelsky, I.V.; Steenbergen, A. van; Gallardo, J.C. [Brookhaven National Lab., Upton, NY (United States)] [and others

    1998-03-01

    The STELLA experiment is being prepared at the BNL Accelerator Test Facility (STF). The goal of the experiment is to demonstrate quasi-monochromatic inverse Cherenkov acceleration (ICA) of electrons bunched to the laser wavelength period. Microbunches on the order of 2 {mu}m in length separated by 10.6 {mu}m will be produced using an inverse free electron laser (IFEL) accelerator driven by a CO{sub 2} laser. The design and simulations for two phases of this experiment including demonstration of 10 MeV and 100 MeV acceleration are presented. (author)

  6. EWSR1-ATF1 chimeric transcript in a myoepithelial tumor of soft tissue : a case report

    NARCIS (Netherlands)

    Flucke, Uta; Mentzel, Thomas; Verdijk, Marian A.; Slootweg, Pieter J.; Creytens, David H.; Suurmeijer, Albert J. H.; Tops, Bastiaan B. J.

    2012-01-01

    Soft tissue myoepithelial tumors, a recently defined entity, include benign and malignant lesions showing a considerable morphological and immunohistochemical heterogeneity. EWSR1 rearrangements are well recognized in this tumor type, and some of the partner genes have been identified. Herein we des

  7. Transverse Laser Beam Shaping in High Brightness Electron Gun at ATF

    CERN Document Server

    Roychowdhury, S

    2005-01-01

    The brightness of electron beams from a photo injector is influenced by the transverse and longitudinal distribution of the laser beam illuminating the cathode. Previous studies at Brookhaven Accelerator Test Facility have shown that formation of an ideal e-beam with lowest transverse emittance requires uniform circular distribution of the emitted electrons. The use of the uniformly distributed power of the laser beam may not lead to that of the emitted electrons because of the non-uniform quantum efficiency. A proper shaping of the laser beam can compensate for this non-uniformity. In this paper we describe the use of digital light processing (DLP) technique based on digital mirror device (DMD) for spatial modulation of the laser beam, for measurements of the quantum efficiency map, and for creating the desirable e-beam density profiles. A DMD is aμelectronic mechanical system (MEMS) comprising of millions of highly reflectiveμmirrors controlled by underlying electronics. We present exper...

  8. Mutations in the unfolded protein response regulator ATF6 cause the cone dysfunction disorder achromatopsia

    NARCIS (Netherlands)

    Kohl, S.; Zobor, D.; Chiang, W.C.; Weisschuh, N.; Staller, J.; Menendez, I.G.; Chang, S.; Beck, S.C.; Garrido, M. Garcia; Sothilingam, V.; Seeliger, M.W.; Stanzial, F.; Benedicenti, F.; Inzana, F.; Heon, E; Vincent, A.; Beis, J.; Strom, T.M.; Rudolph, G.; Roosing, S.; Hollander, A.I. den; Cremers, F.P.M.; Lopez, I.; Ren, H.; Moore, A.T.; Webster, A.R.; Michaelides, M.; Koenekoop, R.K.; Zrenner, E.; Kaufman, R.J.; Tsang, S.H.; Wissinger, B.; Lin, J.H.

    2015-01-01

    Achromatopsia (ACHM) is an autosomal recessive disorder characterized by color blindness, photophobia, nystagmus and severely reduced visual acuity. Using homozygosity mapping and whole-exome and candidate gene sequencing, we identified ten families carrying six homozygous and two compound-heterozyg

  9. Elastic Modulus Measurement of ORNL ATF FeCrAl Alloys

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, Zachary T. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Terrani, Kurt A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Yamamoto, Yukinori [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-10-01

    Elastic modulus and Poisson’s ratio for a number of wrought FeCrAl alloys, intended for accident tolerant fuel cladding application, are determined via resonant ultrasonic spectroscopy. The results are reported as a function of temperature from room temperature to 850°C. The wrought alloys were in the fully annealed and unirradiated state. The elastic modulus for the wrought FeCrAl alloys is at least twice that of Zr-based alloys over the temperature range of this study. The Poisson’s ratio of the alloys was 0.28 on average and increased very slightly with increasing temperature.

  10. ORMDL3 is an inducible lung epithelial gene regulating metalloproteases, chemokines, OAS, and ATF6

    OpenAIRE

    Miller, Marina; Tam, Arvin B.; Cho, Jae Youn; Doherty, Taylor A.; Pham, Alexa; Khorram, Naseem; Rosenthal, Peter; Mueller, James L.; Hoffman, Hal M.; Suzukawa, Maho; Niwa, Maho; Broide, David H.

    2012-01-01

    Orosomucoid like 3 (ORMDL3) has been strongly linked with asthma in genetic association studies, but its function in asthma is unknown. We demonstrate that in mice ORMDL3 is an allergen and cytokine (IL-4 or IL-13) inducible endoplasmic reticulum (ER) gene expressed predominantly in airway epithelial cells. Allergen challenge induces a 127-fold increase in ORMDL3 mRNA in bronchial epithelium in WT mice, with lesser 15-fold increases in ORMDL-2 and no changes in ORMDL-1. Studies of STAT-6–defi...

  11. EWSR1-ATF1 chimeric transcript in a myoepithelial tumor of soft tissue: a case report.

    NARCIS (Netherlands)

    Flucke, U.; Mentzel, T.; Verdijk, M.A.J.; Slootweg, P.J.; Creytens, D.H.; Suurmeijer, A.J.H.; Tops, B.B.J.

    2012-01-01

    Soft tissue myoepithelial tumors, a recently defined entity, include benign and malignant lesions showing a considerable morphological and immunohistochemical heterogeneity. EWSR1 rearrangements are well recognized in this tumor type, and some of the partner genes have been identified. Herein we des

  12. Genetherapy with adenovirus expressing ATF-BPTI hybrid protein inhibits proteolysis by rheumatoid synovial fibroblasts

    NARCIS (Netherlands)

    Laan, W.H. van der; Grimbergen, J.M.; Verheijen, J.H.; Pha, Q.

    1998-01-01

    In rheumatoid arthritis (RA), irreversible joint damage is the result of degradation of articular structures such as cartilage, bone and tendons. The plasminogen activator (PA) system has been shown to be involved in the proteolytic degradation of cartilage matrix by rheumatoid synovial fibroblasts

  13. Development of improved ATF engineering alloy - Mechanical testing of Phase 2 alloy

    Energy Technology Data Exchange (ETDEWEB)

    Anderoglu, Osman [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Lovato, Manuel L. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Maloy, Stuart Andrew [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-06-15

    In this report we present the results on the tensile testing of phase 2 FeCrAl alloys (Mo and Nb added for high temperature strength) developed at Oak Ridge National Laboratory. We also compare FeCrAl with MA956 which is an ODS FeCrAl.

  14. Boric Acid Causes ER Stress and Activates the eIF2alpha/ATF4 and ATF6 Branches of the Unfolded Protein Response in Prostate Cancer Cells and Using Toxicology in the Public Interest

    OpenAIRE

    Kobylewski, Sarah Ellen

    2012-01-01

    Nutritional chemoprevention is a growing area in the field of toxicology. What we do and do not eat has a major impact on the development of cancer. However, it is difficult to show a causal relationship between a natural product and cancer prevention because mechanistic biochemical data are often missing and animals studies can be inconclusive. Both determining and elucidating molecular mechanisms that modulate pathological endpoints are necessary components in the risk assessment process...

  15. THE HEAT-SENSITIVE ANALYSIS OF THE atfes1a MUTANT SEEDS IN ARABIDOPSIS THALIANA%拟南芥atfes1a突变体种子的热敏感性分析

    Institute of Scientific and Technical Information of China (English)

    杨颖; 杨传燕; 刘箭

    2010-01-01

    根据基因芯片数据等生物信息学资料,我们锁定一些未知的且被高温诱导的基因,并获得了一个推测编码蛋白含armadillo/beta-catenin repeat(简称ARM)结构域的突变体salk-021784,该突变体缺失AtFes1A基因,该基因编码一种受高温诱导的ARM 蛋白.利用抗体检测了在拟南芥种子发育过程中AtFes1A的热诱导表达特征, 通过表型分析发现,热处理后的突变体种子萌发率明显低于热处理后的野生型,表明AtFes1A蛋白与拟南芥耐热有关.

  16. An ATF/CREB site is the major regulatory element in the human herpesvirus 6 DNA polymerase promoter.

    OpenAIRE

    Agulnick, A D; Thompson, J R; Ricciardi, R P

    1994-01-01

    Human herpesvirus 6 (HHV-6) is a recently described T-cell pathogen whose medical relevance and molecular biology are just beginning to be addressed. As a first look at the regulation of viral genes, control of the HHV-6 DNA polymerase promoter was examined. Polymerase gene transcription in HHV-6-infected cells was found to initiate from a single site located 115 bases upstream of the translation start codon. A polymerase promoter-chloramphenicol acetyltransferase reporter gene construct fail...

  17. Novel Lobophorins Inhibit Oral Cancer Cell Growth and Induce Atf4- and Chop-Dependent Cell Death in Murine Fibroblasts.

    Science.gov (United States)

    Cruz, Patricia G; Fribley, Andrew M; Miller, Justin R; Larsen, Martha J; Schultz, Pamela J; Jacob, Renju T; Tamayo-Castillo, Giselle; Kaufman, Randal J; Sherman, David H

    2015-08-13

    As part of the International Cooperative Biodiversity Groups (ICBG) Program, we were interested in identifying biologically active unfolded protein response (UPR) inducing compounds from marine microorganisms isolated from Costa Rican biota. With this aim in mind we have now generated more than 33,000 unique prefractionated natural product extracts from marine and terrestrial organisms that have been submitted to the Center of Chemical Genomics (CCG) at the University of Michigan for high throughput screening (HTS). An effective complementary cell-based assay to identify novel modulators of UPR signaling was used for screening extracts. Active fractions were iteratively subjected to reverse-phase HPLC chromatographic analysis, and together with lobophorin A, B, E, and F (1-4), three new lobophorin congeners, designated as CR1 (5), CR2 (6), and CR3 (7) were isolated. Herein, we report that secondary assays revealed that the new lobophorins induced UPR-associated gene expression, inhibited oral squamous cell carcinoma cell growth, and led to UPR-dependent cell death in murine embryonic fibroblast (MEF) cells. PMID:26288688

  18. 28 CFR 16.106 - Exemption of the Bureau of Alcohol, Tobacco, Firearms, and Explosives (ATF)-Limited Access.

    Science.gov (United States)

    2010-07-01

    ... subsection (e)(5) would restrict the ability of trained investigators and intelligence analysts to exercise their judgment in reporting on investigations and impede the development of criminal intelligence... physical safety of witnesses and informants. (10) From subsection (e)(5) because in the collection...

  19. Regulatory interplay of Cockayne syndrome B ATPase and stress-response gene ATF3 following genotoxic stress

    DEFF Research Database (Denmark)

    Kristensen, Hans-Ulrik Svejstrup; Epanchintsev, Alexey; Rauschendorf, Marc-Alexander;

    2013-01-01

    Cockayne syndrome type B ATPase (CSB) belongs to the SwItch/Sucrose nonfermentable family. Its mutations are linked to Cockayne syndrome phenotypes and classically are thought to be caused by defects in transcription-coupled repair, a subtype of DNA repair. Here we show that after UV-C irradiatio...

  20. Prostaglandin F2a activates stress response signaling and induces expression of activating transcription factor 3 (ATF3) in bovine large luteal cells

    Science.gov (United States)

    The pulsatile uterine secretion of prostaglandin F2 alpha (PGF) triggers the regression of the corpus luteum (CL). Recent studies have explored global changes in gene expression in response to PGF that may contribute to structural and functional regression of the CL. Activating transcription facto...

  1. The Study of Advanced Accelerator Physics Research at UCLA Using the ATF at BNL: Vacuum Acceleration by Laser of Free Electrons

    Energy Technology Data Exchange (ETDEWEB)

    Cline, David B. [Univ. of California, Los Angeles, CA (United States)

    2016-09-07

    An experiment was designed and data taken to demonstrate that a tightly focused laser on vacuum can accelerate an electron beam in free space. The experiment was proof-of-principle and showed a clear effect for the laser beam off and on. The size of the effect was about 20% and was consistent over 30 laser and beam shots.

  2. Hypoxia stimulates migration of breast cancer cells via the PERK/ATF4/LAMP3-arm of the unfolded protein response

    NARCIS (Netherlands)

    Nagelkerke, A.; Bussink, J.; Mujcic, H.; Wouters, B.G.; Lehmann, S.; Sweep, F.C.; Span, P.N.

    2013-01-01

    ABSTRACT: INTRODUCTION: The hypoxia-inducible factor (HIF)-1 pathway can stimulate tumor cell migration and metastasis. Furthermore, hypoxic tumors are associated with a poor prognosis. Besides the HIF-1 pathway, the unfolded protein response (UPR) is also induced by hypoxic conditions. The PKR-like

  3. Differences in Enzymatic Properties of the Saccharomyces kudriavzevii and Saccharomyces uvarum Alcohol Acetyltransferases and Their Impact on Aroma-Active Compounds Production

    Science.gov (United States)

    Stribny, Jiri; Querol, Amparo; Pérez-Torrado, Roberto

    2016-01-01

    Higher alcohols and acetate esters belong to the most important yeast secondary metabolites that significantly contribute to the overall flavor and aroma profile of fermented products. In Saccharomyces cerevisiae, esterification of higher alcohols is catalyzed mainly by the alcohol acetyltransferases encoded by genes ATF1 and ATF2. Previous investigation has shown other Saccharomyces species, e.g., S. kudriavzevii and S. uvarum, to vary in aroma-active higher alcohols and acetate esters formation when compared to S. cerevisiae. Here, we aimed to analyze the enzymes encoded by the ATF1 and ATF2 genes from S. kudriavzevii (SkATF1, SkATF2) and S. uvarum (SuATF1, SuATF2). The heterologous expression of the individual ATF1 and ATF2 genes in a host S. cerevisiae resulted in the enhanced production of several higher alcohols and acetate esters. Particularly, an increase of 2-phenylethyl acetate production by the strains that harbored ATF1 and ATF2 genes from S. kudriavzevii and S. uvarum was observed. When grown with individual amino acids as the nitrogen source, the strain that harbored SkATF1 showed particularly high 2-phenylethyl acetate production and the strains with introduced SkATF2 or SuATF2 revealed increased production of isobutyl acetate, isoamyl acetate, and 2-phenylethyl acetate compared to the reference strains with endogenous ATF genes. The alcohol acetyltransferase activities of the individual Atf1 and Atf2 enzymes measured in the cell extracts of the S. cerevisiae atf1 atf2 iah1 triple-null strain were detected for all the measured substrates. This indicated that S. kudriavzevii and S. uvarum Atf enzymes had broad range substrate specificity as S. cerevisiae Atf enzymes. Individual Atf1 enzymes exhibited markedly different kinetic properties since SkAtf1p showed c. twofold higher and SuAtf1p c. threefold higher Km for isoamyl alcohol than ScAtf1p. Together these results indicated that the differences found among the three Saccharomyces species during the

  4. Activating Transcription Factor 4 Confers a Multidrug Resistance Phenotype to Gastric Cancer Cells through Transactivation of SIRT1 Expression

    OpenAIRE

    Hongwu Zhu; Limin Xia; Yongguo Zhang; Honghong Wang; Wenjing Xu; Hao Hu; Jing Wang; Jing Xin; Yi Gang; Sumei Sha; Bin Xu; Daiming Fan; Yongzhan Nie; Kaichun Wu

    2012-01-01

    BACKGROUND: Multidrug resistance (MDR) in gastric cancer remains a major challenge to clinical treatment. Activating transcription factor 4 (ATF4) is a stress response gene involved in homeostasis and cellular protection. However, the expression and function of ATF4 in gastric cancer MDR remains unknown. In this study, we investigate whether ATF4 play a role in gastric cancer MDR and its potential mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated that ATF4 overexpression confered th...

  5. Activating transcription factor 3 is a negative regulator of allergic pulmonary inflammation

    OpenAIRE

    Gilchrist, Mark; Henderson, William R.; Clark, April E.; Simmons, Randi M.; Ye, Xin; Smith, Kelly D.; Aderem, Alan

    2008-01-01

    We recently demonstrated the pivotal role of the transcription factor (TF) activating TF 3 (ATF3) in dampening inflammation. We demonstrate that ATF3 also ameliorates allergen-induced airway inflammation and hyperresponsiveness in a mouse model of human asthma. ATF3 expression was increased in the lungs of mice challenged with ovalbumin allergen, and this was associated with its recruitment to the promoters of genes encoding Th2-associated cytokines. ATF3-deficient mice developed significantl...

  6. Alternatives to traditional transportation fuels 1996

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-12-01

    Interest in alternative transportation fuels (ATF`s) has increased in recent years due to the drives for cleaner air and less dependence upon foreign oil. This report, Alternatives to Traditional Transportation Fuels 1996, provides information on ATFs, as well as the vehicles that consume them.

  7. Negative regulation of TLR-signaling pathways by activating transcription factor-3.

    Science.gov (United States)

    Whitmore, Mark M; Iparraguirre, Amaya; Kubelka, Lindsey; Weninger, Wolfgang; Hai, Tsonwin; Williams, Bryan R G

    2007-09-15

    Activating transcription factor-3 (ATF3) is rapidly induced by LPS in mouse macrophages and regulates TLR4 responses. We show that ATF3 is rapidly induced by various TLRs in mouse macrophages and plasmacytoid dendritic cells (DCs), as well as plasmacytoid and myeloid subsets of human DCs. In primary macrophages from mice with a targeted deletion of the atf3 gene (ATF3-knockout (KO)), TLR-stimulated levels of IL-12 and IL-6 were elevated relative to responses in wild-type macrophages. Similarly, targeted deletion of atf3 correlated with enhanced responsiveness of myeloid DCs to TLR activation as measured by IL-12 secretion. Ectopic expression of ATF3 antagonized TLR-stimulated IL-12p40 activation in a reporter assay. In vivo, CpG-oligodeoxynucleotide, a TLR9 agonist, given i.p. to ATF3-KO mice resulted in enhanced cytokine production from splenocytes. Furthermore, while ATF3-KO mice challenged with a sublethal dose of PR8 influenza virus were delayed in body weight recovery in comparison to wild type, the ATF3-KO mice showed higher titers of serum neutralizing Ab against PR8 5 mo postinfection. Thus, ATF3 behaves as a negative regulatory transcription factor in TLR pathways and, accordingly, deficiency in atf3 alters responses to immunological challenges in vivo. ATF3 dysregulation merits further exploration in diseases such as type I diabetes and cancer, where altered innate immunity has been implicated in their pathogenesis.

  8. The p-eIF2α/ATF4 pathway links endoplasmic reticulum stress to autophagy following the production of reactive oxygen species in mouse spermatocyte-derived cells exposed to dibutyl phthalate.

    Science.gov (United States)

    Zhang, Guowei; Ling, Xi; Liu, Kaijun; Wang, Zhi; Zou, Peng; Gao, Jianfang; Cao, Jia; Ao, Lin

    2016-07-01

    Dibutyl phthalate (DBP) is a widely used plasticizer that has been shown to induce germ cell apoptosis-related testicular atrophy and cause reproductive toxicity. Our previous results indicated that endoplasmic reticulum (ER) stress-activated autophagy served as a self-defense mechanism against DBP-induced germ cell apoptosis. However, the specific pathways that link ER stress and autophagy remain unclear. Here, we showed that exposure to DBP enhanced autophagic flux in mouse spermatocyte-derived GC-2 cells and that the eukaryotic translation initiation factor 2/activating transcription factor 4 pathway mediated ER stress-related autophagy independent of the mTOR and Beclin-1 pathways. Moreover, we demonstrated that DBP treatment led to the generation of reactive oxygen species (ROS) and that the inhibition of ROS by melatonin abrogated both ER stress and autophagy. The results indicated that excessive ROS production might be involved in DBP-induced ER stress and autophagy in GC-2 cells. Thus, ROS may serve as upstream mediators of ER stress and autophagy in DBP-treated GC-2 cells. PMID:27002192

  9. Transgenic Mice with Cardiac-Specific Expression of Activating Transcription Factor 3, a Stress-Inducible Gene, Have Conduction Abnormalities and Contractile Dysfunction

    OpenAIRE

    Okamoto, Yoshichika; Chaves, Alysia; Chen, Jingchun; Kelley, Robert; Jones, Keith; Weed, Harrison G.; Gardner, Kevin L.; Gangi, Lisa; Yamaguchi, Mamoru; Klomkleaw, Wuthichai; Nakayama, Tomohiro; HAMLIN, Robert L.; Carnes, Cynthia; Altschuld, Ruth; Bauer, John

    2001-01-01

    Activating transcription factor 3 (ATF3) is a member of the CREB/ATF family of transcription factors. Previously, we demonstrated that the expression of the ATF3 gene is induced by many stress signals. In this report, we demonstrate that expression of ATF3 is induced by cardiac ischemia coupled with reperfusion (ischemia-reperfusion) in both cultured cells and an animal model. Transgenic mice expressing ATF3 under the control of the α-myosin heavy chain promoter have atrial enlargement, and a...

  10. Activating transcription factor-4 promotes mineralization in vascular smooth muscle cells

    Science.gov (United States)

    Masuda, Masashi; Miyazaki-Anzai, Shinobu; Keenan, Audrey L.; Shiozaki, Yuji; Okamura, Kayo; Chick, Wallace S.; Williams, Kristina; Zhao, Xiaoyun; Rahman, Shaikh Mizanoor; Tintut, Yin; Adams, Christopher M.

    2016-01-01

    Emerging evidence indicates that upregulation of the ER stress–induced pro-osteogenic transcription factor ATF4 plays an important role in vascular calcification, a common complication in patients with aging, diabetes, and chronic kidney disease (CKD). In this study, we demonstrated the pathophysiological role of ATF4 in vascular calcification using global Atf4 KO, smooth muscle cell–specific (SMC-specific) Atf4 KO, and transgenic (TG) mouse models. Reduced expression of ATF4 in global ATF4-haplodeficient and SMC-specific Atf4 KO mice reduced medial and atherosclerotic calcification under normal kidney and CKD conditions. In contrast, increased expression of ATF4 in SMC-specific Atf4 TG mice caused severe medial and atherosclerotic calcification. We further demonstrated that ATF4 transcriptionally upregulates the expression of type III sodium-dependent phosphate cotransporters (PiT1 and PiT2) by interacting with C/EBPβ. These results demonstrate that the ER stress effector ATF4 plays a critical role in the pathogenesis of vascular calcification through increased phosphate uptake in vascular SMCs. PMID:27812542

  11. In Vitro Anticancer Activity of Phlorofucofuroeckol A via Upregulation of Activating Transcription Factor 3 against Human Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    Hyun Ji Eo

    2016-03-01

    Full Text Available Phlorofucofuroeckol A (PFF-A, one of the phlorotannins found in brown algae, has been reported to exert anti-cancer property. However, the molecular mechanism for the anti-cancer effect of PFF-A has not been known. Activating transcription factor 3 (ATF3 has been reported to be associated with apoptosis in colorectal cancer. The present study was performed to investigate the molecular mechanism by which PFF-A stimulates ATF3 expression and apoptosis in human colorectal cancer cells. PFF-A decreased cell viability through apoptosis of human colorectal cancer cells. PFF-A increased ATF3 expression through regulating transcriptional activity. The responsible cis-element for ATF3 transcriptional activation by PFF-A was cAMP response element binding protein (CREB, located between positions −147 and −85 of the ATF3 promoter. Inhibition of p38, c-Jun N-terminal kinases (JNK, glycogen synthase kinase (GSK 3β, and IκB kinase (IKK-α blocked PFF-A-mediated ATF3 expression. ATF3 knockdown by ATF3 siRNA attenuated the cleavage of poly (ADP-ribose polymerase (PARP by PFF-A, while ATF3 overexpression increased PFF-A-mediated cleaved PARP. These results suggest that PFF-A may exert anti-cancer property through inducing apoptosis via the ATF3-mediated pathway in human colorectal cancer cells.

  12. Magnetic field of a combined plasma trap

    Science.gov (United States)

    Kotenko, V. G.; Moiseenko, V. E.; Ågren, O.

    2012-06-01

    This paper presents numerical simulations performed on the structure of a magnetic field created by the magnetic system of a combined plasma trap. The magnetic system includes the stellarator-type magnetic system and one of the mirror-type. For the stellarator type magnetic system the numeric model contains a magnetic system of an l=2 torsatron with the coils of an additional toroidal magnetic field. The mirror-type magnetic system element is considered as being single current-carrying turn enveloping the region of existence of closed magnetic surfaces of the torsatron. The calculations indicate the existence of a vast area of the values of the additional magnetic field magnitude and magnetic field of the single turn where, in principle, the implementation of the closed magnetic surface configuration is quite feasible.

  13. Modular stellarator reactor: a fusion power plant

    International Nuclear Information System (INIS)

    A comparative analysis of the modular stellarator and the torsatron concepts is made based upon a steady-state ignited, DT-fueled, reactor embodiment of each concept for use as a central electric-power station. Parametric tradeoff calculations lead to the selection of four design points for an approx. 4-GWt plant based upon Alcator transport scaling in l = 2 systems of moderate aspect ratio. The four design points represent high-aspect ratio. The four design points represent high-(0.08) and low-(0.04) beta versions of the modular stellarator and torsatron concepts. The physics basis of each design point is described together with supporting engineering and economic analyses. The primary intent of this study is the elucidation of key physics and engineering tradeoffs, constraints, and uncertainties with respect to the ultimate power reactor embodiment

  14. Modular stellarator reactor: a fusion power plant

    Energy Technology Data Exchange (ETDEWEB)

    Miller, R.L.; Bathke, C.G.; Krakowski, R.A.; Heck, F.M.; Green, L.; Karbowski, J.S.; Murphy, J.H.; Tupper, R.B.; DeLuca, R.A.; Moazed, A.

    1983-07-01

    A comparative analysis of the modular stellarator and the torsatron concepts is made based upon a steady-state ignited, DT-fueled, reactor embodiment of each concept for use as a central electric-power station. Parametric tradeoff calculations lead to the selection of four design points for an approx. 4-GWt plant based upon Alcator transport scaling in l = 2 systems of moderate aspect ratio. The four design points represent high-aspect ratio. The four design points represent high-(0.08) and low-(0.04) beta versions of the modular stellarator and torsatron concepts. The physics basis of each design point is described together with supporting engineering and economic analyses. The primary intent of this study is the elucidation of key physics and engineering tradeoffs, constraints, and uncertainties with respect to the ultimate power reactor embodiment.

  15. Different approaches to the thermonuclear fusion problem

    International Nuclear Information System (INIS)

    Some alternative approaches to the problem of a controlled fusion are given in brief. Advantages, shortcomings and problems are considered while developing the following approaches: a corrugated torus, an astron, toroidal Z-pinch, a stellarator, a torsatron, a tormak, a topolotron, a surmak, fusion in a target, irradiated by an electron beam, a dense plasma focus, a compressed linear and fusion in a laser heating solenoid

  16. Active trajectory control for a heavy ion beam probe on the compact helical system

    International Nuclear Information System (INIS)

    A 200 keV heavy ion beam probe (HIBP) on the Compact Helical System torsatron/heliotron uses a newly proposed method in order to control complicated beam trajectories in non-axisymmetrical devices. As a result, the HIBP has successfully measured potential profiles of the toroidal helical plasma. The article will describe the results of the potential profile measurements, together with the HIBP hardware system and procedures to realize the method. (author)

  17. Simultaneous saccharification and fermentation of Agave tequilana fructans by Kluyveromyces marxianus yeasts for bioethanol and tequila production.

    Science.gov (United States)

    Flores, Jose-Axel; Gschaedler, Anne; Amaya-Delgado, Lorena; Herrera-López, Enrique J; Arellano, Melchor; Arrizon, Javier

    2013-10-01

    Agave tequilana fructans (ATF) constitute a substrate for bioethanol and tequila industries. As Kluyveromyces marxianus produces specific fructanases for ATF hydrolysis, as well as ethanol, it can perform simultaneous saccharification and fermentation. In this work, fifteen K. marxianus yeasts were evaluated to develop inoculums with fructanase activity on ATF. These inoculums were added to an ATF medium for simultaneous saccharification and fermentation. All the yeasts, showed exo-fructanhydrolase activity with different substrate specificities. The yeast with highest fructanase activity in the inoculums showed the lowest ethanol production level (20 g/l). Five K. marxianus strains were the most suitable for the simultaneous saccharification and fermentation of ATF. The volatile compounds composition was evaluated at the end of fermentation, and a high diversity was observed between yeasts, nevertheless all of them produced high levels of isobutyl alcohol. The simultaneous saccharification and fermentation of ATF with K. marxianus strains has potential for industrial application.

  18. Transgenic mice with cardiac-specific expression of activating transcription factor 3, a stress-inducible gene, have conduction abnormalities and contractile dysfunction.

    Science.gov (United States)

    Okamoto, Y; Chaves, A; Chen, J; Kelley, R; Jones, K; Weed, H G; Gardner, K L; Gangi, L; Yamaguchi, M; Klomkleaw, W; Nakayama, T; Hamlin, R L; Carnes, C; Altschuld, R; Bauer, J; Hai, T

    2001-08-01

    Activating transcription factor 3 (ATF3) is a member of the CREB/ATF family of transcription factors. Previously, we demonstrated that the expression of the ATF3 gene is induced by many stress signals. In this report, we demonstrate that expression of ATF3 is induced by cardiac ischemia coupled with reperfusion (ischemia-reperfusion) in both cultured cells and an animal model. Transgenic mice expressing ATF3 under the control of the alpha-myosin heavy chain promoter have atrial enlargement, and atrial and ventricular hypertrophy. Microscopic examination showed myocyte degeneration and fibrosis. Functionally, the transgenic heart has reduced contractility and aberrant conduction. Interestingly, expression of sorcin, a gene whose product inhibits the release of calcium from sarcoplasmic reticulum, is increased in these transgenic hearts. Taken together, our results indicate that expression of ATF3, a stress-inducible gene, in the heart leads to altered gene expression and impaired cardiac function. PMID:11485922

  19. Glomerular tubular balance: mediation by luminal hypotonicity.

    Science.gov (United States)

    Häberle, D A; Müller, U; Nagel, W

    1989-01-01

    Late proximal rat tubular segments were microperfused with slightly hypo- or hypertonic artificial late proximal tubular fluid (ATF) at low (11-13 nl/min) or high (30-38 nl/min) perfusion rates. Volume reabsorption, net chloride and solute reabsorption were measured as a function of length. In addition, the transepithelial resistance and voltage (Vte) were measured as a function of the applied osmotic gradient. Hypertonic solutions equilibrated to isotonicity by solute outflow rather than water influx. With hypertonic ATF the lumen positive Vte was decreased compared with free flow or with hypotonic ATF. The resistance was not significantly different between the different groups. In contrast to hypotonic ATF, hypertonic or isotonic ATF was not significantly reabsorbed. In addition, hypotonic ATF maintained its hypotonicity along the perfused segments. Its reabsorption was flow-dependent. Hypotonicity appeared to enhance solute reabsorption. PMID:2725432

  20. Proceedings of US-Japan heliotron-stellarator workshop: Volume 1

    Energy Technology Data Exchange (ETDEWEB)

    1987-01-01

    This paper is the first of four volumes on the US-Japan Heliotron-Stellarator workshop. It contains talks on the Heliotron E experiment, the compact helical system (CHS) program, the status of the ATF project, the status of the W VII-AS, the status of the TJ-II program, the ATF experimental plans, the ATF diagnostics, the compact Helical system, and the CHS experimental program and diagnostics. (LSP)

  1. Proceedings of US-Japan heliotron-stellarator workshop: Volume 1

    International Nuclear Information System (INIS)

    This paper is the first of four volumes on the US-Japan Heliotron-Stellarator workshop. It contains talks on the Heliotron E experiment, the compact helical system (CHS) program, the status of the ATF project, the status of the W VII-AS, the status of the TJ-II program, the ATF experimental plans, the ATF diagnostics, the compact Helical system, and the CHS experimental program and diagnostics

  2. Differential expression of two activating transcription factor 5 isoforms in papillary thyroid carcinoma

    Science.gov (United States)

    Vicari, Luisa; La Rosa, Cristina; Forte, Stefano; Calabrese, Giovanna; Colarossi, Cristina; Aiello, Eleonora; Salluzzo, Salvatore; Memeo, Lorenzo

    2016-01-01

    Background Activating transcription factor 5 (ATF5) is a member of the activating transcription/cAMP response element-binding protein family of basic leucine zipper proteins that plays an important role in cell survival, differentiation, proliferation, and apoptosis. The ATF5 gene generates two transcripts: ATF5 isoform 1 and ATF5 isoform 2. A number of studies indicate that ATF5 could be an attractive target for therapeutic intervention in several tumor types; however, so far, the role of ATF5 has not been investigated in papillary thyroid carcinoma (PTC). Methods Quantitative real-time reverse transcription polymerase chain reaction and immuno-histochemical staining were used to study ATF5 mRNA and protein expression in PTC. Results We report here that ATF5 is expressed more in PTC tissue than in normal thyroid tissue. Furthermore, this is the first study that describes the presence of both ATF5 isoforms in PTC. Conclusion These findings could provide potential applications in PTC cancer treatment.

  3. Dual N- and C-terminal helices are required for endoplasmic reticulum and lipid droplet association of alcohol acetyltransferases in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Jyun-Liang Lin

    Full Text Available In the yeast Saccharomyces cerevisiae two alcohol acetyltransferases (AATases, Atf1 and Atf2, condense short chain alcohols with acetyl-CoA to produce volatile acetate esters. Such esters are, in large part, responsible for the distinctive flavors and aromas of fermented beverages including beer, wine, and sake. Atf1 and Atf2 localize to the endoplasmic reticulum (ER and Atf1 is known to localize to lipid droplets (LDs. The mechanism and function of these localizations are unknown. Here, we investigate potential mechanisms of Atf1 and Atf2 membrane association. Segments of the N- and C-terminal domains of Atf1 (residues 24-41 and 508-525, respectively are predicted to be amphipathic helices. Truncations of these helices revealed that the terminal domains are essential for ER and LD association. Moreover, mutations of the basic or hydrophobic residues in the N-terminal helix and hydrophobic residues in the C-terminal helix disrupted ER association and subsequent sorting from the ER to LDs. Similar amphipathic helices are found at both ends of Atf2, enabling ER and LD association. As was the case with Atf1, mutations to the N- and C-terminal helices of Atf2 prevented membrane association. Sequence comparison of the AATases from Saccharomyces, non-Saccharomyces yeast (K. lactis and P. anomala and fruits species (C. melo and S. lycopersicum showed that only AATases from Saccharomyces evolved terminal amphipathic helices. Heterologous expression of these orthologs in S. cerevisiae revealed that the absence of terminal amphipathic helices eliminates LD association. Combined, the results of this study suggest a common mechanism of membrane association for AATases via dual N- and C-terminal amphipathic helices.

  4. 76 FR 68373 - Proposed Revision to Vintage Date Requirements

    Science.gov (United States)

    2011-11-04

    ... (71 FR 25748) on May 2, 2006. In that earlier rulemaking, TTB liberalized the vintage date... Register (43 FR 37672) by TTB's predecessor agency, the Bureau of Alcohol, Tobacco and Firearms (ATF), on... Federal Register (42 FR 30517) on June 15, 1977, ATF noted that the wine industry advocated that the...

  5. 77 FR 33630 - Residency Requirements for Aliens Acquiring Firearms (2011R-23P)

    Science.gov (United States)

    2012-06-07

    ... for Aliens Acquiring Firearms (2011R-23P) AGENCY: Bureau of Alcohol, Tobacco, Firearms, and Explosives... (ATF) by removing the 90-day State residency requirement for aliens lawfully present in the United... permit ATF to impose a regulatory requirement that aliens lawfully present in the United States...

  6. 78 FR 38555 - Importer Permit Requirements for Tobacco Products and Processed Tobacco, and Other Requirements...

    Science.gov (United States)

    2013-06-27

    ... definition of ``Manufacturer of tobacco products'' to reflect a recent statutory change, and by amending a reference to the sale price of large cigars to incorporate a clarification published in a prior TTB....'' Temporary Rule T.D. ATF-421 On December 22, 1999, ATF published in the Federal Register (64 FR 71918)...

  7. Activating transcription factor-3 induction is involved in the anti-inflammatory action of berberine in RAW264.7 murine macrophages.

    Science.gov (United States)

    Bae, Young-An; Cheon, Hyae Gyeong

    2016-07-01

    Berberine is an isoquinoline alkaloid found in Rhizoma coptidis, and elicits anti-inflammatory effects through diverse mechanisms. Based on previous reports that activating transcription factor-3 (ATF-3) acts as a negative regulator of LPS signaling, the authors investigated the possible involvement of ATF-3 in the anti-inflammatory effects of berberine. It was found berberine concentration-dependently induced the expressions of ATF-3 at the mRNA and protein levels and concomitantly suppressed the LPS-induced productions of proinflammatory cytokines (TNF-α, IL-6, and IL-1β). In addition, ATF-3 knockdown abolished the inhibitory effects of berberine on LPS-induced proinflammatory cytokine production, and prevented the berberine-induced suppression of MAPK phosphorylation, but had little effect on AMPK phosphorylation. On the other hand, the effects of berberine, that is, ATF-3 induction, proinflammatory cytokine inhibition, and MAPK inactivation, were prevented by AMPK knockdown, suggesting ATF-3 induction occurs downstream of AMPK activation. The in vivo administration of berberine to mice with LPS-induced endotoxemia increased ATF-3 expression and AMPK phosphorylation in spleen and lung tissues, and concomitantly reduced the plasma and tissue levels of proinflammatory cytokines. These results suggest berberine has an anti-inflammatory effect on macrophages and that this effect is attributable, at least in part, to pathways involving AMPK activation and ATF-3 induction. PMID:27382358

  8. 76 FR 52862 - Time for Payment of Certain Excise Taxes, and Quarterly Excise Tax Payments for Small Alcohol...

    Science.gov (United States)

    2011-08-24

    ..., as a final rule, regulations contained in a temporary rule pertaining to the semimonthly payments of... include those regulations contained in the temporary rule pertaining to part 19 of the TTB regulations..., 1995, ATF published a temporary rule (T.D. ATF-365) in the Federal Register at 60 FR 33665,...

  9. Activating transcription factor 6 poly morphisms and haplotypes ars associated with impaired glucose homeostasis ans type 2 diabetis in dutch Caucasians

    NARCIS (Netherlands)

    Meex, S.J.; Greevenbroek, van M.M.J.; Ayoubi, T.A.; Vlietinck, R.; Vliet-Ostaptchouk, J.V.; Hofker, M.H.; Vermeulen, V.; Schalkwijk, C.G.; Feskens, E.J.M.; Boer, J.M.A.; Stehouwer, C.D.A.; Kallen, van der C.J.H.; Bruin, de T.W.A.

    2007-01-01

    Context: Activating transcription factor 6 (ATF6) is critical for initiation and full activation of the unfolded protein response. An association between genetic variation in ATF6 and type 2 diabetes (DM2) was recently reported in Pima Indians. Objectives: To investigate the broader significance of

  10. A 55,000-60,000 Mr receptor protein for urokinase-type plasminogen activator. Identification in human tumor cell lines and partial purification

    DEFF Research Database (Denmark)

    Nielsen, L S; Kellerman, G M; Behrendt, N;

    1988-01-01

    The iodinated Mr approximately equal to 15,000 amino-terminal fragment (ATF) of the urokinase-type plasminogen activator (u-PA) molecule bound specifically to the cell surface of all of seven cultured human tumor cell lines studied. Cross-linking of iodinated ATF to the cell surface using a bifun...

  11. Activating transcription factor 4 mediates a multidrug resistance phenotype of esophageal squamous cell carcinoma cells through transactivation of STAT3 expression.

    Science.gov (United States)

    Zhu, Hongwu; Chen, Xiong; Chen, Bin; Chen, Bei; Fan, Jianyong; Song, Weibing; Xie, Ziying; Jiang, Dan; Li, Qiuqiong; Zhou, Meihua; Sun, Dayong; Zhao, Yagang

    2014-11-01

    Multidrug resistance (MDR) is a major challenge to the clinical treatment of esophageal cancer. The stress response gene activating transcription factor 4 (ATF4) is involved in homeostasis and cellular protection. However, relatively little is known about the expression and function of ATF4 in esophageal squamous cell carcinoma (ESCC) MDR. In this study, we investigate the potential role and mechanisms of ATF4 in ESCC MDR. We demonstrated that overexpression of ATF4 promotes the MDR phenotype in ESCC cells, while depletion of ATF4 in the MDR ESCC cell line induces drug re-sensitization. We also demonstrated that ATF4 transactivates STAT3 expression by directly binding to the signal transducers and activators of transcription 3 (STAT3) promoter, resulting in MDR in ESCC cells. Significantly, inhibition of STAT3 by small interfering RNA (siRNA) or a selective inhibitor (JSI-124) reintroduces therapeutic sensitivity. In addition, increased Bcl-2, survivin, and MRP1 expression levels were observed in ATF4-overexpressing cells. In conclusion, ATF4 may promote MDR in ESCC cells through the up-regulation of STAT3 expression, and thus is an attractive therapeutic target to combat therapeutic resistance in ESCC.

  12. 78 FR 76322 - Agency Information Collection Activities: Proposed Collection; Comments Requested: FFL Out-of...

    Science.gov (United States)

    2013-12-17

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF JUSTICE Bureau... Justice (DOJ), Bureau of Alcohol, Tobacco, Firearms and Explosives (ATF), will submit the following... information, please contact Tracey Robertson, Tracey.Robertson@atf.gov or (304) 616-4647, Chief,...

  13. Interrogation of Related Clinical Pan-Azole-Resistant Aspergillus fumigatus Strains: G138C, Y431C, and G434C Single Nucleotide Polymorphisms in cyp51A, Upregulation of cyp51A, and Integration and Activation of Transposon Atf1 in the cyp51A Promoter ▿ †

    OpenAIRE

    Albarrag, Ahmed M.; Anderson, Michael J.; Howard, Susan J.; Robson, Geoff D.; Warn, Peter A.; Sanglard, Dominique; David W Denning

    2011-01-01

    Multiple Aspergillus fumigatus isolates from a patient with two aspergillomas complicating chronic pulmonary aspergillosis were pan-azole resistant. Microsatellite typing was identical for all isolates despite major phenotypic and some growth rate differences. Three different cyp51A mutations were found (G138C, Y431C, and G434C), of which the first two were demonstrated by heterologous expression in a hypersusceptible Saccharomyces cerevisiae strain to be at least partly responsible for eleva...

  14. Advanced fusion concepts: project summaries

    International Nuclear Information System (INIS)

    This report contains descriptions of the activities of all the projects supported by the Advanced Fusion Concepts Branch of the Office of Fusion Energy, US Department of Energy. These descriptions are project summaries of each of the individual projects, and contain the following: title, principle investigators, funding levels, purpose, approach, progress, plans, milestones, graduate students, graduates, other professional staff, and recent publications. Information is given for each of the following programs: (1) reverse-field pinch, (2) compact toroid, (3) alternate fuel/multipoles, (4) stellarator/torsatron, (5) linear magnetic fusion, (6) liners, and (7) Tormac

  15. Modular coils: a promising toroidal-reactor-coil system

    International Nuclear Information System (INIS)

    The concept of modular coils originated from a need to find reactor-relevant stellarator windings, but its usefulness can be extended to provide an externally applied, additional rotational transform in tokamaks. Considerations of (1) basic principles of modular coils, (2) types of coils, (3) types of configurations (general, helically symmetric, helically asymmetric, with magnetic well, with magnetic hill), (4) types of rotational transform profile, and (5) structure and origin of ripples are given. These results show that modular coils can offer a wide range of vacuum magnetic field configurations, some of which cannot be obtained with the classical stellarator or torsatron coil configuration

  16. Development and Testing of Atomic Beam-Based Plasma Edge Diagnostics in the CIEMAT Fusion Devices

    International Nuclear Information System (INIS)

    In this report the development of plasma edge diagnostic based on atomic beam techniques fir their application in the CIEMAT fusion devices is described. The characterisation of the beams in laboratory experiments at the CSIC, together with first results in the Torsatron TJ-II are reported. Two types of beam diagnostics have been developed: a thermal (effusive) Li and a supersonic, pulsed He beams. This work has been carried out in collaboration between the institutions mentioned above under partial financial support by EURATOM. (Author) 17 refs

  17. Pulsed supersonic helium beams for plasma edge diagnosis

    Science.gov (United States)

    Diez-Rojo, T.; Herrero, V. J.; Tanarro, I.; Tabarés, F. L.; Tafalla, D.

    1997-03-01

    An experimental setup for the production of pulsed supersonic He beams to be used for plasma edge diagnosis in fusion devices is described. A compromise between compact design, low cost, and good quality of the probe beams has been met. The main characteristics of the generated beams, such as pulse shape, absolute flux intensity, and velocity distribution, differ in general from those expected for ideal beam performance and have been determined and optimized experimentally. A first test of this He beam source at the TJ-I UP Torsatron in Madrid is also reported.

  18. Pulsed supersonic helium beams for plasma edge diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Diez-Rojo, T.; Herrero, V.J.; Tanarro, I. [Instituto de Estructura de la Materia (CSIC), Serrano 123, 28006 Madrid (Spain); Tabares, F.L.; Tafalla, D. [Asociacion EURATOM-CIEMAT para Fusion, Avenue Complutense 22, 28040 Madrid (Spain)

    1997-03-01

    An experimental setup for the production of pulsed supersonic He beams to be used for plasma edge diagnosis in fusion devices is described. A compromise between compact design, low cost, and good quality of the probe beams has been met. The main characteristics of the generated beams, such as pulse shape, absolute flux intensity, and velocity distribution, differ in general from those expected for ideal beam performance and have been determined and optimized experimentally. A first test of this He beam source at the TJ-I UP Torsatron in Madrid is also reported. {copyright} {ital 1997 American Institute of Physics.}

  19. Design of The Scanning Control Module of LED Screen Based on CPLD%基于CPLD的LED显示屏扫描控制模块的设计

    Institute of Scientific and Technical Information of China (English)

    聂雄

    2007-01-01

    基于AT89S52单片机和ATF1508AS可编程逻辑器件实现LED显示屏的硬件设计.采用Verilog HDL对ATF1508AS进行编程,实现LED显示屏扫描控制模块的硬件描述语言程序设计.ATF1508AS的应用,简化了LED显示屏的系统结构,提高了显示屏的刷新率.

  20. 77 FR 39262 - Agency Information Collection Activities; Proposed Collection; Comments Requested: Student and...

    Science.gov (United States)

    2012-07-02

    ... of Alcohol, Tobacco, Firearms and Explosives Agency Information Collection Activities; Proposed Collection; Comments Requested: Student and Supervisor Training Validation Surveys The Department of Justice (DOJ), Bureau of Alcohol, Tobacco, Firearms ] and Explosives (ATF), will be submitting the...

  1. The artificial gene Jazz, a transcriptional regulator of utrophin, corrects the dystrophic pathology in mdx mice.

    Science.gov (United States)

    Di Certo, Maria Grazia; Corbi, Nicoletta; Strimpakos, Georgios; Onori, Annalisa; Luvisetto, Siro; Severini, Cinzia; Guglielmotti, Angelo; Batassa, Enrico Maria; Pisani, Cinzia; Floridi, Aristide; Benassi, Barbara; Fanciulli, Maurizio; Magrelli, Armando; Mattei, Elisabetta; Passananti, Claudio

    2010-03-01

    The absence of the cytoskeletal protein dystrophin results in Duchenne muscular dystrophy (DMD). The utrophin protein is the best candidate for dystrophin replacement in DMD patients. To obtain therapeutic levels of utrophin expression in dystrophic muscle, we developed an alternative strategy based on the use of artificial zinc finger transcription factors (ZF ATFs). The ZF ATF 'Jazz' was recently engineered and tested in vivo by generating a transgenic mouse specifically expressing Jazz at the muscular level. To validate the ZF ATF technology for DMD treatment we generated a second mouse model by crossing Jazz-transgenic mice with dystrophin-deficient mdx mice. Here, we show that the artificial Jazz protein restores sarcolemmal integrity and prevents the development of the dystrophic disease in mdx mice. This exclusive animal model establishes the notion that utrophin-based therapy for DMD can be efficiently developed using ZF ATF technology and candidates Jazz as a novel therapeutic molecule for DMD therapy.

  2. 76 FR 10066 - Agency Information Collection Activities: Proposed Collection; Comments Requested

    Science.gov (United States)

    2011-02-23

    ... technological collection techniques or other forms of information technology, e.g., permitting electronic... existence and validity of a legal entity before ATF approves the transfer of an NFA firearm to that...

  3. 76 FR 35016 - Agency Information Collection Activities; Proposed Collection; Comments Requested: Investigator...

    Science.gov (United States)

    2011-06-15

    ... Collection; Comments Requested: Investigator Integrity Questionnaire ACTION: 30-Day Notice and request for... Form/Collection: Investigator Integrity Questionnaire. (3) Agency form number, if any, and the... ATF utilizes the services of contract investigators to conduct security/suitability investigations...

  4. 77 FR 17502 - Agency Information Collection Activities: Proposed Collection; Comments Requested: Strategic...

    Science.gov (United States)

    2012-03-26

    ... Collection; Comments Requested: Strategic Planning Environmental Assessment Outreach ACTION: 60-Day Notice of... Explosives (ATF), will be submitting the following information collection request to the Office of Management... instrument with instructions or additional information, please contact Jacqueline Pitts, Office of...

  5. Steam Oxidation of FeCrAl and SiC in the Severe Accident Test Station (SATS)

    Energy Technology Data Exchange (ETDEWEB)

    Pint, Bruce A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Unocic, Kinga A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Terrani, Kurt A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-08-01

    Numerous research projects are directed towards developing accident tolerant fuel (ATF) concepts that will enhance safety margins in light water reactors (LWR) during severe accident scenarios. In the U.S. program, the high temperature steam oxidation performance of ATF solutions has been evaluated in the Severe Accident Test Station (SATS) at Oak Ridge National Laboratory (ORNL) since 2012 [1-3] and this facility continues to support those efforts in the ATF community. Compared to the current UO2/Zr-based alloy fuel system, alternative cladding materials can offer slower oxidation kinetics and a smaller enthalpy of oxidation that can significantly reduce the rate of heat and hydrogen generation in the core during a coolant-limited severe accident [4-5]. Thus, steam oxidation behavior is a key aspect of the evaluation of ATF concepts. This report summarizes recent work to measure steam oxidation kinetics of FeCrAl and SiC specimens in the SATS.

  6. Present status and first results of the final focus beam line at the KEK Accelerator Test Facility

    CERN Document Server

    Bambade, P; Amann, J; Angal-Kalinin, D; Apsimon, R; Araki, S; Aryshev, A; Bai, S; Bellomo, P; Bett, D; Blair, G; Bolzon, B; Boogert, S; Boorman, G; Burrows, P N; Christian, G; Coe, P; Constance, B; Delahaye, J P; Deacon, L; Elsen, E; Faus-Golfe, A; Fukuda, M; Gao, J; Geffroy, N; Gianfelice-Wendt, E; Guler, H; Hayano, H; Heo, A Y; Honda, Y; Huang, J Y; Hwang, W H; Iwashita, Y; Jeremie, A; Jones, J; Kamiya, Y; Karataev, P; Kim, E S; Kim, H S; Kim, S H; Komamiya, S; Kubo, K; Kume, T; Kuroda, S; Lam, B; Lyapin, A; Masuzawa, M; McCormick, D; Molloy, S; Naito, T; Nakamura, T; Nelson, J; Okamoto, D; Okugi, T; Oroku, M; Park, Y J; Parker, B; Paterson, E; Perry, C; Pivi, M; Raubenheimer, T; Renier, Y; Resta-Lopez, J; Rimbault, C; Ross, M; Sanuki, T; Scarfe, A; Schulte, D; Seryi, A; Spencer, C; Suehara, T; Sugahara, R; Swinson, C; Takahashi, T; Tauchi, T; Terunuma, N; Tomas, R; Urakawa, J; Urner, D; Verderi, M; Wang, M H; Warden, M; Wendt, M; White, G; Wittmer, W; Wolski, A; Woodley, M; Yamaguchi, Y; Yamanaka, T; Yan, Y; Yoda, H; Yokoya, K; Zhou, F; Zimmermann, F

    2010-01-01

    ATF2 is a final-focus test beam line which aims to focus the low emittance beam from the ATF damping ring to a vertical size of about 37 nm and to demonstrate nanometer level beam stability. Several advanced beam diagnostics and feedback tools are used. In December 2008, construction and installation were completed and beam commissioning started, supported by an international team of Asian, European, and U.S. scientists. The present status and first results are described.

  7. Present Status And First Results of the Final Focus Beam Line at the KEK Accelerator Test Facility

    Energy Technology Data Exchange (ETDEWEB)

    Bambade, P.; /Orsay /KEK, Tsukuba; Alabau Pons, M.; /Valencia U., IFIC; Amann, J.; /SLAC; Angal-Kalinin, D.; /Daresbury; Apsimon, R.; /Oxford U., JAI; Araki, S.; Aryshev, A.; /KEK, Tsukuba; Bai, S.; /Beijing, Inst. High Energy Phys.; Bellomo, P.; /SLAC; Bett, D.; /Oxford U., JAI; Blair, G.; /Royal Holloway, U. of London; Bolzon, B.; /Savoie U.; Boogert, S.; Boorman, G.; /Royal Holloway, U. of London; Burrows, P.N.; Christian, G.; Coe, P.; Constance, B.; /Oxford U., JAI; Delahaye, Jean-Pierre; /CERN; Deacon, L.; /Royal Holloway, U. of London; Elsen, E.; /DESY /Valencia U., IFIC /KEK, Tsukuba /Beijing, Inst. High Energy Phys. /Savoie U. /Fermilab /Ecole Polytechnique /KEK, Tsukuba /Kyungpook Natl. U. /KEK, Tsukuba /Pohang Accelerator Lab. /Kyoto U., Inst. Chem. Res. /Savoie U. /Daresbury /Tokyo U. /Royal Holloway, U. of London /Kyungpook Natl. U. /Pohang Accelerator Lab. /Tokyo U. /KEK, Tsukuba /SLAC /University Coll. London /KEK, Tsukuba /SLAC /Royal Holloway, U. of London /KEK, Tsukuba /Tokyo U. /SLAC /Tohoku U. /KEK, Tsukuba /Tokyo U. /Pohang Accelerator Lab. /Brookhaven /SLAC /Oxford U., JAI /SLAC /Orsay /KEK, Tsukuba /Oxford U., JAI /Orsay /Fermilab /Tohoku U. /Manchester U. /CERN /SLAC /Tokyo U. /KEK, Tsukuba /Oxford U., JAI /Hiroshima U. /KEK, Tsukuba /CERN /KEK, Tsukuba /Oxford U., JAI /Ecole Polytechnique /SLAC /Oxford U., JAI /Fermilab /SLAC /Liverpool U. /SLAC /Tokyo U. /SLAC /Tokyo U. /KEK, Tsukuba /SLAC /CERN

    2011-11-11

    ATF2 is a final-focus test beam line which aims to focus the low emittance beam from the ATF damping ring to a vertical size of about 37 nm and to demonstrate nanometer level beam stability. Several advanced beam diagnostics and feedback tools are used. In December 2008, construction and installation were completed and beam commissioning started, supported by an international team of Asian, European, and U.S. scientists. The present status and first results are described.

  8. STELLA Experiment - Microbunch Diagnostic

    Energy Technology Data Exchange (ETDEWEB)

    He, P.; Liu, Y.; Cline, D. B.; Babzien, M.; Gallardo, J. C.; Kusche, K. P.; Pogorelsky, I. V.; Skaritka, J.; van Steenbergen, A.; Yakimenko, V.; Kimura, W. D.

    1998-07-01

    A microbunch diagnostic system is built at the Accelerator Test Facility (ATF) of Brookhaven National Laboratory for monitoring microbunches (10-fs bunch length) produced by the Inverse Free Electron Laser accelerator in Staged Electron Laser Acceleration experiment. It is similar to one already demonstrated at the ATF. With greatly improved beam optics conditions higher order harmonic coherent transition radiation will be measurable to determine the microbunch length and shape.

  9. Endoplasmic reticulum stress in periimplantation embryos

    OpenAIRE

    Michalak, Marek; Gye, Myung Chan

    2015-01-01

    Stress coping mechanisms are critical to minimize or overcome damage caused by ever changing environmental conditions. They are designed to promote cell survival. The unfolded protein response (UPR) pathway is mobilized in response to the accumulation of unfolded proteins, ultimately in order to regain endoplasmic reticulum (ER) homeostasis. Various elements of coping responses to ER stress including Perk, Ask1, Bip, Chop, Gadd34, Ire1, Atf4, Atf6, and Xbp1 have been identified and were found...

  10. Transport modeling of ECH and neutral-beam-heated plasmas in the advanced toroidal facility

    Energy Technology Data Exchange (ETDEWEB)

    Howe, H.C.; Horton, L.D.; Crume, E.C.; Harris, J.H.; Isler, R.C.; Wilgen, J.B.; Wing, W.R.

    1989-01-01

    Results of time-dependent transport modeling of the ATF plasmas are compared with a typical ungettered, neutral-beam-heated discharge. A summary of ATF machine parameters is given by Murakami. The model is adjusted to give agreement between measured diagnostics signals and the corresponding values inferred from the model plasma. With this agreement, the main features of the discharge are reproduced including the radiation-induced temperature collapse. 7 refs., 6 figs.

  11. Intermedin/adrenomedullin 2 is a stress-inducible gene controlled by activating transcription factor 4.

    Science.gov (United States)

    Kovaleva, Irina E; Garaeva, Alisa A; Chumakov, Peter M; Evstafieva, Alexandra G

    2016-09-15

    Intermedin or adrenomedullin 2 is a set of calcitonin-related peptides with a putative tumor angiogenesis promoting activity that are formed by proteolytic processing of the ADM2 gene product. It has been proposed that the ADM2 gene is regulated by the estrogen response element (ERE) and hypoxia response elements (HRE) found within its promoter region. In the present study we reveal a functional mechanism by which ADM2 participates in the unfolded protein response (UPR) and in responses to the mitochondrial respiration chain inhibition. We show that the ADM2 gene is controlled by activating transcription factor 4 (ATF4), the principal regulator of the integrated stress response (ISR). The upregulation of ADM2 mRNA could be prevented by the pharmacological ISR inhibitor ISRIB and by the downregulation of ATF4 with specific shRNA, while ectopic expression of ATF4 cDNA resulted in a notable increase in ADM2 gene transcription. A potential ATF4-binding site was identified in the coding region of the ADM2 gene and the requirement of this site during the ATF4-mediated ADM2 gene promoter activation was validated by the luciferase reporter assay. Mutagenesis of the putative ATF4-response element prevented the induction of luciferase activity in response to ATF4 overproduction, as well as in response to mitochondrial electron transfer chain inhibition by piericidin A and ER stress induction by tunicamycin and brefeldin A. Since ADM2 was shown to inhibit ATF4 expression during myocardial ER stress, a feedback mechanism could be proposed for the ADM2 regulation under ER stress conditions. PMID:27328454

  12. Convective Heat Transfer Coefficients of Automatic Transmission Fluid Jets with Implications for Electric Machine Thermal Management: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Bennion, Kevin; Moreno, Gilberto

    2015-09-29

    Thermal management for electric machines (motors/ generators) is important as the automotive industry continues to transition to more electrically dominant vehicle propulsion systems. Cooling of the electric machine(s) in some electric vehicle traction drive applications is accomplished by impinging automatic transmission fluid (ATF) jets onto the machine's copper windings. In this study, we provide the results of experiments characterizing the thermal performance of ATF jets on surfaces representative of windings, using Ford's Mercon LV ATF. Experiments were carried out at various ATF temperatures and jet velocities to quantify the influence of these parameters on heat transfer coefficients. Fluid temperatures were varied from 50 degrees C to 90 degrees C to encompass potential operating temperatures within an automotive transaxle environment. The jet nozzle velocities were varied from 0.5 to 10 m/s. The experimental ATF heat transfer coefficient results provided in this report are a useful resource for understanding factors that influence the performance of ATF-based cooling systems for electric machines.

  13. A Novel Gene Delivery System Targeting Urokinase Receptor

    Institute of Scientific and Technical Information of China (English)

    Xing-Hui SUN; Li TAN; Chun-Yang LI; Chang TONG; Jin FAN; Ping LI; Yun-Song ZHU

    2004-01-01

    Recombinant proteins that combine different functions required for cell targeting and intracellular delivery of DNA present an attractive approach for the development of nonviral gene delivery vectors. Here, we described a novel protein termed ATF-lys10 which facilitated cell-specific gene transfer via receptor-mediated endocytosis. ATF-lys 10 was composed of the amino-terminal fragment of urokinase and ten lysines at the carboxyl terminus. Bacterially expressed ATF-lys 10 protein existed in soluble form, and had antigenicity of human urokinase. Purified ATF-lys 10 specifically bound to uPAR-expressing cells and formed protein-DNA complexes with plasmid pGL3-control. After neutralization of excess negative charge with poly-L-lysine, these complexes served as a specific gene delivery vector for uPAR-expressing cells. Lysosomotropic compounds, such as chloroquine, drastically increased the ATF-lysl0 mediated gene delivery efficiency. Our results suggest that the recombinant protein ATF-lys 10 with the properties of DNA binding and tumor cell targeting represents a promising method for gene transfer and expression in tumor cells.

  14. Beam test of multi-bunch energy compensation system in the accelerator test facility at KEK

    International Nuclear Information System (INIS)

    A beam test of the multi-bunch energy compensation system (ECS) was performed using the ΔF method with the 2856±4.327 HMz accelerating structures in the accelerator test facility (ATF) at KEK. The 1.54 GeV S-band linac of the ATF was designed to accelerate a multi-bunch beam the consists of 20 bunches with 2.8 ns spacing. The multi-bunch beam with 2.0 x 1010 electrons/bunch has an energy deviation of about 8.5% at the end of the linac due to transient beam loading without ECS. The ATF linac is the injector of the ATF damping ring (DR), whose energy acceptance is ±0.5%. The beam loading compensation system is necessary in the ATF linac for the successful injection of multi-bunch into DR. The rf system of the linac consists of 8 regular rf units with the SLED system and 2 ECS rf units without the SLED system. The accelerating structures of the regular units are driven at 2856 MHz and the 2 ECS structures are operated with slightly different rf frequencies of 2856±4.327 MHz. In the beam test, we have succeeded in compressing the multi-bunch energy spread within the energy acceptance of the DR using ΔF ECS. The principle of the beam loading compensation system of KEK-ATF and the experimental results are described in this paper. (author)

  15. Functionalized milk-protein-coated magnetic nanoparticles for MRI-monitored targeted therapy of pancreatic cancer.

    Science.gov (United States)

    Huang, Jing; Qian, Weiping; Wang, Liya; Wu, Hui; Zhou, Hongyu; Wang, Andrew Yongqiang; Chen, Hongbo; Yang, Lily; Mao, Hui

    2016-01-01

    Engineered nanocarriers have emerged as a promising platform for cancer therapy. However, the therapeutic efficacy is limited by low drug loading efficiency, poor passive targeting to tumors, and severe systemic side effects. Herein, we report a new class of nanoconstructs based on milk protein (casein)-coated magnetic iron oxide (CNIO) nanoparticles for targeted and image-guided pancreatic cancer treatment. The tumor-targeting amino-terminal fragment (ATF) of urokinase plasminogen activator and the antitumor drug cisplatin (CDDP) were engineered on this nanoplatform. High drug loading (~25 wt%) and sustained release at physiological conditions were achieved through the exchange and encapsulation strategy. These ATF-CNIO-CDDP nanoparticles demonstrated actively targeted delivery of CDDP to orthotopic pancreatic tumors in mice. The effective accumulation and distribution of ATF-CNIO-CDDP was evidenced by magnetic resonance imaging, based on the T2-weighted contrast resulting from the specific accumulation of ATF-CNIO-CDDP in the tumor. Actively targeted delivery of ATF-CNIO-CDDP led to improved therapeutic efficacy in comparison with free CDDP and nontargeted CNIO-CDDP treatment. Meanwhile, less systemic side effects were observed in the nanocarrier-treated groups than that in the group treated with free CDDP. Hematoxylin and Eosin and Sirius Red staining of tumor sections revealed the possible disruption of stroma during the treatment with ATF-CNIO-CDDP. Overall, our results suggest that ATF-CNIO-CDDP can be an effective theranostic platform for active targeting-enhanced and image-guided cancer treatment while simultaneously reducing the systemic toxicity.

  16. Activating transcription factor 4 and X box binding protein 1 of Litopenaeus vannamei transcriptional regulated white spot syndrome virus genes Wsv023 and Wsv083.

    Directory of Open Access Journals (Sweden)

    Xiao-Yun Li

    Full Text Available In response to endoplasmic reticulum (ER stress, the signaling pathway termed unfolded protein response (UPR is activated. To investigate the role of UPR in Litopenaeus vannamei immunity, the activating transcription factor 4 (designated as LvATF4 which belonged to a branch of the UPR, the [protein kinase RNA (PKR-like ER kinase, (PERK]-[eukaryotic initiation factor 2 subunit alpha (eIF2α] pathway, was identified and characterized. The full-length cDNA of LvATF4 was 1972 bp long, with an open reading frame of 1299 bp long that encoded a 432 amino acid protein. LvATF4 was highly expressed in gills, intestines and stomach. For the white spot syndrome virus (WSSV challenge, LvATF4 was upregulated in the gills after 3 hpi and increased by 1.9-fold (96 hpi compared to the mock-treated group. The LvATF4 knock-down by RNA interference resulted in a lower cumulative mortality of L. vannamei under WSSV infection. Reporter gene assays show that LvATF4 could upregulate the expression of the WSSV gene wsv023 based on the activating transcription factor/cyclic adenosine 3', 5'-monophosphate response element (ATF/CRE. Another transcription factor of L. vannamei, X box binding protein 1 (designated as LvXBP1, has a significant function in [inositol-requiring enzyme-1(IRE1 - (XBP1] pathway. This transcription factor upregulated the expression of the WSSV gene wsv083 based on the UPR element (UPRE. These results suggest that in L. vannamei UPR signaling pathway transcription factors are important for WSSV and might facilitate WSSV infection.

  17. A novel dual kinase function of the RET proto-oncogene negatively regulates activating transcription factor 4-mediated apoptosis.

    Science.gov (United States)

    Bagheri-Yarmand, Rozita; Sinha, Krishna M; Gururaj, Anupama E; Ahmed, Zamal; Rizvi, Yasmeen Q; Huang, Su-Chen; Ladbury, John E; Bogler, Oliver; Williams, Michelle D; Cote, Gilbert J; Gagel, Robert F

    2015-05-01

    The RET proto-oncogene, a tyrosine kinase receptor, is widely known for its essential role in cell survival. Germ line missense mutations, which give rise to constitutively active oncogenic RET, were found to cause multiple endocrine neoplasia type 2, a dominant inherited cancer syndrome that affects neuroendocrine organs. However, the mechanisms by which RET promotes cell survival and prevents cell death remain elusive. We demonstrate that in addition to cytoplasmic localization, RET is localized in the nucleus and functions as a tyrosine-threonine dual specificity kinase. Knockdown of RET by shRNA in medullary thyroid cancer-derived cells stimulated expression of activating transcription factor 4 (ATF4), a master transcription factor for stress-induced apoptosis, through activation of its target proapoptotic genes NOXA and PUMA. RET knockdown also increased sensitivity to cisplatin-induced apoptosis. We observed that RET physically interacted with and phosphorylated ATF4 at tyrosine and threonine residues. Indeed, RET kinase activity was required to inhibit the ATF4-dependent activation of the NOXA gene because the site-specific substitution mutations that block threonine phosphorylation increased ATF4 stability and activated its targets NOXA and PUMA. Moreover, chromatin immunoprecipitation assays revealed that ATF4 occupancy increased at the NOXA promoter in TT cells treated with tyrosine kinase inhibitors or the ATF4 inducer eeyarestatin as well as in RET-depleted TT cells. Together these findings reveal RET as a novel dual kinase with nuclear localization and provide mechanisms by which RET represses the proapoptotic genes through direct interaction with and phosphorylation-dependent inactivation of ATF4 during the pathogenesis of medullary thyroid cancer.

  18. Fluoride removal from water using activated and MnO2-coated Tamarind Fruit (Tamarindus indica) shell: batch and column studies.

    Science.gov (United States)

    Sivasankar, V; Ramachandramoorthy, T; Chandramohan, A

    2010-05-15

    The present work is concerned with the defluoridation capacities of activated (ATFS) and MnO(2)-coated Tamarind Fruit Shell (MTFS), using batch and column sorption techniques. In the batch technique, the dynamics of fluoride sorption, with respect to pH, [F](o) and sorbent dose, was studied. The applicability of pseudo-first order for ATFS and Ritchie-second order for MTFS was observed. The kinetics data were found to fit well with Temkin isotherm for ATFS and Langmuir for MTFS. The interaction of co-ions in the defluoridation capacity of the sorbent was studied. Column experiments were carried out under a constant fluoride concentration of 2mg/l, flow rate and different bed depths. The capacities of the breakthrough and exhaustion points increased with increase in the bed depth for ATFS unlike MTFS. The Thomson model was applied to the column experimental results. The characterization of the sorbents, ATFS and MTFS, was done using the FTIR, SEM and XRD techniques.

  19. Protective coupling of mitochondrial function and protein synthesis via the eIF2α kinase GCN-2.

    Directory of Open Access Journals (Sweden)

    Brooke M Baker

    Full Text Available Cells respond to defects in mitochondrial function by activating signaling pathways that restore homeostasis. The mitochondrial peptide exporter HAF-1 and the bZip transcription factor ATFS-1 represent one stress response pathway that regulates the transcription of mitochondrial chaperone genes during mitochondrial dysfunction. Here, we report that GCN-2, an eIF2α kinase that modulates cytosolic protein synthesis, functions in a complementary pathway to that of HAF-1 and ATFS-1. During mitochondrial dysfunction, GCN-2-dependent eIF2α phosphorylation is required for development as well as the lifespan extension observed in Caenorhabditis elegans. Reactive oxygen species (ROS generated from dysfunctional mitochondria are required for GCN-2-dependent eIF2α phosphorylation but not ATFS-1 activation. Simultaneous deletion of ATFS-1 and GCN-2 compounds the developmental defects associated with mitochondrial stress, while stressed animals lacking GCN-2 display a greater dependence on ATFS-1 and stronger induction of mitochondrial chaperone genes. These findings are consistent with translational control and stress-dependent chaperone induction acting in complementary arms of the UPR(mt.

  20. Measurement of impulse peak insertion loss from two acoustic test fixtures and four hearing protector conditions with an acoustic shock tube

    Directory of Open Access Journals (Sweden)

    William J Murphy

    2015-01-01

    Full Text Available Impulse peak insertion loss (IPIL was studied with two acoustic test fixtures and four hearing protector conditions at the E-A-RCAL Laboratory. IPIL is the difference between the maximum estimated pressure for the open-ear condition and the maximum pressure measured when a hearing protector is placed on an acoustic test fixture (ATF. Two models of an ATF manufactured by the French-German Research Institute of Saint-Louis (ISL were evaluated with high-level acoustic impulses created by an acoustic shock tube at levels of 134 decibels (dB, 150 dB, and 168 dB. The fixtures were identical except that the E-A-RCAL ISL fixture had ear canals that were 3 mm longer than the National Institute for Occupational Safety and Health (NIOSH ISL fixture. Four hearing protection conditions were tested: Combat Arms earplug with the valve open, ETYPlugs ® earplug, TacticalPro headset, and a dual-protector ETYPlugs earplug with TacticalPro earmuff. The IPILs measured for the E-A-RCAL fixture were 1.4 dB greater than the National Institute for Occupational Safety and Health (NIOSH ISL ATF. For the E-A-RCAL ISL ATF, the left ear IPIL was 2.0 dB greater than the right ear IPIL. For the NIOSH ATF, the right ear IPIL was 0.3 dB greater than the left ear IPIL.

  1. Economic Evaluation Guide for alternative transportation fuels

    Energy Technology Data Exchange (ETDEWEB)

    de Percin, D.; Werner, J.F. Jr.

    1992-12-31

    The production of this Economic Evaluation Guide is one activity of AVFCAP. The guide is intended for use by project managers and fleet operators in the public sector. Public fleets have been identified as one of the most likely areas where ATFs will first gain widespread use, because of existing and impending state and federal legislative mandates, as well as for practical reasons such as centralized servicing and refueling. The purpose of this guide is to provide balanced decision-support information to project managers who are considering conducting, or currently managing, ATF demonstration programs. Information for this guide was gathered as part of a related AVFCAP activity, the development of an Information Resource Database. Economic issues related to the development and implementation of ATF programs at the local government level are extremely complex, and require an analysis of federal policies and national and international economics that is generally beyond the scope of local government project managers. The intent of this guide is to examine the information available on the economic evaluation of ATFs, and identify key elements that will help local governments realistically assess the potential costs and savings of an ATF program. The guide also discusses how these various economic factors are related, and how local government priorities affect how different factors are weighed.

  2. Economic Evaluation Guide for alternative transportation fuels

    Energy Technology Data Exchange (ETDEWEB)

    de Percin, D.; Werner, J.F. Jr.

    1992-01-01

    The production of this Economic Evaluation Guide is one activity of AVFCAP. The guide is intended for use by project managers and fleet operators in the public sector. Public fleets have been identified as one of the most likely areas where ATFs will first gain widespread use, because of existing and impending state and federal legislative mandates, as well as for practical reasons such as centralized servicing and refueling. The purpose of this guide is to provide balanced decision-support information to project managers who are considering conducting, or currently managing, ATF demonstration programs. Information for this guide was gathered as part of a related AVFCAP activity, the development of an Information Resource Database. Economic issues related to the development and implementation of ATF programs at the local government level are extremely complex, and require an analysis of federal policies and national and international economics that is generally beyond the scope of local government project managers. The intent of this guide is to examine the information available on the economic evaluation of ATFs, and identify key elements that will help local governments realistically assess the potential costs and savings of an ATF program. The guide also discusses how these various economic factors are related, and how local government priorities affect how different factors are weighed.

  3. ORNL Analysis of Operational and Safety Performance for Candidate Accident Tolerant Fuel and Cladding Concepts

    International Nuclear Information System (INIS)

    Enhanced accident-tolerant fuels (ATFs) are being developed by the US Department of Energy Office of Nuclear Energy Fuel Cycle Research and Development Program to replace standard Zircaloy cladding and/or UO2 fuel in light water reactors. Proposed ATF concepts seek to reduce severe accident (SA) risks by increasing the coping time available to operators for accident response, reducing the extent and rate of heat and hydrogen production from steam oxidation, or enhancing fission product retention. Candidate ATF concepts require analyses to demonstrate adequate performance during normal operation and worthwhile improvements in SA scenarios. Two key ATF areas are being developed at Oak Ridge National Laboratory: (1) alternate cladding materials, including advanced iron-chromium-aluminium (FeCrAl) alloys and silicon carbide (SiC) composites, and (2) fully ceramic microencapsulated (FCM) fuel, which uses coated fuel particles embedded in an SiC matrix. Reactor physics analyses examining candidate ATF clad materials in a pressurized water reactor (PWR), with preliminary assessments of combinations of fuel enrichment and cladding thickness required to match existing cycle lengths and economic factors such as fuel costs, are presented. SA analyses including updated analyses of how FeCrAl cladding and channel box impact SA scenarios in a boiling water reactor (BWR) are also discussed. (author)

  4. Low viscosity automatic transmission fluids with enhanced friction durability

    Institute of Scientific and Technical Information of China (English)

    Kenji Yatsunami; Samuel H. Tersigni; TANG Hong- zhi; Lee D. Saathoff; Christopher S. Cleveland; Mark Jones

    2009-01-01

    This study focused on the development of a new low viscosity automatic transmission fluid (ATF) with enhanced friction durability to meet the needs of new step type automatic transmissions. Recent high fuel prices encourage increased efficiency in the driveline, including the transmission. Reduction in fluid viscosity and wider use of slip control in torque con-verter clutches are two ways to practically improve fuel efficiency. Increased torque and more shifting is seen with a variety of new transmission hardware platforms, such as wet starting clutches, dual clutches and seven - or eight - speed ATs.This suggests the need for enhanced levels of friction durability from the ATF. The new challenge from this hardware for the ATF formulator lies in the need to simultaneously meet the wear, friction durability and torque capacity requirements at low viscosity in a cost- effective manner. This report introduced a new low viscosity fluid that represents a different commercial ATF formulation style. The new chemistry employs a low viscosity for increased fuel economy, while easily doubling the friction durability of current conven-tional ATFs and offering higher torque and better EP.

  5. Small molecule proteostasis regulators that reprogram the ER to reduce extracellular protein aggregation

    Science.gov (United States)

    Plate, Lars; Cooley, Christina B; Chen, John J; Paxman, Ryan J; Gallagher, Ciara M; Madoux, Franck; Genereux, Joseph C; Dobbs, Wesley; Garza, Dan; Spicer, Timothy P; Scampavia, Louis; Brown, Steven J; Rosen, Hugh; Powers, Evan T; Walter, Peter; Hodder, Peter; Wiseman, R Luke; Kelly, Jeffery W

    2016-01-01

    Imbalances in endoplasmic reticulum (ER) proteostasis are associated with etiologically-diverse degenerative diseases linked to excessive extracellular protein misfolding and aggregation. Reprogramming of the ER proteostasis environment through genetic activation of the Unfolded Protein Response (UPR)-associated transcription factor ATF6 attenuates secretion and extracellular aggregation of amyloidogenic proteins. Here, we employed a screening approach that included complementary arm-specific UPR reporters and medium-throughput transcriptional profiling to identify non-toxic small molecules that phenocopy the ATF6-mediated reprogramming of the ER proteostasis environment. The ER reprogramming afforded by our molecules requires activation of endogenous ATF6 and occurs independent of global ER stress. Furthermore, our molecules phenocopy the ability of genetic ATF6 activation to selectively reduce secretion and extracellular aggregation of amyloidogenic proteins. These results show that small molecule-dependent ER reprogramming, achieved through preferential activation of the ATF6 transcriptional program, is a promising strategy to ameliorate imbalances in ER function associated with degenerative protein aggregation diseases. DOI: http://dx.doi.org/10.7554/eLife.15550.001 PMID:27435961

  6. In vacuum diamond sensor scanner for beam halo measurements in the beam line at the KEK Accelerator Test Facility

    Science.gov (United States)

    Liu, S.; Bogard, F.; Cornebise, P.; Faus-Golfe, A.; Fuster-Martínez, N.; Griesmayer, E.; Guler, H.; Kubytskyi, V.; Sylvia, C.; Tauchi, T.; Terunuma, N.; Bambade, P.

    2016-10-01

    The investigation of beam halo transverse distributions is important for the understanding of beam losses and the control of backgrounds in Future Linear Colliders (FLC). A novel in vacuum diamond sensor (DSv) scanner with four strips has been designed and developed for the investigation of the beam halo transverse distributions and also for the diagnostics of Compton recoil electrons after the interaction point (IP) of ATF2, a low energy (1.3 GeV) prototype of the final focus system for the ILC and CLIC linear collider projects. Using the DSv, a dynamic range of ∼106 has been successfully demonstrated and confirmed for the first time in simultaneous beam core (∼109 electrons) and beam halo (∼103 electrons) measurements at ATF2. This report presents the characterization, performance studies and tests of diamond sensors using an α source, as well as using the electron beams at PHIL, a low energy < 5 MeV photo-injector at LAL, and at ATF2. First beam halo measurement results using the DSv at ATF2 with different beam intensities and vacuum levels are also presented. Such measurements not only allow one to evaluate the different sources of beam halo generation but also to define the requirements for a suitable collimation system to be installed at ATF2, as well as to optimize its performance during future operation.

  7. Submission of FeCrAl Feedstock for Support of AFC ATR-2 Irradiations

    Energy Technology Data Exchange (ETDEWEB)

    Field, Kevin G. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Barrett, Kristine E. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Sun, Zhiqian [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Yamamoto, Yukinori [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2016-09-16

    The Advanced Test Reactor (ATR) is currently being used to test accident tolerant fuel (ATF) forms destined for commercial nuclear power plant deployment. One irradiation program using the ATR for ATF concepts, Accident Tolerant Fuel-2 (ATF-2), is a water loop irradiation test using miniaturized fuel pins as test articles. This complicated testing configuration requires a series of pre-test experiments and verification including a flowing loop autoclave test and a sensor qualification test (SQT) prior to full test train deployment within the ATR. In support of the ATF-2 irradiation program, Oak Ridge National Laboratory (ORNL) has supplied two different Generation II FeCrAl alloys in rod stock form to Idaho National Laboratory (INL). These rods will be machined into dummy pins for deployment in the autoclave test and SQT. Post-test analysis of the dummy pins will provide initial insight into the performance of Generation II FeCrAl alloys in the ATF-2 irradiation experiment as well as within a commercial nuclear reactor.

  8. Submission of FeCrAl feedstock for support of AFC ATR-2 Irradiations

    Energy Technology Data Exchange (ETDEWEB)

    Field, Kevin G [ORNL; Barrett, Kristine E. [Idaho National Laboratory (INL); Sun, Zhiqian [ORNL; Yamamoto, Yukinori [ORNL

    2016-09-01

    The Advanced Test Reactor (ATR) is currently being used to test accident tolerant fuel (ATF) forms destined for commercial nuclear power plant deployment. One irradiation program using the ATR for ATF concepts, Accident Tolerant Fuel-2 (ATF-2), is a water loop irradiation test using miniaturized fuel pins as test articles. This complicated testing configuration requires a series of pre-test experiments and verification including a flowing loop autoclave test and a sensor qualification test (SQT) prior to full test train deployment within the ATR. In support of the ATF-2 irradiation program, Oak Ridge National Laboratory (ORNL) has supplied two different Generation II FeCrAl alloys in rod stock form to Idaho National Laboratory (INL). These rods will be machined into dummy pins for deployment in the autoclave test and SQT. Post-test analysis of the dummy pins will provide initial insight into the performance of Generation II FeCrAl alloys in the ATF-2 irradiation experiment as well as within a commercial nuclear reactor.

  9. Up-regulation of activating transcription factor 4 induces severe loss of dopamine nigral neurons in a rat model of Parkinson's disease.

    Science.gov (United States)

    Gully, Joseph C; Sergeyev, Valeriy G; Bhootada, Yogesh; Mendez-Gomez, Hector; Meyers, Craig A; Zolotukhin, Sergey; Gorbatyuk, Marina S; Gorbatyuk, Oleg S

    2016-08-01

    Activating transcription factor 4 (ATF4) is a member of the PERK signaling pathway, which directly binds endoplasmic reticulum stress target genes and plays a crucial role in both adaptations to stress and activation of apoptosis. Previous publications demonstrated conflicting evidence on the role of ATF4 in the pathogenesis of neurodegenerative disorders. In this study, we used recombinant adeno-associate virus (rAAV)-mediated gene transfer to investigate if the sustained up-regulation of ATF4 launches a pro-survival or pro-death trend in the dopamine (DA) cells of the substantia nigra pars compacta in a rat model of Parkinson-like neurodegeneration induced by human alpha-synuclein (αS) overexpression. We showed that ATF4 does not protect nigral DA neurons against an αS-induced pathology. Moreover, the rAAV-mediated overexpression of ATF4 resulted in severe nigra-striatal degeneration via activation of caspases 3/7. PMID:27233218

  10. Rapid ester biosynthesis screening reveals a high activity alcohol-O-acyltransferase (AATase) from tomato fruit.

    Science.gov (United States)

    Lin, Jyun-Liang; Zhu, Jie; Wheeldon, Ian

    2016-05-01

    Ethyl and acetate esters are naturally produced in various yeasts, plants, and bacteria. The biosynthetic pathways that produce these esters share a common reaction step, the condensation of acetyl/acyl-CoA with an alcohol by alcohol-O-acetyl/acyltransferase (AATase). Recent metabolic engineering efforts exploit AATase activity to produce fatty acid ethyl esters as potential diesel fuel replacements as well as short- and medium-chain volatile esters as fragrance and flavor compounds. These efforts have been limited by the lack of a rapid screen to quantify ester biosynthesis. Enzyme engineering efforts have also been limited by the lack of a high throughput screen for AATase activity. Here, we developed a high throughput assay for AATase activity and used this assay to discover a high activity AATase from tomato fruit, Solanum lycopersicum (Atf-S.l). Atf1-S.l exhibited broad specificity towards acyl-CoAs with chain length from C4 to C10 and was specific towards 1-pentanol. The AATase screen also revealed new acyl-CoA substrate specificities for Atf1, Atf2, Eht1, and Eeb1 from Saccharomyces cerevisiae, and Atf-C.m from melon fruit, Cucumis melo, thus increasing the pool of characterized AATases that can be used in ester biosynthesis of ester-based fragrance and flavor compounds as well as fatty acid ethyl ester biofuels. PMID:26814045

  11. Comparison of different estimation methods of accident atmospheric dispersion factors for a representative inland nuclear power plant

    International Nuclear Information System (INIS)

    The applicability of atmospheric diffusion models in complex terrains and low wind speed conditions was discussed in this paper. The accident atmospheric dispersion factors (ATFs) of Taohuajiang nuclear power plant were calculated by using two methods: the probabilistic method recommended by the U.S. Nuclear regulatory Commission (NRC) and the three dimensional objective diagnostic wind field model coupled with Lagrangian trajectory puff model to simulate the 8760 hourly emissions of radioactive nuclides. The results indicate that the maximum hourly accident ATFs calculated by the probabilistic method are conservative in exclusion area boundary (EAB). However, in some directions, accident ATFs calculated using probabilistic method is smaller than that using Lagrangian puff model, as well as some accident ATFs in remote sectors are larger than those in close sectors. Moreover, results calculated by probabilistic method are smaller in long-term release situation. Therefore, accident ATFs obtained according to the regulatory guides may not conservative in some cases, and atmospheric diffusion model should be selected carefully when a nuclear plant is located at a site with complex environmental conditions. (authors)

  12. A Taiwanese Propolis Derivative Induces Apoptosis through Inducing Endoplasmic Reticular Stress and Activating Transcription Factor-3 in Human Hepatoma Cells

    Directory of Open Access Journals (Sweden)

    Fat-Moon Suk

    2013-01-01

    Full Text Available Activating transcription factor-(ATF- 3, a stress-inducible transcription factor, is rapidly upregulated under various stress conditions and plays an important role in inducing cancer cell apoptosis. NBM-TP-007-GS-002 (GS-002 is a Taiwanese propolin G (PPG derivative. In this study, we examined the antitumor effects of GS-002 in human hepatoma Hep3B and HepG2 cells in vitro. First, we found that GS-002 significantly inhibited cell proliferation and induced cell apoptosis in dose-dependent manners. Several main apoptotic indicators were found in GS-002-treated cells, such as the cleaved forms of caspase-3, caspase-9, and poly(ADP-ribose polymerase (PARP. GS-002 also induced endoplasmic reticular (ER stress as evidenced by increases in ER stress-responsive proteins including glucose-regulated protein 78 (GRP78, growth arrest- and DNA damage-inducible gene 153 (GADD153, phosphorylated eukaryotic initiation factor 2α (eIF2α, phosphorylated protein endoplasmic-reticular-resident kinase (PERK, and ATF-3. The induction of ATF-3 expression was mediated by mitogen-activated protein kinase (MAPK signaling pathways in GS-002-treated cells. Furthermore, we found that GS-002 induced more cell apoptosis in ATF-3-overexpressing cells. These results suggest that the induction of apoptosis by the propolis derivative, GS-002, is partially mediated through ER stress and ATF-3-dependent pathways, and GS-002 has the potential for development as an antitumor drug.

  13. Fusion theory and computations

    International Nuclear Information System (INIS)

    It is proposed to carry out theoretical studies of the equilibrium, stability, transport and heating properties of high-temperature fusion plasmas. Continued emphasis will be placed on the effective interface of fusion theory and computations with the local Alcator, Versator, Constance and Torex experimental programs. The proposed research includes but will not be limited to the following types of studies: (a) investigation of RF heating of toroidal plasmas, (b) investigation of the MHD equilibrium and stability properties of tokamak plasmas, (c) develop the basic understanding of a wide variety of non-linear and turbulent phenomena, including stochastic magnetic fields, clumps and nonlinear saturation of linear instabilities, (d) investigate the effects of ambipolar fields on transport and stability properties of toroidal plasmas. Investigate high-beat stability properties of tandem-mirror systems, and (e) investigation of the MHD equilibrium and stability properties of Torsatron/Stellarator configurations

  14. Plasma physics and controlled nuclear fusion research 1994. V. 1. Proceedings of the fifteenth international conference

    International Nuclear Information System (INIS)

    This volume contains (i) the traditional Artsimovich Memorial Lecture; (ii) nine presentations giving an overview of toroidal confinement systems (TFTR, JT-60U, JET, DIII-D, TORE SUPRA, Alcator C-Mod, JFT-2M and T-10 tokamaks and the Wendelstein 7-AS stellarator), (iii) twenty-three presentations on core plasma physics (mostly on charged-particle transport and improved confinement regimes), (iv) eight presentations on plasma heating and current drive, (v) twelve presentations on divertors and edge physics, (vi) thirteen on concept optimization (shaping of magnetic field configuration, control of plasma profiles and of disruptions, a.o.), and (vii) six on helical systems (stellarators, including torsatron/heliotron). Refs, figs and tabs

  15. Massachusetts Institute of Technology, Plasma Fusion Center, technical research programs

    Energy Technology Data Exchange (ETDEWEB)

    1982-02-01

    Research programs have produced significant results on four fronts: (1) the basic physics of high-temperature fusion plasmas (plasma theory, RF heating, development of advanced diagnostics and small-scale experiments on the Versator tokamak and Constance mirror devices); (2) major confinement results on the Alcator A and C tokamaks, including pioneering investigations of the equilibrium, stability, transport and radiation properties of fusion plasmas at high densities, temperatures and magnetic fields; (3) development of a new and innovative design for axisymmetric tandem mirrors with inboard thermal barriers, with initial operation of the TARA tandem mirror experimental facility scheduled for 1983; and (4) a broadly based program of fusion technology and engineering development that addresses problems in several critical subsystem areas (e.g., magnet systems, superconducting materials development, environmental and safety studies, advanced gyrotron development for RF heating, preconceptual design studies of torsatrons and stellarators, and advanced tokamak design and reactor studies).

  16. Alternative approaches to plasma confinement

    Science.gov (United States)

    Roth, J. R.

    1978-01-01

    The paper discusses 20 plasma confinement schemes each representing an alternative to the tokamak fusion reactor. Attention is given to: (1) tokamak-like devices (TORMAC, Topolotron, and the Extrap concept), (2) stellarator-like devices (Torsatron and twisted-coil stellarators), (3) mirror machines (Astron and reversed-field devices, the 2XII B experiment, laser-heated solenoids, the LITE experiment, the Kaktus-Surmac concept), (4) bumpy tori (hot electron bumpy torus, toroidal minimum-B configurations), (5) electrostatically assisted confinement (electrostatically stuffed cusps and mirrors, electrostatically assisted toroidal confinement), (6) the Migma concept, and (7) wall-confined plasmas. The plasma parameters of the devices are presented and the advantages and disadvantages of each are listed.

  17. Fructanase and fructosyltransferase activity of non-Saccharomyces yeasts isolated from fermenting musts of Mezcal.

    Science.gov (United States)

    Arrizon, Javier; Morel, Sandrine; Gschaedler, Anne; Monsan, Pierre

    2012-04-01

    Fructanase and fructosyltransferase are interesting for the tequila process and prebiotics production (functional food industry). In this study, one hundred thirty non-Saccharomyces yeasts isolated from "Mezcal de Oaxaca" were screened for fructanase and fructosyltransferase activity. On solid medium, fifty isolates grew on Agave tequilana fructans (ATF), inulin or levan. In liquid media, inulin and ATF induced fructanase activities of between 0.02 and 0.27U/ml depending of yeast isolate. High fructanase activity on sucrose was observed for Kluyveromyces marxianus and Torulaspora delbrueckii, while the highest fructanase activity on inulin and ATF was observed for Issatchenkia orientalis, Cryptococcus albidus, and Candida apicola. Zygosaccharomyces bisporus and Candida boidinii had a high hydrolytic activity on levan. Sixteen yeasts belonging to K. marxianus, T. delbrueckii and C. apicola species were positive for fructosyltransferase activity. Mezcal microbiota proved to showed to be a source for new fructanase and fructosyltransferases with potential application in the tequila and food industry.

  18. Discrimination of different forms of the murine urokinase plasminogen activator receptor on the cell surface using monoclonal antibodies

    DEFF Research Database (Denmark)

    Rasch, M.G.; Pass, J.; Illemann, M.;

    2008-01-01

    of saturation with the amino-terminal fragment of uPA, ATF. However, the signal intensity obtained using another uPAR domain I specific mAb, mR1, was significantly reduced upon ATF saturation. Furthermore, when adding ATF, mR4 selectively stained the cleaved receptor. Applying these newly generated mAbs, we...... and pathological extracellular tissue remodelling processes. uPA can also cleave uPAR, resulting in liberation of the amino-terminal domain I, which encompasses binding sites for both uPA and the adhesion molecule, vitronectin. In order to localise the different uPAR forms on the plasma membrane of murine monocyte...

  19. Enhanced Accident Tolerant LWR Fuels: Metrics Development

    Energy Technology Data Exchange (ETDEWEB)

    Shannon Bragg-Sitton; Lori Braase; Rose Montgomery; Chris Stanek; Robert Montgomery; Lance Snead; Larry Ott; Mike Billone

    2013-09-01

    The Department of Energy (DOE) Fuel Cycle Research and Development (FCRD) Advanced Fuels Campaign (AFC) is conducting research and development on enhanced Accident Tolerant Fuels (ATF) for light water reactors (LWRs). This mission emphasizes the development of novel fuel and cladding concepts to replace the current zirconium alloy-uranium dioxide (UO2) fuel system. The overall mission of the ATF research is to develop advanced fuels/cladding with improved performance, reliability and safety characteristics during normal operations and accident conditions, while minimizing waste generation. The initial effort will focus on implementation in operating reactors or reactors with design certifications. To initiate the development of quantitative metrics for ATR, a LWR Enhanced Accident Tolerant Fuels Metrics Development Workshop was held in October 2012 in Germantown, MD. This paper summarizes the outcome of that workshop and the current status of metrics development for LWR ATF.

  20. Polysaccharide-rich fraction of Agaricus brasiliensis enhances the candidacidal activity of murine macrophages

    Directory of Open Access Journals (Sweden)

    Priscila Raquel Martins

    2008-05-01

    Full Text Available A polysaccharide-rich fraction (ATF of medicinal mushroom Agaricus brasiliensis was evaluated on the candidacidal activity, H2O2 and nitric oxide (NO production, and expression of mannose receptors by murine peritoneal macrophages. Mice received three intraperitoneal (i.p. injections of ATF and after 48 h their peritoneal resident macrophages were assayed against Candida albicans yeast forms. The treatment increased fungicidal activity and it was associated with higher levels of H2O2, whereas NO production was not affected. We also found that the treatment enhances mannose receptor expression by peritoneal macrophages, which are involved in the attachment and phagocytosis of non-opsonized microorganisms. Treatment of animals with ATF was able to enhance the clearance of C. albicans during the first 6 h after the experimental i.p. infection. Our results suggest that this extract can increase host resistance against some infectious agents through the stimulation of microbicidal activity of macrophages.

  1. Micron-scale laser-wire scanner for the KEK Accelerator Test Facility extraction line

    Science.gov (United States)

    Boogert, Stewart T.; Blair, Grahame A.; Boorman, Gary; Bosco, Alessio; Deacon, Lawrence C.; Karataev, Pavel; Aryshev, Alexander; Fukuda, Masafumi; Terunuma, Nobihiro; Urakawa, Junji; Corner, Laura; Delerue, Nicolas; Foster, Brian; Howell, David; Newman, Myriam; Senanayake, Rohan; Walczak, Roman; Ganaway, Fred

    2010-12-01

    A laser-wire transverse electron beam size measurement system has been constructed and operated at the Accelerator Test Facility (ATF) extraction line at KEK. The construction of the system is described in detail along with the environment of the ATF related to the laser wire. A special set of electron beam optics was developed to generate an approximately 1μm vertical focus at the laser-wire location. The results of our operation at the ATF extraction line are presented, where a minimum rms electron beam size of 4.8±0.3μm was measured, and smaller electron beam sizes can be measured by developing the method further. The beam size at the laser-wire location was changed using quadrupoles and the resulting electron beam size measured, and vertical emittance extracted.

  2. Severe Accident Scoping Simulations of Accident Tolerant Fuel Concepts for BWRs

    Energy Technology Data Exchange (ETDEWEB)

    Robb, Kevin R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-08-01

    Accident-tolerant fuels (ATFs) are fuels and/or cladding that, in comparison with the standard uranium dioxide Zircaloy system, can tolerate loss of active cooling in the core for a considerably longer time period while maintaining or improving the fuel performance during normal operations [1]. It is important to note that the currently used uranium dioxide Zircaloy fuel system tolerates design basis accidents (and anticipated operational occurrences and normal operation) as prescribed by the US Nuclear Regulatory Commission. Previously, preliminary simulations of the plant response have been performed under a range of accident scenarios using various ATF cladding concepts and fully ceramic microencapsulated fuel. Design basis loss of coolant accidents (LOCAs) and station blackout (SBO) severe accidents were analyzed at Oak Ridge National Laboratory (ORNL) for boiling water reactors (BWRs) [2]. Researchers have investigated the effects of thermal conductivity on design basis accidents [3], investigated silicon carbide (SiC) cladding [4], as well as the effects of ATF concepts on the late stage accident progression [5]. These preliminary analyses were performed to provide initial insight into the possible improvements that ATF concepts could provide and to identify issues with respect to modeling ATF concepts. More recently, preliminary analyses for a range of ATF concepts have been evaluated internationally for LOCA and severe accident scenarios for the Chinese CPR1000 [6] and the South Korean OPR-1000 [7] pressurized water reactors (PWRs). In addition to these scoping studies, a common methodology and set of performance metrics were developed to compare and support prioritizing ATF concepts [8]. A proposed ATF concept is based on iron-chromium-aluminum alloys (FeCrAl) [9]. With respect to enhancing accident tolerance, FeCrAl alloys have substantially slower oxidation kinetics compared to the zirconium alloys typically employed. During a severe accident, Fe

  3. Electric Motor Thermal Management for Electric Traction Drives (Presentation)

    Energy Technology Data Exchange (ETDEWEB)

    Bennion, K.; Cousineau, J.; Moreno, G.

    2014-09-01

    Thermal constraints place significant limitations on how electric motors ultimately perform. Finite element analysis and computational fluid dynamics modeling approaches are being increasingly utilized in the design and analysis of electric motors. As the models become more sophisticated, it is important to have detailed and accurate knowledge of material thermal properties and convective heat transfer coefficients. In this work, the thermal properties and inter-lamination thermal contact resistances were measured for different stator lamination materials. Also, convective heat transfer coefficients of automatic transmission fluid (ATF) jets were measured to better understand the heat transfer of ATF impinging on motor copper windings. Experiments were carried out at various ATF temperatures and jet velocities to quantify the influence of these parameters on heat transfer coefficients.

  4. Mitigating the effects of higher order multipole fields in the magnets of the Accelerator Test Facility 2 at KEK

    Institute of Scientific and Technical Information of China (English)

    BAI Sha; P. Bambade; WANG Dou; GAO Jie; M. Woodley; M. Masuzawa

    2012-01-01

    The ATF2 project is the final focus system prototype for the ILC and CLIC linear collider projects,with the purpose of reaching a 37nm vertical beam size at the interaction point.In the nanometer beam size regime,higher order multipoles in magnets become a crucial point for consideration.The strength and rotation angle of the ATF2 QEA magnets were reconstructed from the IHEP measurements and compared with the KEK ones to be identical.Based on the study of the skew multipoles sensitivity,we report on the analysis of the possible mitigation of the measured multipoles.A suggestion is given which will benefit the ATF2 present commissioning to reach the goal beam size,and also the reduced β optics in future.

  5. Evaluation of Physical Characteristics of PWR Cores with Accident Tolerant Fuels

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Dae Hee; Hong, Ser Gi [Kyung Hee University, Yongin (Korea, Republic of); In, Wang Kee [KAERI, Daejeon (Korea, Republic of)

    2015-10-15

    The accident tolerant fuels (ATF) considered in this work includes metallic microcell UO{sub 2} pellets and outer Cr-based alloy coating on cladding, which is being developed in KAERI (Korea Atomic Energy Research Institute). Chromium metals have been used in many fields because of its hardness and corrosion-resistance. The use of the chromium metal in nuclear fuel rod can enhance the conductivity of pellets and corrosion-resistance of cladding. The objective of this work is to study the neutronic performances and characteristics of the commercial PWR core loaded the ATF-bearing assemblies. In this work, we studied the PWR cores which are loaded with ATF assemblies to improve the safety of reactor core. The ATF rod consists of the metallic microcell UO2 pellet which includes chromium of 3.34 wt% and the outer 0.05mm thick coating of Cr-based alloy with atomic number ratio of 85:15. We performed the cycle-by-cycle reload core analysis from the cycle 8 at which the ATF fuel assemblies start to be loaded into the core. The target nuclear power plant is the Hanbit-3 nuclear power plant. From the analysis, it was found that 1) the uranium enrichment is required to be increased up to 5.20/4.70 wt% in order to satisfy a required cycle length of 480 EFPDs, 2) the cycle length for the core using ATF fuel assemblies with the same uranium enrichments as those in the reference UO{sub 2} fueled core is decreased from 480 EFPDs to 430 EFPDs.

  6. Positive regulation by γ-aminobutyric acid B receptor subunit-1 of chondrogenesis through acceleration of nuclear translocation of activating transcription factor-4.

    Science.gov (United States)

    Takahata, Yoshifumi; Hinoi, Eiichi; Takarada, Takeshi; Nakamura, Yukari; Ogawa, Shinya; Yoneda, Yukio

    2012-09-28

    A view that signaling machineries for the neurotransmitter γ-aminobutyric acid (GABA) are functionally expressed by cells outside the central nervous system is now prevailing. In this study, we attempted to demonstrate functional expression of GABAergic signaling molecules by chondrocytes. In cultured murine costal chondrocytes, mRNA was constitutively expressed for metabotropic GABA(B) receptor subunit-1 (GABA(B)R1), but not for GABA(B)R2. Immunohistochemical analysis revealed the predominant expression of GABA(B)R1 by prehypertrophic to hypertrophic chondrocytes in tibial sections of newborn mice. The GABA(B)R agonist baclofen failed to significantly affect chondrocytic differentiation determined by Alcian blue staining and alkaline phosphatase activity in cultured chondrocytes, whereas newborn mice knocked out of GABA(B)R1 (KO) showed a decreased body size and delayed calcification in hyoid bone and forelimb and hindlimb digits. Delayed calcification was also seen in cultured metatarsals from KO mice with a marked reduction of Indian hedgehog gene (Ihh) expression. Introduction of GABA(B)R1 led to synergistic promotion of the transcriptional activity of activating transcription factor-4 (ATF4) essential for normal chondrogenesis, in addition to facilitating ATF4-dependent Ihh promoter activation. Although immunoreactive ATF4 was negligibly detected in the nucleus of chondrocytes from KO mice, ATF4 expression was again seen in the nucleus and cytoplasm after the retroviral introduction of GABA(B)R1 into cultured chondrocytes from KO mice. In nuclear extracts of KO chondrocytes, a marked decrease was seen in ATF4 DNA binding. These results suggest that GABA(B)R1 positively regulates chondrogenesis through a mechanism relevant to the acceleration of nuclear translocation of ATF4 for Ihh expression in chondrocytes. PMID:22879594

  7. 基于单片机控制的数字温度计的设计%Design of digital thermometer based on microcontroller

    Institute of Scientific and Technical Information of China (English)

    胡明钦

    2011-01-01

    Aiming at the requirement of high-precision temperature measurement on most practical application occasions, this paper presented a design scheme of high-precision thermometer based on ATF1504 and smallest system of single-chip computer and adopted by same accuracy frequency measurement technique. In this design, ATF1504 chip is as a programmable logic device, and NTC (Negative Temperature Coefficient)is as temperature sensor. The small accuracy frequency measurement technique is adopted in the thermometer using ATF1504 chip and single-chip computer, which realized temperature precision measurement The experiment results show that the measurement temperature relative error of the designed thermometer is less than 0.3% . The experiments on most practical application occasions show that the thermometer possesses stable operation and high reliability.%基于实际应用中许多场合对温度高精度测量的需求,利用ATF1504芯片与单片机最小系统,采用等精度频率测量技术,设计了一款高精度数字温度计.该方案采用ATF1504芯片作为可编程逻辑器件,以高灵敏度负温度系数热敏电阻为温度传感器.利用ATF1504芯片与单片机配合完成待测信号频率的精确测量,从而实现温度的精确测量.实验数据表明该温度计的测温相对误差小于0.3%.

  8. Psychological stress, cocaine and natural reward each induce endoplasmic reticulum stress genes in rat brain.

    Science.gov (United States)

    Pavlovsky, A A; Boehning, D; Li, D; Zhang, Y; Fan, X; Green, T A

    2013-08-29

    Our prior research has shown that the transcription of endoplasmic reticulum (ER) stress transcription factors activating transcription factor 3 (ATF3) and ATF4 are induced by amphetamine and restraint stress in rat striatum. However, presently the full extent of ER stress responses to psychological stress or cocaine, and which of the three ER stress pathways is activated is unknown. The current study examines transcriptional responses of key ER stress target genes subsequent to psychological stress or cocaine. Rats were subjected to acute or repeated restraint stress or cocaine treatment and mRNA was isolated from dorsal striatum, medial prefrontal cortex and nucleus accumbens brain tissue. ER stress gene mRNA expression was measured using quantitative polymerase chain reaction (PCR) and RNA sequencing. Restraint stress and cocaine-induced transcription of the classic ER stress-induced genes (BIP, CHOP, ATF3 and GADD34) and of two other ER stress components x-box binding protein 1 (XBP1) and ATF6. In addition, rats living in an enriched environment (large group cage with novel toys changed daily) exhibited rapid induction of GADD34 and ATF3 after 30 min of exploring novel toys, suggesting these genes are also involved in normal non-pathological signaling. However, environmental enrichment, a paradigm that produces protective addiction and depression phenotypes in rats, attenuated the rapid induction of ATF3 and GADD34 after restraint stress. These experiments provide a sensitive measure of ER stress and, more importantly, these results offer good evidence of the activation of ER stress mechanisms from psychological stress, cocaine and natural reward. Thus, ER stress genes may be targets for novel therapeutic targets for depression and addiction. PMID:23644055

  9. The p16-specific reactivation and inhibition of cell migration through demethylation of CpG islands by engineered transcription factors.

    Science.gov (United States)

    Zhang, Baozhen; Xiang, Shengyan; Zhong, Qiming; Yin, Yanru; Gu, Liankun; Deng, Dajun

    2012-10-01

    Methylation of CpG islands inactivates transcription of tumor suppressor genes including p16 (CDKN2A). Inhibitors of DNA methylation and histone deacylation are recognized as useful cancer therapeutic chemicals through reactivation of the expression of methylated genes. However, these inhibitors are not target gene-specific, so that they lead to serious side effects as regular cytotoxic chemotherapy agents. To explore the feasibility of methylated gene-specific reactivation by artificial transcription factors, we engineered a set of Sp1-like seven-finger zinc-finger proteins (7ZFPs) targeted to a 21-bp sequence of the p16 promoter and found that these 7ZFPs could bind specifically to the target p16 promoter probe. Then the p16-specific artificial transcription factors (p16ATFs) were made from these 7ZFPs and the transcription activator VP64. Results showed that transient transfection of some p16ATFs selectively up-regulated the endogenous p16 expression in the p16-active 293T cells. Moreover, the transient transfection of the representative p16ATF-6I specifically reactivated p16 expression in the p16-methylated H1299 and AGS cells pretreated with a nontoxic amount of 5'-aza-deoxycytidine (20 and 80 nM, respectively). In addition, stable transfection of the p16ATF induced demethylation of p16 CpG island and trimethylation of histone H3K4, and inhibited recruitment of DNA methyltransferase 1 and trimethylation of H3K9 and H3K27 in the p16 promoter in H1299 cells without 5'-aza-deoxycytidine pretreatment. Notably, inhibition of cell migration and invasion was observed in these p16-reactivated cells induced by transient and stable p16ATF transfection. These results demonstrate that p16ATF not only specifically reactivates p16 expression through demethylation of CpG islands, but also restores methylated p16 function. PMID:22738793

  10. Prevention of Paclitaxel-induced allodynia by Minocycline: Effect on loss of peripheral nerve fibers and infiltration of macrophages in rats

    Directory of Open Access Journals (Sweden)

    Xin Wen-Jun

    2010-11-01

    Full Text Available Abstract Background Although paclitaxel is a frontline antineoplastic agent for treatment of solid tumors, the paclitaxel-evoked pain syndrome is a serious problem for patients. There is currently no valid drug to prevent or treat the paclitaxel-induced allodynia, partly due to lack of understanding regarding the cellular mechanism. Studies have shown that minocycline, an inhibitor of microglia/macrophage, prevented neuropathic pain and promoted neuronal survival in animal models of neurodegenerative disease. Recently, Cata et al also reported that minocycline inhibited allodynia induced by low-dose paclitaxel (2 mg/kg in rats, but the mechanism is still unclear. Results Here, we investigate by immunohistochemistry the change of intraepidermal nerve fiber (IENF in the hind paw glabrous skin, expression of macrophage and activating transcription factor 3 (ATF3 in DRG at different time points after moderate-dose paclitaxel treatment (cumulative dose 24 mg/kg; 3 × 8 mg/kg in rats. Moreover, we observe the effect of minocycline on the IENF, macrophages and ATF3. The results showed that moderate-dose paclitaxel induced a persisted, gradual mechanical allodynia, which was accompanied by the loss of IENF in the hind paw glabrous skin and up-regulation of macrophages and ATF3 in DRG in rats. The expressions of ATF3 mainly focus on the NF200-positive cells. More importantly, we observed that pretreatment of minocycline at dose of 30 mg/kg or 50 mg/kg, but not 5 mg/kg, prevented paclitaxel-evoked allodynia. The evidence from immunohistochemistry showed that 30 mg/kg minocycline rescued the degeneration of IENF, attenuated infiltration of macrophages and up-regulation of ATF3 induced by paclitaxel treatment in rats. Conclusions Minocycline prevents paclitaxel-evoked allodynia, likely due to its inhibition on loss of IENF, infiltration of macrophages and up-regulation of ATF3 in rats. The finding might provide potential target for preventing paclitaxel

  11. Interseismic Deformation of the Altyn Tagh Fault Determined by Interferometric Synthetic Aperture Radar (InSAR) Measurements

    OpenAIRE

    Sen Zhu; Caijun Xu; Yangmao Wen; Yang Liu

    2016-01-01

    The Altyn Tagh Fault (ATF) is one of the major left-lateral strike-slip faults in the northeastern area of the Tibetan Plateau. In this study, the interseismic deformation across the ATF at 85°E was measured using 216 interferograms from 33 ENVISAT advanced synthetic aperture radar images on a descending track acquired from 2003 to 2010, and 66 interferograms from 15 advanced synthetic aperture radar images on an ascending track acquired from 2005 to 2010. To retrieve the pattern of interseis...

  12. Design of the ILC Prototype FONT4 Digital Intra-Train Beam-Based Feedback System

    Energy Technology Data Exchange (ETDEWEB)

    Burrows, P.; /Queen Mary, U. of London; Christian, G.B.; Hartin, A.F.; Dabiri Khah, H.; White, G.R.; /Oxford U.; Clarke, C.C.; Perry, C.; /Oxford Instruments; Kalinin, A.; /Daresbury; McCormick, D.J.; Molloy, S.; Ross, M.C.; /SLAC

    2007-04-16

    We present the design of the FONT4 digital intra-train beam position feedback system prototype and preliminary results of initial beam tests at the Accelerator Test Facility (ATF) at KEK. The feedback system incorporates a fast analogue beam position monitor (BPM) front-end signal processor, a digital feedback board, and a kicker driver amplifier. The short bunchtrain, comprising 3 electron bunches separated by c. 150ns, in the ATF extraction line was used to test components of the prototype feedback system.

  13. NOVA TEHNOLOGIJA ADITIVA OTPORNIH NA TRENJE I NJIHOVA PRIMJENA U AUTOMATSKIM PRIJENOSNICIMA

    OpenAIRE

    Tersigni, Samuel H.; Saathoff, Lee D.; Cleveland, Christopher

    2010-01-01

    Ovaj rad prikazuje razvoj tehnologije novih aditiva koja omogućuje formulaciju fluida za automatske prijenosnike (ATF-Automatic Transmission Fluids) na osnovi mineralnih ulja sa značajno poboljšanom otpornošću na trenje. U radu se uspoređuju performance trenja tehnologije novih aditiva kod komercijalno dostupnih ATF-a u Europi, Aziji i Sjevernoj Americi pri industrijski standardnim testovima trenja kao što su SAE No’2 rig (SAE No'2 mjerna oprema) i Low Velocity Friction Apparatus (aparatura z...

  14. Design of the ILC Prototype FONT4 Digital Intra-Train Beam-Based Feedback System

    International Nuclear Information System (INIS)

    We present the design of the FONT4 digital intra-train beam position feedback system prototype and preliminary results of initial beam tests at the Accelerator Test Facility (ATF) at KEK. The feedback system incorporates a fast analogue beam position monitor (BPM) front-end signal processor, a digital feedback board, and a kicker driver amplifier. The short bunchtrain, comprising 3 electron bunches separated by c. 150ns, in the ATF extraction line was used to test components of the prototype feedback system

  15. Endoplasmic Reticulum Stress-Induced Activation of Activating Transcription Factor 6 Decreases Insulin Gene Expression via Up-Regulation of Orphan Nuclear Receptor Small Heterodimer Partner

    OpenAIRE

    Seo, Hye-Young; Kim, Yong Deuk; Lee, Kyeong-Min; Min, Ae-Kyung; Kim, Mi-Kyung; Kim, Hye-Soon; Won, Kyu-Chang; Park, Joong-Yeol; Lee, Ki-Up; Choi, Hueng-Sik; Park, Keun-Gyu; Lee, In-Kyu

    2008-01-01

    The highly developed endoplasmic reticulum (ER) structure of pancreatic β-cells is a key factor in β-cell function. Here we examined whether ER stress-induced activation of activating transcription factor (ATF)-6 impairs insulin gene expression via up-regulation of the orphan nuclear receptor small heterodimer partner (SHP; NR0B2), which has been shown to play a role in β-cell dysfunction. We examined whether ER stress decreases insulin gene expression, and this process is mediated by ATF6. A...

  16. Optimization of parameters for the inline-injection system at Brookhaven Accelerator Test Facility

    Energy Technology Data Exchange (ETDEWEB)

    Parsa, Z. [Brookhaven National Lab., Upton, NY (United States); Ko, S.K. [Ulsan Univ. (Korea, Republic of)

    1995-10-01

    We present some of our parameter optimization results utilizing code PARMLEA, for the ATF Inline-Injection System. The new solenoid-Gun-Solenoid -- Drift-Linac Scheme would improve the beam quality needed for FEL and other experiments at ATF as compared to the beam quality of the original design injection system. To optimize the gain in the beam quality we have considered various parameters including the accelerating field gradient on the photoathode, the Solenoid field strengths, separation between the gun and entrance to the linac as well as the (type size) initial charge distributions. The effect of the changes in the parameters on the beam emittance is also given.

  17. Estimativa da degradabilidade ruminal de quatro genótipos de sorgo (Sorghum bicolor (L. Moench utilizando a técnica in situ - DOI: 10.4025/actascianimsci.v27i4.1150 Estimation of ruminal degradability of four genotypes of sorghum (Sorghum bicolor (L. Moench using in situ technique - DOI: 10.4025/actascianimsci.v27i4.1150

    Directory of Open Access Journals (Sweden)

    Eloísa de Oliveira Simões Saliba

    2005-03-01

    Full Text Available O experimento foi conduzido com o objetivo de avaliar a degradabilidade in situ da matéria seca (MS, da fibra em detergente neutro (FDN e da fibra em detergente ácido (FDA do material original de quatro genótipos de sorgo (ATF53*9929036; ATF54*9929036; CMSXS217*9929012 e VOLUMAX. Foram utilizadas 4 vacas Holandesas providas de fistula ruminal alimentadas com silagem de sorgo “ad libitun” e dois quilos de concentrado. O delineamento experimental foi o de blocos inteiramente ao acaso, com quatro repetições (animais, em arranjo de parcelas subdivididas. Os genótipos constituíram as parcelas e os tempos de digestão as sub-parcelas. O genótipo VOLUMAX foi o que apresentou a maior degradabilidade efetiva (DE da MS (56,22; 53,35 e 50,90% em relação aos demais em todas as taxas de passagem (2, 5 e 8%/h respectivamente e os genótipos ATF53*992903 e ATF54*9929036 obtiveram a maior DE da FDN (32,17 e 33,47%, respectivamente e FDA (34,81 e 35,50%, respectivamente para uma taxa de passagem de 2%/hThis experiment was carried out to evaluate “in situ” degradability of dry matter, neutral detergent fiber (NDF and acid detergent fiber (ADF of four sorghum genotypes (ATF53*9929036; ATF54*9929036; 217*9929012 and VOLUMAX. Four Holstein cows with ruminal fistula were fed on sorghum silage “ad libitum”, and 2.0 kg of concentrate. The animals were alloted in a randomized block design, with four replicates, in a split plot arrangement. The genotypes were considered the parcels and the incubation time the sub-parcels. The higher effective dry matter degradability were found in VOLUMAX genotype, (56.22; 53.35 and 50.90% for all passage rates, (2; 5 and 8%/h, respectively. The genotypes ATF53*992903 and ATF54*9929036 showed higher NDF effective degradability, 32.17 and 33.47% respectively, and ADF effective degradability, 34.81 and 35.50%, at 2%/h passage rate

  18. A Scoping Analysis Of The Impact Of SiC Cladding On Late-Phase Accident Progression Involving Core–Concrete Interaction

    Energy Technology Data Exchange (ETDEWEB)

    Farmer, M. T. [Argonne National Lab. (ANL), Argonne, IL (United States)

    2015-11-01

    The overall objective of the current work is to carry out a scoping analysis to determine the impact of ATF on late phase accident progression; in particular, the molten core-concrete interaction portion of the sequence that occurs after the core debris fails the reactor vessel and relocates into containment. This additional study augments previous work by including kinetic effects that govern chemical reaction rates during core-concrete interaction. The specific ATF considered as part of this study is SiC-clad UO2.

  19. Heat Stress Induces Apoptosis through a Ca2+-Mediated Mitochondrial Apoptotic Pathway in Human Umbilical Vein Endothelial Cells

    OpenAIRE

    Li Li; Hongping Tan; Zhengtao Gu; Zhifeng Liu; Yan Geng; Yunsong Liu; Huasheng Tong; Youqing Tang; Junmin Qiu; Lei Su

    2014-01-01

    Background Heat stress can be acutely cytotoxic, and heat stress-induced apoptosis is a prominent pathological feature of heat-related illnesses, although the precise mechanisms by which heat stress triggers apoptosis are poorly defined. Methods The percentages of viability and cell death were assessed by WST-1 and LDH release assays. Apoptosis was assayed by DNA fragmentation and caspase activity. Expression of cleaved PARP, Apaf-1, phospho-PERK, Phospho-eIF2a, ATF4, XBP-1s, ATF6, GRP78, pho...

  20. Westinghouse accident tolerant fuel program. Current results and future plans

    Energy Technology Data Exchange (ETDEWEB)

    Ray, Sumit; Xu, Peng; Lahoda, Edward; Hallstadius, Lars; Boylan, Frank [Westinghouse Electric Company LLC, Hopkins, SC (United States)

    2016-07-15

    This paper discusses the current status, results from initial tests, as well as the future direction of the Westinghouse's Accident Tolerant Fuel (ATF) program. The current preliminary testing is addressed that is being performed on these samples at the Massachusetts Institute of Technology (MIT) test reactor, initial results from these tests, as well as the technical learning from these test results. In the Westinghouse ATF approach, higher density pellets play a significant role in the development of an integrated fuel system.

  1. Propagation of a beam halo in accelerator test facility 2 at KEK

    Institute of Scientific and Technical Information of China (English)

    BAI Sha; P.Bambade; GAO Jie

    2013-01-01

    The beam halo is a major issue for interaction region (IR) backgrounds at many colliders,for example,future linear colliders,B factories,and also it is an important problem at ATF2.In this paper,we report on the halo propagation along the ATF2 beam line with realistic apertures,the nonlinear optics influence on the increasing number of halo particles input is analyzed,and the transmitted halo particles distribution just before the last BPM is then described,the results from which will benefit the Compton recoil electrons measurement.

  2. Creep and locking of a low-angle normal fault: Insights from the Altotiberina fault in the Northern Apennines (Italy)

    Science.gov (United States)

    Anderlini, L.; Serpelloni, E.; Belardinelli, M. E.

    2016-05-01

    While low-angle normal faults have been recognized worldwide from geological studies, whether these structures are active or capable of generating big earthquakes is still debated. We provide new constraints on the role and modes of the Altotiberina fault (ATF) in accommodating extension in the Northern Apennines. We model GPS velocities to study block kinematics, faults slip rates and interseismic coupling of the ATF, which is active and accounts, with its antithetic fault, for a large part of the observed chain normal 3 mm/yr tectonic extension. A wide portion of the ATF creeps at the long-term slip rate (1.7 ± 0.3 mm/yr), but the shallow locked portions are compatible with M > 6.5 earthquakes. We suggest that positive stress accumulation due to ATF creep is most likely released by more favorable oriented splay faults, whose rupture may propagate downdip along low-angle normal fault surface and reduce the probability of occurrence of a seismic rupture of the shallower locked portion.

  3. 77 FR 36433 - Proposed Establishment of the Elkton Oregon Viticultural Area

    Science.gov (United States)

    2012-06-19

    ... Federal Register on March 29, 1984 (49 FR 12246). According to T.D. ATF-170, the Umpqua Valley... (69 FR 70889). The Southern Oregon viticultural area boundary encompasses the established Umpqua.... To the west, the Coast Range casts a rain shadow on the south and east parts of the Southern...

  4. 77 FR 56539 - Revision to Vintage Date Requirements

    Science.gov (United States)

    2012-09-13

    ... in the Federal Register (76 FR 68373) proposing to amend Sec. 4.27 to allow vintage labeling for... the Federal Register (43 FR 37672) by TTB's predecessor agency, the Bureau of Alcohol, Tobacco and... published in the Federal Register (42 FR 30517) on June 15, 1977, ATF noted that the wine industry...

  5. Reinstate the Damaged VEGF Signaling Pathway with VEGF-activating Transcription Factor

    Institute of Scientific and Technical Information of China (English)

    Yao-guo Yang; Heng Guan; Chang-wei Liu; Yong-jun Li

    2009-01-01

    Objective To investigate the role of vascular endothelial growth factor-activating transcriptional factor(VEGF-ATF)on the VEGF signaling pathway in diabetes mellitus.Methods Totally,20 C57BL/6 mice fed with high fat diet was induced into diabetes mellitus.Ten diabetes mellitus mice received a lower limb muscle injection with VEGF-ATF plasmid,and another ten were as control.VEGF-ATF is an engineered transcription factor designed to increase VEGF expression.Three days later,mice were sacrificed and the injected gastrocnemius was used for analysis.VEGF mRNA and protein expressions were examined by real-time PCR and ELISA respectively.VEGF receptor 2 mRNA expression was tested with RT-PCR.Phosphorylated Akt,Akt,endothelial nitric oxide synthase(eNOS),and phosphorylated eNOS were assessed by western blot.Results At 3 days post-injection,in mice with diabetes mellitus,VEGF gene transfer increased VEGF mRNA copies and VEGF protein expression in injected muscles compared with control;and reinstated the impaired VEGF signaling pathway with increasing the ratios of phosphorylated Akt/Akt and phosphorylated eNOS/eNOS.However,it did not affect the expression of VEGF receptor 2 mRNA.Conclusion Gene transfer with VEGF-ATF is able to reinstate the impaired VEGF downstream pathway,and potentially promote therapeutic angiogenesis in mice with diabetes mcllitus.

  6. SSX2 is a novel DNA-binding protein that antagonizes polycomb group body formation and gene repression

    DEFF Research Database (Denmark)

    Gjerstorff, Morten; Greve, Katrine Buch Vidén; Møller, Jesper Bonnet;

    2-mediated derepression of the PcG target gene ATF3 is associated with widespread binding of SSX2 to this gene and a reduction in BMI1 and histone H3K27me3 at the proximal promoter. SSX2 binds double-stranded DNA in a sequence non-specific manner, suggesting that it modulates PcG activity through...

  7. 78 FR 58049 - Proposed Establishment of the Adelaida District, Creston District, El Pomar District, Paso Robles...

    Science.gov (United States)

    2013-09-20

    ... alluvial calcareous soils soils with silty sandy, and terrace soils, of residual and clay loam gravelly..., at 74 FR 3425). Overview of the Paso Robles Viticultural Area The Paso Robles viticultural area... with Monterey County (see T.D. ATF-148, published in the Federal Register on October 4, 1983, at 48...

  8. 76 FR 5473 - Technical Corrections to the TTB Regulations

    Science.gov (United States)

    2011-02-01

    ... nonbeverage drawback is available, and this change was incorporated into part 17 by T.D. ATF-379 (61 FR 31412... its regulations. These amendments correct grammatical, spelling and typographical errors, update cross... other non-substantive corrections and clarifications. These amendments do not change the...

  9. 78 FR 2363 - Notification of Deletion of a System of Records; Automated Trust Funds Database

    Science.gov (United States)

    2013-01-11

    ... Agriculture (USDA) published in the Federal Register (73 FR 23414- 23416, Docket No. APHIS-2008-0026) a system of records notice establishing the Automated Trust Funds (ATF) database system of records. The...; ] DEPARTMENT OF AGRICULTURE Office of the Secretary Notification of Deletion of a System of Records;...

  10. Experiment list: SRX150420 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available s=Leukemia Chronic Myelogenous 67204862,91.9,16.4,23635 GSM935340: Harvard ChipSeq K562 ATF1 (06-325) std so...urce_name=K562 || biomaterial_provider=ATCC || lab=Harvard || lab description=Struhl - Harvard University ||

  11. Experiment list: SRX150471 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available s=Leukemia Chronic Myelogenous 34337514,69.2,8.6,1665 GSM935391: Harvard ChipSeq K562 ATF3 std source_name=K...562 || biomaterial_provider=ATCC || lab=Harvard || lab description=Struhl - Harvard University || datatype=C

  12. An Integrated Real-Time Beamforming and Postfiltering System for Nonstationary Noise Environments

    Directory of Open Access Journals (Sweden)

    Gannot Sharon

    2003-01-01

    Full Text Available We present a novel approach for real-time multichannel speech enhancement in environments of nonstationary noise and time-varying acoustical transfer functions (ATFs. The proposed system integrates adaptive beamforming, ATF identification, soft signal detection, and multichannel postfiltering. The noise canceller branch of the beamformer and the ATF identification are adaptively updated online, based on hypothesis test results. The noise canceller is updated only during stationary noise frames, and the ATF identification is carried out only when desired source components have been detected. The hypothesis testing is based on the nonstationarity of the signals and the transient power ratio between the beamformer primary output and its reference noise signals. Following the beamforming and the hypothesis testing, estimates for the signal presence probability and for the noise power spectral density are derived. Subsequently, an optimal spectral gain function that minimizes the mean square error of the log-spectral amplitude (LSA is applied. Experimental results demonstrate the usefulness of the proposed system in nonstationary noise environments.

  13. Astrometric telescope facility. Preliminary systems definition study. Volume 3: Cost estimate

    Science.gov (United States)

    Sobeck, Charlie (Editor)

    1987-01-01

    The results of the Astrometric Telescope Facility (ATF) Preliminary System Definition Study conducted in the period between March and September 1986 are described. The main body of the report consists primarily of the charts presented at the study final review which was held at NASA Ames Research Center on July 30 and 31, 1986. The charts have been revised to reflect the results of that review. Explanations for the charts are provided on the adjoining pages where required. Note that charts which have been changed or added since the review are dated 10/1/86; unchanged charts carry the review date 7/30/86. In addition, a narrative summary is presented of the study results and two appendices. The first appendix is a copy of the ATF Characteristics and Requirements Document generated as part of the study. The second appendix shows the inputs to the Space Station Mission Requirements Data Base submitted in May 1986. The report is issued in three volumes. Volume 1 contains an executive summary of the ATF mission, strawman design, and study results. Volume 2 contains the detailed study information. Volume 3 has the ATF cost estimate, and will have limited distribution.

  14. Acquisition of Chemoresistance and Other Malignancy-related Features of Colorectal Cancer Cells Are Incremented by Ribosome-inactivating Stress.

    Science.gov (United States)

    Oh, Chang-Kyu; Lee, Seung Joon; Park, Seong-Hwan; Moon, Yuseok

    2016-05-01

    Colorectal cancer (CRC) as an environmental disease is largely influenced by accumulated epithelial stress from diverse environmental causes. We are exposed to ribosome-related insults, including ribosome-inactivating stress (RIS), from the environment, dietary factors, and medicines, but their physiological impacts on the chemotherapy of CRC are not yet understood. Here we revealed the effects of RIS on chemosensitivity and other malignancy-related properties of CRC cells. First, RIS led to bidirectional inhibition of p53-macrophage inhibitory cytokine 1 (MIC-1)-mediated death responses in response to anticancer drugs by either enhancing ATF3-linked antiapoptotic signaling or intrinsically inhibiting MIC-1 and p53 expression, regardless of ATF3. Second, RIS enhanced the epithelial-mesenchymal transition and biogenesis of cancer stem-like cells in an ATF3-dependent manner. These findings indicate that gastrointestinal exposure to RIS interferes with the efficacy of chemotherapeutics, mechanistically implying that ATF3-linked malignancy and chemoresistance can be novel therapeutic targets for the treatment of environmentally aggravated cancers.

  15. 75 FR 9827 - Proposed Expansion of the Santa Maria Valley Viticultural Area (2008R-287P)

    Science.gov (United States)

    2010-03-04

    ... predecessor agency, published T.D. ATF-89 in the Federal Register (46 FR 39811), establishing the Santa Maria... its intersection with U.S. Route 101, according to the written boundary description and accompanying... nestled along foothills, slightly above the valley floor. A graph in the petition presents...

  16. 75 FR 81846 - Expansion of the Santa Maria Valley Viticultural Area

    Science.gov (United States)

    2010-12-29

    ..., published T.D. ATF-89 in the Federal Register at 46 FR 39811 (August 5, 1981), establishing the Santa Maria... Hills to its intersection with U.S. Route 101, according to the boundary description and USGS maps... graph in the petition presents heat accumulation data recorded in 2004 at the two stations. The...

  17. Activating transcription factor 6 derepression mediates neuroprotection in Huntington disease

    Science.gov (United States)

    Naranjo, José R.; Zhang, Hongyu; Villar, Diego; González, Paz; Dopazo, Xose M.; Morón-Oset, Javier; Higueras, Elena; Oliveros, Juan C.; Arrabal, María D.; Prieto, Angela; Cercós, Pilar; González, Teresa; De la Cruz, Alicia; Casado-Vela, Juan; Rábano, Alberto; Valenzuela, Carmen; Gutierrez-Rodriguez, Marta; Li, Jia-Yi; Mellström, Britt

    2016-01-01

    Deregulated protein and Ca2+ homeostasis underlie synaptic dysfunction and neurodegeneration in Huntington disease (HD); however, the factors that disrupt homeostasis are not fully understood. Here, we determined that expression of downstream regulatory element antagonist modulator (DREAM), a multifunctional Ca2+-binding protein, is reduced in murine in vivo and in vitro HD models and in HD patients. DREAM downregulation was observed early after birth and was associated with endogenous neuroprotection. In the R6/2 mouse HD model, induced DREAM haplodeficiency or blockade of DREAM activity by chronic administration of the drug repaglinide delayed onset of motor dysfunction, reduced striatal atrophy, and prolonged life span. DREAM-related neuroprotection was linked to an interaction between DREAM and the unfolded protein response (UPR) sensor activating transcription factor 6 (ATF6). Repaglinide blocked this interaction and enhanced ATF6 processing and nuclear accumulation of transcriptionally active ATF6, improving prosurvival UPR function in striatal neurons. Together, our results identify a role for DREAM silencing in the activation of ATF6 signaling, which promotes early neuroprotection in HD. PMID:26752648

  18. 77 FR 33625 - Firearms Disabilities for Certain Nonimmigrant Aliens (2001R-332P)

    Science.gov (United States)

    2012-06-07

    ... firearms disabilities for nonimmigrant aliens (67 FR 5422). On that same date, ATF also published in the Federal Register a proposed rule soliciting comments on the interim regulations (Notice No. 935, 67 FR... States.'' 67 FR 5424. In short, the permit process is designed to ensure that the nonimmigrant aliens...

  19. Activating transcription factor 6 derepression mediates neuroprotection in Huntington disease.

    Science.gov (United States)

    Naranjo, José R; Zhang, Hongyu; Villar, Diego; González, Paz; Dopazo, Xose M; Morón-Oset, Javier; Higueras, Elena; Oliveros, Juan C; Arrabal, María D; Prieto, Angela; Cercós, Pilar; González, Teresa; De la Cruz, Alicia; Casado-Vela, Juan; Rábano, Alberto; Valenzuela, Carmen; Gutierrez-Rodriguez, Marta; Li, Jia-Yi; Mellström, Britt

    2016-02-01

    Deregulated protein and Ca2+ homeostasis underlie synaptic dysfunction and neurodegeneration in Huntington disease (HD); however, the factors that disrupt homeostasis are not fully understood. Here, we determined that expression of downstream regulatory element antagonist modulator (DREAM), a multifunctional Ca2+-binding protein, is reduced in murine in vivo and in vitro HD models and in HD patients. DREAM downregulation was observed early after birth and was associated with endogenous neuroprotection. In the R6/2 mouse HD model, induced DREAM haplodeficiency or blockade of DREAM activity by chronic administration of the drug repaglinide delayed onset of motor dysfunction, reduced striatal atrophy, and prolonged life span. DREAM-related neuroprotection was linked to an interaction between DREAM and the unfolded protein response (UPR) sensor activating transcription factor 6 (ATF6). Repaglinide blocked this interaction and enhanced ATF6 processing and nuclear accumulation of transcriptionally active ATF6, improving prosurvival UPR function in striatal neurons. Together, our results identify a role for DREAM silencing in the activation of ATF6 signaling, which promotes early neuroprotection in HD. PMID:26752648

  20. Shikonin Suppresses Skin Carcinogenesis via Inhibiting Cell Proliferation.

    Science.gov (United States)

    Li, Wenjuan; Zhang, Chunjing; Ren, Amy; Li, Teena; Jin, Rong; Li, Guohong; Gu, Xin; Shi, Runhua; Zhao, Yunfeng

    2015-01-01

    The M2 isoform of pyruvate kinase M2 (PKM2) has been shown to be up-regulated in human skin cancers. To test whether PKM2 may be a target for chemoprevention, shikonin, a natural product from the root of Lithospermum erythrorhizon and a specific inhibitor of PKM2, was used in a chemically-induced mouse skin carcinogenesis study. The results revealed that shikonin treatment suppressed skin tumor formation. Morphological examinations and immunohistochemical staining of the skin epidermal tissues suggested that shikonin inhibited cell proliferation without inducing apoptosis. Although shikonin alone suppressed PKM2 activity, it did not suppress tumor promoter-induced PKM2 activation in the skin epidermal tissues at the end of the skin carcinogenesis study. To reveal the potential chemopreventive mechanism of shikonin, an antibody microarray analysis was performed, and the results showed that the transcription factor ATF2 and its downstream target Cdk4 were up-regulated by chemical carcinogen treatment; whereas these up-regulations were suppressed by shikonin. In a promotable skin cell model, the nuclear levels of ATF2 were increased during tumor promotion, whereas this increase was inhibited by shikonin. Furthermore, knockdown of ATF2 decreased the expression levels of Cdk4 and Fra-1 (a key subunit of the activator protein 1. In summary, these results suggest that shikonin, rather than inhibiting PKM2 in vivo, suppresses the ATF2 pathway in skin carcinogenesis. PMID:25961580

  1. 77 FR 27001 - Proposed Establishment of the Ancient Lakes of Columbia Valley Viticultural Area

    Science.gov (United States)

    2012-05-08

    ... USGS map markings. Ancient Lakes of Columbia Valley Petition TTB received a petition from Joan R... grapevine growth (``General Viticulture,'' by Albert J. Winkler, University of California Press, 1974, pages... by T.D. ATF-190, which published in the Federal Register (49 FR 44895) on November 13, 1984. T.D....

  2. 19 CFR 19.38 - Supervision of exportation.

    Science.gov (United States)

    2010-04-01

    ... cigarettes and cigars from ATF export bonded warehouses (see 27 CFR part 290) in conjunction with exportation... 19 Customs Duties 1 2010-04-01 2010-04-01 false Supervision of exportation. 19.38 Section 19.38... Supervision of exportation. (a) Sales ticket withdrawals. Conditionally duty-free merchandise withdrawn...

  3. A Laser-Wire System for the International Linear Collider

    Energy Technology Data Exchange (ETDEWEB)

    Delerue, N.; Dixit, S.; Gannaway, F.; Howell, D.; Qurshi, M.; Blair, G.; Boogert, S.; Boorman, G.; Driouichi, C.; Deacon, L.; Aryshev, A.; Karataev, P.; Terunuma, N.; Urakawa, J.; Brachmann, A.; Frisch, J.; Ross, M.; /Oxford U. /Royal Holloway, U. of London /KEK, Tsukuba /SLAC

    2009-04-30

    A new laser-wire has been installed in the extraction line of the ATF at KEK. It aims at demonstrating that laser-wires can be used to measure micrometre scale beam size. In parallel, studies have been made to specify a laser suitable for the ILC laser-wires.

  4. Pheromone synthesis in a biomicroreactor coated with anti-adsorption polyelectrolyte multilayer

    NARCIS (Netherlands)

    Dimov, Nikolay; Munoz, Lourdes; Carot-Sans, Gerard; Verhoeven, Michel L.P.M.; Bula, Wojciech P.; Kocer, Gülistan; Guerrero, Angel; Gardeniers, Han J.G.E.

    2011-01-01

    To prepare a biosynthetic module in an infochemical communication project, we designed a silicon/glass microreactor with anti-adsorption polyelectrolytemultilayer coating and immobilized alcohol acetyl transferase (atf), one of the key biosynthetic enzymes of the pheromone of Spodoptera littoralis,

  5. Lipotoxic brain microvascular injury is mediated by activating transcription factor 3-dependent inflammatory and oxidative stress pathways.

    Science.gov (United States)

    Aung, Hnin Hnin; Altman, Robin; Nyunt, Tun; Kim, Jeffrey; Nuthikattu, Saivageethi; Budamagunta, Madhu; Voss, John C; Wilson, Dennis; Rutledge, John C; Villablanca, Amparo C

    2016-06-01

    Dysfunction of the cerebrovasculature plays an important role in vascular cognitive impairment (VCI). Lipotoxic injury of the systemic endothelium in response to hydrolyzed triglyceride-rich lipoproteins (TGRLs; TGRL lipolysis products) or a high-fat Western diet (WD) suggests similar mechanisms may be present in brain microvascular endothelium. We investigated the hypothesis that TGRL lipolysis products cause lipotoxic injury to brain microvascular endothelium by generating increased mitochondrial superoxide radical generation, upregulation of activating transcription factor 3 (ATF3)-dependent inflammatory pathways, and activation of cellular oxidative stress and apoptotic pathways. Human brain microvascular endothelial cells were treated with human TGRL lipolysis products that induced intracellular lipid droplet formation, mitochondrial superoxide generation, ATF3-dependent transcription of proinflammatory, stress response, and oxidative stress genes, as well as activation of proapoptotic cascades. Male apoE knockout mice were fed a high-fat/high-cholesterol WD for 2 months, and brain microvessels were isolated by laser capture microdissection. ATF3 gene transcription was elevated 8-fold in the hippocampus and cerebellar brain region of the WD-fed animals compared with chow-fed control animals. The microvascular injury phenotypes observed in vitro and in vivo were similar. ATF3 plays an important role in mediating brain microvascular responses to acute and chronic lipotoxic injury and may be an important preventative and therapeutic target for endothelial dysfunction in VCI. PMID:27087439

  6. 49 CFR 40.225 - What form is used for an alcohol test?

    Science.gov (United States)

    2010-10-01

    ... colored paper, or have clearly discernable borders or designation statements on Copy 2 and Copy 3. When... foreign-language version of the ATF approved by ODAPC. You may use such a non-English language form only in a situation where both the employee and BAT/STT understand and can use the form in that language....

  7. 75 FR 44173 - Implementation of the USA PATRIOT Improvement and Reauthorization Act of 2005 Regarding...

    Science.gov (United States)

    2010-07-28

    ..., and Explosives, U.S. Department of Justice, 99 New York Avenue, NE., Washington, DC 20226; Attn: ATF... Explosives; U.S. Department of Justice; ] 99 New York Avenue, NE., Washington, DC 20226, telephone (202) 648... the years have established that organized crime has been involved in the diversion of legal...

  8. 75 FR 3160 - Commerce in Explosives-Storage of Shock Tube With Detonators (2005R-3P)

    Science.gov (United States)

    2010-01-20

    ... Alcohol, Tobacco, Firearms, and Explosives, U.S. Department of Justice, 99 New York Avenue, NE... the Organized Crime Control Act of 1970. One of the stated purposes of the Act is to reduce the... hours at: ATF Reading Room, Room 1E-063, 99 New York Avenue, NE., Washington, DC 20226; telephone:...

  9. Metrics for the evaluation of light water reactor accident tolerant fuel

    International Nuclear Information System (INIS)

    The safe, reliable and economic operation of the nation’s nuclear power reactor fleet has always been a top priority for the nuclear industry. Continual improvement of technology, including advanced materials and nuclear fuels, remains central to the industry’s success. Enhancing the accident tolerance of LWRs became a topic of serious discussion following the 2011 Great East Japan Earthquake, resulting tsunami, and subsequent damage to the Fukushima Daiichi nuclear power plant complex. The overall goal of accident tolerant fuel (ATF) development is to identify alternative fuel system technologies to further enhance the safety, competitiveness, and economics of commercial nuclear power. The complex multiphysics behavior of LWR nuclear fuel in the integrated reactor system makes defining specific material or design improvements difficult; as such, establishing desirable performance attributes is critical in guiding the design and development of fuels and cladding with enhanced accident tolerance. The U.S. Department of Energy is sponsoring multiple teams to develop ATF concepts within multiple national laboratories, universities, and the nuclear industry. Concepts under investigation offer both evolutionary and revolutionary changes to the current nuclear fuel system. This paper summarizes technical evaluation methodology proposed in the U.S. to aid in the optimization and down-selection of candidate ATF designs. This methodology will continue to be refined via input from the research community and industry, such that it is available to support the planned down-selection of ATF concepts in 2016. (author)

  10. 78 FR 14046 - Proposed Establishment of the Moon Mountain District Sonoma County Viticultural Area

    Science.gov (United States)

    2013-03-04

    ... advertisements. Part 9 of the TTB regulations (27 CFR part 9) sets forth standards for the preparation and... quality, reputation, or other characteristic of a wine made from grapes grown in an area to its geographic... established by T.D. ATF-96, which was published in the Federal Register on December 4, 1981 (46 FR 59238)....

  11. 78 FR 8018 - Establishment of the Indiana Uplands Viticultural Area and Modification of the Ohio River Valley...

    Science.gov (United States)

    2013-02-05

    ... origin on wine labels and in wine advertisements. Part 9 of the TTB regulations (27 CFR part 9) sets... designations allow vintners and consumers to attribute a given quality, reputation, or other characteristic of..., Kentucky, Ohio, and part of West Virginia; see T.D. ATF-144, published in the Federal Register (48 FR...

  12. 76 FR 77696 - Establishment of the Naches Heights Viticultural Area

    Science.gov (United States)

    2011-12-14

    ... appellations of origin on wine labels and in wine advertisements. Part 9 of the TTB regulations (27 CFR part 9... designations allow vintners and consumers to attribute a given quality, reputation, or other characteristic of... Valley viticultural area was established by T.D. ATF-190, published in the Federal Register (49 FR...

  13. 77 FR 51698 - Authorization To Seize Property Involved in Drug Offenses for Administrative Forfeiture (2012R-9P)

    Science.gov (United States)

    2012-08-27

    ... its regulations to allow the Director of the Bureau of Alcohol, Tobacco, Firearms, and Explosives (ATF... Programs and Services, Bureau of Alcohol, Tobacco, Firearms, and Explosives, U.S. Department of Justice, 99... can be perfected in 60-90 days for minimal cost, including the statutorily required advertisement...

  14. Laser Wire and Beam Position Monitor tests

    CERN Document Server

    Boogert, S T; Lyapin, A; Nevay, L; Snuverink, J

    2013-01-01

    This subtask involved two main activities; Firstly the development and subsequent usage of high resolution beam position monitors (BPM) for the International Linear Collider (ILC) and Compact Linear Collider projects (CLIC); and secondly the development of a laser-wire (LW) transverse beam size measurement systems. This report describes the technical progress achieved at a large-scale test ILC compatible BPM system installed at the Accelerator Test Facility 2 (ATF2). The ATF2 is an energy-scaled demonstration system for the final focus systems required to deliver the particle beams to collision at the ILC and CLIC. The ATF2 cavity beam position monitor system is one of the largest of its kind and rivals systems used at free electron lasers. The ATF2 cavity beam position system has achieved a position resolutionof 250 nm (with signal attuenation) and 27 nm (without attenuation). The BPM system has been used routinely for lattice diagnostics, beam based alignment and wakefield measurements. Extensive experience...

  15. Activating transcription factor 6 derepression mediates neuroprotection in Huntington disease.

    Science.gov (United States)

    Naranjo, José R; Zhang, Hongyu; Villar, Diego; González, Paz; Dopazo, Xose M; Morón-Oset, Javier; Higueras, Elena; Oliveros, Juan C; Arrabal, María D; Prieto, Angela; Cercós, Pilar; González, Teresa; De la Cruz, Alicia; Casado-Vela, Juan; Rábano, Alberto; Valenzuela, Carmen; Gutierrez-Rodriguez, Marta; Li, Jia-Yi; Mellström, Britt

    2016-02-01

    Deregulated protein and Ca2+ homeostasis underlie synaptic dysfunction and neurodegeneration in Huntington disease (HD); however, the factors that disrupt homeostasis are not fully understood. Here, we determined that expression of downstream regulatory element antagonist modulator (DREAM), a multifunctional Ca2+-binding protein, is reduced in murine in vivo and in vitro HD models and in HD patients. DREAM downregulation was observed early after birth and was associated with endogenous neuroprotection. In the R6/2 mouse HD model, induced DREAM haplodeficiency or blockade of DREAM activity by chronic administration of the drug repaglinide delayed onset of motor dysfunction, reduced striatal atrophy, and prolonged life span. DREAM-related neuroprotection was linked to an interaction between DREAM and the unfolded protein response (UPR) sensor activating transcription factor 6 (ATF6). Repaglinide blocked this interaction and enhanced ATF6 processing and nuclear accumulation of transcriptionally active ATF6, improving prosurvival UPR function in striatal neurons. Together, our results identify a role for DREAM silencing in the activation of ATF6 signaling, which promotes early neuroprotection in HD.

  16. Bioleaching of two different types of chalcopyrite by Acidithiobacillus ferrooxidans

    Science.gov (United States)

    Dong, Ying-bo; Lin, Hai; Fu, Kai-bin; Xu, Xiao-fang; Zhou, Shan-shan

    2013-02-01

    Two different types of chalcopyrite (pyritic chalcopyrite and porphyry chalcopyrite) were bioleached with Acidithiobacillus ferrooxidans ATF6. The bioleaching of the pyritic chalcopyrite and porphyry chalcopyrite is quite different. The copper extraction reaches 46.96% for the pyritic chalcopyrite after 48-d leaching, but it is only 14.50% for the porphyry chalcopyrite. Proper amounts of initial ferrous ions can improve the efficiency of copper extraction for the two different types of chalcopyrite. The optimum dosage of ferrous ions for the pyritic chalcopyrite and porphyry chalcopyrite is different. The adsorption of ATF6 on the pyritic chalcopyrite and porphyry chalcopyrite was also studied in this paper. It is found that ATF6 is selectively adsorbed by the two different types of chalcopyrite; the higher adsorption onto the pyritic chalcopyrite than the porphyry chalcopyrite leads to the higher copper dissolution rate of the pyritic chalcopyrite. In addition, the zeta-potential of chalcopyrite before and after bioleaching further confirms that ATF6 is more easily adsorbed onto the pyritic chalcopyrite.

  17. A laser-wire system for the International Linear Collider

    Indian Academy of Sciences (India)

    Nicolas Delerue; Sudhir Dixit; Fred Gannaway; David Howell; Myriam Qurshi; Grahame Blair; Stewart Boogert; Gary Boorman; Chafik Driouichi; Lawerence Deacon; Alexander Aryshev; Pavel Karataev; Nobuhiro Terunnuma; Junji urakawa; Axel Brachmann; Joe Frisch; Marc Ross

    2007-12-01

    A new laser-wire has been installed in the extraction line of the ATF at KEK. It aims at demonstrating that laser-wires can be used to measure micrometre scale beam size. In parallel, studies have been made to specify a laser suitable for the ILC laser-wires.

  18. Shikonin Suppresses Skin Carcinogenesis via Inhibiting Cell Proliferation.

    Science.gov (United States)

    Li, Wenjuan; Zhang, Chunjing; Ren, Amy; Li, Teena; Jin, Rong; Li, Guohong; Gu, Xin; Shi, Runhua; Zhao, Yunfeng

    2015-01-01

    The M2 isoform of pyruvate kinase M2 (PKM2) has been shown to be up-regulated in human skin cancers. To test whether PKM2 may be a target for chemoprevention, shikonin, a natural product from the root of Lithospermum erythrorhizon and a specific inhibitor of PKM2, was used in a chemically-induced mouse skin carcinogenesis study. The results revealed that shikonin treatment suppressed skin tumor formation. Morphological examinations and immunohistochemical staining of the skin epidermal tissues suggested that shikonin inhibited cell proliferation without inducing apoptosis. Although shikonin alone suppressed PKM2 activity, it did not suppress tumor promoter-induced PKM2 activation in the skin epidermal tissues at the end of the skin carcinogenesis study. To reveal the potential chemopreventive mechanism of shikonin, an antibody microarray analysis was performed, and the results showed that the transcription factor ATF2 and its downstream target Cdk4 were up-regulated by chemical carcinogen treatment; whereas these up-regulations were suppressed by shikonin. In a promotable skin cell model, the nuclear levels of ATF2 were increased during tumor promotion, whereas this increase was inhibited by shikonin. Furthermore, knockdown of ATF2 decreased the expression levels of Cdk4 and Fra-1 (a key subunit of the activator protein 1. In summary, these results suggest that shikonin, rather than inhibiting PKM2 in vivo, suppresses the ATF2 pathway in skin carcinogenesis.

  19. Effect of astrocyte-targeted production of IL-6 on traumatic brain injury and its impact on the cortical transcriptome

    DEFF Research Database (Denmark)

    Quintana, Albert; Molinero, Amalia; Borup, Rehannah;

    2008-01-01

    stress (Atf4). Furthermore, the presence of IL-6 altered the expression of genes involved in hemostasis (Vwf), cell migration and proliferation (Cap2), and synaptic activity (Vamp2). All these changes in gene expression could underlie the phenotype of the GFAP-IL6 mice after injury, but many other...

  20. Variation in genes related to hepatic lipid metabolism and changes in waist circumference and body weight

    DEFF Research Database (Denmark)

    Meidtner, Karina; Fisher, Eva; Angquist, Lars;

    2014-01-01

    We analysed single nucleotide polymorphisms (SNPs) tagging the genetic variability of six candidate genes (ATF6, FABP1, LPIN2, LPIN3, MLXIPL and MTTP) involved in the regulation of hepatic lipid metabolism, an important regulatory site of energy balance for associations with body mass index (BMI...

  1. Bunch transverse emittance increase in electron storage rings

    Institute of Scientific and Technical Information of China (English)

    GAO Jie

    2009-01-01

    In this paper a theoretical framework to estimate the bunch transverse emittance growing in electron storage rings due to short range transverse wakefield of the machine is established. New equilibrium emittance equations are derived and applied to explain the experimentally obtained results in ATF damping ring. This equation will be useful for linear collider damping ring design.

  2. Closed orbit response to quadrupole strength variation

    Energy Technology Data Exchange (ETDEWEB)

    Wolski, Andrzej; Zimmermann, Frank

    2004-01-20

    We derive two formulae relating the variation in closed orbit in a storage ring to variations in quadrupole strength, neglecting nonlinear and dispersive effects. These formulae correct results previously reported [1,2,3]. We compare the results of the formulae applied to the ATF with simulations using MAD, and consider their application to beam-based alignment.

  3. Effects of chronic renal failure rat serum on histone acetyltransferase p300 and activation of activating transcription factor 4 of arterial smooth muscle cells cultured in vitro

    Institute of Scientific and Technical Information of China (English)

    张耀全

    2014-01-01

    Objective To investigate the effects of the rat serum with chronic renal failure(CRF)on ubiquitin-proteasome pathway,histone acetyltransferase p300 and activation of activating transcription factor 4(ATF4)of rat arterial vascular smooth muscle cells(VSMCs)cultured in vitro,and explore the possible mechanism.Methods Objective To establish the rat model of

  4. Interaction of Restin with transcription factors

    Institute of Scientific and Technical Information of China (English)

    WU; Yousheng; LU; Fan; QI; Yinxin; WANG; Ruihua; ZHANG; Jia

    2005-01-01

    Restin, a member of melanoma-associated antigen superfamily gene, was first cloned from differentiated leukemia cell induced by all trans-retinoic acid, and was able to inhibit cell proliferation, but the molecular mechanism was not clear. Since Restin was localized in cell nucleus, and its homolog member, Necdin (neuronal growth suppressor factor), could interact with transcription factors p53 and E2F1, we proposed that Restin might also function as Necdin through interacting with some transcription factors. In this study, transcription factors p53, AP1,ATFs and E2Fs were cloned and used in the mammalian two-hybrid system to identify their interaction with Restin. The results showed that only ATF3 had a strong interaction with Restin. It is interesting to know that ATF3 was an important transcription factor for G1 cell cycle initiation in physiological stress response. It was possible that the inhibition of cell proliferation by Restin might be related with the inhibition of ATF3 activity.

  5. Effect of injury on S1 dorsal root ganglia in an experimental model of neuropathic faecal incontinence.

    LENUS (Irish Health Repository)

    Peirce, C

    2011-08-01

    An experimental model of neuropathic faecal incontinence has recently been established. This study aimed to quantify and compare the effect of crush and compression injury on first-order sensory neurones of the inferior rectal nerve (IRN) using a nuclear marker of axonal injury, activating transcription factor (ATF) 3.

  6. 75 FR 31285 - Decision-Making Authority Regarding the Denial, Suspension, or Revocation of a Federal Firearms...

    Science.gov (United States)

    2010-06-03

    ... petition for judicial review of such action. In such case, when the DIO found that justice so required, the... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF JUSTICE Bureau...: Bureau of Alcohol, Tobacco, Firearms, and Explosives (ATF), Department of Justice. ACTION: Final...

  7. Functionalized milk-protein-coated magnetic nanoparticles for MRI-monitored targeted therapy of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Huang J

    2016-07-01

    Full Text Available Jing Huang,1,2 Weiping Qian,3 Liya Wang,1,2 Hui Wu,1 Hongyu Zhou,3 Andrew Yongqiang Wang,4 Hongbo Chen,5 Lily Yang,3 Hui Mao1,2 1Department of Radiology and Imaging Sciences, 2Center for Systems Imaging, 3Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA; 4Ocean Nanotech LLC, Springdale, AR, USA; 5School of Life and Environmental Sciences, Guilin University of Electronic Technology, Guilin, Guangxi, People’s Republic of China Abstract: Engineered nanocarriers have emerged as a promising platform for cancer therapy. However, the therapeutic efficacy is limited by low drug loading efficiency, poor passive targeting to tumors, and severe systemic side effects. Herein, we report a new class of nanoconstructs based on milk protein (casein-coated magnetic iron oxide (CNIO nanoparticles for targeted and image-guided pancreatic cancer treatment. The tumor-targeting amino-terminal fragment (ATF of urokinase plasminogen activator and the antitumor drug cisplatin (CDDP were engineered on this nanoplatform. High drug loading (~25 wt% and sustained release at physiological conditions were achieved through the exchange and encapsulation strategy. These ATF-CNIO-CDDP nanoparticles demonstrated actively targeted delivery of CDDP to orthotopic pancreatic tumors in mice. The effective accumulation and distribution of ATF-CNIO-CDDP was evidenced by magnetic resonance imaging, based on the T2-weighted contrast resulting from the specific accumulation of ATF-CNIO-CDDP in the tumor. Actively targeted delivery of ATF-CNIO-CDDP led to improved therapeutic efficacy in comparison with free CDDP and nontargeted CNIO-CDDP treatment. Meanwhile, less systemic side effects were observed in the nanocarrier-treated groups than that in the group treated with free CDDP. Hematoxylin and Eosin and Sirius Red staining of tumor sections revealed the possible disruption of stroma during the treatment with ATF-CNIO-CDDP. Overall, our results suggest that

  8. Progress on the Westinghouse Accident Tolerant Fuel Programme

    International Nuclear Information System (INIS)

    The Westinghouse led team on accident tolerant fuel (ATF) has made significant progress over the last decade on the development of economically attractive cladding and fuel options to utility customers that have the potential for increased tolerance for beyond design basis accidents. Since the occurrence of the Fukushima Daiichi accident in 2011, Westinghouse has become increasingly focused on ATF development and has accelerated the programme with support from the Department of Energy (DOE). The Westinghouse ATF designs have been motivated by significantly enhanced accident tolerance, simplified designs for future Nuclear Steam Supply Systems (NSSS), and substantially improved fuel cycle costs. To date, Westinghouse, working with its partners, has a basic concept for silicon carbide (SiC) ceramic cladding and advanced pellet designs and has also performed early tests to show viability of the chosen concepts. The Westinghouse ATF concepts include: deposition of oxidation resistant titanium-aluminium-carbide (Ti2AlC) coatings on zirconium alloy as a mid-term cladding product and SiC composites as the long-term cladding product. Regarding fuels, uranium silicide (U3Si2) pellets are being developed as a mid-term fuel product, and waterproofed uranium nitride (U15N) as the long-term fuel product. The Westinghouse ATF Program, in conjunction with its partner General Atomics, continues to advance SiC technology in the areas of fabrication, testing, and modelling. High temperature oxidation tests are ongoing at the Massachusetts Institute of Technology (MIT) to evaluate accident tolerance of this cladding. While initial efforts regarding the deposition of oxidation resistant coatings on zirconium alloy cladding did not perform as desired, the University of Wisconsin is continuing to optimize deposition parameters. Critical work also continues in the area of advanced pellet development on both U3Si2 and waterproofed uranium nitride fuels at Idaho National Laboratory (INL

  9. MK3 controls Polycomb target gene expression via negative feedback on ERK

    Directory of Open Access Journals (Sweden)

    Prickaerts Peggy

    2012-08-01

    Full Text Available Abstract Background Gene-environment interactions are mediated by epigenetic mechanisms. Polycomb Group proteins constitute part of an epigenetic cellular transcriptional memory system that is subject to dynamic modulation during differentiation. Molecular insight in processes that control dynamic chromatin association and dissociation of Polycomb repressive complexes during and beyond development is limited. We recently showed that MK3 interacts with Polycomb repressive complex 1 (PRC1. The functional relevance of this interaction, however, remained poorly understood. MK3 is activated downstream of mitogen- and stress-activated protein kinases (M/SAPKs, all of which fulfill crucial roles during development. We here use activation of the immediate-early response gene ATF3, a bona fide PRC1 target gene, as a model to study how MK3 and its effector kinases MAPK/ERK and SAPK/P38 are involved in regulation of PRC1-dependent ATF3 transcription. Results Our current data show that mitogenic signaling through ERK, P38 and MK3 regulates ATF3 expression by PRC1/chromatin dissociation and epigenetic modulation. Mitogenic stimulation results in transient P38-dependent H3S28 phosphorylation and ERK-driven PRC1/chromatin dissociation at PRC1 targets. H3S28 phosphorylation by itself appears not sufficient to induce PRC1/chromatin dissociation, nor ATF3 transcription, as inhibition of MEK/ERK signaling blocks BMI1/chromatin dissociation and ATF3 expression, despite induced H3S28 phosphorylation. In addition, we establish that concomitant loss of local H3K27me3 promoter marking is not required for ATF3 activation. We identify pERK as a novel signaling-induced binding partner of PRC1, and provide evidence that MK3 controls ATF3 expression in cultured cells via negative regulatory feedback on M/SAPKs. Dramatically increased ectopic wing vein formation in the absence of Drosophila MK in a Drosophila ERK gain-of-function wing vein patterning model, supports the

  10. Late Cenozoic transpressional mountain building directly north of the Altyn Tagh Fault in the Sanweishan and Nanjieshan, North Tibetan Foreland, China

    Science.gov (United States)

    Cunningham, Dickson; Zhang, Jin; Li, Yanfeng

    2016-09-01

    For many tectonicists, the structural development of the northern Tibetan Plateau stops at the Altyn Tagh Fault (ATF). This study challenges that assumption. Structural field observations and remote sensing analysis indicate that the Sanweishan and Nanjieshan basement cored ridges of the Archean Dunhuang Block, which interrupt the north Tibetan foreland directly north of the ATF, are bound and cut by an array of strike-slip, thrust and oblique-slip faults that have been active in the Quaternary and remain potentially active. The Sanweishan is a SE-tilted block that is bound on its NW margin by a steep south-dipping thrust fault that has also accommodated sinistral strike-slip displacements. The Nanjieshan consists of parallel, but offset basement ridges that record NNW and SSE thrust displacements and sinistral strike-slip. Regional folds characterize the extreme eastern Nanjieshan and appear to have formed above blind thrust faults which break the surface further west. Previously published magnetotelluric data suggest that the major faults of the Sanweishan and Nanjieshan ultimately root to the south within conductive zones that are inferred to merge into the ATF. Therefore, although the southern margin of the Dunhuang Block focuses significant deformation along the ATF, the adjacent cratonic basement to the north is also affected. Collectively, the ATF and structurally linked Sanweishan and Nanjieshan fault array represent a regional asymmetric half-flower structure that is dominated by non-strain partitioned sinistral transpression. The NW-trending Dengdengshan thrust fault system near Yumen City appears to define the northeastern limit of the Sanweishan-Nanjieshan block, which may be regionally viewed as the most northern, but early-stage expression of Tibetan Plateau growth into a slowly deforming, mechanically stiff Archean craton.

  11. Genetic interactions due to constitutive and inducible gene regulation mediated by the unfolded protein response in C. elegans.

    Directory of Open Access Journals (Sweden)

    Xiaohua Shen

    2005-09-01

    Full Text Available The unfolded protein response (UPR is an adaptive signaling pathway utilized to sense and alleviate the stress of protein folding in the endoplasmic reticulum (ER. In mammals, the UPR is mediated through three proximal sensors PERK/PEK, IRE1, and ATF6. PERK/PEK is a protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 to inhibit protein synthesis. Activation of IRE1 induces splicing of XBP1 mRNA to produce a potent transcription factor. ATF6 is a transmembrane transcription factor that is activated by cleavage upon ER stress. We show that in Caenorhabditis elegans, deletion of either ire-1 or xbp-1 is synthetically lethal with deletion of either atf-6 or pek-1, both producing a developmental arrest at larval stage 2. Therefore, in C. elegans, atf-6 acts synergistically with pek-1 to complement the developmental requirement for ire-1 and xbp-1. Microarray analysis identified inducible UPR (i-UPR genes, as well as numerous constitutive UPR (c-UPR genes that require the ER stress transducers during normal development. Although ire-1 and xbp-1 together regulate transcription of most i-UPR genes, they are each required for expression of nonoverlapping sets of c-UPR genes, suggesting that they have distinct functions. Intriguingly, C. elegans atf-6 regulates few i-UPR genes following ER stress, but is required for the expression of many c-UPR genes, indicating its importance during development and homeostasis. In contrast, pek-1 is required for induction of approximately 23% of i-UPR genes but is dispensable for the c-UPR. As pek-1 and atf-6 mainly act through sets of nonoverlapping targets that are different from ire-1 and xbp-1 targets, at least two coordinated responses are required to alleviate ER stress by distinct mechanisms. Finally, our array study identified the liver-specific transcription factor CREBh as a novel UPR gene conserved during metazoan evolution.

  12. Fermentation of Apple Juice with a Selected Yeast Strain Isolated from the Fermented Foods of Himalayan Regions and Its Organoleptic Properties.

    Science.gov (United States)

    Kanwar, S S; Keshani

    2016-01-01

    Twenty-three Saccharomyces cerevisiae strains isolated from different fermented foods of Western Himalayas have been studied for strain level and functional diversity in our department. Among these 23 strains, 10 S. cerevisiae strains on the basis of variation in their brewing traits were selected to study their organoleptic effect at gene level by targeting ATF1 gene, which is responsible for ester synthesis during fermentation. Significant variation was observed in ATF1 gene sequences, suggesting differences in aroma and flavor of their brewing products. Apple is a predominant fruit in Himachal Pradesh and apple cider is one of the most popular drinks all around the world hence, it was chosen for sensory evaluation of six selected yeast strains. Organoleptic studies and sensory analysis suggested Sc21 and Sc01 as best indigenous strains for soft and hard cider, respectively, indicating their potential in enriching the local products with enhanced quality. PMID:27446050

  13. Kinetics and mechanism of uncatalyzed and ruthenium(III)-catalyzed oxidation of formamidine derivative by hexacyanoferrate(III) in aqueous alkaline medium

    Indian Academy of Sciences (India)

    AHMED FAWZY

    2016-05-01

    The catalytic effect of ruthenium(III) on the oxidation of N,N-dimethyl-N-(4H-1,2,4-triazol-3-yl) formamidine (ATF) by hexacyanoferrate(III) (HCF) was studied spectrophotometrically in aqueous alkalinemedium. Both uncatalyzed and catalyzed reactions showed first order kinetics with respect to [HCF],whereas the reaction orders with respect to [ATF] and $[OH^{-}]$ were apparently less than unity over the concentrationrange studied. A first order dependence with respect to $[Ru^{III}]$ was obtained. Increasing ionic strengthincreased the rate of uncatalyzed reaction and decreased the rate of the catalyzed one Plausible mechanisticschemes of oxidation reactions have been proposed. In both cases, the final oxidation products are identifiedas aminotriazole, dimethyl amine and carbon dioxide. The rate laws associated with the reaction mechanismsare derived. The reaction constants involved in the different steps of the mechanisms were calculated. Theactivation and thermodynamic parameters have been computed and discussed.

  14. Standards for bullets and casings

    Directory of Open Access Journals (Sweden)

    J.F Song

    2002-11-01

    The Office of Law Enforcement Standards (OLES at the National Institute of Standards and Technology (NIST manages research in many different disciplines of forensic science. One of these projects supports the National Integrated Ballistics Information Network (NIBIN. NIST digitized six bullet signatures from samples provided by the Bureau of Alcohol, Tobacco, and Firearms (ATF and the Federal Bureau of Investigation (FBI. Using these signatures as a virtual standard, NIST’s Instrument Shop manufactured 20 reference materials (RM 8240 standard bullets using a numerically-controlled diamond turning machine. Test results show high reproducibility of the bullet signatures on standard bullets. NIST has also developed a new parameter for bullet signature comparisons, using autocorrelation functions, and proposed a diagram for tracing local ballistics measurements to the National Laboratory Center of the ATF and to the FBI. Using an electro-forming process, NIST has manufactured prototype standard casings and test results show high reproducibility for the casing signatures.

  15. Dynamic Evaluation of the Contact Characteristics and Three-Dimensional Motion for the Ankle Joint with Lateral Ligament Injuries

    Science.gov (United States)

    Kawakami, Kensaku; Omori, Go; Terashima, Shojiro; Sakamoto, Makoto; Hara, Toshiaki

    The purpose of this study was to clarify the dynamic changes in contact pressure distribution and three-dimensional ankle joint motion before and after lateral ligament injuries. Five fresh and frozen intact cadaveric ankles were examined. Each ankle was mounted on a specially designed frame that preserved five degrees of freedom motion. The direct linear transformation technique was used to measure the three-dimensional ankle motion, and a pressure-sensitive conductive rubber sensor was inserted into the talocrural joint space to determine the contact pressure distribution. The contact area on the talus for intact ankle moved anteriorly and laterally with increasing dorsiflexion. An area of high pressure was observed in the medial aspect of the articular surface after the ligament was cut. Supination significantly increased after a combined anterior talofibular ligament (ATF) and calcaneofibular ligament (CF) were cut in comparison with after only an ATF was cut, and no significant differences were observed in motional properties under each experimental condition.

  16. Electric Motor Thermal Management R&D; NREL (National Renewable Energy Laboratory)

    Energy Technology Data Exchange (ETDEWEB)

    Bennion, Kevin

    2015-06-09

    Thermal constraints place significant limitations on how electric motors ultimately perform. Without the ability to remove heat, the motor cannot operate without sacrificing performance, efficiency, and reliability. Finite element analysis and computational fluid dynamics modeling approaches are being increasingly utilized in the design and analysis of electric motors. As the models become more sophisticated, it is important to have detailed and accurate knowledge of both the passive thermal performance and the active cooling performance. In this work, we provide an overview of research characterizing both passive and active thermal elements related to electric motor thermal management. To better characterize the passive thermal performance, work is being performed to measure motor material thermal properties and thermal contact resistances. The active cooling performance of automatic transmission fluid (ATF) jets is also being measured to better understand the heat transfer coefficients of ATF impinging on motor copper windings.

  17. Very high resolution optical transition radiation imaging system: Comparison between simulation and experiment

    CERN Document Server

    Bolzon, B; Aumeyr, Thomas; Boogert, Stewart Takashi; Karataev, Pavel; Kruchinin, Konstantin; Lefevre, Thibaut; Mazzoni, Stefano; Nevay, Laurence James; Shevelev, M; Terunuma, N; Urakawa, J; Welsch, Carsten

    2015-01-01

    Optical transition radiation (OTR) has become a commonly used method for 2D beam imaging measurements. In the Accelerator Test Facility 2 (ATF2) at KEK, beam sizes smaller than the OTR point spread function have been measured. Simulations of the OTR imaging system have been performed using the ZEMAX software to study the effects of optical errors such as aberrations, diffraction, and misalignments of optical components. This paper presents a comparison of simulations of the OTR point spread function with experimental data obtained at ATF2. It shows how the quantification and control of optical errors impacts on optimizing the resolution of the system. We also show that the OTR point spread function needs to be predicted accurately to optimize any optical system and to predict the error made on measurement.

  18. Antec starts serial production; Antec startet Serienfertigung

    Energy Technology Data Exchange (ETDEWEB)

    Iken, J.

    2001-01-12

    Thuringian producer Antec Solar has produced CdTe modules to near maturity. Serial production is envisaged for January 2001. The CdTe modules will be marketed under the name ATF (Advanced Thin Film Technology). Full production capacityis expected for mid-2002. [German] Die Fertigung von Cadmium-Tellurid-Modulen (CdTe) beim thueringischen Unternehmen Antec Solar steht vor der Serienreife. Die Nullserie wurde Anfang November gestartet und erfolgreich abgeschlossen: 'Die Produktion ist angelaufen, die ersten Module sind gefertigt'. Der Start der Serienproduktion ist fuer Anfang Januar 2001 vorgesehen. Die volle Produktionskapazitaet fuer die CdTe-Module, die Antec unter dem Namen ATF (Advanced Thin Film Technology) vermarkten will, soll Mitte naechsten Jahres erreicht werden. (orig./AKF)

  19. Influence of g-phase on the high- temperature oxidation of NiAl-Fe alloys

    Directory of Open Access Journals (Sweden)

    Maurício de Jesus Monteiro

    1999-07-01

    Full Text Available The oxidation of NiAl, NiAl-20at.%Fe and NiAl-30at.%Fe at 1000-1100 °C in air has been studied. Pure NiAl shows excellent oxidation resistance due to the formation of an Al2O3 layer. NiAl-20Fe also shows good oxidation resistance due to the formation of an Al2O3 scale on a b-phase substrate. Moreover, some nodules consisting of mixed oxides of Fe and Ni grow over the ductile g-phase surface incorporated to the b-phase substrate. NiAl-30Fe alloy undergoes a much faster oxidation due to the formation of a non-protective Fe and Ni-rich scale, which is extremely susceptible to spallation. The addition of Fe to NiAl is detrimental to its oxidation resistance.

  20. Altered DNA methylation of glycolytic and lipogenic genes in liver from obese and type 2 diabetic patients

    DEFF Research Database (Denmark)

    Kirchner, Henriette; Sinha, Indranil; Gao, Hui;

    2016-01-01

    in four of these genes in liver of severely obese non-diabetic and type 2 diabetic patients, suggesting epigenetic regulation of transcription by altered ATF-DNA binding. CONCLUSION: Severely obese non-diabetic and type 2 diabetic patients have distinct alterations in the hepatic methylome...... and transcriptome, with hypomethylation of several genes controlling glucose metabolism within the ATF-motif regulatory site. Obesity appears to shift the epigenetic program of the liver towards increased glycolysis and lipogenesis, which may exacerbate the development of insulin resistance.......OBJECTIVE: Epigenetic modifications contribute to the etiology of type 2 diabetes. METHOD: We performed genome-wide methylome and transcriptome analysis in liver from severely obese men with or without type 2 diabetes and non-obese men to discover aberrant pathways underlying the development...

  1. HTLV-1 Tax Protein Stimulation of DNA Binding of bZIP Proteins by Enhancing Dimerization

    Science.gov (United States)

    Wagner, Susanne; Green, Michael R.

    1993-10-01

    The Tax protein of human T cell leukemia virus type-1 (HTLV-I) transcriptionally activates the HTLV-I promoter. This activation requires binding sites for activating transcription factor (ATF) proteins, a family of cellular proteins that contain basic region-leucine zipper (bZIP) DNA binding domains. Data are presented showing that Tax increases the in vitro DNA binding activity of multiple ATF proteins. Tax also stimulated DNA binding by other bZIP proteins, but did not affect DNA binding proteins that lack a bZIP domain. The increase in DNA binding occurred because Tax promotes dimerization of the bZIP domain in the absence of DNA, and the elevated concentration of the bZIP homodimer then facilitates the DNA binding reaction. These results help explain how Tax activates viral transcription and transforms cells.

  2. Adenovirus-induced alterations in host cell gene expression prior to the onset of viral gene expression.

    Science.gov (United States)

    Granberg, Fredrik; Svensson, Catharina; Pettersson, Ulf; Zhao, Hongxing

    2006-09-15

    In this report, we have studied gene expression profiles in human primary lung fibroblasts (IMR-90) during the very early phase of an adenovirus infection. Eight out of twelve genes with known functions encoded transcription factors linked to two major cellular processes; inhibition of cell growth (ATF3, ATF4, KLF4, KLF6 and ELK3) and immune response (NR4A1 and CEBPB), indicating that the earliest consequences of an adenovirus infection are growth arrest and induction of an immune response. A time course analysis showed that the induction of these immediate-early response genes was transient and suppressed after the onset of the adenovirus early gene expression. PMID:16860366

  3. Manipulations of Double Electron Beams within One RF Period for Seeded SM-LWFA Experiment

    CERN Document Server

    Zhou, Feng; Cline, David B; Kimura, Wayne D; Yakimenko, Vitaly

    2005-01-01

    Although seeded SM-LWFA only requires one electron beam to initiate the laser wakefield, it would be highly desirable to have a second electron beam traveling after the first one to probe the accelerated electrons. To create and preserve significant amount of wakefield in the STELLA SM-LWFA experiment, the first e-beam needs to be tiny (<40 microns FWHM) in size and short in length within the plasma. To probe the wakefield which is damped within 10 ps for certain plasma density, the separation between the first and second beams needs to be within one RF period and the second e-beam must have smaller energy spread and smaller size. Design of double beams in one RF period to meet the strict requirements and the preliminary beam study at BNL-ATF facility are presented. The scheme of double beams with ATF bunch compressor is also discussed.

  4. Microarray expression analysis of genes involved in innate immune memory in peritoneal macrophages

    Directory of Open Access Journals (Sweden)

    Keisuke Yoshida

    2016-03-01

    Full Text Available Immunological memory has been believed to be a feature of the adaptive immune system for long period, but recent reports suggest that the innate immune system also exhibits memory-like reaction. Although evidence of innate immune memory is accumulating, no in vivo experimental data has clearly implicated a molecular mechanism, or even a cell-type, for this phenomenon. In this study of data deposited into Gene Expression Omnibus (GEO under GSE71111, we analyzed the expression profile of peritoneal macrophages isolated from mice pre-administrated with toll-like receptor (TLR ligands, mimicking pathogen infection. In these macrophages, increased expression of a group of innate immunity-related genes was sustained over a long period of time, and these genes overlapped with ATF7-regulated genes. We conclude that ATF7 plays an important role in innate immune memory in macrophages.

  5. Fully ceramic microencapsulated fuels. Characteristics and potential LWR applications

    International Nuclear Information System (INIS)

    This paper summarizes the characteristics of the fully ceramic microencapsulated (FCM) fuel concept and two potential light water reactor (LWR) applications of FCM fuels: for actinide management and as an accident tolerant fuel (ATF). Recent progress in FCM fuel development includes production of uranium mononitride kernels, fabrication of FCM pellets and pins, and irradiation testing of matrix samples and FCM pellets. Potential applications of FCM fuel in LWRs appear promising based upon studies performed by several organizations; however, further efforts are needed to investigate various design aspects in further detail and explore promising new areas of research such as new fuel pin and assembly designs or alternate materials of interest. Current challenges in FCM fuel development and LWR applications for FCM fuels include low heavy metal fuel loading densities and increased uncertainties in analysis due to several different factors. Overall, LWR FCM concepts appear feasible for both actinide management and as an ATF. (author)

  6. The stabilisation of final focus system

    Indian Academy of Sciences (India)

    P A Coe; D Urner; A Reichold

    2007-12-01

    The StaFF (stabilisation of final focus) system will use interferometers to monitor the relative positions and orientations of several key components in the beam-delivery and interaction region. Monitoring the relative positions of the ILC final focus quadrupole magnets will be the most demanding application, where mutual and beam-relative stability will have a direct impact on machine luminosity. Established, laser-based frequency scanning interferometry (FSI) and fixed-frequency interferometry (FFI) offer positional resolution at length scales of the laser wavelength (1500 nm to 1560 nm) and a thousandth of the wavelength, respectively. As part of the ATF at KEK, StaFF will use interferometers to measure lines of a geodetic network to record relative motion between two beam position monitors. Interferometers are being designed and tested in Oxford prior to deployment at the ATF.

  7. TGF-mediated oscillations in the proximal intratubular pressure: differences between spontaneously hypertensive rats and Wistar-Kyoto rats

    DEFF Research Database (Denmark)

    Holstein-Rathlou, N H; Leyssac, P P

    1986-01-01

    A highly sensitive oscillatory tubulo-glomerular feedback (TGF) response has previously been demonstrated in normotensive Sprague-Dawley rats. The purpose of the present study was to examine whether such as oscillating TGF-response could be elicited in Wistar-Kyoto rats (WKY) and genetically...... hypertensive rats (SHR) and furthermore if any differences in the TGF-response characteristics between SHR and WKY rats could be detected. The closed loop function of the TGF-system was studied. In 12-18-week-old WKY rats regular oscillations in the intratubular pressure occurred spontaneously. The median...... fluid (ATF). When furosemide was added to the ATF in a concentration of 0.1 mM, the oscillations were abolished in both strains of rats. It is concluded that, in both strains of rats the oscillatory phenomena depend upon TGF activity. It is suggested that the irregular pattern of the oscillations...

  8. Estimates of CSR Instability Thresholds for Various Storage Rings

    CERN Document Server

    Zimmermann, Frank

    2010-01-01

    We review the key predictions and conditions by several authors for the onset of longitudinal instabilities due to coherent synchrotron radiation (CSR), and evaluate them numerically for various storage rings, namely the KEKB High Energy Ring (HER) & Low Energy Ring (LER), SuperKEKB HER & LER, old and new designs of the SuperKEKB Damping Ring (DR), SuperB HER & LER, CLIC DR (2009 and 2010 design parameters), SLC DR, and ATF DR. We show that the theoretical uncertainty in the instability onset is at least at the level of 20-30% in bunch intensity. More importantly, we present some doubts about the general applicability for many of these storage rings of some commonly used formulae. To cast further light on these questions, an experiment at lower beam energy on the ATF Damping Ring is proposed.

  9. Physics models in the toroidal transport code PROCTR

    Energy Technology Data Exchange (ETDEWEB)

    Howe, H.C.

    1990-08-01

    The physics models that are contained in the toroidal transport code PROCTR are described in detail. Time- and space-dependent models are included for the plasma hydrogenic-ion, helium, and impurity densities, the electron and ion temperatures, the toroidal rotation velocity, and the toroidal current profile. Time- and depth-dependent models for the trapped and mobile hydrogenic particle concentrations in the wall and a time-dependent point model for the number of particles in the limiter are also included. Time-dependent models for neutral particle transport, neutral beam deposition and thermalization, fusion heating, impurity radiation, pellet injection, and the radial electric potential are included and recalculated periodically as the time-dependent models evolve. The plasma solution is obtained either in simple flux coordinates, where the radial shift of each elliptical, toroidal flux surface is included to maintain an approximate pressure equilibrium, or in general three-dimensional torsatron coordinates represented by series of helical harmonics. The detailed coupling of the plasma, scrape-off layer, limiter, and wall models through the neutral transport model makes PROCTR especially suited for modeling of recycling and particle control in toroidal plasmas. The model may also be used in a steady-state profile analysis mode for studying energy and particle balances starting with measured plasma profiles.

  10. Multi-Channel Detector Arrays for Heavy Ion Beam Probes

    Science.gov (United States)

    Aceto, Steven; Beckstead, Jeffrey; Castracane, James; Iguchi, H.; Fujisawa, A.; Demers, Diane; Schatz, John

    1997-11-01

    InterScience, Inc. has developed a multiple slit detector array for use with heavy ion beam probes. The first array was a twenty element array installed on the TEXT tokamak. An initial set of data was obtained with this array prior to the shutdown on the TEXT tokamak in December of 1995. More recently, a smaller detector array has been developed for use in the CHS torsatron in Nagoya. This array is smaller than the TEXT array, with ten elements, but contains two prototype sets of detector plates to determine the beam position. The operating conditions in CHS are expected to be much harsher than in TEXT, with ECH and NBI plasmas. Trajectory simulations allowed for the design of a tilted detector array in the CHS vacuum vessel. First tests of the CHS array will begin in the late summer of 1997. Other candidate machines for detector arrays are the MST reversed field pinch, in which a beam probe is expected to be installed in late 1997 or early 1998 and the Large Helical Device (LHD) which is expected to be operational in 1998. Design issues, trajectory simulations and array test results will be presented. Supported in part by the U.S. Department of Energy under Grant #DE-FG02-94ER81788

  11. Research on stellarator-mirror fission-fusion hybrid

    Science.gov (United States)

    Moiseenko, V. E.; Kotenko, V. G.; Chernitskiy, S. V.; Nemov, V. V.; Ågren, O.; Noack, K.; Kalyuzhnyi, V. N.; Hagnestål, A.; Källne, J.; Voitsenya, V. S.; Garkusha, I. E.

    2014-09-01

    The development of a stellarator-mirror fission-fusion hybrid concept is reviewed. The hybrid comprises of a fusion neutron source and a powerful sub-critical fast fission reactor core. The aim is the transmutation of spent nuclear fuel and safe fission energy production. In its fusion part, neutrons are generated in deuterium-tritium (D-T) plasma, confined magnetically in a stellarator-type system with an embedded magnetic mirror. Based on kinetic calculations, the energy balance for such a system is analyzed. Neutron calculations have been performed with the MCNPX code, and the principal design of the reactor part is developed. Neutron outflux at different outer parts of the reactor is calculated. Numerical simulations have been performed on the structure of a magnetic field in a model of the stellarator-mirror device, and that is achieved by switching off one or two coils of toroidal field in the Uragan-2M torsatron. The calculations predict the existence of closed magnetic surfaces under certain conditions. The confinement of fast particles in such a magnetic trap is analyzed.

  12. Curvature dependance of blob dynamics in TJ-K

    Energy Technology Data Exchange (ETDEWEB)

    Garland, Stephen; Ramisch, Mirko [Institut fuer Grenzflaechenverfahrenstechnik und Plasmatechnologie, Universitaet Stuttgart (Germany); Fuchert, Golo [Institut Jean Lamour, Universite de Lorraine (France)

    2014-07-01

    Turbulent transport in the scrape-off layer (SOL) is an important area of investigation in magnetic confinement fusion research. Relatively dense and hot, field-aligned, filament-like structures (blobs) have been observed to propagate radially through the SOL in many fusion devices, and contribute significantly to SOL transport. The torsatron TJ-K operates with a low-temperature plasma, allowing Langmuir probe measurements in the entire plasma volume. Despite the low temperature, investigations are relevant to fusion research due to dimensionless plasma parameters similar to those in the edge region of fusion plasmas. Analytical blob models link blob velocity in the SOL to blob polarisation, which can be driven by magnetic field line curvature. In TJ-K, average blob dynamics can be studied in detail using a 2D movable probe and a conditional averaging technique. In addition, a fast camera can be used to supplement probe data, and provide information on individual blob trajectories. With these tools, the connection between magnetic field line curvature and the poloidal component of blob velocity has been studied. Taking into account background E x B flows, initial investigations suggest a correlation between the poloidal component of blob velocity and averaged geodesic magnetic field line curvature.

  13. Curvature dependence of blob dynamics in TJ-K

    Energy Technology Data Exchange (ETDEWEB)

    Garland, Stephen; Ramisch, Mirko; Hirth, Thomas [Institut fuer Grenzflaechenverfahrenstechnik und Plasmatechnologie, Universitaet Stuttgart (Germany)

    2015-05-01

    Turbulent transport in the scrape-off layer (SOL) is an important area of investigation in magnetic confinement fusion research. Relatively dense and hot, field-aligned, filament-like structures (blobs) have been observed to propagate radially through the SOL in many fusion devices, and contribute significantly to SOL transport. The torsatron TJ-K is well suited to turbulence studies since it operates with a low-temperature plasma, allowing Langmuir probe measurements in the entire plasma volume. Despite the low temperature, investigations are relevant to fusion research due to dimensionless plasma parameters similar to those in the edge region of fusion plasmas. Blob dynamics have been studied in the SOL of TJ-K using a 2D movable probe and the conditional averaging technique. In addition, emissive probes have been used to determine equilibrium electric fields, allowing the calculation of background E x B flows. Experimentally deduced centre of mass radial and poloidal blob velocity components have been compared to an analytical blob model, which has been simplified to express blob velocity in terms of the magnetic field curvature vector. Experimental radial blob velocity components compare well to the model, confirming the normal curvature drive of blob polarisation. On the other hand, poloidal velocity components are comparable to the model only when background E x B flow is also taken into account.

  14. Stellarator News, Issue 38, March 1995

    CERN Document Server

    Rome, J A

    1995-01-01

    Stellarator News, an international journal of the stellarator community, is Published by Fusion Energy Division, Oak Ridge National Laboratory, James A. Rome, Editor In the March 1995 issue . . . **** Exerpts from the U.S. Congress Office of Technology Assment report on TPX and Alternate Concepts. **** Edge transport and turbulence studies on U-3M The turbulent-driven particle flow is shown to be comparable with the equilibrium flow at the boundary of the configuration under Alfven-heating conditions in the U-3M torsatron. **** Topological aspects of island divertor studies on W7-AS The structure of the edge plasma in W7-AS, observed with probes, television camera, and H-alpha light agrees at low beta with vacuum field calculations: the low-valued resonances at iotabar=5/m are resolved for m = 8 to 11; external perturbations are not significant at the edge, even for iotabar = 5/10. **** 140-GHz second harmonic O-mode electron cyclotron heating at W7-AS First experimental results are presented of 140-GHz secon...

  15. Physics models in the toroidal transport code PROCTR

    International Nuclear Information System (INIS)

    The physics models that are contained in the toroidal transport code PROCTR are described in detail. Time- and space-dependent models are included for the plasma hydrogenic-ion, helium, and impurity densities, the electron and ion temperatures, the toroidal rotation velocity, and the toroidal current profile. Time- and depth-dependent models for the trapped and mobile hydrogenic particle concentrations in the wall and a time-dependent point model for the number of particles in the limiter are also included. Time-dependent models for neutral particle transport, neutral beam deposition and thermalization, fusion heating, impurity radiation, pellet injection, and the radial electric potential are included and recalculated periodically as the time-dependent models evolve. The plasma solution is obtained either in simple flux coordinates, where the radial shift of each elliptical, toroidal flux surface is included to maintain an approximate pressure equilibrium, or in general three-dimensional torsatron coordinates represented by series of helical harmonics. The detailed coupling of the plasma, scrape-off layer, limiter, and wall models through the neutral transport model makes PROCTR especially suited for modeling of recycling and particle control in toroidal plasmas. The model may also be used in a steady-state profile analysis mode for studying energy and particle balances starting with measured plasma profiles

  16. Parametric systems analysis of the Modular Stellarator Reactor (MSR)

    International Nuclear Information System (INIS)

    The close coupling in the stellarator/torsatron/heliotron (S/T/H) between coil design (peak field, current density, forces), magnetics topology (transform, shear, well depth), and plasma performance (equilibrium, stability, transport, beta) complicates the reactor assessment more so than for most magnetic confinement systems. In order to provide an additional degree of resolution of this problem for the Modular Stellarator Reactor (MSR), a parametric systems model has been developed and applied. This model reduces key issues associted ith plasma performance, first-wall/blanket/shield (FW/B/S), and coil design to a simple relationship between beta, system geometry, and a number of indicators of overall plant performance. The results of this analysis can then be used to guide more detailed, multidimensional plasma, magnetics, and coil design efforts towards technically and economically viable operating regimes. In general, it is shown that beta values > 0.08 may be needed if the MSR approach is to be substantially competitive with other approaches to magnetic fusion in terms of system power density, mass utilization, and cost for total power output around 4.0 GWt; lower powers will require even higher betas

  17. Development of Co-Pilgering Process for Manufacturing Double Clad Tubes for Accident Tolerant Fuel

    International Nuclear Information System (INIS)

    Accident Tolerant Fuels (ATF) are those that, in comparison with the standard UO2 - Zr system, can tolerate loss of active cooling in the core for a considerably longer time period (depending on the accident scenario), while maintaining or improving the fuel performance during normal operations. ATF cladding development efforts focus on materials with more benign steam reaction. For this, advanced steels (e.g. FeCrAl), refractory metals (e.g. Mo), ceramic cladding (SiC), Innovative alloys with dopants, zirconium alloy with coating or sleeve are being developed. Single material like zirconium alloy as clad may not be compatible with both fuel and coolant at elevated temperatures in accident scenario. Double clad tube is one of the prime concepts which has to be explored to develop ATF cladding. Two different clad materials- one oxidant resistant (like FeCrAl) and the other, fuel compatible (like Zr-4) constitute together as outer and inner tube to form ATF cladding. Bonding two different tubes in controlled thickness ratios and with almost no gap in between is utmost difficult. Different types of processes are available for production of double clad tubes such as coating, co-extrusion, co- drawing, internal expansion/external compaction, explosive bonding, co-pilgering etc,. Nuclear Fuel Complex (NFC), India has successfully demonstrated manufacturing of double clad tube by co-pilgering process where in outer cladding is of modified 9Cr-1Mo Steel and inner liner is of zircaloy-4. Considering different deformation behaviour of above materials during pilgering, fabrication of double clad tube is very critical. Optimization of tube dimensions like outer diameter and wall thickness at pre and final stages during pilgering is very important to achieve the required overall tube dimension and bonding between the tubes. This paper gives the methodology of manufacture of Double Clad Tubes by pilgering and the bonding between the two materials achieved in this process

  18. Tocotrienols are needed for normal bone calcification in growing female rats.

    Science.gov (United States)

    Norazlina, Mohamed; Ima-Nirwana, Soelaiman; Abul Gapor, Mohd Top; Abdul Kadir Khalid, B

    2002-01-01

    In this study the effects of vitamin E deficiency and supplementation on bone calcification were determined using 4-month-old female Sprague-Dawley rats. The rats weighed between 180 and 200 g. The study was divided in three parts. In experiment I the rats were given normal rat chow (RC, control group), a vitamin E deficient (VED) diet or a 50% vitamin E deficient (50%VED) diet. In experiment 2 the rats were given VED supplemented with 30 mg/kg palm vitamin E (PVE30), 60 mg/kg palm vitamin E (PVE60) or 30 mg/kg pure alpha-tocopherol (ATF). In experiment 3 the rats were fed RC and given the same supplements as in experiment 2. The treatment lasted 8 months. Vitamin E derived from palm oil contained a mixture of ATF and tocotrienols. Rats on the VED and 50%VED diets had lower bone calcium content in the left femur compared to the RC group (91.6 +/- 13.3 mg and 118.3 +/- 26.0 mg cf 165.7 +/- 15.2 mg; P VED group with PVE60 improved bone calcification in the left femur (133.6 +/- 5.0 mg compared with 91.6 +/- 13.3 mg; P VED group. Supplementing the RC group with PVE30, PVE60 or ATF did not cause any significant changes in bone calcium content. In conclusion, vitamin E deficiency impaired bone calcification. Supplementation with the higher dose of palm vitamin E improved bone calcium content, but supplementation with pure ATF alone did not. This effect may be attributed to the tocotrienol content of palm vitamin E. Therefore, tocotrienols play an important role in bone calcification.

  19. Unfolded Protein Response and PERK Kinase as a New Therapeutic Target in the Pathogenesis of Alzheimer's Disease.

    Science.gov (United States)

    Rozpedek, Wioletta; Markiewicz, Lukasz; Diehl, J Alan; Pytel, Dariusz; Majsterek, Ireneusz

    2015-01-01

    Recent evidence suggests that the development of Alzheimer's disease (AD) and related cognitive loss is due to mutations in the Amyloid Precursor Protein (APP) gene on chromosome 21 and increased activation of eukaryotic translation initiation factor-2α (eIF2α) phosphorylation. The high level of misfolded and unfolded proteins loading in Endoplasmic Reticulum (ER) lumen triggers ER stress and as a result Unfolded Protein Response (UPR) pathways are activated. Stress-dependent activation of the protein kinase RNA-like endoplasmic reticulum kinase (PERK) leads to the significant elevation of phospho-eIF2α. That attenuates general translation and, on the other hand, promotes the preferential synthesis of Activating Transcription Factor 4 (ATF4) and secretase β (BACE1) - a pivotal enzyme responsible for the initiation of the amyloidogenic pathway resulting in the generation of the amyloid β (Aβ) variant with high ability to form toxic senile plaques in AD brains. Moreover, excessive, long-term stress conditions may contribute to inducing neuronal death by apoptosis as a result of the overactivated expression of pro-apoptotic proteins via ATF4. These findings allow to infer that dysregulated translation, increased expression of BACE1 and ATF4, as a result of eIF2α phosphorylation, may be a major contributor to structural and functional neuronal loss resulting in memory impairment. Thus, blocking PERK-dependent eIF2α phosphorylation through specific, small-molecule PERK branch inhibitors seems to be a potential treatment strategy for AD individuals. That may contribute to the restoration of global translation rates and reduction of expression of ATF4 and BACE1. Hence, the treatment strategy can block accelerated β -amyloidogenesis by reduction in APP cleaving via the BACE1-dependent amyloidogenic pathway.

  20. Unfolded Protein Response and PERK Kinase as a New Therapeutic Target in the Pathogenesis of Alzheimer’s Disease

    Science.gov (United States)

    Rozpędek, Wioletta; Markiewicz, Łukasz; Diehl, J. Alan; Pytel, Dariusz; Majsterek, Ireneusz

    2016-01-01

    Recent evidence suggests that the development of Alzheimer’s disease (AD) and related cognitive loss is due to mutations in the Amyloid Precursor Protein (APP) gene on chromosome 21 and increased activation of eukaryotic translation initiation factor-2α (eIF2α) phosphorylation. The high level of misfolded and unfolded proteins loading in Endoplasmic Reticulum (ER) lumen triggers ER stress and as a result Unfolded Protein Response (UPR) pathways are activated. Stress-dependent activation of the protein kinase RNA-like endoplasmic reticulum kinase (PERK) leads to the significant elevation of phospho-eIF2α. That attenuates general translation and, on the other hand, promotes the preferential synthesis of Activating Transcription Factor 4 (ATF4) and secretase β (BACE1) - a pivotal enzyme responsible for the initiation of the amyloidogenic pathway resulting in the generation of the amyloid β (Aβ) variant with high ability to form toxic senile plaques in AD brains. Moreover, excessive, long-term stress conditions may contribute to inducing neuronal death by apoptosis as a result of the overactivated expression of pro-apoptotic proteins via ATF4. These findings allow to infer that dysregulated translation, increased expression of BACE1 and ATF4, as a result of eIF2α phosphorylation, may be a major contributor to structural and functional neuronal loss resulting in memory impairment. Thus, blocking PERK-dependent eIF2α phosphorylation through specific, small-molecule PERK branch inhibitors seems to be a potential treatment strategy for AD individuals. That may contribute to the restoration of global translation rates and reduction of expression of ATF4 and BACE1. Hence, the treatment strategy can block accelerated β-amyloidogenesis by reduction in APP cleaving via the BACE1-dependent amyloidogenic pathway. PMID:26282939

  1. Proceedings of the CAP meetings, November 1990--February 1991

    International Nuclear Information System (INIS)

    This report contains viewgraph material on the following topics: on beam emittance -- application to ATF; a review of Brookhaven Accelerator Test Facility (AFT); on development of a superconducting RFQ at Stony Brook University; development of new methods for charged particle acceleration at Yerevan Physics Institute; theory of high gain free electron laser; on ultra violet free electron laser at BNL; high luminosity at SSC; and nonlinear dynamics studies of accelerators

  2. Chronic lymphocytic leukemia and B and T cells differ in their response to cyclic nucleotide phosphodiesterase inhibitors.

    Science.gov (United States)

    Meyers, John A; Su, Derrick W; Lerner, Adam

    2009-05-01

    Phosphodiesterase (PDE)4 inhibitors, which activate cAMP signaling by reducing cAMP catabolism, are known to induce apoptosis in B lineage chronic lymphocytic leukemia (CLL) cells but not normal human T cells. The explanation for such differential sensitivity remains unknown. In this study, we report studies contrasting the response to PDE4 inhibitor treatment in CLL cells and normal human T and B cells. Affymetrix gene chip analysis in the three cell populations following treatment with the PDE4 inhibitor rolipram identified a set of up-regulated transcripts with unusually high fold changes in the CLL samples, several of which are likely part of compensatory negative feedback loops. The high fold changes were due to low basal transcript levels in CLL cells, suggesting that cAMP-mediated signaling may be unusually tightly regulated in this cell type. Rolipram treatment augmented cAMP levels and induced ATF-1/CREB serine 63/133 phosphorylation in both B lineage cell types but not T cells. As treatment with the broad-spectrum PDE inhibitor 3-isobutyl-1-methylxanthine induced T cell CREB phosphorylation, we tested a series of family-specific PDE inhibitors for their ability to mimic 3-isobutyl-1-methylxanthine-induced ATF-1/CREB phosphorylation. Whereas PDE3 inhibitors alone had no effect, the combination of PDE3 and PDE4 inhibitors induced ATF-1/CREB serine 63/133 phosphorylation in T cells. Consistent with this observation, PDE3B transcript and protein levels were low in CLL cells but easily detectable in T cells. Combined PDE3/4 inhibition did not induce T cell apoptosis, suggesting that cAMP-mediated signal transduction that leads to robust ATF-1/CREB serine 63/133 phosphorylation is not sufficient to induce apoptosis in this lymphoid lineage.

  3. Advanced Fuels Campaign FY 2014 Accomplishments Report

    Energy Technology Data Exchange (ETDEWEB)

    Lori Braase; W. Edgar May

    2014-10-01

    The overall goal of ATF development is to identify alternative fuel system technologies to further enhance the safety, competitiveness, and economics of commercial nuclear power. The complex multiphysics behavior of LWR nuclear fuel in the integrated reactor system makes defining specific material or design improvements difficult; as such, establishing desirable performance attributes is critical in guiding the design and development of fuels and cladding with enhanced accident tolerance.

  4. The influence of applied tensile stress on power loss in Co-rich amorphous Co-Fe-Si-B ribbons with induced magnetic anisotropy

    DEFF Research Database (Denmark)

    Nielsen, H; Nielsen, K; Nielsen, Otto V

    1982-01-01

    The influence on power loss PTof applied tensile stress σ in amorphous (Co0.89Fe0.11)72Mo3Si15B10(lambda_{s} > 0) and Co73Mo2Si15B10(lambda_{s} <0) ribbons with different induced magnetic anisotropy Kuis reported. The losses are measured under sinusoidal flux conditions atf = 50Hz,J_{max} = 0.57T...

  5. Seleção de linhagens de sorgo granífero eficientes e responsivas à aplicação de fósforo

    Directory of Open Access Journals (Sweden)

    Fabricio Rodrigues

    2014-08-01

    Full Text Available O objetivo deste trabalho foi selecionar linhagens de sorgo simultaneamente responsivas ao fósforo e com elevada eficiência produtiva quanto a esse nutriente. Foram avaliadas 36 linhagens endogâmicas, em delineamento de blocos ao acaso, com duas repetições. Os caracteres usados para avaliação da eficiência produtiva foram produtividade média e eficiências de absorção, de utilização e de uso de fósforo, com e sem adubação fosfatada. Para análise da responsividade ao nutriente, foram avaliados caracteres de produtividade relativa e de eficiências de recuperação aparente, fisiológica e agronômica. Há variabilidade genética entre as linhagens quanto às eficiências de absorção, de utilização e de uso do fósforo, e quanto à responsividade ao nutriente, o que sugere a possibilidade de produção de híbridos destinados a nichos de mercado diferentes. As linhagens mais responsivas foram P9401, BR007B, BR008B, SC414-12E e SC566, e as mais eficientes, sob baixa disponibilidade de fósforo, foram ATF40B, SC566, BR005R, CMSXS225 e BR012 (R6. As linhagens ATF40B, ATF54 (f61, ATF54 (f596, QL3 e SC566 apresentaram melhor desempenho simultâneo das diferentes eficiências avaliadas e da responsividade ao fósforo. Apenas a avaliação do caráter produtividade, sob diferentes disponibilidades de fósforo, já permite identificar linhagens eficientes e responsivas ao fósforo.

  6. Ionization Chambers for Monitoring in High-Intensity Neutrino Beams

    CERN Document Server

    McDonald, J; Velissaris, C; Erwin, A R; Ping, H; Viren, B M; Diwan, M V

    2002-01-01

    Radiation-hard ionization chambers were tested using an intense electron beam from the accelerator test facility (ATF) at the Brookhaven National Laboratory (BNL). The detectors were designed to be used as the basic element for monitoring muons in the Main Injector Neutrino beamline (NuMI) at the Fermi National Accelerator Laboratory (FNAL). Measurements of linearity of response, voltage dependence, and the onset of ionization saturation as a function of gap voltage were performed.

  7. Source characteristics of 2000 small earthquakes nucleating on the Alto Tiberina fault system (central Italy).

    Science.gov (United States)

    Munafo, I.; Malagnini, L.; Tinti, E.; Chiaraluce, L.; Di Stefano, R.; Valoroso, L.

    2014-12-01

    The Alto Tiberina Fault (ATF) is a 60 km long east-dipping low-angle normal fault, located in a sector of the Northern Apennines (Italy) undergoing active extension since the Quaternary. The ATF has been imaged by analyzing the active source seismic reflection profiles, and the instrumentally recorded persistent background seismicity. The present study is an attempt to separate the contributions of source, site, and crustal attenuation, in order to focus on the mechanics of the seismic sources on the ATF, as well on the synthetic and the antithetic structures within the ATF hanging-wall (i.e. Colfiorito fault, Gubbio fault and Umbria Valley fault). In order to compute source spectra, we perform a set of regressions over the seismograms of 2000 small earthquakes (-0.8 < ML< 4) recorded between 2010 and 2014 at 50 permanent seismic stations deployed in the framework of the Alto Tiberina Near Fault Observatory project (TABOO) and equipped with three-components seismometers, three of which located in shallow boreholes. Because we deal with some very small earthquakes, we maximize the signal to noise ratio (SNR) with a technique based on the analysis of peak values of bandpass-filtered time histories, in addition to the same processing performed on Fourier amplitudes. We rely on a tool called Random Vibration Theory (RVT) to completely switch from peak values in the time domain to Fourier spectral amplitudes. Low-frequency spectral plateau of the source terms are used to compute moment magnitudes (Mw) of all the events, whereas a source spectral ratio technique is used to estimate the corner frequencies (Brune spectral model) of a subset of events chosen over the analysis of the noise affecting the spectral ratios. So far, the described approach provides high accuracy over the spectral parameters of earthquakes of localized seismicity, and may be used to gain insights into the underlying mechanics of faulting and the earthquake processes.

  8. Paleoseismology of the Xorxol Segment of the Central Altyn Tagh Fault, Xinjiang, China

    Directory of Open Access Journals (Sweden)

    Z. Y. Qiao

    2003-06-01

    Full Text Available Although the Altyn Tagh Fault (ATF is thought to play a key role in accommodating India-Eurasian convergence, little is known about its earthquake history. Studies of this strike-slip fault are important for interpretation of the role of faulting versus distributed deformation in the accommodation of the India- Eurasia collision. In addition, the > 1200 km long fault represents one of the most important and exemplary intracontinental strike-slip faults in the world. We mapped fault trace geometry and interpreted paleoseismic trench exposures to characterize the seismogenic behavior of the ATF. We identified 2 geometric segment boundaries in a 270 km long reach of the central ATF. These boundaries define the westernmost Wuzhunxiao, the Central Pingding, and the easternmost Xorxol (also written as Suekuli or Suo erkuli segments. In this paper, we present the results from the Camel paleoseismic site along the Xorxol Segment at 91.759°E, 38.919°N. There evidence for the last two earthquakes is clear and 14C dates from layers exposed in the excavation bracket their ages. The most recent earthquake occurred between 1456 and 1775 cal A.D. and the penultimate event was between 60 and 980 cal A.D. Combining the Camel interpretations with our published results for the central ATF, we conclude that multiple earthquakes with shorter rupture lengths (?? 50 km rather than complete rupture of the Xorxol Segment better explain the paleoseismic data. We found 2-3 earthquakes in the last 2-3 kyr. When coupled with typical amounts of slip per event (5-10 m, the recurrence times are tentatively consistent with 1-2 cm/yr slip rates. This result favors models that consider the broader distribution of collisional deformation, rather than those with northward motion of India into Asia absorbed along a few faults bounding rigid blocks.

  9. BNL ACCELERATOR TEST FACILITY CONTROL SYSTEM UPGRADE.

    Energy Technology Data Exchange (ETDEWEB)

    MALONE,R.; BEN-ZVI,I.; WANG,X.; YAKIMENKO,V.

    2001-06-18

    Brookhaven National Laboratory's Accelerator Test Facility (ATF) has embarked on a complete upgrade of its decade old computer system. The planned improvements affect every major component: processors (Intel Pentium replaces VAXes), operating system (Linux/Real-Time Linux supplants OpenVMS), and data acquisition equipment (fast Ethernet equipment replaces CAMAC serial highway.) This paper summarizes the strategies and progress of the upgrade along with plans for future expansion.

  10. Disruption of the ribosomal P complex leads to stress-induced autophagy.

    Science.gov (United States)

    Artero-Castro, Ana; Perez-Alea, Mileidys; Feliciano, Andrea; Leal, Jose A; Genestar, Mónica; Castellvi, Josep; Peg, Vicente; Ramón Y Cajal, Santiago; Lleonart, Matilde E L

    2015-01-01

    The human ribosomal P complex, which consists of the acidic ribosomal P proteins RPLP0, RPLP1, and RPLP2 (RPLP proteins), recruits translational factors, facilitating protein synthesis. Recently, we showed that overexpression of RPLP1 immortalizes primary cells and contributes to transformation. Moreover, RPLP proteins are overexpressed in human cancer, with the highest incidence in breast carcinomas. It is thought that disruption of the P complex would directly affect protein synthesis, causing cell growth arrest and eventually apoptosis. Here, we report a distinct mechanism by which cancer cells undergo cell cycle arrest and induced autophagy when RPLP proteins are downregulated. We found that absence of RPLP0, RPLP1, or RPLP2 resulted in reactive oxygen species (ROS) accumulation and MAPK1/ERK2 signaling pathway activation. Moreover, ROS generation led to endoplasmic reticulum (ER) stress that involved the EIF2AK3/PERK-EIF2S1/eIF2α-EIF2S2-EIF2S3-ATF4/ATF-4- and ATF6/ATF-6-dependent arms of the unfolded protein response (UPR). RPLP protein-deficient cells treated with autophagy inhibitors experienced apoptotic cell death as an alternative to autophagy. Strikingly, antioxidant treatment prevented UPR activation and autophagy while restoring the proliferative capacity of these cells. Our results indicate that ROS are a critical signal generated by disruption of the P complex that causes a cellular response that follows a sequential order: first ROS, then ER stress/UPR activation, and finally autophagy. Importantly, inhibition of the first step alone is able to restore the proliferative capacity of the cells, preventing UPR activation and autophagy. Overall, our results support a role for autophagy as a survival mechanism in response to stress due to RPLP protein deficiency.

  11. 油品知识讲座(四)自动变速器油%Auto Transmission Oil

    Institute of Scientific and Technical Information of China (English)

    马旭东

    2008-01-01

    @@ 自动变速器油,简称ATF(Automatic Transmission Fluid).从油品分类的角度看,自动变速器油ATF属于润滑油大类中的液力传动油的一种.自动变速器油既是自动变速器的润滑剂,又是自动变速器的工作介质.

  12. Report on Reactor Physics Assessment of Candidate Accident Tolerant Fuel Cladding Materials in LWRs

    Energy Technology Data Exchange (ETDEWEB)

    Powers, Jeffrey J. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); George, Nathan [Univ. of Tennessee, Knoxville, TN (United States); Maldonado, G. Ivan [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Worrall, Andrew [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-08-28

    This work focuses on ATF concepts being researched at Oak Ridge National Laboratory (ORNL), expanding on previous studies of using alternate cladding materials in pressurized water reactors (PWRs). The neutronic performance of two leading alternate cladding materials were assessed in boiling water reactors (BWRs): iron-chromium-aluminum (FeCrAl) cladding, and silicon carbide (SiC)-based composite cladding. This report fulfills ORNL Milestone M3FT-15OR0202332 within the fiscal year 2015 (FY15)

  13. Modulation of the Akt Pathway Reveals a Novel Link with PERK/eIF2α, which Is Relevant during Hypoxia

    OpenAIRE

    Blaustein, Matías; Pérez-Munizaga, Daniela; Sánchez, Manuel Alejandro; Urrutia, Carolina; Grande, Alicia; Risso, Guillermo; Srebrow, Anabella; Alfaro, Jennifer; Colman-Lerner, Alejandro

    2013-01-01

    The unfolded protein response (UPR) and the Akt signaling pathway share several regulatory functions and have the capacity to determine cell outcome under specific conditions. However, both pathways have largely been studied independently. Here, we asked whether the Akt pathway regulates the UPR. To this end, we used a series of chemical compounds that modulate PI3K/Akt pathway and monitored the activity of the three UPR branches: PERK, IRE1 and ATF6. The antiproliferative and antiviral drug ...

  14. Axotomy of tributaries of the pelvic and pudendal nerves induces changes in the neurochemistry of mouse dorsal root ganglion neurons and the spinal cord.

    Science.gov (United States)

    McCarthy, Carly J; Tomasella, Eugenia; Malet, Mariana; Seroogy, Kim B; Hökfelt, Tomas; Villar, Marcelo J; Gebhart, G F; Brumovsky, Pablo R

    2016-05-01

    Using immunohistochemical techniques, we characterized changes in the expression of several neurochemical markers in lumbar 4-sacral 2 (L4-S2) dorsal root ganglion (DRG) neuron profiles (NPs) and the spinal cord of BALB/c mice after axotomy of the L6 and S1 spinal nerves, major tributaries of the pelvic (targeting pelvic visceral organs) and pudendal (targeting perineum and genitalia) nerves. Sham animals were included. Expression of cyclic AMP-dependent transcription factor 3 (ATF3), calcitonin gene-related peptide (CGRP), transient receptor potential cation channel subfamily V, member 1 (TRPV1), tyrosine hydroxylase (TH) and vesicular glutamate transporters (VGLUT) types 1 and -2 was analysed seven days after injury. L6-S1 axotomy induced dramatic de novo expression of ATF3 in many L6-S1 DRG NPs, and parallel significant downregulations in the percentage of CGRP-, TRPV1-, TH- and VGLUT2-immunoreactive (IR) DRG NPs, as compared to their expression in uninjured DRGs (contralateral L6-S1-AXO; sham mice); VGLUT1 expression remained unaltered. Sham L6-S1 DRGs only showed a small ipsilateral increase in ATF3-IR NPs (other markers were unchanged). L6-S1-AXO induced de novo expression of ATF3 in several lumbosacral spinal cord motoneurons and parasympathetic preganglionic neurons; in sham mice the effect was limited to a few motoneurons. Finally, a moderate decrease in CGRP- and TRPV1-like-immunoreactivities was observed in the ipsilateral superficial dorsal horn neuropil. In conclusion, injury of a mixed visceral/non-visceral nerve leads to considerable neurochemical alterations in DRGs matched, to some extent, in the spinal cord. Changes in these and potentially other nociception-related molecules could contribute to pain due to injury of nerves in the abdominopelvic cavity. PMID:25749859

  15. Heat stress induces apoptosis through a Ca²⁺-mediated mitochondrial apoptotic pathway in human umbilical vein endothelial cells.

    Directory of Open Access Journals (Sweden)

    Li Li

    Full Text Available Heat stress can be acutely cytotoxic, and heat stress-induced apoptosis is a prominent pathological feature of heat-related illnesses, although the precise mechanisms by which heat stress triggers apoptosis are poorly defined.The percentages of viability and cell death were assessed by WST-1 and LDH release assays. Apoptosis was assayed by DNA fragmentation and caspase activity. Expression of cleaved PARP, Apaf-1, phospho-PERK, Phospho-eIF2a, ATF4, XBP-1s, ATF6, GRP78, phospho-IP3R, RYR and SERCA was estimated by Western blot. The effect of calcium overload was determined using flow cytometric analysis with the fluorescent probe Fluo-3/AM. The generation of ROS (O2-, H2O2, NO was labeled by confocal laser scanning microscopy images of fluorescently and flow cytometry.In this study, we found that heat stress in HUVEC cells activated initiators of three major unfolded protein response (UPR signaling transduction pathways: PERK-eIF2a-ATF4, IRE1-XBP-1S and ATF6 to protect against ER stress, although activation declined over time following cessation of heat stress. Furthermore, we show that intense heat stress may induce apoptosis in HUVEC cells through the calcium-mediated mitochondrial apoptotic pathway, as indicated by elevation of cytoplasmic Ca2+, expression of Apaf-1, activation of caspase-9 and caspase-3, PARP cleavage, and ultimately nucleosomal DNA fragmentation; Reactive oxygen species (ROS appear to act upstream in this process. In addition, we provide evidence that IP3R upregulation may promote influx of Ca2+ into the cytoplasm after heat stress.Our findings describe a novel mechanism for heat stress-induced apoptosis in HUVEC cells: following elevation of cytoplasm Ca2+, activation of the mitochondrial apoptotic pathway via the IP3R upregulation, with ROS acting as an upstream regulator of the process.

  16. Challenges and Opportunities for Commercialization of Enhanced Accident Tolerant Fuel or Light Water Reactors: A Utility-Informed Perspective

    International Nuclear Information System (INIS)

    There is consensus within the global research and development (R&D) community that the barriers to deployment of accident tolerant fuel (ATF) for commercial use in the near-future are too high and carry too much risk for any one organization to succeed alone. International collaboration is needed to leverage existing and new resources and expertise. Efforts are now underway to bring key entities together to share experiences and identify gaps and opportunities to leverage resources. In the wake of Fukushima Daiichi, momentum and funding currently exist in many countries for R&D targeting enhanced accident tolerance fuel (and other non-fuel reactor components) for Generation II/III/III+ light-water reactors (LWRs) with the goal of fundamentally changing severe accident outcomes while also maintaining or even improving fuel and reactor system performance under normal operations. While funding and interest are relatively high at present, the long time frames required for implementing substantial changes to in-core components and fuel designs demand a stable and sustained R&D focus. Likewise, the geographic dispersion and scarcity of key experimental and test facilities further highlight the need for coordination of experimental programmes and testing whenever possible and appropriate. Success in ATF development will come with the investment by, engagement of, and collaboration among the many key entities involved in the arduous path from early research through commercial deployment. As utilities are the ultimate customer for any new technology targeting enhanced performance and accident tolerance for LWRs, a clear understanding of nuclear plant operator needs and constraints is essential for the success of the global ATF R&D enterprise. Ultimately, the safety and performance benefits from ATF related investment will be realized only to the extent that new technologies are widely adopted and deployed in operating reactors. (author)

  17. LONGITUDINAL DENSITY MODULATION OF UNSTABLE BUNCHES EMITTING COHERENT IR.

    Energy Technology Data Exchange (ETDEWEB)

    PODOBEDOV,B.; CARR,G.L.; KRAMER,S.L.; MURPHY,J.B.

    2001-06-18

    Brookhaven National Laboratory's Accelerator Test Facility (ATF) has embarked on a complete upgrade of its decade old computer system. The planned improvements affect every major component: processors (Intel Pentium replaces VAXes), operating system (Linux/Real-Time Linux supplants OpenVMS), and data acquisition equipment (fast Ethernet equipment replaces CAMAC serial highway.) This paper summarizes the strategies and progress of the upgrade along with plans for future expansion.

  18. Developments in Reactor and Economic Modelling Considering the Performance of Accident Tolerant Fuels

    International Nuclear Information System (INIS)

    Accident tolerant fuel (ATF) technology is being developed to enhance the safety performance of nuclear fuels and cladding. The development and testing of ATF materials by NNL through its Nuclear Fuel Centre of Excellence is being complemented by parallel developments in fuel performance modelling, in addition to reactor physics and economic calculations to optimise ATF fuel. An approach for preliminary optimisation of ATF fuel pin and cladding parameters, in typical commercial PWRs is described, including an initial optimisation of uranium nitride (UN) fuel pellet dimensions and enrichment (combined with zirconium cladding) and for silicon carbide composite (SiC) clad fuel (combined with uranium oxide fuel (UO2)). In order to optimise pin reactivity, pellet diameter is less for UN compared with UO2. A lower feed enrichment was required to give an equilibrium energy output close to the equivalent UO2 fuel. Modelling this design indicates that there is a potential economic benefit, through lower fuel assembly costs, when using optimised UN fuel compared with standard UO2 PWR fuel. For standard UO2 fuel, full core calculations have examined the reactivity benefit when replacing zircaloy clad for SiC. Calculations assume idealised SiC clad thicknesses similar to those used with current zircaloy clads. An economic analysis, considering current cost estimates of SiC clad manufacture, indicates SiC clad fuel assembly costs are significantly increased. However, there remains scope for offsetting these increased fuel costs through optimised reactor operation by taking advantage of the reduced parasitic neutron absorption or higher temperature tolerance of SiC clad. An initial assessment is also undertaken of how the performance of the higher density uranium nitride fuel compares against key PWR safety measures: considering pin power peaking, shutdown margin, moderator temperature coefficients, boron reactivity worth, delayed neutron fractions and boration limits. All

  19. The Second National Ballistics Imaging Comparison (NBIC-2)

    OpenAIRE

    Vorburger, TV; Yen, J; Song, JF; Thompson, RM; Renegar, TB; Zheng, A.; Tong, M; Ols, M

    2015-01-01

    In response to the guidelines issued by the American Society of Crime Laboratory Directors/Laboratory Accreditation Board (ASCLD/LAB-International) to establish traceability and quality assurance in U.S. crime laboratories, NIST and the ATF initiated a joint project, entitled the National Ballistics Imaging Comparison (NBIC). The NBIC project aims to establish a national traceability and quality system for ballistics identifications in crime laboratories utilizing ATF’s National Integrated Ba...

  20. Searches for skin injury-related genes induced by ionizing radiation

    International Nuclear Information System (INIS)

    This review describes investigations concerning the skin and radiation exposure, and molecular effects of radiation on the skin partly based on authors' studies on searches in the title and for signaling cascade. Depending on the dose and its rate, radiation induces injuries like erythema, edema, alopecia, erosion, ulcer and cancer. Comprehensive analysis of the skin injury-related genes is now possible on the human genome chips (DNA micro-array) and on RNA/protein obtained from exposed epidermal keratinocytes and dermal fibroblasts using such molecular biological means as reverse transcription polymerase chain reaction (RT-PCR), Northern/Western blotting and cyto/histochemistry. Authors have actually revealed that mRNA of ATF3, which regulates the gene transcription, is increased depending on the dose in the exposed human keratinocytes, and ATF3 is accumulated in the nucleus. Authors have also studied the up- and down-streams of signaling cascade of ATF3 to show phosphorylations of p53 and H2AX at exposure to high dose radiation in cells above and in intact mouse. Basic findings in the skin like above can be useful in future for estimation of exposed dose and for risk assessment as well as the present hematological findings. (T.I)

  1. 非典型症状与双相障碍%Atypical features and bipolar disorder

    Institute of Scientific and Technical Information of China (English)

    彭代辉; 黄悦琦; 江开达

    2016-01-01

    Bipolar Disorder (BD) features with various of clinical symptoms, leading to the misdiagnosis of major depressive disorder (MDD). The atypical features (ATFs) are regarded as one of valuable index to idenitfy BD from depressed paitents. The ATFs should be helpful to the differenital diagnose of the two diseases. In this forum, we discussed the issue of the relaiton between the ATFs and BD.%概述:双相障碍(Bipolar Disorder,BD)临床症状多样,容易被误诊为抑郁症(Major depressive disorder, MDD)。非典型症状(Atypical Features,ATFs)是一个有用的指标,可以从抑郁状态中识别出双相障碍,有助于双相障碍与抑郁症的鉴别诊断。本文就非典型症状与双相障碍的相关性问题进行讨论。

  2. Severe Accident Test Station Activity Report

    Energy Technology Data Exchange (ETDEWEB)

    Pint, Bruce A [ORNL; Terrani, Kurt A [ORNL

    2015-06-01

    Enhancing safety margins in light water reactor (LWR) severe accidents is currently the focus of a number of international R&D programs. The current UO2/Zr-based alloy fuel system is particularly susceptible since the Zr-based cladding experiences rapid oxidation kinetics in steam at elevated temperatures. Therefore, alternative cladding materials that offer slower oxidation kinetics and a smaller enthalpy of oxidation can significantly reduce the rate of heat and hydrogen generation in the core during a coolant-limited severe accident. In the U.S. program, the high temperature steam oxidation performance of accident tolerant fuel (ATF) cladding solutions has been evaluated in the Severe Accident Test Station (SATS) at Oak Ridge National Laboratory (ORNL) since 2012. This report summarizes the capabilities of the SATS and provides an overview of the oxidation kinetics of several candidate cladding materials. A suggested baseline for evaluating ATF candidates is a two order of magnitude reduction in the steam oxidation resistance above 1000ºC compared to Zr-based alloys. The ATF candidates are categorized based on the protective external oxide or scale that forms during exposure to steam at high temperature: chromia, alumina, and silica. Comparisons are made to literature and SATS data for Zr-based alloys and other less-protective materials.

  3. Electric Motor Thermal Management R&D (Presentation)

    Energy Technology Data Exchange (ETDEWEB)

    Bennion, K.

    2014-11-01

    Thermal constraints place significant limitations on how electric motors ultimately perform. Without the ability to remove heat, the motor cannot operate without sacrificing performance, efficiency, and reliability. Finite element analysis and computational fluid dynamics modeling approaches are being increasingly utilized in the design and analysis of electric motors. As the models become more sophisticated, it is important to have detailed and accurate knowledge of both the passive thermal performance and the active cooling performance. In this work, we provide an overview of research characterizing both passive and active thermal elements related to electric motor thermal management. To better characterize the passive thermal performance, the effective thermal properties and inter-lamination thermal contact resistances were measured for different stator lamination materials. The active cooling performance of automatic transmission fluid (ATF) jets was also measured to better understand the heat transfer coefficients of ATF impinging on motor copper windings. Ford's Mercon LV was the ATF evaluated in this study. The presentation provides an overview of prior work with a focus on describing future plans for research to be performed during FY15.

  4. In vacuum diamond sensor scanner for beam halo measurements in the beam line at the KEK Accelerator Test Facility

    CERN Document Server

    Liu, Shan; Cornebise, Patrick; Faus-Golfe, Angeles; Fuster-Martínez, Nuria; Griesmayer, Erich; Guler, Hayg; Kubytskyi, Viacheslav; Sylvia, Christophe; Toshiaki, Tauchi; Terunuma, Nobuhiro; Bambade, Philip

    2015-01-01

    The investigation of beam halo transverse distributions is important for the understanding of beam losses and the control of backgrounds in Future Linear Colliders (FLC). A novel in vacuum diamond sensor (DSv) scanner with four strips has been designed and developed for the investigation of the beam halo transverse distributions and also for the diagnostics of Compton recoil electrons after the interaction point (IP) of ATF2, a low energy (1.3 GeV) prototype of the final focus system for the ILC and CLIC linear collider projects. Using the DSv, a dynamic range of $\\sim10^6$ has been successfully demonstrated and confirmed for the first time by simultaneous beam core ($\\sim10^9$ electrons) and beam halo ($\\sim10^3$ electrons) measurements at ATF2. This report presents the characterization, performance studies and tests of the diamond sensors using an $\\alpha$ source as well as using the electron beams at PHIL, a low energy ($< 10$ MeV) photo-injector at LAL, and at ATF2. First beam halo measurement results ...

  5. Ship detection for high resolution optical imagery with adaptive target filter

    Science.gov (United States)

    Ju, Hongbin

    2015-10-01

    Ship detection is important due to both its civil and military use. In this paper, we propose a novel ship detection method, Adaptive Target Filter (ATF), for high resolution optical imagery. The proposed framework can be grouped into two stages, where in the first stage, a test image is densely divided into different detection windows and each window is transformed to a feature vector in its feature space. The Histograms of Oriented Gradients (HOG) is accumulated as a basic feature descriptor. In the second stage, the proposed ATF highlights all the ship regions and suppresses the undesired backgrounds adaptively. Each detection window is assigned a score, which represents the degree of the window belonging to a certain ship category. The ATF can be adaptively obtained by the weighted Logistic Regression (WLR) according to the distribution of backgrounds and targets of the input image. The main innovation of our method is that we only need to collect positive training samples to build the filter, while the negative training samples are adaptively generated by the input image. This is different to other classification method such as Support Vector Machine (SVM) and Logistic Regression (LR), which need to collect both positive and negative training samples. The experimental result on 1-m high resolution optical images shows the proposed method achieves a desired ship detection performance with higher quality and robustness than other methods, e.g., SVM and LR.

  6. Activation of Satellite Glial Cells in Rat Trigeminal Ganglion after Upper Molar Extraction

    International Nuclear Information System (INIS)

    The neurons in the trigeminal ganglion (TG) are surrounded by satellite glial cells (SGCs), which passively support the function of the neurons, but little is known about the interactions between SGCs and TG neurons after peripheral nerve injury. To examine the effect of nerve injury on SGCs, we investigated the activation of SGCs after neuronal damage due to the extraction of the upper molars in rats. Three, 7, and 10 days after extraction, animals were fixed and the TG was removed. Cryosections of the ganglia were immunostained with antibodies against glial fibrillary acidic protein (GFAP), a marker of activated SGCs, and ATF3, a marker of damaged neurons. After tooth extraction, the number of ATF3-immunoreactive (IR) neurons enclosed by GFAP-IR SGCs had increased in a time-dependent manner in the maxillary nerve region of the TG. Although ATF3-IR neurons were not detected in the mandibular nerve region, the number of GFAP-IR SGCs increased in both the maxillary and mandibular nerve regions. Our results suggest that peripheral nerve injury affects the activation of TG neurons and the SGCs around the injured neurons. Moreover, our data suggest the existence of a neuronal interaction between maxillary and mandibular neurons via SGC activation

  7. Genes and Gene Networks Involved in Sodium Fluoride-Elicited Cell Death Accompanying Endoplasmic Reticulum Stress in Oral Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Yoshiaki Tabuchi

    2014-05-01

    Full Text Available Here, to understand the molecular mechanisms underlying cell death induced by sodium fluoride (NaF, we analyzed gene expression patterns in rat oral epithelial ROE2 cells exposed to NaF using global-scale microarrays and bioinformatics tools. A relatively high concentration of NaF (2 mM induced cell death concomitant with decreases in mitochondrial membrane potential, chromatin condensation and caspase-3 activation. Using 980 probe sets, we identified 432 up-regulated and 548 down-regulated genes, that were differentially expressed by >2.5-fold in the cells treated with 2 mM of NaF and categorized them into 4 groups by K-means clustering. Ingenuity® pathway analysis revealed several gene networks from gene clusters. The gene networks Up-I and Up-II included many up-regulated genes that were mainly associated with the biological function of induction or prevention of cell death, respectively, such as Atf3, Ddit3 and Fos (for Up-I and Atf4 and Hspa5 (for Up-II. Interestingly, knockdown of Ddit3 and Hspa5 significantly increased and decreased the number of viable cells, respectively. Moreover, several endoplasmic reticulum (ER stress-related genes including, Ddit3, Atf4 and Hapa5, were observed in these gene networks. These findings will provide further insight into the molecular mechanisms of NaF-induced cell death accompanying ER stress in oral epithelial cells.

  8. The Mitochondrial Unfolded Protein Response Protects against Anoxia in Caenorhabditis elegans

    Science.gov (United States)

    Peña, Salvador; Sherman, Teresa; Brookes, Paul S.; Nehrke, Keith

    2016-01-01

    The mitochondrial unfolded protein response (UPRmt) is a surveillance pathway that defends proteostasis in the “powerhouse” of the cell. Activation of the UPRmt protects against stresses imposed by reactive oxygen species, respiratory chain deficits, and pathologic bacteria. Consistent with the UPRmt’s role in adaption, we found that either its pharmacological or genetic activation by ethidium bromide (EtBr) or RNAi of the mitochondrial AAA-protease spg-7 was sufficient to reduce death in an anoxia-based Caenorhabditis elegans model of ischemia-reperfusion injury. The UPRmt-specific transcription factor atfs-1 was necessary for protection and atfs-1 gain-of-function (gf) mutants were endogenously protected from both death and dysfunction. Neurons exhibited less axonal degeneration following non-lethal anoxia-reperfusion (A-R) when the UPRmt was pre-activated, and consistent with the concept of mitochondrial stress leading to cell non-autonomous (ie. “remote”) effects, we found that restricted activation of the UPRmt in neurons decreased A-R death. However, expression of the atfs-1(gf) mutant in neurons, which resulted in a robust activation of a neuronal UPRmt, did not upregulate the UPRmt in distal tissues, nor did it protect the worms from A-R toxicity. These findings suggest that remote signaling requires additional component(s) acting downstream of de facto mitochondrial stress. PMID:27459203

  9. Late Quaternary sinistral slip rate along the Altyn Tagh fault and its structural transformation model

    Institute of Scientific and Technical Information of China (English)

    XU; Xiwei; P.; Tapponnier; J.; Van; Der; Woerd; F.; J.; Ryer

    2005-01-01

    Based on technical processing of high-resolution SPOT images and aerophotos,detailed mapping of offset landforms in combination with field examination and displacement measurement, and dating of offset geomorphic surfaces by using carbon fourteen (14C), cosmogenic nuclides (10Be+26Al) and thermoluminescence (TL) methods, the Holocene sinistral slip rates on different segments of the Altyn Tagh Fault (ATF) are obtained. The slip rates reach 17.5±2 mm/a on the central and western segments west of Aksay Town, 11±3.5 mm/a on the Subei-Shibaocheng segment, 4.8± 1.0 mm/a on the Sulehe segment and only 2.2± 0.2 mm/a on the Kuantanshan segment, an easternmost segment of the ATF. The sudden change points for loss of sinistral slip rates are located at the Subei, Shibaocheng and Shulehe triple junctions where NW-trending active thrust faults splay from the ATF and propagate southeastward. Slip vector analyses indicate that the loss of the sinistral slip rates from west to east across a triple junction has structurally transformed into local crustal shortening perpendicular to the active thrust faults and strong uplifting of the thrust sheets to form the NW-trending Danghe Nanshan,Daxueshan and Qilianshan Ranges. Therefore, the eastward extrusion of the northern Qinghai-Tibetan Plateau is limited and this is in accord with "the imbricated thrusting transformation-limited extrusion model".

  10. Molecular photoacoustic tomography of breast cancer using receptor targeted magnetic iron oxide nanoparticles as contrast agents.

    Science.gov (United States)

    Xi, Lei; Grobmyer, Stephen R; Zhou, Guangyin; Qian, Weiping; Yang, Lily; Jiang, Huabei

    2014-06-01

    In this report, we present a breast imaging technique combining high-resolution near-infrared (NIR) light induced photoacoustic tomography (PAT) with NIR dye-labeled amino-terminal fragments of urokinase plasminogen activator receptor (uPAR) targeted magnetic iron oxide nanoparticles (NIR830-ATF-IONP) for breast cancer imaging using an orthotopic mouse mammary tumor model. We show that accumulation of the targeted nanoparticles in the tumor led to photoacoustic contrast enhancement due to the high absorption of iron oxide nanoparticles (IONP). NIR fluorescence images were used to validate specific delivery of NIR830-ATF-IONP to mouse mammary tumors. We found that systemic delivery of the targeted IONP produced 4- and 10-fold enhancement in photoacoustic signals in the tumor, compared to the tumor of the mice that received non-targeted IONP or control mice. The use of targeted nanoparticles allowed imaging of tumors located as deep as 3.1 cm beneath the normal tissues. Our study indicates the potential of the combination of photoacoustic tomography and receptor-targeted NIR830-ATF-IONP as a clinical tool that can provide improved specificity and sensitivity for breast cancer detection.

  11. Crystal structure of the urokinase receptor in a ligand-free form

    DEFF Research Database (Denmark)

    Xu, Xiang; Gårdsvoll, Henrik; Yuan, Cai;

    2012-01-01

    . The structure of uPAR(H47C/N259C) in complex with ATF resembles the wild-type uPAR·ATF complex, demonstrating that these mutations do not perturb the uPA binding properties of uPAR. The present structure of uPAR(H47C/N259C) provides the first structural definition of uPAR in its ligand-free form, which...... with this multifunctional role, uPAR binds several extracellular ligands, including uPA and vitronectin. Structural studies suggest that uPAR possesses structural flexibility. It is, however, not clear whether this flexibility is an inherent property of the uPAR structure per se or whether it is induced upon ligand binding....... The crystal structure of human uPAR in its ligand-free state would clarify this issue, but such information remains unfortunately elusive. We now report the crystal structures of a stabilized, human uPAR (H47C/N259C) in its ligand-free form to 2.4 Å and in complex with amino-terminal fragment (ATF) to 3.2 Å...

  12. Helicobacter pylori VacA enhances prostaglandin E2 production through induction of cyclooxygenase 2 expression via a p38 mitogen-activated protein kinase/activating transcription factor 2 cascade in AZ-521 cells

    DEFF Research Database (Denmark)

    Hisatsune, Junzo; Yamasaki, Eiki; Nakayama, Masaaki;

    2007-01-01

    Treatment of AZ-521 cells with Helicobacter pylori VacA increased cyclooxygenase 2 (COX-2) mRNA in a time- and dose-dependent manner. A p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580, blocked elevation of COX-2 mRNA levels, whereas PD98059, which blocks the Erk1/2 cascade......A-induced COX-2 expression. In parallel with COX-2 expression, VacA increased prostaglandin E(2) (PGE(2)) production, which was inhibited by SB203580 and NS-398, a COX-2 inhibitor. VacA-induced PGE(2) production was markedly attenuated in AZ-521 cells stably expressing DN-p38. VacA increased transcription...... promoter activation. The reduction of ATF-2 expression in AZ-521 cells transformed with ATF-2-small interfering RNA duplexes resulted in suppression of COX-2 expression. Thus, VacA enhances PGE(2) production by AZ-521 cells through induction of COX-2 expression via the p38 MAPK/ATF-2 cascade, leading...

  13. The BNL Accelerator Test Facility and experimental program

    International Nuclear Information System (INIS)

    The Accelerator Test Facility (ATF) at BNL is a users' facility for experiments in Accelerator and Beam Physics. The ATF provides high brightness electron beams and high power laser pulses synchronized to the electron beam, suitable for studies of new methods of high gradient acceleration and state of the art free electron lasers. The electrons are produced by a laser photocathode rf gun and accelerated to 50 to 100 MeV by two traveling wave accelerator sections. The lasers include a 10 mJ, 10 ps Nd:YAG laser and a 100 mJ, 10 ps CO2 laser. A number of users from National Laboratories, universities and industry take part in experiments at the ATF. The experimental program includes various acceleration schemes, Free-Electron Laser experiments and a program on the development of high brightness electron beams. The AFT's experimental program commenced in early 1991 at an energy of about 4 MeV. The full program, with 50 MeV and the High power laser will begin operation this year. 28 refs., 4 figs

  14. 汽车自动变速器油的技术现状与发展趋势%Current Technology and Development Trends of Automatic Transmission Fluids

    Institute of Scientific and Technical Information of China (English)

    李茂生; 杜群贵; 贾继欣

    2014-01-01

    The types,characteristics and developing direction of vehicle automatic transmission,and the technical re-quirement,current technological state and development trend of automatic transmission fluids (ATF/CVTF ) were de-scribed.The tribological characteristics and evaluation method of ATF/CVTF were introduced.The development and appli-cation of new automatic transmission fluids and its corresponding evaluation test methods of physical and chemical proper-ties,friction characteristics and wear state,the development of the specifications and standard of automatic transmission flu-ids are key common technologies for development of automatic transmission.%论述汽车自动变速器(AT、CVT)的类型、特点及发展方向,以及与其配套的变速器油(ATF、CVTF)的技术现状和发展趋势,介绍ATF/CVTF的摩擦学特性及其评价方法。开发和应用新型自动变速器油及其相应的摩擦特性测试方法、磨损状态评定手段和油品理化性能测试方法及台架试验方法,制定自动变速器油的规格标准,是促进自动变速器发展的关键共性技术。

  15. Results from DR and Instrumentation Test Facilities

    CERN Document Server

    Urakawa, Junji

    2005-01-01

    The KEK Accelerator Test Facility (ATF) is a 1.3GeV storage ring capable of producing ultra-low emittance electron beams and has a beam extraction line for ILC R&D. The ATF has proven to be an ideal place for researches with small, stable beams. 2x1010 single bunch and low current 20 bunch-train with 2.8nsec bunch spacing have been extracted to develop Nano-Cavity BPM’s, FONT, Nano Beam Orbit handling (FEATHER), Optical Diffraction Radiation (ODR) monitor, a precision multi-bunch laser-based beam profile monitor and polarized positron beam generation via backward-Compton scattering by the international collaboration. A set of three cavity BPM's is installed in the ATF extraction line on a set of extremely stiff supports. The KEK group installed another set of three BPM's, with their own support mechanism. The full set of 6 will prove extremely useful. In the DR (Damping Ring), we are researching the fast ion instability, micro-wave instability with four sets of damping wiggler and developing pul...

  16. Porcine Circovirus 2 Deploys PERK Pathway and GRP78 for Its Enhanced Replication in PK-15 Cells

    Directory of Open Access Journals (Sweden)

    Yingshan Zhou

    2016-02-01

    Full Text Available Porcine circovirus type 2 (PCV2 infection induces autophagy and apoptosis. These cellular responses could be connected with endoplasmic reticulum (ER stress. It remains unknown if PCV2 induces ER stress and if autophagy or apoptosis is primary to PCV2 infection or secondary responses following ER stress. Here, we demonstrate that PCV2 triggered unfolded protein response (UPR in PK-15 cells by activating the PERK/eIF2α pathway without concomitant activation of IRE1 or ATF6. Since ATF4 and CHOP were induced later than PERK/eIF2α, it is clear that persistent PCV2 infection could lead to selective activation of PERK via the PERK-eIF2α-ATF4-CHOP axis. Therefore, PERK activation could be part of the pro-apoptotic signaling via induced expression of CHOP by PCV2. Since PERK inhibition by GSK2606414 or RNA silencing or suppression of eIF2α dephosphorylation by salubrinal limited viral replication, we suppose that PCV2 deploys UPR to enhance its replication. Over-expression of GRP78 or treatment with tauroursodeoxycholic acid could enhance viral capsid expression and/or viral titers, indicating that these chaperones, endogenous or exogenous, could help correct folding of viral proteins. Our findings provide the first evidence that ER stress plays a role in the pathogenesis of PCV2 infection probably as part of autophagic and apoptotic responses.

  17. Porcine Circovirus 2 Deploys PERK Pathway and GRP78 for Its Enhanced Replication in PK-15 Cells.

    Science.gov (United States)

    Zhou, Yingshan; Qi, Baozhu; Gu, Yuanxing; Xu, Fei; Du, Huahua; Li, Xiaoliang; Fang, Weihuan

    2016-02-01

    Porcine circovirus type 2 (PCV2) infection induces autophagy and apoptosis. These cellular responses could be connected with endoplasmic reticulum (ER) stress. It remains unknown if PCV2 induces ER stress and if autophagy or apoptosis is primary to PCV2 infection or secondary responses following ER stress. Here, we demonstrate that PCV2 triggered unfolded protein response (UPR) in PK-15 cells by activating the PERK/eIF2α pathway without concomitant activation of IRE1 or ATF6. Since ATF4 and CHOP were induced later than PERK/eIF2α, it is clear that persistent PCV2 infection could lead to selective activation of PERK via the PERK-eIF2α-ATF4-CHOP axis. Therefore, PERK activation could be part of the pro-apoptotic signaling via induced expression of CHOP by PCV2. Since PERK inhibition by GSK2606414 or RNA silencing or suppression of eIF2α dephosphorylation by salubrinal limited viral replication, we suppose that PCV2 deploys UPR to enhance its replication. Over-expression of GRP78 or treatment with tauroursodeoxycholic acid could enhance viral capsid expression and/or viral titers, indicating that these chaperones, endogenous or exogenous, could help correct folding of viral proteins. Our findings provide the first evidence that ER stress plays a role in the pathogenesis of PCV2 infection probably as part of autophagic and apoptotic responses. PMID:26907328

  18. Late Cenozoic sedimentary process and its response to the slip history of the central Altyn Tagh fault, NW China

    Institute of Scientific and Technical Information of China (English)

    陈正乐; 张岳桥; 陈宣华; 王小凤; A.S.Ramon; W.B.Zack

    2001-01-01

    The ENE-striking Altyn Tagh fault (ATF), extending along the northern edge of the Tibetan Plateau, is one of the major important strike-slip faults, and has been known as one of the key areas to debate the eastward extrusion and crustral shortening models of the Tibetan Plateau during and after India-Asia collision. This paper mainly presents new evidence of Late Cenozoic sedimentary process to reconstruct the slip history of the ATF during the Late Cenozoic. Field measurements and laboratory analyses of the sedimentary characteristics in the Late Cenozoic basins in the central Altyn Tagh fault suggest that Late Cenozoic sedimentary sequence should be divided into three units according to facies changes. The paleo-topography reconstruction shows that the sedimentation in these basins was tightly related with the fault, indicating that the ATF has experienced at least three stages of strike slipping in the Late Cenozoic. New geological data from the Late Cenozoic sedimentary basins and the formation of th

  19. Single ingestion of soy β-conglycinin induces increased postprandial circulating FGF21 levels exerting beneficial health effects.

    Science.gov (United States)

    Hashidume, Tsutomu; Kato, Asuka; Tanaka, Tomohiro; Miyoshi, Shoko; Itoh, Nobuyuki; Nakata, Rieko; Inoue, Hiroyasu; Oikawa, Akira; Nakai, Yuji; Shimizu, Makoto; Inoue, Jun; Sato, Ryuichiro

    2016-01-01

    Soy protein β-conglycinin has serum lipid-lowering and anti-obesity effects. We showed that single ingestion of β-conglycinin after fasting alters gene expression in mouse liver. A sharp increase in fibroblast growth factor 21 (FGF21) gene expression, which is depressed by normal feeding, resulted in increased postprandial circulating FGF21 levels along with a significant decrease in adipose tissue weights. Most increases in gene expressions, including FGF21, were targets for the activating transcription factor 4 (ATF4), but not for peroxisome proliferator-activated receptor α. Overexpression of a dominant-negative form of ATF4 significantly reduced β-conglycinin-induced increases in hepatic FGF21 gene expression. In FGF21-deficient mice, β-conglycinin effects were partially abolished. Methionine supplementation to the diet or primary hepatocyte culture medium demonstrated its importance for activating liver or hepatocyte ATF4-FGF21 signaling. Thus, dietary β-conglycinin intake can impact hepatic and systemic metabolism by increasing the postprandial circulating FGF21 levels. PMID:27312476

  20. Pichia pastoris as a host for secretion of toxic saporin chimeras.

    Science.gov (United States)

    Lombardi, Alessio; Bursomanno, Sara; Lopardo, Teresa; Traini, Roberta; Colombatti, Marco; Ippoliti, Rodolfo; Flavell, David J; Flavell, Sopsamorn U; Ceriotti, Aldo; Fabbrini, Maria Serena

    2010-01-01

    Most of the targeting moieties, such as antibody fragments or growth factor domains, used to construct targeted toxins for anticancer therapy derive from secretory proteins. These normally fold in the oxidative environment of the endoplasmic reticulum, and hence their folding in bacterial cells can be quite inefficient. For instance, only low amounts of properly folded antimetastatic chimera constituted by the amino-terminal fragment of human urokinase (ATF) fused to the plant ribosome-inactivating protein saporin could be recovered. ATF-saporin was instead secreted efficiently when expressed in eukaryotic cells protected from autointoxication with neutralizing anti-saporin antibodies. Pichia pastoris is a microbial eukaryotic host where these domains can fold into a transport-competent conformation and reach the extracellular medium. We show here that despite some host toxicity codon-usage optimization greatly increased the expression levels of active saporin but not those of an active-site mutant SAP-KQ in GS115 (his4) strain. The lack of any toxicity associated with expression of the latter confirmed that toxicity is due to saporin catalytic activity. Nevertheless, GS115 (his4) cells in flask culture secreted 3.5 mg/L of a histidine-tagged ATF-saporin chimera showing an IC(50) of 6 x 10(-11) M against U937 cells, thus demonstrating the suitability of this expression platform for secretion of toxic saporin-based chimeras. PMID:19786581

  1. A Mutation in Caenorhabditis elegans NDUF-7 Activates the Mitochondrial Stress Response and Prolongs Lifespan via ROS and CED-4.

    Science.gov (United States)

    Rauthan, Manish; Ranji, Parmida; Abukar, Ragda; Pilon, Marc

    2015-06-01

    The mevalonate pathway is responsible for the synthesis of cholesterol, coenzyme Q, and prenyl groups essential for small GTPase modification and function, and for the production of dolichols important for protein glycosylation. Statins, i.e., cholesterol-lowering drugs that inhibit the rate-limiting enzyme in the mevalonate pathway, HMG-CoA reductase, are lethal to Caenorhabditis elegans even though this animal lacks the branch of the mevalonate pathway that leads to cholesterol synthesis. To better understand the effects of statins that are not related to cholesterol, we have adopted the strategy of isolating statin-resistant C. elegans mutants. Previously, we showed that such mutants often have gain-of-function mutations in ATFS-1, a protein that activates the mitochondrial unfolded protein response. Here, we describe the isolation of a statin-resistant mutant allele of the NDUF-7 protein, which is a component of complex I in the mitochondrial electron transport chain. The novel nduf-7(et19) mutant also exhibits constitutive and ATFS-1-dependent activation of the mitochondrial unfolded protein response (UPR(mt)) and prolonged life span, both of which are mediated through production of ROS. Additionally, lifespan extension, but not activation, of the mitochondrial unfolded protein response was dependent on the pro-apoptotic gene ced-4. We conclude that the nduf-7(et19) mutant allele causes an increase in reactive oxygen species that activate ATFS-1, hence UPR(mt)-mediated statin resistance, and extends life span via CED-4.

  2. LIGHT WATER REACTOR ACCIDENT TOLERANT FUELS IRRADIATION TESTING

    Energy Technology Data Exchange (ETDEWEB)

    Carmack, William Jonathan [Idaho National Laboratory; Barrett, Kristine Eloise [Idaho National Laboratory; Chichester, Heather Jean MacLean [Idaho National Laboratory

    2015-09-01

    The purpose of Accident Tolerant Fuels (ATF) experiments is to test novel fuel and cladding concepts designed to replace the current zirconium alloy uranium dioxide (UO2) fuel system. The objective of this Research and Development (R&D) is to develop novel ATF concepts that will be able to withstand loss of active cooling in the reactor core for a considerably longer time period than the current fuel system while maintaining or improving the fuel performance during normal operations, operational transients, design basis, and beyond design basis events. It was necessary to design, analyze, and fabricate drop-in capsules to meet the requirements for testing under prototypic LWR temperatures in Idaho National Laboratory's Advanced Test Reactor (ATR). Three industry led teams and one DOE team from Oak Ridge National Laboratory provided fuel rodlet samples for their new concepts for ATR insertion in 2015. As-built projected temperature calculations were performed on the ATF capsules using the BISON fuel performance code. BISON is an application of INL’s Multi-physics Object Oriented Simulation Environment (MOOSE), which is a massively parallel finite element based framework used to solve systems of fully coupled nonlinear partial differential equations. Both 2D and 3D models were set up to examine cladding and fuel performance.

  3. Electric Motor Thermal Management R&D. Annual Report

    Energy Technology Data Exchange (ETDEWEB)

    Bennion, Kevin [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2016-04-01

    With the push to reduce component volumes, lower costs, and reduce weight without sacrificing performance or reliability, the challenges associated with thermal management increase for power electronics and electric motors. Thermal management for electric motors will become more important as the automotive industry continues the transition to more electrically dominant vehicle propulsion systems. The transition to more electrically dominant propulsion systems leads to higher-power duty cycles for electric drive systems. Thermal constraints place significant limitations on how electric motors ultimately perform, and as thermal management improves, there will be a direct trade-off between motor performance, efficiency, cost, and the sizing of electric motors to operate within the thermal constraints. The goal of this research project is to support broad industry demand for data, analysis methods, and experimental techniques to improve and better understand motor thermal management. Work in FY15 focused on two areas related to motor thermal management: passive thermal performance and active convective cooling. Passive thermal performance emphasized the thermal impact of materials and thermal interfaces among materials within an assembled motor. The research tasks supported the publication of test methods and data for thermal contact resistances and direction-dependent thermal conductivity within an electric motor. Active convective cooling focused on measuring convective heat-transfer coefficients using automatic transmission fluid (ATF). Data for average convective heat transfer coefficients for direct impingement of ATF jets was published. Also, experimental hardware for mapping local-scale and stator-scale convective heat transfer coefficients for ATF jet impingement were developed.

  4. Evaluation of a Bladder Cancer Cluster in a Population of Criminal Investigators with the Bureau of Alcohol, Tobacco, Firearms and Explosives—Part 1: The Cancer Incidence

    Directory of Open Access Journals (Sweden)

    Susan R. Davis

    2012-01-01

    Full Text Available This study investigated a bladder cancer cluster in a cohort of employees, predominately criminal investigators, participating in a medical surveillance program with the United States Bureau of Alcohol, Tobacco, Firearms and Explosives (ATF between 1995 and 2007. Standardized incidence ratios (SIRs were used to compare cancer incidences in the ATF population and the US reference population. Seven cases of bladder cancer (five cases verified by pathology report at time of analysis were identified among a total employee population of 3,768 individuals. All cases were white males and criminal investigators. Six of seven cases were in the 30 to 49 age range at the time of diagnosis. The SIRs for white male criminal investigators undergoing examinations were 7.63 (95% confidence interval = 3.70–15.75 for reported cases and 5.45 (2.33–12.76 for verified cases. White male criminal investigators in the ATF population are at statistically significant increased risk for bladder cancer.

  5. Endoplasmic reticulum stress impairment in the spinal dorsal horn of a neuropathic pain model.

    Science.gov (United States)

    Zhang, Enji; Yi, Min-Hee; Shin, Nara; Baek, Hyunjung; Kim, Sena; Kim, Eunjee; Kwon, Kisang; Lee, Sunyeul; Kim, Hyun-Woo; Chul Bae, Yong; Kim, Yonghyun; Kwon, O-Yu; Lee, Won Hyung; Kim, Dong Woon

    2015-01-01

    Endoplasmic reticulum (ER) stress has been implicated in neurodegenerative diseases, but its role in neuropathic pain remains unclear. In this study, we examined the ER stress and the unfolded protein response (UPR) activation in a L5 spinal nerve ligation (SNL)-induced rat neuropathic pain model. SNL-induced neuropathic pain was assessed behaviorally using the CatWalk system, and histologically with microglial activation in the dorsal spinal horn. L5 SNL induced BIP upregulation in the neuron of superficial laminae of dorsal spinal horn. It also increased the level of ATF6 and intracellular localization into the nuclei in the neurons. Moreover, spliced XBP1 was also markedly elevated in the ipsilateral spinal dorsal horn. The PERK-elF2 pathway was activated in astrocytes of the spinal dorsal horn in the SNL model. In addition, electron microscopy revealed the presence of swollen cisternae in the dorsal spinal cord after SNL. Additionally, inhibition of the ATF6 pathway by intrathecal treatment with ATF6 siRNA reduced pain behaviors and BIP expression in the dorsal horn. The results suggest that ER stress might be involved in the induction and maintenance of neuropathic pain. Furthermore, a disturbance in UPR signaling may render the spinal neurons vulnerable to peripheral nerve injury or neuropathic pain stimuli. PMID:26109318

  6. Installation of a Thomson scattering diagnostic on the Compact Toroidal Hybrid Experiment

    Science.gov (United States)

    Traverso, P. J.; Maurer, D. A.; Ennis, D. A.; Hartwell, G. J.; Cianciosa, M. R.

    2015-11-01

    A Thomson scattering system is being commissioned for the non-axisymmetric plasmas of the Compact Toroidal Hybrid (CTH), a five-field period current-carrying torsatron. The initial system takes a single point measurement on the magnetic axis and will be used to assess options for an expansion to a multi-point system to enable better 3D equilibrium reconstructions using the V3FIT code. A single point measurement will reduce the uncertainty in the reconstructed peak pressure by an order of magnitude for both current-carrying plasmas and future gyrotron-heated stellarator plasmas. The beam, generated by a frequency doubled Continuum 2 J, Nd:YaG laser, is passed vertically through an entrance Brewster window and a two-aperture optical baffle system to minimize stray light. The beam line is designed to propagate ~ 8 m to the mid-plane of the CTH device with the beam diameter < 3 mm inside the plasma volume. An Andor iStar DH740-18U-C3 image intensified CCD camera is used in conjunction with a Holospec f/1.8 spectrograph to collect the red-shifted scattered light from 532-580 nm. A single point system will initially measure plasmas with core electron temperatures of 100 to 200 eV and densities of 5 ×1018 to 5 ×1019 m-3. This work is supported by U.S. Department of Energy Grant No. DE-FG02-00ER54610.

  7. Calculation of continuum damping of Alfvén eigenmodes in tokamak and stellarator equilibria

    Energy Technology Data Exchange (ETDEWEB)

    Bowden, G. W.; Hole, M. J. [Plasma Theory and Modelling, Research School of Physics and Engineering, Australian National University, Acton 2601, Australian Capital Territory (Australia); Könies, A. [Max-Planck-Institut für Plasmaphysik, EURATOM-Association, D-17491 Greifswald (Germany)

    2015-09-15

    In an ideal magnetohydrodynamic (MHD) plasma, shear Alfvén eigenmodes may experience dissipationless damping due to resonant interaction with the shear Alfvén continuum. This continuum damping can make a significant contribution to the overall growth/decay rate of shear Alfvén eigenmodes, with consequent implications for fast ion transport. One method for calculating continuum damping is to solve the MHD eigenvalue problem over a suitable contour in the complex plane, thereby satisfying the causality condition. Such an approach can be implemented in three-dimensional ideal MHD codes which use the Galerkin method. Analytic functions can be fitted to numerical data for equilibrium quantities in order to determine the value of these quantities along the complex contour. This approach requires less resolution than the established technique of calculating damping as resistivity vanishes and is thus more computationally efficient. The complex contour method has been applied to the three-dimensional finite element ideal MHD Code for Kinetic Alfvén waves. In this paper, we discuss the application of the complex contour technique to calculate the continuum damping of global modes in tokamak as well as torsatron, W7-X and H-1NF stellarator cases. To the authors' knowledge, these stellarator calculations represent the first calculation of continuum damping for eigenmodes in fully three-dimensional equilibria. The continuum damping of global modes in W7-X and H-1NF stellarator configurations investigated is found to depend sensitively on coupling to numerous poloidal and toroidal harmonics.

  8. Calculation of continuum damping of Alfvén eigenmodes in tokamak and stellarator equilibria

    International Nuclear Information System (INIS)

    In an ideal magnetohydrodynamic (MHD) plasma, shear Alfvén eigenmodes may experience dissipationless damping due to resonant interaction with the shear Alfvén continuum. This continuum damping can make a significant contribution to the overall growth/decay rate of shear Alfvén eigenmodes, with consequent implications for fast ion transport. One method for calculating continuum damping is to solve the MHD eigenvalue problem over a suitable contour in the complex plane, thereby satisfying the causality condition. Such an approach can be implemented in three-dimensional ideal MHD codes which use the Galerkin method. Analytic functions can be fitted to numerical data for equilibrium quantities in order to determine the value of these quantities along the complex contour. This approach requires less resolution than the established technique of calculating damping as resistivity vanishes and is thus more computationally efficient. The complex contour method has been applied to the three-dimensional finite element ideal MHD Code for Kinetic Alfvén waves. In this paper, we discuss the application of the complex contour technique to calculate the continuum damping of global modes in tokamak as well as torsatron, W7-X and H-1NF stellarator cases. To the authors' knowledge, these stellarator calculations represent the first calculation of continuum damping for eigenmodes in fully three-dimensional equilibria. The continuum damping of global modes in W7-X and H-1NF stellarator configurations investigated is found to depend sensitively on coupling to numerous poloidal and toroidal harmonics

  9. Calculation of continuum damping of Alfvén eigenmodes in tokamak and stellarator equilibria

    Science.gov (United States)

    Bowden, G. W.; Hole, M. J.; Könies, A.

    2015-09-01

    In an ideal magnetohydrodynamic (MHD) plasma, shear Alfvén eigenmodes may experience dissipationless damping due to resonant interaction with the shear Alfvén continuum. This continuum damping can make a significant contribution to the overall growth/decay rate of shear Alfvén eigenmodes, with consequent implications for fast ion transport. One method for calculating continuum damping is to solve the MHD eigenvalue problem over a suitable contour in the complex plane, thereby satisfying the causality condition. Such an approach can be implemented in three-dimensional ideal MHD codes which use the Galerkin method. Analytic functions can be fitted to numerical data for equilibrium quantities in order to determine the value of these quantities along the complex contour. This approach requires less resolution than the established technique of calculating damping as resistivity vanishes and is thus more computationally efficient. The complex contour method has been applied to the three-dimensional finite element ideal MHD Code for Kinetic Alfvén waves. In this paper, we discuss the application of the complex contour technique to calculate the continuum damping of global modes in tokamak as well as torsatron, W7-X and H-1NF stellarator cases. To the authors' knowledge, these stellarator calculations represent the first calculation of continuum damping for eigenmodes in fully three-dimensional equilibria. The continuum damping of global modes in W7-X and H-1NF stellarator configurations investigated is found to depend sensitively on coupling to numerous poloidal and toroidal harmonics.

  10. The expression meaning of activating transcription factor 3,activating transcription factor 4 and ki-67 in skin squamous cell carcinoma%活化转录因子3、4和ki-67在皮肤鳞癌中的表达意义

    Institute of Scientific and Technical Information of China (English)

    李春; 周为军; 宋朝辉; 李朝阳; 余萍; 曾学文; 郭智龙

    2015-01-01

    Objective To discuss the expression of activating transcription factor 3,activating transcription factor 4(ATF3,4)and ki-67 in skin squamous carcinomas and basal cell carcinomas and their clinical significances. Methods Using immunohistochemical method to detect ATF3,4 and ki-67 expression in 96 cases of skin squamous carcinoma and 118 cases of basal cell carcinoma tissues,which were randomly selected from the hospital preserved in pathology department,then analysis the meaning of expression. Results ATF3,4 in skin squamous carcinomas is higher than that in basal cell carcinomas,the differences were statistically significant(P=0.003 and 0.001, respectively), but there was no difference for ki-67(P=0.718).Positive correlation could be found between ATF3,4 expression strength and skin squamous cell carcinoma differentiation(r=0.395,P=0.000;r=0.303,P=0.001,respectively). Conclusion ATF3,4 may be used as the reliable differential protein markers between skin squamous cell carcinoma and basal cell carcinoma,and they be seen as malignant degree and prognosis indexes of cutaneous squamous cell.%目的:探讨活化转录因子3、4和ki-67在皮肤鳞癌和基底细胞癌中的表达及其临床意义。方法:从笔者所在医院病理科储存的蜡块中随机选择96例皮肤鳞癌和118例基底细胞癌标本,采用免疫组织化学方法检测组织中活化转录因子3、4和ki-67的表达,分析其表达意义。结果:活化转录因子3、4在皮肤鳞癌中的表达较基底细胞癌高,差异有统计学意义(P值分别为0.003和0.001)。Ki-67在两种皮肤癌中的表达无显著差异(P值为0.718)。ATF3、4的表达强度和皮肤鳞癌分化程度成正相关,即分化程度低越低,表达强度越高(r=0.395 P=0.000和r=0.303 P=0.001)。结论:活化转录因子3、4可以作为鉴别皮肤鳞癌和基底细胞癌可靠的蛋白标记物和皮肤鳞癌恶性程度及预后的判断指标。

  11. Steam Oxidation Testing in the Severe Accident Test Station

    Energy Technology Data Exchange (ETDEWEB)

    Pint, Bruce A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); McMurray, Jake W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2016-08-01

    Since 2011, Oak Ridge National Laboratory (ORNL) has been conducting high temperature steam oxidation testing of candidate alloys for accident tolerant fuel (ATF) cladding. These concepts are designed to enhance safety margins in light water reactors (LWR) during severe accident scenarios. In the US ATF community, the Severe Accident Test Station (SATS) has been evaluating candidate materials (including coatings) since 2012. Compared to the current UO2/Zr-based alloy fuel system, alternative cladding materials need to offer slower oxidation kinetics and a smaller enthalpy of oxidation in order to significantly reduce the rate of heat and hydrogen generation in the core during a coolant-limited severe accident. The steam oxidation behavior of candidate materials is a key metric in the evaluation of ATF concepts and also an important input into models. However, prior modeling work of FeCrAl cladding has used incomplete information on the physical properties of FeCrAl. Also, the steam oxidation data being collected at 1200°-1700°C is unique as no prior work has considered steam oxidation of alloys at such high temperatures. In some cases, the results have been difficult to interpret and more fundamental information is needed such as the stability of alumina in flowing steam at 1400°-1500°C. This report summarizes recent work to measure the steam oxidation kinetics of candidate alloys, the evaporation rate of alumina in steam and the development of integral data on FeCrAl compared to conventional Zr-based cladding.

  12. Alterations in leukocyte transcriptional control pathway activity associated with major depressive disorder and antidepressant treatment.

    Science.gov (United States)

    Mellon, S H; Wolkowitz, O M; Schonemann, M D; Epel, E S; Rosser, R; Burke, H B; Mahan, L; Reus, V I; Stamatiou, D; Liew, C-C; Cole, S W

    2016-01-01

    Major depressive disorder (MDD) is associated with a significantly elevated risk of developing serious medical illnesses such as cardiovascular disease, immune impairments, infection, dementia and premature death. Previous work has demonstrated immune dysregulation in subjects with MDD. Using genome-wide transcriptional profiling and promoter-based bioinformatic strategies, we assessed leukocyte transcription factor (TF) activity in leukocytes from 20 unmedicated MDD subjects versus 20 age-, sex- and ethnicity-matched healthy controls, before initiation of antidepressant therapy, and in 17 of the MDD subjects after 8 weeks of sertraline treatment. In leukocytes from unmedicated MDD subjects, bioinformatic analysis of transcription control pathway activity indicated an increased transcriptional activity of cAMP response element-binding/activating TF (CREB/ATF) and increased activity of TFs associated with cellular responses to oxidative stress (nuclear factor erythroid-derived 2-like 2, NFE2l2 or NRF2). Eight weeks of antidepressant therapy was associated with significant reductions in Hamilton Depression Rating Scale scores and reduced activity of NRF2, but not in CREB/ATF activity. Several other transcriptional regulation pathways, including the glucocorticoid receptor (GR), nuclear factor kappa-B cells (NF-κB), early growth response proteins 1-4 (EGR1-4) and interferon-responsive TFs, showed either no significant differences as a function of disease or treatment, or activities that were opposite to those previously hypothesized to be involved in the etiology of MDD or effective treatment. Our results suggest that CREB/ATF and NRF2 signaling may contribute to MDD by activating immune cell transcriptome dynamics that ultimately influence central nervous system (CNS) motivational and affective processes via circulating mediators. PMID:27219347

  13. RFX transcription factor DAF-19 regulates 5-HT and innate immune responses to pathogenic bacteria in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Yusu Xie

    Full Text Available In Caenorhabditis elegans the Toll-interleukin receptor domain adaptor protein TIR-1 via a conserved mitogen-activated protein kinase (MAPK signaling cascade induces innate immunity and upregulates serotonin (5-HT biosynthesis gene tph-1 in a pair of ADF chemosensory neurons in response to infection. Here, we identify transcription factors downstream of the TIR-1 signaling pathway. We show that common transcription factors control the innate immunity and 5-HT biosynthesis. We demonstrate that a cysteine to tyrosine substitution in an ARM motif of the HEAT/Arm repeat region of the TIR-1 protein confers TIR-1 hyperactivation, leading to constitutive tph-1 upregulation in the ADF neurons, increased expression of intestinal antimicrobial genes, and enhanced resistance to killing by the human opportunistic pathogen Pseudomonas aeruginosa PA14. A forward genetic screen for suppressors of the hyperactive TIR-1 led to the identification of DAF-19, an ortholog of regulatory factor X (RFX transcription factors that are required for human adaptive immunity. We show that DAF-19 concerts with ATF-7, a member of the activating transcription factor (ATF/cAMP response element-binding B (CREB family of transcription factors, to regulate tph-1 and antimicrobial genes, reminiscent of RFX-CREB interaction in human immune cells. daf-19 mutants display heightened susceptibility to killing by PA14. Remarkably, whereas the TIR-1-MAPK-DAF-19/ATF-7 pathway in the intestinal immunity is regulated by DKF-2/protein kinase D, we found that the regulation of tph-1 expression is independent of DKF-2 but requires UNC-43/Ca(2+/calmodulin-dependent protein kinase (CaMK II. Our results suggest that pathogenic cues trigger a common core-signaling pathway via tissue-specific mechanisms and demonstrate a novel role for RFX factors in neuronal and innate immune responses to infection.

  14. Onconase responsive genes in human mesothelioma cells: implications for an RNA damaging therapeutic agent

    Directory of Open Access Journals (Sweden)

    Maizel Jacob V

    2010-02-01

    Full Text Available Abstract Background Onconase represents a new class of RNA-damaging drugs. Mechanistically, Onconase is thought to internalize, where it degrades intracellular RNAs such as tRNA and double-stranded RNA, and thereby suppresses protein synthesis. However, there may be additional or alternative mechanism(s of action. Methods In this study, microarray analysis was used to compare gene expression profiles in untreated human malignant mesothelioma (MM cell lines and cells exposed to 5 μg/ml Onconase for 24 h. A total of 155 genes were found to be regulated by Onconase that were common to both epithelial and biphasic MM cell lines. Some of these genes are known to significantly affect apoptosis (IL-24, TNFAIP3, transcription (ATF3, DDIT3, MAFF, HDAC9, SNAPC1 or inflammation and the immune response (IL-6, COX-2. RT-PCR analysis of selected up- or down-regulated genes treated with varying doses and times of Onconase generally confirmed the expression array findings in four MM cell lines. Results Onconase treatment consistently resulted in up-regulation of IL-24, previously shown to have tumor suppressive activity, as well as ATF3 and IL-6. Induction of ATF3 and the pro-apoptotic factor IL-24 by Onconase was highest in the two most responsive MM cell lines, as defined by DNA fragmentation analysis. In addition to apoptosis, gene ontology analysis indicated that pathways impacted by Onconase include MAPK signaling, cytokine-cytokine-receptor interactions, and Jak-STAT signaling. Conclusions These results provide a broad picture of gene activity after treatment with a drug that targets small non-coding RNAs and contribute to our overall understanding of MM cell response to Onconase as a therapeutic strategy. The findings provide insights regarding mechanisms that may contribute to the efficacy of this novel drug in clinical trials of MM patients who have failed first line chemotherapy or radiation treatment.

  15. An atypical unfolded protein response in heat shocked cells.

    Directory of Open Access Journals (Sweden)

    Lonneke Heldens

    Full Text Available BACKGROUND: The heat shock response (HSR and the unfolded protein response (UPR are both activated by proteotoxic stress, although in different compartments, and share cellular resources. How these resources are allocated when both responses are active is not known. Insight in possible crosstalk will help understanding the consequences of failure of these systems in (age-related disease. RESULTS: In heat stressed HEK293 cells synthesis of the canonical UPR transcription factors XBP1s and ATF4 was detected as well as HSF1 independent activation of the promoters of the ER resident chaperones HSPA5 (BiP and DNAJB9 (ERdj4. However, the heat stress activation of the DNAJB9 promoter, a XBP1s target, was not blocked in cells expressing a dominant negative IRE1α mutant, and thus did not require XBP1s. Furthermore, the DNA element required for heat stress activation of the DNAJB9 promoter is distinct from the ATF4 and ATF6 target elements; even though inhibition of eIF2α phosphorylation resulted in a decreased activation of the DNAJB9 promoter upon heat stress, suggesting a role for an eIF2α phosphorylation dependent product. CONCLUSIONS: The initial step in the UPR, synthesis of transcription factors, is activated by heat stress but the second step, transcriptional transactivation by these factors, is blocked and these pathways of the UPR are thus not productive. Expression of canonical ER chaperones is part of the response of heat stressed cells but another set of transcription factors has been recruited to regulate expression of these ER chaperones.

  16. Survey of Thermal-Fluids Evaluation and Confirmatory Experimental Validation Requirements of Accident Tolerant Cladding Concepts with Focus on Boiling Heat Transfer Characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Nicholas R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Wysocki, Aaron J. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Terrani, Kurt A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Ali, Amir [Univ. of New Mexico, Albuquerque, NM (United States); Liu, Maolong [Univ. of New Mexico, Albuquerque, NM (United States); Blandford, Edward [Univ. of New Mexico, Albuquerque, NM (United States)

    2016-06-01

    The U.S. Department of Energy Office of Nuclear Energy (DOE-NE) Advanced Fuels Campaign (AFC) is working closely with the nuclear industry to develop fuel and cladding candidates with potentially enhanced accident tolerance, also known as accident tolerant fuel (ATF). Thermal-fluids characteristics are a vital element of a holistic engineering evaluation of ATF concepts. One vital characteristic related to boiling heat transfer is the critical heat flux (CHF). CHF plays a vital role in determining safety margins during normal operation and also in the progression of potential transient or accident scenarios. This deliverable is a scoping survey of thermal-fluids evaluation and confirmatory experimental validation requirements of accident tolerant cladding concepts with a focus on boiling heat transfer characteristics. The key takeaway messages of this report are: 1. CHF prediction accuracy is important and the correlations may have significant uncertainty. 2. Surface conditions are important factors for CHF, primarily the wettability that is characterized by contact angle. Smaller contact angle indicates greater wettability, which increases the CHF. Surface roughness also impacts wettability. Results in the literature for pool boiling experiments indicate changes in CHF by up to 60% for several ATF cladding candidates. 3. The measured wettability of FeCrAl (i.e., contact angle and roughness) indicates that CHF should be investigated further through pool boiling and flow boiling experiments. 4. Initial measurements of static advancing contact angle and surface roughness indicate that FeCrAl is expected to have a higher CHF than Zircaloy. The measured contact angle of different FeCrAl alloy samples depends on oxide layer thickness and composition. The static advancing contact angle tends to decrease as the oxide layer thickness increases.

  17. Intratumoral injection of taxol in vivo suppresses A549 tumor showing cytoplasmic vacuolization.

    Science.gov (United States)

    Wang, Chaoyang; Chen, Tongsheng

    2012-04-01

    Based on our recent in vitro studies, this report was designed to explore the mechanism by which high concentration of taxol (70 µM) induced paraptosis-like cell death in human lung carcinoma (A549) cells, and to evaluate the therapeutic efficacy of taxol using A549 tumor-bearing mice in vivo. Exposure of cells to taxol induced time-dependent cytotoxicity and cytoplasmic vacuolization without the involvement of Bax, Bak, Mcl-1, Bcl-XL, and caspase-3. Although taxol treatment induced activating transcription factor 6 (ATF6) cleavage indicative of endoplasmic reticulum (ER) stress, silencing ATF6 by shATF6 did not prevent taxol-induced both cytotoxcity and cytoplasmic vacuolization, suggesting that taxol-induced cytoplasmic vacuolization and cell death were not due to ER stress. Moreover, taxol-treated cells did not show DNA fragmentation and loss of mitochondrial membrane potential, the typical characteristics of apoptosis. In addition, taxol-induced cytoplasmic vacuolization did not show the cellular lysis, the characteristics of oncosis, and positive of β-galactosidase, the characteristic of senescence, indicating that taxol induced paraptosis-like cell death is neither oncosis nor senescence. Moreover, our in vivo data showed that intratumoral injection of taxol (50 mg/kg) in A549 tumor xenograft mice on day 1 and day 19 potently suppressed tumor growth showing significant ER vacuolization without toxicity. In conclusion, high concentration of taxol exhibits a significant anticancer activity by inducing paraptosis-like cell death in vitro and in vivo, without significant toxicity, suggesting a promising therapeutic strategy for apoptosis-resistance cancer by inducing ER vacuolization.

  18. Status Report on Activities of the Systems Assessment Task Force, OECD-NEA Expert Group on Accident Tolerant Fuels for LWRs

    Energy Technology Data Exchange (ETDEWEB)

    Bragg-Sitton, Shannon Michelle [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2015-09-01

    The Organization for Economic Cooperation and Development /Nuclear Energy Agency (OECD/NEA) Nuclear Science Committee approved the formation of an Expert Group on Accident Tolerant Fuel (ATF) for LWRs (EGATFL) in 2014. Chaired by Kemal Pasamehmetoglu, INL Associate Laboratory Director for Nuclear Science and Technology, the mandate for the EGATFL defines work under three task forces: (1) Systems Assessment, (2) Cladding and Core Materials, and (3) Fuel Concepts. Scope for the Systems Assessment task force includes definition of evaluation metrics for ATF, technology readiness level definition, definition of illustrative scenarios for ATF evaluation, parametric studies, and selection of system codes. The Cladding and Core Materials and Fuel Concepts task forces will identify gaps and needs for modeling and experimental demonstration; define key properties of interest; identify the data necessary to perform concept evaluation under normal conditions and illustrative scenarios; identify available infrastructure (internationally) to support experimental needs; and make recommendations on priorities. Where possible, considering proprietary and other export restrictions (e.g., International Traffic in Arms Regulations), the Expert Group will facilitate the sharing of data and lessons learned across the international group membership. The Systems Assessment Task Force is chaired by Shannon Bragg-Sitton (INL), while the Cladding Task Force will be chaired by a representative from France (Marie Moatti, Electricite de France [EdF]) and the Fuels Task Force will be chaired by a representative from Japan (Masaki Kurata, Japan Atomic Energy Agency [JAEA]). This report provides an overview of the Systems Assessment Task Force charter and status of work accomplishment.

  19. Alterations in leukocyte transcriptional control pathway activity associated with major depressive disorder and antidepressant treatment

    Science.gov (United States)

    Mellon, S H; Wolkowitz, O M; Schonemann, M D; Epel, E S; Rosser, R; Burke, H B; Mahan, L; Reus, V I; Stamatiou, D; Liew, C -C; Cole, S W

    2016-01-01

    Major depressive disorder (MDD) is associated with a significantly elevated risk of developing serious medical illnesses such as cardiovascular disease, immune impairments, infection, dementia and premature death. Previous work has demonstrated immune dysregulation in subjects with MDD. Using genome-wide transcriptional profiling and promoter-based bioinformatic strategies, we assessed leukocyte transcription factor (TF) activity in leukocytes from 20 unmedicated MDD subjects versus 20 age-, sex- and ethnicity-matched healthy controls, before initiation of antidepressant therapy, and in 17 of the MDD subjects after 8 weeks of sertraline treatment. In leukocytes from unmedicated MDD subjects, bioinformatic analysis of transcription control pathway activity indicated an increased transcriptional activity of cAMP response element-binding/activating TF (CREB/ATF) and increased activity of TFs associated with cellular responses to oxidative stress (nuclear factor erythroid-derived 2-like 2, NFE2l2 or NRF2). Eight weeks of antidepressant therapy was associated with significant reductions in Hamilton Depression Rating Scale scores and reduced activity of NRF2, but not in CREB/ATF activity. Several other transcriptional regulation pathways, including the glucocorticoid receptor (GR), nuclear factor kappa-B cells (NF-κB), early growth response proteins 1–4 (EGR1–4) and interferon-responsive TFs, showed either no significant differences as a function of disease or treatment, or activities that were opposite to those previously hypothesized to be involved in the etiology of MDD or effective treatment. Our results suggest that CREB/ATF and NRF2 signaling may contribute to MDD by activating immune cell transcriptome dynamics that ultimately influence central nervous system (CNS) motivational and affective processes via circulating mediators. PMID:27187237

  20. Hepatoprotective Effect of Quercetin on Endoplasmic Reticulum Stress and Inflammation after Intense Exercise in Mice through Phosphoinositide 3-Kinase and Nuclear Factor-Kappa B

    Directory of Open Access Journals (Sweden)

    Yuhan Tang

    2016-01-01

    Full Text Available The mechanisms underlying intense exercise-induced liver damage and its potential treatments remain unclear. We explored the hepatoprotection and mechanisms of quercetin, a naturally occurring flavonoid, in strenuous exercise-derived endoplasmic reticulum stress (ERS and inflammation. Intense exercise (28 m/min at a 5° slope for 90 min resulted in the leakage of aminotransferases in the BALB/C mice. The hepatic ultrastructural malformations and oxidative stress levels were attenuated by quercetin (100 mg/kg·bw. Intense exercise and thapsigargin- (Tg- induced ERS (glucose-regulated protein 78, GRP78 and inflammatory cytokines levels (IL-6 and TNF-α were decreased with quercetin. Furthermore, quercetin resulted in phosphoinositide 3-kinase (PI3K induction, Ca2+ restoration, and blockade of the activities of Jun N-terminal kinase (JNK, activating transcription factor 6 (ATF6 and especially NF-κB (p65 and p50 nuclear translocation. A PI3K inhibitor abrogated the protection of quercetin on ERS and inflammation of mouse hepatocytes. SP600125 (JNK inhibitor, AEBSF (ATF6 inhibitor, and especially PDTC (NF-κB inhibitor enhanced the quercetin-induced protection against Tg stimulation. Collectively, intense exercise-induced ERS and inflammation were attenuated by quercetin. PI3K/Akt activation and JNK, ATF6, and especially NF-κB suppression were involved in the protection. Our results highlight a novel preventive strategy for treating ERS and inflammation-mediated liver damage induced by intense exercise using natural phytochemicals.

  1. Extending laser plasma accelerators into the mid-IR spectral domain with a next-generation ultra-fast CO2 laser

    Science.gov (United States)

    Pogorelsky, I. V.; Babzien, M.; Ben-Zvi, I.; Polyanskiy, M. N.; Skaritka, J.; Tresca, O.; Dover, N. P.; Najmudin, Z.; Lu, W.; Cook, N.; Ting, A.; Chen, Y.-H.

    2016-03-01

    Expanding the scope of relativistic plasma research to wavelengths longer than the λ/≈   0.8-1.1 μm range covered by conventional mode-locked solid-state lasers would offer attractive opportunities due to the quadratic scaling of the ponderomotive electron energy and critical plasma density with λ. Answering this quest, a next-generation mid-IR laser project is being advanced at the BNL ATF as a part of the user facility upgrade. We discuss the technical approach to this conceptually new 100 TW, 100 fs, λ  =   9-11 μm CO2 laser BESTIA (Brookhaven Experimental Supra-Terawatt Infrared at ATF) that encompasses several innovations applied for the first time to molecular gas lasers. BESTIA will enable new regimes of laser plasma accelerators. One example is shock-wave ion acceleration (SWA) from gas jets. We review ongoing efforts to achieve stable, monoenergetic proton acceleration by dynamically shaping the plasma density profile from a hydrogen gas target with laser-produced blast waves. At its full power, 100 TW BESTIA promises to achieve proton beams at an energy exceeding 200 MeV. In addition to ion acceleration in over-critical plasma, the ultra-intense mid-IR BESTIA will open up new opportunities in driving wakefields in tenuous plasmas, expanding the landscape of laser wakefield accelerator (LWFA) studies into the unexplored long-wavelength spectral domain. Simple wavelength scaling suggests that a 100 TW CO2 laser beam will be capable of efficiently generating plasma ‘bubbles’ a thousand times greater in volume compared with a near-IR solid state laser of an equivalent power. Combined with a femtosecond electron linac available at the ATF, this wavelength scaling will facilitate the study of external seeding and staging of LWFAs.

  2. Hepatoprotective Effect of Quercetin on Endoplasmic Reticulum Stress and Inflammation after Intense Exercise in Mice through Phosphoinositide 3-Kinase and Nuclear Factor-Kappa B

    Science.gov (United States)

    Tang, Yuhan; Li, Juan; Gao, Chao; Xu, Yanyan; Li, Yanyan; Yu, Xiao; Wang, Jing; Liu, Liegang

    2016-01-01

    The mechanisms underlying intense exercise-induced liver damage and its potential treatments remain unclear. We explored the hepatoprotection and mechanisms of quercetin, a naturally occurring flavonoid, in strenuous exercise-derived endoplasmic reticulum stress (ERS) and inflammation. Intense exercise (28 m/min at a 5° slope for 90 min) resulted in the leakage of aminotransferases in the BALB/C mice. The hepatic ultrastructural malformations and oxidative stress levels were attenuated by quercetin (100 mg/kg·bw). Intense exercise and thapsigargin- (Tg-) induced ERS (glucose-regulated protein 78, GRP78) and inflammatory cytokines levels (IL-6 and TNF-α) were decreased with quercetin. Furthermore, quercetin resulted in phosphoinositide 3-kinase (PI3K) induction, Ca2+ restoration, and blockade of the activities of Jun N-terminal kinase (JNK), activating transcription factor 6 (ATF6) and especially NF-κB (p65 and p50 nuclear translocation). A PI3K inhibitor abrogated the protection of quercetin on ERS and inflammation of mouse hepatocytes. SP600125 (JNK inhibitor), AEBSF (ATF6 inhibitor), and especially PDTC (NF-κB inhibitor) enhanced the quercetin-induced protection against Tg stimulation. Collectively, intense exercise-induced ERS and inflammation were attenuated by quercetin. PI3K/Akt activation and JNK, ATF6, and especially NF-κB suppression were involved in the protection. Our results highlight a novel preventive strategy for treating ERS and inflammation-mediated liver damage induced by intense exercise using natural phytochemicals. PMID:27504150

  3. The Tocotrienol-Rich Fraction Is Superior to Tocopherol in Promoting Myogenic Differentiation in the Prevention of Replicative Senescence of Myoblasts.

    Directory of Open Access Journals (Sweden)

    Shy Cian Khor

    Full Text Available Aging results in a loss of muscle mass and strength. Myoblasts play an important role in maintaining muscle mass through regenerative processes, which are impaired during aging. Vitamin E potentially ameliorates age-related phenotypes. Hence, this study aimed to determine the effects of the tocotrienol-rich fraction (TRF and α-tocopherol (ATF in protecting myoblasts from replicative senescence and promoting myogenic differentiation. Primary human myoblasts were cultured into young and senescent stages and were then treated with TRF or ATF for 24 h, followed by an analysis of cell proliferation, senescence biomarkers, cellular morphology and differentiation. Our data showed that replicative senescence impaired the normal regenerative processes of myoblasts, resulting in changes in cellular morphology, cell proliferation, senescence-associated β-galactosidase (SA-β-gal expression, myogenic differentiation and myogenic regulatory factors (MRFs expression. Treatment with both TRF and ATF was beneficial to senescent myoblasts in reclaiming the morphology of young cells, improved cell viability and decreased SA-β-gal expression. However, only TRF treatment increased BrdU incorporation in senescent myoblasts, as well as promoted myogenic differentiation through the modulation of MRFs at the mRNA and protein levels. MYOD1 and MYOG gene expression and myogenin protein expression were modulated in the early phases of myogenic differentiation. In conclusion, the tocotrienol-rich fraction is superior to α-tocopherol in ameliorating replicative senescence-related aberration and promoting differentiation via modulation of MRFs expression, indicating vitamin E potential in modulating replicative senescence of myoblasts.

  4. The Alto Tiberina Near Fault Observatory (northern Apennines, Italy

    Directory of Open Access Journals (Sweden)

    Lauro Chiaraluce

    2014-06-01

    Full Text Available The availability of multidisciplinary and high-resolution data is a fundamental requirement to understand the physics of earthquakes and faulting. We present the Alto Tiberina Near Fault Observatory (TABOO, a research infrastructure devoted to studying preparatory processes, slow and fast deformation along a fault system located in the upper Tiber Valley (northern Apennines, dominated by a 60 km long low-angle normal fault (Alto Tiberina, ATF active since the Quaternary. TABOO consists of 50 permanent seismic stations covering an area of 120 × 120 km2. The surface seismic stations are equipped with 3-components seismometers, one third of them hosting accelerometers. We instrumented three shallow (250 m boreholes with seismometers, creating a 3-dimensional antenna for studying micro-earthquakes sources (detection threshold is ML 0.5 and detecting transient signals. 24 of these sites are equipped with continuous geodetic GPS, forming two transects across the fault system. Geochemical and electromagnetic stations have been also deployed in the study area. In 36 months TABOO recorded 19,422 events with ML ≤ 3.8 corresponding to 23.36e-04 events per day per squared kilometres; one of the highest seismicity rate value observed in Italy. Seismicity distribution images the geometry of the ATF and its antithetic/synthetic structures located in the hanging-wall. TABOO can allow us to understand the seismogenic potential of the ATF and therefore contribute to the seismic hazard assessment of the area. The collected information on the geometry and deformation style of the fault will be used to elaborate ground shaking scenarios adopting diverse slip distributions and rupture directivity models.

  5. ER-stress in Alzheimer's disease: turning the scale?

    Science.gov (United States)

    Endres, Kristina; Reinhardt, Sven

    2013-01-01

    Pathogenic mechanisms of Alzheimer's disease (AD) are intensely investigated as it is the most common form of dementia and burdens society by its costs and social demands. While key molecules such as A-beta peptides and tau have been identified decades ago, it is still enigmatic what drives the disease in its sporadic manifestation. Synthesis of A-beta peptides as well as phosphorylation of tau proteins comprise normal cellular functions and occur in principle in the healthy as well as in dementia-affected persons. Dyshomeostasis of Amyloid Precursor Protein (APP) cleavage, energy metabolism or kinase/phosphatase activity due to stressors has been suggested as a trigger of the disease. One way for cells to escape stress based on dysfunction of ER is the unfolded protein response - the UPR. This pathway is composed out of three different routes that differ in proteins involved, targets and consequences for cell fate: activation of transmembrane ER resident kinases IRE1-alpha and PERK or monomerization of membrane-anchored activating transcription factor 6 (ATF6) induce activation of versatile transcription factors (XBP-1, eIF2-alpha/ATF4 and ATF6 P50). These bind to specific DNA sequences on target gene promoters and on one hand attenuate general ER-prone protein synthesis and on the other equip the cell with tools to de-stress. If cells fail in stress compensation, this signaling also is able to evoke apoptosis. In this review we summarized knowledge on how APP processing and phosphorylation of tau might be influenced by ER-stress signaling. In addition, we depicted the effects UPR itself seems to have on molecules closely related to AD and describe what is known about UPR in AD animal models as well as in human patients. PMID:24319643

  6. Onconase responsive genes in human mesothelioma cells: implications for an RNA damaging therapeutic agent

    International Nuclear Information System (INIS)

    Onconase represents a new class of RNA-damaging drugs. Mechanistically, Onconase is thought to internalize, where it degrades intracellular RNAs such as tRNA and double-stranded RNA, and thereby suppresses protein synthesis. However, there may be additional or alternative mechanism(s) of action. In this study, microarray analysis was used to compare gene expression profiles in untreated human malignant mesothelioma (MM) cell lines and cells exposed to 5 μg/ml Onconase for 24 h. A total of 155 genes were found to be regulated by Onconase that were common to both epithelial and biphasic MM cell lines. Some of these genes are known to significantly affect apoptosis (IL-24, TNFAIP3), transcription (ATF3, DDIT3, MAFF, HDAC9, SNAPC1) or inflammation and the immune response (IL-6, COX-2). RT-PCR analysis of selected up- or down-regulated genes treated with varying doses and times of Onconase generally confirmed the expression array findings in four MM cell lines. Onconase treatment consistently resulted in up-regulation of IL-24, previously shown to have tumor suppressive activity, as well as ATF3 and IL-6. Induction of ATF3 and the pro-apoptotic factor IL-24 by Onconase was highest in the two most responsive MM cell lines, as defined by DNA fragmentation analysis. In addition to apoptosis, gene ontology analysis indicated that pathways impacted by Onconase include MAPK signaling, cytokine-cytokine-receptor interactions, and Jak-STAT signaling. These results provide a broad picture of gene activity after treatment with a drug that targets small non-coding RNAs and contribute to our overall understanding of MM cell response to Onconase as a therapeutic strategy. The findings provide insights regarding mechanisms that may contribute to the efficacy of this novel drug in clinical trials of MM patients who have failed first line chemotherapy or radiation treatment

  7. The SARS Coronavirus 3a protein causes endoplasmic reticulum stress and induces ligand-independent downregulation of the type 1 interferon receptor.

    Directory of Open Access Journals (Sweden)

    Rinki Minakshi

    Full Text Available The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV is reported to cause apoptosis of infected cells and several of its proteins including the 3a accessory protein, are pro-apoptotic. Since the 3a protein localizes to the endoplasmic reticulum (ER-Golgi compartment, its role in causing ER stress was investigated in transiently transfected cells. Cells expressing the 3a proteins showed ER stress based on activation of genes for the ER chaperones GRP78 and GRP94. Since ER stress can cause differential modulation of the unfolded protein response (UPR, which includes the inositol-requiring enzyme 1 (IRE-1, activating transcription factor 6 (ATF6 and PKR-like ER kinase (PERK pathways, these were individually tested in 3a-expressing cells. Only the PERK pathway was found to be activated in 3a-expressing cells based on (1 increased phosphorylation of eukaryotic initiation factor 2 alpha (eIF2alpha and inhibitory effects of a dominant-negative form of eIF2alpha on GRP78 promoter activity, (2 increased translation of activating transcription factor 4 (ATF4 mRNA, and (3 ATF4-dependent activation of the C/EBP homologous protein (CHOP gene promoter. Activation of PERK affects innate immunity by suppression of type 1 interferon (IFN signaling. The 3a protein was found to induce serine phosphorylation within the IFN alpha-receptor subunit 1 (IFNAR1 degradation motif and to increase IFNAR1 ubiquitination. Confocal microscopic analysis showed increased translocation of IFNAR1 into the lysosomal compartment and flow cytometry showed reduced levels of IFNAR1 in 3a-expressing cells. These results provide further mechanistic details of the pro-apoptotic effects of the SARS-CoV 3a protein, and suggest a potential role for it in attenuating interferon responses and innate immunity.

  8. THE MECHANICAL AND SHIELDING DESIGN OF A PORTABLE SPECTROMETER AND BEAM DUMP ASSEMBLY AT BNLS ACCELERATOR TEST FACILITY.

    Energy Technology Data Exchange (ETDEWEB)

    HU,J.P.; CASEY,W.R.; HARDER,D.A.; PJEROV,S.; RAKOWSKY,G.; SKARITKA,J.R.

    2002-09-05

    A portable assembly containing a vertical-bend dipole magnet has been designed and installed immediately down-beam of the Compton electron-laser interaction chamber on beamline 1 of the Accelerator Test Facility (ATF) at Brookhaven National Laboratory (BNL). The water-cooled magnet designed with field strength of up to 0.7 Tesla will be used as a spectrometer in the Thompson scattering and vacuum acceleration experiments, where field-dependent electron scattering, beam focusing and energy spread will be analyzed. This magnet will deflect the ATF's 60 MeV electron-beam 90{sup o} downward, as a vertical beam dump for the Compton scattering experiment. The dipole magnet assembly is portable, and can be relocated to other beamlines at the ATF or other accelerator facilities to be used as a spectrometer or a beam dump. The mechanical and shielding calculations are presented in this paper. The structural rigidity and stability of the assembly were studied. A square lead shield surrounding the assembly's Faraday Cup was designed to attenuate the radiation emerging from the 1 inch-copper beam stop. All photons produced were assumed to be sufficiently energetic to generate photoneutrons. A safety evaluation of groundwater tritium contamination due to the thermal neutron capturing by the deuterium in water was performed, using updated Monte Carlo neutron-photon coupled transport code (MCNP). High-energy neutron spallation, which is a potential source to directly generate radioactive tritium and sodium-22 in soil, was conservatively assessed in verifying personal and environmental safety.

  9. Final report on accident tolerant fuel performance analysis of APMT-Steel Clad/UO₂ fuel and APMT-Steel Clad/UN-U₃Si₅ fuel concepts

    Energy Technology Data Exchange (ETDEWEB)

    Unal, Cetin [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Galloway, Jack D. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2014-09-12

    In FY2014 our group completed and documented analysis of new Accident Tolerant Fuel (ATF) concepts using BISON. We have modeled the viability of moving from Zircaloy to stainless steel cladding in traditional light water reactors (LWRs). We have explored the reactivity penalty of this change using the MCNP-based burnup code Monteburns, while attempting to minimize this penalty by increasing the fuel pellet radius and decreasing the cladding thickness. Fuel performance simulations using BISON have also been performed to quantify changes to structural integrity resulting from thinner stainless steel claddings. We account for thermal and irradiation creep, fission gas swelling, thermal swelling and fuel relocation in the models for both Zircaloy and stainless steel claddings. Additional models that account for the lower oxidation stainless steel APMT are also invoked where available. Irradiation data for HT9 is used as a fallback in the absence of appropriate models. In this study the isotopic vectors within each natural element are varied to assess potential reactivity gains if advanced enrichment capabilities were levied towards cladding technologies. Recommendations on cladding thicknesses for a robust cladding as well as the constitutive components of a less penalizing composition are provided. In the first section (section 1-3), we present results accepted for publication in the 2014 TOPFUEL conference regarding the APMT/UO₂ ATF concept (J. Galloway & C. Unal, Accident Tolerant and Neutronically Favorable LWR Cladding, Proceedings of WRFPM 2014, Sendai, Japan, Paper No.1000050). Next we discuss our preliminary findings from the thermo-mechanical analysis of UN-U₃Si₅ fuel with APMT clad. In this analysis we used models developed from limited data that need to be updated when the irradiation data from ATF-1 test is available. Initial results indicate a swelling rate less than 1.5% is needed to prevent excessive clad stress.

  10. Polynomial algebra reveals diverging roles of the unfolded protein response in endothelial cells during ischemia-reperfusion injury.

    Science.gov (United States)

    Le Pape, Sylvain; Dimitrova, Elena; Hannaert, Patrick; Konovalov, Alexander; Volmer, Romain; Ron, David; Thuillier, Raphaël; Hauet, Thierry

    2014-08-25

    The unfolded protein response (UPR)--the endoplasmic reticulum stress response--is found in various pathologies including ischemia-reperfusion injury (IRI). However, its role during IRI is still unclear. Here, by combining two different bioinformatical methods--a method based on ordinary differential equations (Time Series Network Inference) and an algebraic method (probabilistic polynomial dynamical systems)--we identified the IRE1α-XBP1 and the ATF6 pathways as the main UPR effectors involved in cell's adaptation to IRI. We validated these findings experimentally by assessing the impact of their knock-out and knock-down on cell survival during IRI.

  11. Regulation of eIF2α phosphorylation in hindlimb-unloaded and STS-135 space-flown mice

    Science.gov (United States)

    Zhao, Liming; Tanjung, Nancy; Swarnkar, Gaurav; Ledet, Eric; Yokota, Hiroki

    2012-09-01

    Various environmental stresses elevate the phosphorylation level of eukaryotic translation initiation factor 2 alpha (eIF2α) and induce transcriptional activation of a set of stress responsive genes such as activating transcription factors 3 and 6 (ATF3 and ATF6), CCAAT/enhancer-binding protein homologous protein (CHOP), and Xbp1 (X-box binding protein 1). These stress sources include radiation, oxidation, and stress to the endoplasmic reticulum, and it is recently reported that unloading by hindlimb unloading is such a stress source. No studies, however, have examined the phosphorylation level of eIF2α (eIF2α-p) using skeletal samples that have experienced microgravity in space. In this study we addressed a question: Does a mouse tibia flown in space show altered levels of eIF2α-p? To address this question, we obtained STS-135 flown samples that were harvested 4-7 h after landing. The tibia and femur isolated from hindlimb unloaded mice were employed as non-flight controls. The effects of loading were also investigated in non- flight controls. Results indicate that the level of eIF2α-p of the non-flight controls was elevated during hindlimb unloading and reduced after being released from unloading. Second, the eIF2α-p level of space-flown samples was decreased, and mechanical loading to the tibia caused the reduction of the eIF2α-p level. Third, the mRNA levels of ATF3, ATF6, and CHOP were lowered in space-flown samples as well as in the non-flight samples 4-7 h after being released from unloading. Collectively, the results herein indicated that a release from hindlimb unloading and a return to normal weight environment from space provided a suppressive effect to eIF2α-linked stress responses and that a period of 2-4 h is sufficient to induce this suppressive outcome.

  12. microRNA-26a modulates inflammatory response induced by toll-like receptor 4 stimulation in microglia.

    Science.gov (United States)

    Kumar, Asit; Bhatia, Harsharan Singh; de Oliveira, Antonio Carlos Pinheiro; Fiebich, Bernd L

    2015-12-01

    MiRNAs, a family of small non-coding RNAs, have emerged as novel post-transcriptional regulators of numerous cellular responses. Although the involvement of miRNAs in the regulation of neuroinflammation in various neurological diseases has been previously studied, their role in the production of inflammatory mediators during microglia activation is poorly understood. In this study, the role of miR-26a has been investigated in the modulation of inflammatory response in cultured microglia. Using real-time PCR, the expression of miR-26a was studied in toll-like receptors 4 stimulated primary mouse microglia. miR-26a expression was found to be rapidly reduced after the stimulation of toll-like receptors 4 in microglia. Over-expression of miR-26a significantly decreased the production of inflammatory cytokines such as tumor necrosis factor α and IL-6, whereas knockdown of miR-26a increased the expression of these mediators. Furthermore, using in silico analysis, we identified that the activating transcription factor (ATF) 2 is directly targeted by miR-26a. This finding was confirmed by loss and gain of function studies. Similar to the effect of miR-26a over-expression, knockdown of activating transcription factor 2 inhibited the production of proinflammatory cytokines, particularly IL-6. Taken together, our results suggest the involvement of miR-26a in the regulation of the production of proinflammatory cytokines in microglia. We proposed that in microglia, activation of toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS) down-regulates miR-26a. The down-regulation of this miR increases expression of activating transcription factor 2 (ATF2). This event, in addition to the activation of ATF2 by c-Jun N-terminal kinase (JNK), increases interleukin-6 (IL-6) production. On the other hand, miR-26a also increases the production of tumor necrosis factor α (TNFα) by a mechanism independent of ATF2.

  13. Inhibition of HMG-CoA reductase induces the UPR pathway in C. elegans

    DEFF Research Database (Denmark)

    Olsen, Louise Cathrine Braun; Hansen, Nadia Jin Storm; Pilon, Marc;

    -requiring enzyme-1 (IRE-1), and activating transcription factor-6 (ATF-6). Using a transgenic GFP reporter strain of the model organism C. elegans, we have recently identified that inhibition of the enzyme HMG-CoA reductase (HMG-CoAR) with Fluvastatin and knock down of HMG-CoAR using RNA interference (RNAi) both...... including farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) which are necessary for posttranslational prenylation of several small G proteins. C. elegans are cholesterol auxotrophs, which enable us to investigate the isoprenoid branch and its role in UPR induction. We found...

  14. Energy stabilization of 1.5 GeV S-Band linac

    OpenAIRE

    Kuriki, M.; Hayano, H; Naito, T.; Okugi, T.; Vogel, V.

    2000-01-01

    KEK-ATF is studying low emittance, multi-bunch electron beam for the future linear collider. The energy instability of the 1.5 GeV linac has been a problem making the beam injection to the damping ring unstable. Because the unstable beam generates also large amount of the radiation, the beam current is limited by the KEK radiation safety policy much lower than what we expect. Stabilizing the S-band linac is therefore important not only to improve the beam quality, but also to clear the radiat...

  15. Approach to compact terawatt CO2 laser system for particle acceleration

    International Nuclear Information System (INIS)

    A compact table-top 20-GW 50-ps CO2 laser system is in operation for strong-field physics studies at the ATF. We propose scaling up of the picosecond CO2 laser to a terawatt peak power level to meet the requirements of advanced laser accelerators. Computer modeling shows that a relatively compact single-beam picosecond CO2 laser system with a high-pressure x-ray picosecond amplifier of a 10-cm aperture is potentially scalable to the ∼1-TW peak power level

  16. Laserwire at the Accelerator Test Facility 2 with Sub-Micrometre Resolution

    OpenAIRE

    Nevay, L. J.; Boogert, S.T.; Karataev, P.; Kruchinin, K.; Corner, L; Howell, D. F.; Walczak, R.; Aryshev, A.; Urakawa, J.; Terunuma, N.

    2014-01-01

    A laserwire transverse electron beam size measurement system has been developed and operated at the Accelerator Test Facility 2 (ATF2) at KEK. Special electron beam optics were developed to create an approximately 1 x 100 {\\mu}m (vertical x horizontal) electron beam at the laserwire location, which was profiled using a 150 mJ, 71 ps laser pulse with a wavelength of 532 nm. The precise characterisation of the laser propagation allows the non-Gaussian transverse profiles of the electron beam ca...

  17. Study on the Explicit Formula of the Triangular Flat Shell Element Based on the Analytical Trial Functions for Anisotropy Material

    Directory of Open Access Journals (Sweden)

    Xiang-Rong Fu

    2013-01-01

    Full Text Available This paper presents a novel way to formulate the triangular flat shell element. The basic analytical solutions of membrane and bending plate problem for anisotropy material are studied separately. Combining with the conforming displacement along the sides and hybrid element strategy, the triangular flat shell elements based on the analytical trial functions (ATF for anisotropy material are formulated. By using the explicit integral formulae of the triangular element, the matrices used in proposed shell element are calculated efficiently. The benchmark examples showed the high accuracy and high efficiency.

  18. ORMEC: a three-dimensional MHD spectral inverse equilibrium code

    International Nuclear Information System (INIS)

    The Oak Ridge Moments Equilibrium Code (ORMEC) is an efficient computer code that has been developed to calculate three-dimensional MHD equilibria using the inverse spectral method. The fixed boundary formulation, which is based on a variational principle for the spectral coefficients (moments) of the cylindrical coordinates R and Z, is described and compared with the finite difference code BETA developed by Bauer, Betancourt, and Garabedian. Calculations for the Heliotron, Wendelstein VIIA, and Advanced Toroidal Facility (ATF) configurations are performed to establish the accuracy and mesh convergence properties for the spectral method. 16 refs., 13 figs

  19. Analysis of Flow Cytometry DNA Damage Response Protein Activation Kinetics Following X-rays and High Energy Iron Nuclei Exposure

    Energy Technology Data Exchange (ETDEWEB)

    Universities Space Research Association; Chappell, Lori J.; Whalen, Mary K.; Gurai, Sheena; Ponomarev, Artem; Cucinotta, Francis A.; Pluth, Janice M.

    2010-12-15

    We developed a mathematical method to analyze flow cytometry data to describe the kinetics of {gamma}H2AX and pATF2 phosphorylations ensuing various qualities of low dose radiation in normal human fibroblast cells. Previously reported flow cytometry kinetic results for these DSB repair phospho-proteins revealed that distributions of intensity were highly skewed, severely limiting the detection of differences in the very low dose range. Distributional analysis reveals significant differences between control and low dose samples when distributions are compared using the Kolmogorov-Smirnov test. Radiation quality differences are found in the distribution shapes and when a nonlinear model is used to relate dose and time to the decay of the mean ratio of phosphoprotein intensities of irradiated samples to controls. We analyzed cell cycle phase and radiation quality dependent characteristic repair times and residual phospho-protein levels with these methods. Characteristic repair times for {gamma}H2AX were higher following Fe nuclei as compared to X-rays in G1 cells (4.5 {+-} 0.46 h vs 3.26 {+-} 0.76 h, respectively), and in S/G2 cells (5.51 {+-} 2.94 h vs 2.87 {+-} 0.45 h, respectively). The RBE in G1 cells for Fe nuclei relative to X-rays for {gamma}H2AX was 2.05 {+-} 0.61 and 5.02 {+-} 3.47, at 2 h and 24-h postirradiation, respectively. For pATF2, a saturation effect is observed with reduced expression at high doses, especially for Fe nuclei, with much slower characteristic repair times (>7 h) compared to X-rays. RBEs for pATF2 were 0.66 {+-} 0.13 and 1.66 {+-} 0.46 at 2 h and 24 h, respectively. Significant differences in {gamma}H2AX and pATF2 levels comparing irradiated samples to control were noted even at the lowest dose analyzed (0.05 Gy) using these methods of analysis. These results reveal that mathematical models can be applied to flow cytometry data to uncover important and subtle differences following exposure to various qualities of low dose radiation.

  20. Research and development of innovative technologies for nuclear reactor core material with enhanced safety

    International Nuclear Information System (INIS)

    In order to clarify the fundamental corrosion resistant properties of silicon carbide (SiC) ceramics, corrosion behavior in aqueous environments of several silicon carbide ceramics with different amounts of sintering additive was studied. In a water corrosion test, the corrosion rate of SiC ceramics increased as the amount of sintering additives increased. For the exposure test in a high temperature steam environment, SiC ceramics indicated higher corrosion resistance than zirconium alloy. The observed characteristics were favorable for SiC composite to be a candidate material applicable to the accident tolerant fuel (ATF). (author)

  1. Coordinated induction of GST and MRP2 by cAMP in Caco-2 cells: Role of protein kinase A signaling pathway and toxicological relevance

    International Nuclear Information System (INIS)

    The cAMP pathway is a universal signaling pathway regulating many cellular processes including metabolic routes, growth and differentiation. However, its effects on xenobiotic biotransformation and transport systems are poorly characterized. The effect of cAMP on expression and activity of GST and MRP2 was evaluated in Caco-2 cells, a model of intestinal epithelium. Cells incubated with the cAMP permeable analog dibutyryl cyclic AMP (db-cAMP: 1,10,100 μM) for 48 h exhibited a dose–response increase in GST class α and MRP2 protein expression. Incubation with forskolin, an activator of adenylyl cyclase, confirmed the association between intracellular cAMP and upregulation of MRP2. Consistent with increased expression of GSTα and MRP2, db-cAMP enhanced their activities, as well as cytoprotection against the common substrate 1-chloro-2,4-dinitrobenzene. Pretreatment with protein kinase A (PKA) inhibitors totally abolished upregulation of MRP2 and GSTα induced by db-cAMP. In silico analysis together with experiments consisting of treatment with db-cAMP of Caco-2 cells transfected with a reporter construct containing CRE and AP-1 sites evidenced participation of these sites in MRP2 upregulation. Further studies involving the transcription factors CREB and AP-1 (c-JUN, c-FOS and ATF2) demonstrated increased levels of total c-JUN and phosphorylation of c-JUN and ATF2 by db-cAMP, which were suppressed by a PKA inhibitor. Co-immunoprecipitation and ChIP assay studies demonstrated that db-cAMP increased c-JUN/ATF2 interaction, with further recruitment to the region of the MRP2 promoter containing CRE and AP-1 sites. We conclude that cAMP induces GSTα and MRP2 expression and activity in Caco-2 cells via the PKA pathway, thus regulating detoxification of specific xenobiotics. - Highlights: • cAMP positively modulates the expression and activity of GST and MRP2 in Caco-2 cells. • Such induction resulted in increased cytoprotection against chemical injury. • PKA

  2. Inhibition of mitochondrial genome expression triggers the activation of CHOP-10 by a cell signaling dependent on the integrated stress response but not the mitochondrial unfolded protein response.

    Science.gov (United States)

    Michel, Sebastien; Canonne, Morgane; Arnould, Thierry; Renard, Patricia

    2015-03-01

    Mitochondria-to-nucleus communication, known as retrograde signaling, is important to adjust the nuclear gene expression in response to organelle dysfunction. Among the transcription factors described to respond to mitochondrial stress, CHOP-10 is activated by respiratory chain inhibition, mitochondrial accumulation of unfolded proteins and mtDNA mutations. In this study, we show that altered/impaired expression of mtDNA induces CHOP-10 expression in a signaling pathway that depends on the eIF2α/ATF4 axis of the integrated stress response rather than on the mitochondrial unfolded protein response.

  3. Crustal Structure and Moho Geometry around the Alto Tiberina Fault (Northern Apennines) from Receiver Functions

    Science.gov (United States)

    Licciardi, A.; Chiaraluce, L.; Piana Agostinetti, N.; Amato, A.

    2013-12-01

    The Alto Tiberina Fault (ATF) is an unique example of active low angle normal fault (dip ≈ 15°), detected in the Northern Apennines from the interpretation of passive and active seismic data. This NW-SE striking structure has been mapped for a about 50 km along dip and is thought to have accumulated a total of 2 km of displacement in the last 2 Ma. In the last years, a dense, high resolution seismic network has been deployed in the area surrounding the ATF, with the aim of better understanding the physical mechanisms of earthquakes nucleation of such geological feature and assessing the potentially associated seismic hazard. In this context, a good knowledge of the elastic properties of rocks at depth is the starting points for building accurate and consistent physical models of ATF's style of deformation. We carried out a teleseismic receiver functions (RF) study on the 42 broadband seismic stations, using about 800 events from teleseismic distances, recorded from January 2010 to December 2011. We selected an average of about 70 high S/N ratio RFs per station, achieving a good azimuthal coverage for most of the stations. We separated the isotropic and the anisotropic component of the RF data-set through the harmonic decomposition. For each station, we performed a Monte Carlo inversion (using a reversible jump Markov chain Monte Carlo algorithm) of the isotropic component of the RF data-set, obtaining 1-D Vs profiles from the surface to 60km depth. This kind of inversion does not suffer of the problems related to the choice of a particular starting model, and has the advantage of inferring the degree of complexity (i.e. the number of layers) of the resulting model, directly from the data themselves. Preliminary results show an increasing level of structural complexity moving from west to east across the target area. A clear and shallow (~25 km) Moho is observed from the velocity profiles in the westernmost part of the region. Along the easternmost part, crustal

  4. Proceedings of the Start-up Meeting of the OECD-NEA Expert Group on Accident Tolerant Fuels for LWRs, 28-29 April 2014, OECD-NEA HQ

    International Nuclear Information System (INIS)

    Under the guidance of the OECD-NEA Nuclear Science Committee, the expert group acts as a forum for scientific and technical information exchange on advanced light water reactor (LWR) fuels with enhanced accident tolerance. The expert group focusses on the fundamental properties and behaviour under normal operations and accident conditions for advanced core materials and components (fuels, cladding, control rods, etc.). The materials considered are applicable to Gen II and Gen III Light Water Reactors, as well as Gen III+ reactors under construction. The objective of the expert group is to define and coordinate a programme of work to help advance the scientific knowledge needed to provide the technical underpinning for the development of advanced LWR fuels with enhanced accident tolerance compared to currently used zircaloy/UO2 fuel systems, as well as other non-fuel core components with important roles in LWR performance under accident conditions. This document brings together the available presentations (slides) given at the Start-up Meeting of the OECD-NEA Expert Group on Accident Tolerant Fuels for LWRs. Content: 1 - Final Agenda; 2 - Draft mandate of EGATFL: Discussion of Scope and Objectives (K. Pasamehmetoglu, INL); 3 - Technical updates since the 2. meeting on ATF (28-29 October 2013): - Overview on ATF R and D in Japan (M. Kurata, JAEA); - Update on Development of Enhanced Accident Tolerant Fuel for Light Water Reactors in the United States (S. Bragg-Sitton, INL); - EPRI Update Since the 2. OECD/NEA Meeting on ATF - 28-29 October 2013 (A. Sowder, EPRI); - Accident Tolerant Fuel (ATF) Development: KAERI's R and D Status (Y.H. Koo, KAERI); - Accident Tolerant Fuel Research Activities in China General Nuclear Power Corporation - CGN (Y. Zhou, CGN); - ATF R and D Status and Perspectives (Th. Forgeron, CEA); - Proposals of NRC 'Kurchatov Institute' on Contributions to Collaborative Framework on ATF Activity (Y. Zvonarev, NRC KI); - Input to the

  5. Lipid-soluble cigarette smoking particles induce expression of inflammatory and extracellular-matrix-related genes in rat cerebral arteries

    DEFF Research Database (Denmark)

    Vikman, Petter; Xu, Cang-Bao; Edvinsson, Lars

    2009-01-01

    receptor 1 and 2 (AT(1) and AT(2)), interleukin 6 and inducible nitric oxide synthase (iNOS) were investigated at mRNA level by real-time PCR and/or at protein level by immunohistochemistry. In addition, the activity of three mitogen-activated protein kinases (p38, ERK 1/2 and SAPK...... factor ATF-2 and Elk-1. However, ERK 1/2 and SAPK/JNK activities were markedly expressed in the control (organ culture per se with DMSO), and DSP failed to further enhance the activation of ERK 1/2 and SAPK/JNK in the cerebral arteries. CONCLUSIONS: DSP induces cerebral vessel inflammation...

  6. A scheme to compensate the transient beam loading in TW electron linacs

    International Nuclear Information System (INIS)

    A scheme to compensate the transient beam loading of the TW electron linac operated in multi-bunch mode is described. The proposed method is to excite an auxiliary cavity located at the end of the accelerator section with the residual rf power, which comes out of the section after one filling time, with properly adjusted phase and amplitude of the field. The transient energy gain of the electron beam in passing through the cavity will compensate the transient energy loss due to beam loading in the accelerator section. The parameters of ATF of Brookhaven National Laboratory are used for calculation as an example to illustrate the result of computation

  7. Solution structure and dynamics of GCN4 cognate DNA: NMR investigations

    OpenAIRE

    Khandelwal, Purnima; Panchal, S. C.; Radha, P. K.; Hosur, R V

    2001-01-01

    A 12 bp long GCN4-binding, self-complementary duplex DNA d(CATGACGTCATG)2 has been investigated by NMR spectroscopy to study the structure and dynamics of the molecule in aqueous solution. The NMR structure of the DNA obtained using simulated annealing and iterative relaxation matrix calculations compares quite closely with the X-ray structure of ATF/CREB DNA in complex with GCN4 protein (DNA-binding domain). The DNA is also seen to be curved in the free state and ...

  8. Contemporary management of blunt aortic trauma.

    Science.gov (United States)

    Dubose, J J; Azizzadeh, A; Estrera, A L; Safi, H J

    2015-10-01

    Blunt thoracic aortic injury (BTAI) remains a common cause of death following blunt mechanisms of trauma. Among patients who survive to reach hospital care, significant advances in diagnosis and treatment afford previously unattainable survival. The Society for Vascular Surgery (SVS) guidelines provide current best-evidence suggestions for treatment of BTAI. However, several key areas of controversy regarding optimal BTAI care remain. These include the refinement of selection criteria, timing for treatment and the need for long-term follow-up data. In addition, the advent of the Aortic Trauma Foundation (ATF) represents an important development in collaborative research in this field. PMID:25868973

  9. Frictional Behavior of Fe-based Cladding Candidates for PWR

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Young-Ho; Kim, Hyung-Kyu [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Byun, Thak Sang [Oak Ridge National Lab., Oak Ridge (United States)

    2014-10-15

    After the recent nuclear disaster at Fukushima Daiichi reactors, there is a growing consensus on the development of new fuel systems (i.e., accident-tolerant fuel, ATF) that have high safety margins under design-basis accident (DBA) and beyond design-basis accident (BDBA). A common objective of various developing candidates is to archive the outstanding corrosion-resistance under severe accidents such as DBA and DBDA conditions for decreasing hydrogen production and increasing coping time to respond to severe accidents. ATF could be defined as new fuel/cladding system with enhanced accident tolerant to loss of active cooling in the core for a considerably longer time period under severe accidents while maintaining or improving the fuel performance during normal operations. This means that, in normal operating conditions, new fuel systems should be applicable to current operating PWRs for suppressing various degradation mechanisms of current fuel assembly without excessive design changes. When considering that one of the major degradation mechanisms of PWR fuel assemblies is a grid-to-rod fretting (GTRF), it is necessary to examine the tribological behavior of various ATF candidates at initial development stage. In this study, friction and reciprocating wear behavior of two kinds of Fe-based ATF candidates were examined with a reciprocating wear tests at room temperature (RT) air and water. The objective is to examine the compatibilities of these Fe-based alloys against current Zr-based alloy properties, which is used as major structural materials of PWR fuel assemblies. The reciprocating wear behaviors of Fe-based accident-tolerant fuel cladding candidates against current Zr-based alloy has been studied using a reciprocating sliding wear tester in room temperature air and water. Frictional behavior and wear depth were used for evaluating the applicability and compatibilities of Fe-based candidates without significant design changes of PWR fuel assemblies

  10. Profiling of histone H3 lysine 9 trimethylation levels predicts transcription factor activity and survival in acute myeloid leukemia

    DEFF Research Database (Denmark)

    Müller-Tidow, Carsten; Klein, Hans-Ulrich; Hascher, Antje;

    2010-01-01

    . The altered genomic regions showed an overrepresentation of cis-binding sites for ets and c-AMP response elements (CREs) for transcription factors of the CREB/CREM/ATF1 family. The decrease in H3K9me3 levels at CREs was associated with increased CRE-driven promoter activity in AML blasts in vivo. AML......Acute Myeloid Leukemia (AML) is commonly associated with alterations in transcription factors due to altered expression or gene mutations. These changes might induce leukemia- specific patterns of histone modifications. We used ChIP-Chip to analyze histone H3 Lysine 9 trimethylation (H3K9me3...

  11. Silicon recovery from silicon-iron alloys by electrorefining in molten fluorides

    OpenAIRE

    Massot, Laurent; Bieber, Anne-Laure; Gibilaro, Mathieu; Cassayre, Laurent; Taxil, Pierre; Chamelot, Pierre

    2013-01-01

    International audience Electrorefining of a silicon-iron material (Si-4.7at%Fe) in molten NaF-KF at 850°C has been investigated in view of recovering pure Si, using electrochemical techniques, SEM-EDS and ICP-AES analyses. The selective electrochemical dissolution of Si was evidenced. Electrorefining runs led to a maximum Si recovery of 80% of the initial Si contained in the material, in the form of a dense deposit at the cathode, with very high current efficiencies. The Si purity has been...

  12. Distinct Roles for the NF-κB RelA Subunit during Antiviral Innate Immune Responses▿ †

    OpenAIRE

    Basagoudanavar, Suresh H.; Thapa, Roshan J.; Nogusa, Shoko; Wang, Junmei; Beg, Amer A.; Balachandran, Siddharth

    2011-01-01

    Production of type I interferons (IFNs; prominently, IFN-α/β) following virus infection is a pivotal antiviral innate immune response in higher vertebrates. The synthesis of IFN-β proceeds via the virus-induced assembly of the transcription factors IRF-3/7, ATF-2/c-Jun, and NF-κB on the ifnβ promoter. Surprisingly, recent data indicate that the NF-κB subunit RelA is not essential for virus-stimulated ifnβ expression. Here, we show that RelA instead sustains autocrine IFN-β signaling prior to ...

  13. Coordinated induction of GST and MRP2 by cAMP in Caco-2 cells: Role of protein kinase A signaling pathway and toxicological relevance

    Energy Technology Data Exchange (ETDEWEB)

    Arana, Maite Rocío, E-mail: arana@ifise-conicet.gov.ar [Instituto de Fisiología Experimental (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas (UNR), Suipacha 570, 2000 Rosario (Argentina); Tocchetti, Guillermo Nicolás, E-mail: gtocchetti@live.com.ar [Instituto de Fisiología Experimental (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas (UNR), Suipacha 570, 2000 Rosario (Argentina); Domizi, Pablo, E-mail: domizi@ibr-conicet.gov.ar [Instituto de Biología Molecular y Celular de Rosario (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas (UNR), Suipacha 570, 2000 Rosario (Argentina); Arias, Agostina, E-mail: agoarias@yahoo.com.ar [Instituto de Fisiología Experimental (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas (UNR), Suipacha 570, 2000 Rosario (Argentina); Rigalli, Juan Pablo, E-mail: jprigalli@gmail.com [Instituto de Fisiología Experimental (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas (UNR), Suipacha 570, 2000 Rosario (Argentina); Ruiz, María Laura, E-mail: ruiz@ifise-conicet.gov.ar [Instituto de Fisiología Experimental (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas (UNR), Suipacha 570, 2000 Rosario (Argentina); and others

    2015-09-01

    The cAMP pathway is a universal signaling pathway regulating many cellular processes including metabolic routes, growth and differentiation. However, its effects on xenobiotic biotransformation and transport systems are poorly characterized. The effect of cAMP on expression and activity of GST and MRP2 was evaluated in Caco-2 cells, a model of intestinal epithelium. Cells incubated with the cAMP permeable analog dibutyryl cyclic AMP (db-cAMP: 1,10,100 μM) for 48 h exhibited a dose–response increase in GST class α and MRP2 protein expression. Incubation with forskolin, an activator of adenylyl cyclase, confirmed the association between intracellular cAMP and upregulation of MRP2. Consistent with increased expression of GSTα and MRP2, db-cAMP enhanced their activities, as well as cytoprotection against the common substrate 1-chloro-2,4-dinitrobenzene. Pretreatment with protein kinase A (PKA) inhibitors totally abolished upregulation of MRP2 and GSTα induced by db-cAMP. In silico analysis together with experiments consisting of treatment with db-cAMP of Caco-2 cells transfected with a reporter construct containing CRE and AP-1 sites evidenced participation of these sites in MRP2 upregulation. Further studies involving the transcription factors CREB and AP-1 (c-JUN, c-FOS and ATF2) demonstrated increased levels of total c-JUN and phosphorylation of c-JUN and ATF2 by db-cAMP, which were suppressed by a PKA inhibitor. Co-immunoprecipitation and ChIP assay studies demonstrated that db-cAMP increased c-JUN/ATF2 interaction, with further recruitment to the region of the MRP2 promoter containing CRE and AP-1 sites. We conclude that cAMP induces GSTα and MRP2 expression and activity in Caco-2 cells via the PKA pathway, thus regulating detoxification of specific xenobiotics. - Highlights: • cAMP positively modulates the expression and activity of GST and MRP2 in Caco-2 cells. • Such induction resulted in increased cytoprotection against chemical injury. • PKA

  14. Determination of Soil Base—Soluble Se by Anodic Stripping Voltammetry with Aurum Thin—Film Electrode

    Institute of Scientific and Technical Information of China (English)

    YANGZENG; HEYING; 等

    1994-01-01

    Determination of soil Se by anodic stripping voltammetry(ASV) with aurum thin-film electrode(ATFE)overcomes the interference of gold peak with selenium peak,and thus has a higher sensitivity with the miniumum detectable concentration being 0.017μg/mL,the standard deviation of the measured results leww than 0.012μg/g,the coefficient of variation lwoer than 10% ,and the recovery rate between 86% to 103%.Besides the measurement conditions,the digestion of soil sample was also studied in detail.

  15. Uniform {sup 15}N- and {sup 15}N/{sup 13}C-labeling of proteins in mammalian cells and solution structure of the amino terminal fragment of u-PA

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, A.P.; Petros, A.M.; Meadows, R.P.; Mazar, A.P.; Nettesheim, D.G.; Pederson, T.M.; Fesik, S.W. [Abbott Laboratories, Abbott Park, IL (United States)

    1994-12-01

    Urokinase-type plasminogen activator (u-PA) is a 54-kDa glycoprotein that catalyzes the conversion of plasminogen to plasmin, a broad-specificity protease responsible for the degradation of fibrin clots and extracellular matrix components. The u-PA protein consists of three individual modules: a growth factor domain (GFD), a kringle, and a serine protease domain. The amino terminal fragment (ATF) includes the GFD-responsible for u-PA binding to its receptor-and the kringle domains. This protein was expressed and uniformly {sup 15}N-and {sup 15}N/{sup 13}C-labeled in mammalian cells by methods that will be described. In addition, we present the three-dimensional structure of ATF that was derived from 1299 NOE-derived distance restraints along with the {phi} angle and hydrogen bonding restraints. Although the individual domains in the structures were highly converged, the two domains are structurally independent. The overall structures of the individual domains are very similar to the structures of homologous proteins. However, important structural differences between the growth factor domain of u-PA and other homologous proteins were observed in the region that has been implicated in binding the urokinase receptor. These results may explain, in part, why other growth factors show no appreciable affinity for the urokinase receptor.

  16. RNA-Seq transcriptome analysis of porcine cloned and in vitro fertilized blastocysts

    Institute of Scientific and Technical Information of China (English)

    XU Wei-hua; LI Zi-cong; OUYANG Zhi-ping; YU Bo; SHI Jun-song; LIU De-wu; WU Zhen-fang

    2015-01-01

    Somatic nuclear transfer technology has become increasingly promising in biomedicine and agriculture. Whereas the approach remains inefifcient and underlying mechanisms remain ambiguous. Although cloned embryos have similar in vitro developmental capacity as in vitro fertilized (IVF) embryos before implantation, they appeared to have much lower ful-term developmental efifciency in pig and cattle, and thus it would be reasonable to postulate that profound distinction at the molecular level should exist between them. Herein, RNA sequencing technique was used to screen differential y expressed genes in cloned and IVF blastocysts, and in total 628 differential y expressed transcripts were obtained, among which, 280 transcripts are up-regulated and 348 transcripts are down-regulated in cloned blastocysts. Moreover, one statistical y signiifcant pathway associated with endoplasmic reticulum (ER) protein processing was enriched, and some ER-stress markers such as ATF4, ATF6, PDIA3, HSPA1B, HSP40 and HSP90 between cloned and IVF blastocysts were suggested. Additional y, some developmental y important genes such as lipid metabolism related genes (MGLL, DDHD2 and FADS2) and epigenetic modiifcation genes (DNMT1, KDM5C and MBD3L5) were found differential y expressed be-tween cloned and IVF embryos.

  17. Fimbriae have distinguishable roles in Proteus mirabilis biofilm formation.

    Science.gov (United States)

    Scavone, Paola; Iribarnegaray, Victoria; Caetano, Ana Laura; Schlapp, Geraldine; Härtel, Steffen; Zunino, Pablo

    2016-07-01

    Proteus mirabilis is one of the most common etiological agents of complicated urinary tract infections, especially those associated with catheterization. This is related to the ability of P. mirabilis to form biofilms on different surfaces. This pathogen encodes 17 putative fimbrial operons, the highest number found in any sequenced bacterial species so far. The present study analyzed the role of four P. mirabilis fimbriae (MR/P, UCA, ATF and PMF) in biofilm formation using isogenic mutants. Experimental approaches included migration over catheter, swimming and swarming motility, the semiquantitative assay based on adhesion and crystal violet staining, and biofilm development by immunofluorescence and confocal microscopy. Different assays were performed using LB or artificial urine. Results indicated that the different fimbriae contribute to the formation of a stable and functional biofilm. Fimbriae revealed particular associated roles. First, all the mutants showed a significantly reduced ability to migrate across urinary catheter sections but neither swimming nor swarming motility were affected. However, some mutants formed smaller biofilms compared with the wild type (MRP and ATF) while others formed significantly larger biofilms (UCA and PMF) showing different bioarchitecture features. It can be concluded that P. mirabilis fimbriae have distinguishable roles in the generation of biofilms, particularly in association with catheters. PMID:27091004

  18. Oxidative DNA damage induces the ATM-mediated transcriptional suppression of the Wnt inhibitor WIF-1 in systemic sclerosis and fibrosis.

    Science.gov (United States)

    Svegliati, Silvia; Marrone, Giusi; Pezone, Antonio; Spadoni, Tatiana; Grieco, Antonella; Moroncini, Gianluca; Grieco, Domenico; Vinciguerra, Maria; Agnese, Savina; Jüngel, Astrid; Distler, Oliver; Musti, Anna Maria; Gabrielli, Armando; Avvedimento, Enrico V

    2014-09-01

    Systemic sclerosis (SSc) is an autoimmune disease characterized by extensive visceral organ and skin fibrosis. SSc patients have increased production of autoreactive antibodies and Wnt signaling activity. We found that expression of the gene encoding Wnt inhibitor factor 1 (WIF-1) was decreased in fibroblasts from SSc patient biopsies. WIF-1 deficiency in SSc patient cells correlated with increased abundance of the Wnt effector β-catenin and the production of collagen. Knocking down WIF-1 in normal fibroblasts increased Wnt signaling and collagen production. WIF-1 loss and DNA damage were induced in normal fibroblasts by either SSc patient immunoglobulins or oxidative DNA-damaging agents, such as ultraviolet light, hydrogen peroxide, or bleomycin. The DNA damage checkpoint kinase ataxia telangiectasia mutated (ATM) mediated WIF-1 silencing through the phosphorylation of the transcription factor c-Jun, which in turn activated the expression of the gene encoding activating transcription factor 3 (ATF3). ATF3 and c-Jun were recruited together with histone deacetylase 3 (HDAC3) to the WIF-1 promoter and inhibited WIF-1 expression. Preventing the accumulation of reactive oxygen species or inhibiting the activation of ATM, c-Jun, or HDACs restored WIF-1 expression in cultured SSc patient cells. Trichostatin A, an HDAC inhibitor, prevented WIF-1 loss, β-catenin induction, and collagen accumulation in an experimental fibrosis model. Our findings suggest that oxidative DNA damage induced by SSc autoreactive antibodies enables Wnt activation that contributes to fibrosis. PMID:25185156

  19. TBL2 is a novel PERK-binding protein that modulates stress-signaling and cell survival during endoplasmic reticulum stress.

    Directory of Open Access Journals (Sweden)

    Yoshinori Tsukumo

    Full Text Available Under ER stress, PKR-like ER-resident kinase (PERK phosphorylates translation initiation factor eIF2α, resulting in repression of global protein synthesis and concomitant upregulation of the translation of specific mRNAs such as activating transcription factor 4 (ATF4. This PERK function is important for cell survival under ER stress and poor nutrient conditions. However, mechanisms of the PERK signaling pathway are not thoroughly understood. Here we identify transducin (beta-like 2 (TBL2 as a novel PERK-binding protein. We found that TBL2 is an ER-localized type-I transmembrane protein and preferentially binds to the phosphorylated form of PERK, but not another eIF2α kinase GCN2 or ER-resident kinase IRE1, under ER stress. Immunoprecipitation analysis using various deletion mutants revealed that TBL2 interacts with PERK via the N-terminus proximal region and also associates with eIF2α via the WD40 domain. In addition, TBL2 knockdown can lead to impaired ATF4 induction under ER stress or poor nutrient conditions such as glucose and oxygen deprivation. Consistently, TBL2 knockdown rendered cells vulnerable to stresses similarly to PERK knockdown. Thus, TBL2 serves as a potential regulator of the PERK pathway.

  20. Selenoprotein S/SEPS1 modifies endoplasmic reticulum stress in Z variant alpha1-antitrypsin deficiency.

    LENUS (Irish Health Repository)

    Kelly, Emer

    2009-06-19

    Z alpha(1)-antitrypsin (ZAAT) deficiency is a disease associated with emphysematous lung disease and also with liver disease. The liver disease of AAT deficiency is associated with endoplasmic reticulum (ER) stress. SEPS1 is a selenoprotein that, through a chaperone activity, decreases ER stress. To determine the effect of SEPS1 on ER stress in ZAAT deficiency, we measured activity of the grp78 promoter and levels of active ATF6 as markers of the unfolded protein response in HepG2 cells transfected with the mutant form of AAT, a ZAAT transgene. We evaluated levels of NFkappaB activity as a marker of the ER overload response. To determine the effect of selenium supplementation on the function of SEPS1, we investigated glutathione peroxidase activity, grp78 promoter activity, and NFkappaB activity in the presence or absence of selenium. SEPS1 reduced levels of active ATF6. Overexpression of SEPS1 also inhibited grp78 promoter and NFkappaB activity, and this effect was enhanced in the presence of selenium supplementation. This finding demonstrates a role for SEPS1 in ZAAT deficiency and suggests a possible therapeutic potential for selenium supplementation.

  1. Infusion of glucose and lipids at physiological rates causes acute endoplasmic reticulum stress in rat liver.

    Science.gov (United States)

    Boden, Guenther; Song, Weiwei; Duan, Xunbao; Cheung, Peter; Kresge, Karen; Barrero, Carlos; Merali, Salim

    2011-07-01

    Endoplasmic reticulum (ER) stress has recently been implicated as a cause for obesity-related insulin resistance; however, what causes ER stress in obesity has remained uncertain. Here, we have tested the hypothesis that macronutrients can cause acute (ER) stress in rat liver. Examined were the effects of intravenously infused glucose and/or lipids on proximal ER stress sensor activation (PERK, eIF2-α, ATF4, Xbox protein 1 (XBP1s)), unfolded protein response (UPR) proteins (GRP78, calnexin, calreticulin, protein disulphide isomerase (PDI), stress kinases (JNK, p38 MAPK) and insulin signaling (insulin/receptor substrate (IRS) 1/2 associated phosphoinositol-3-kinase (PI3K)) in rat liver. Glucose and/or lipid infusions, ranging from 23.8 to 69.5 kJ/4 h (equivalent to between ~17% and ~50% of normal daily energy intake), activated the proximal ER stress sensor PERK and ATF6 increased the protein abundance of calnexin, calreticulin and PDI and increased two GRP78 isoforms. Glucose and glucose plus lipid infusions induced comparable degrees of ER stress, but only infusions containing lipid activated stress kinases (JNK and p38 MAPK) and inhibited insulin signaling (PI3K). In summary, physiologic amounts of both glucose and lipids acutely increased ER stress in livers 12-h fasted rats and dependent on the presence of fat, caused insulin resistance. We conclude that this type of acute ER stress is likely to occur during normal daily nutrient intake.

  2. Reactor physics assessment of alternate cladding materials

    International Nuclear Information System (INIS)

    A preliminary reactor physics assessment has been performed for candidate alternate cladding materials to replace zirconium alloys in enhanced accident tolerant fuel (ATF) concepts for light water reactors. Proposed ATF concepts seek to reduce severe accident risks by increasing the coping time available to operators for accident response and reducing the extent and rate of heat and hydrogen production from steam oxidation. Candidate materials in this neutronics-focused study included austenitic stainless steel 310SS, alumina-forming ferritic alloys (FeCrAl), and silicon carbide (SiC). Historic 304SS cladding and Zircaloy were considered as reference points. Initial results indicate that the metallic options require increased uranium enrichments and/or decreased cladding thicknesses to match the operating cycle lengths achieved with Zircaloy; FeCrAl offered the smallest reactivity penalty, whereas 310SS showed large negative impacts. Ceramic SiC cladding performed well if cladding thicknesses remained similar to those for Zircaloy, but large clad thickness increases led to negative impacts. Fuel pellet relative radial power distributions were similar for all clad materials analyzed. Finally, an economic assessment found that 310SS or FeCrAl could increase fuel pellet costs by 15–36%, while SiC fuel pellet costs were very similar to Zircaloy. (author)

  3. Structural transition and softening in Al–Fe intermetallic compounds induced by high energy ball milling

    Energy Technology Data Exchange (ETDEWEB)

    Basariya, M. Raviathul, E-mail: ravia80@gmail.com [CSIR-National Metallurgical Laboratory, Jamshedpur 831007 (India); Department of Metallurgical Engineering, Indian Institute of Technology (BHU), Varanasi 221005 (India); Roy, Rajat K.; Pramanick, A.K.; Srivastava, V.C. [CSIR-National Metallurgical Laboratory, Jamshedpur 831007 (India); Mukhopadhyay, N.K. [Department of Metallurgical Engineering, Indian Institute of Technology (BHU), Varanasi 221005 (India)

    2015-06-25

    In the present investigation, powders of as-cast ingots of Al–25 at%Fe and Al–34.5 at%Fe alloys close to Al{sub 3}Fe and Al{sub 2}Fe intermetallic phases are subjected to high energy ball milling to understand the possibility of formation of amorphous and/or nanocrystalline phases or any other metastable phases. The development of microstructure, evolution of various metastable phases and their stability are investigated by x-ray diffraction (XRD) and transmission electron microscopy (TEM) techniques. Mechanical milling of the alloys, up to 50 h, was carried out in high energy planetary ball mill. It resulted in phase transformation from monoclinic and triclinic structures of Al{sub 3}Fe and Al{sub 2}Fe, respectively, to orthorhombic structure pertaining to Al{sub 5}Fe{sub 2} phase and structural transformation from crystalline to amorphous phase. Hardness measurements revealed a transition from hardening to softening behavior in these mechanically milled alloys undergoing prolonged milling. The softening effect in the milled powders, having a composite structure involving nanocrystalline and amorphous phases, is attributed to the competing phenomenon of grain size reduction and amorphous phase formation with increasing milling time.

  4. DLK-1, SEK-3 and PMK-3 Are Required for the Life Extension Induced by Mitochondrial Bioenergetic Disruption in C. elegans

    Science.gov (United States)

    Lane, Rebecca K.; Borror, Megan B.; Bokov, Alex F.; Link, Christopher D.; Rea, Shane L.

    2016-01-01

    Mitochondrial dysfunction underlies numerous age-related pathologies. In an effort to uncover how the detrimental effects of mitochondrial dysfunction might be alleviated, we examined how the nematode C. elegans not only adapts to disruption of the mitochondrial electron transport chain, but in many instances responds with extended lifespan. Studies have shown various retrograde responses are activated in these animals, including the well-studied ATFS-1-dependent mitochondrial unfolded protein response (UPRmt). Such processes fall under the greater rubric of cellular surveillance mechanisms. Here we identify a novel p38 signaling cascade that is required to extend life when the mitochondrial electron transport chain is disrupted in worms, and which is blocked by disruption of the Mitochondrial-associated Degradation (MAD) pathway. This novel cascade is defined by DLK-1 (MAP3K), SEK-3 (MAP2K), PMK-3 (MAPK) and the reporter gene Ptbb-6::GFP. Inhibition of known mitochondrial retrograde responses does not alter induction of Ptbb-6::GFP, instead induction of this reporter often occurs in counterpoint to activation of SKN-1, which we show is under the control of ATFS-1. In those mitochondrial bioenergetic mutants which activate Ptbb-6::GFP, we find that dlk-1, sek-3 and pmk-3 are all required for their life extension. PMID:27420916

  5. Reactive oxygen species (ROS) production triggered by prostaglandin D2 (PGD2) regulates lactate dehydrogenase (LDH) expression/activity in TM4 Sertoli cells.

    Science.gov (United States)

    Rossi, Soledad P; Windschüttl, Stefanie; Matzkin, María E; Rey-Ares, Verónica; Terradas, Claudio; Ponzio, Roberto; Puigdomenech, Elisa; Levalle, Oscar; Calandra, Ricardo S; Mayerhofer, Artur; Frungieri, Mónica B

    2016-10-15

    Reactive oxygen species (ROS) regulate testicular function in health and disease. We previously described a prostaglandin D2 (PGD2) system in Sertoli cells. Now, we found that PGD2 increases ROS and hydrogen peroxide (H2O2) generation in murine TM4 Sertoli cells, and also induces antioxidant enzymes expression suggesting that defense systems are triggered as an adaptive stress mechanism that guarantees cell survival. ROS and specially H2O2 may act as second messengers regulating signal transduction pathways and gene expression. We describe a stimulatory effect of PGD2 on lactate dehydrogenase (LDH) expression via DP1/DP2 receptors, which is prevented by the antioxidant N-acetyl-L-cysteine and the PI3K/Akt pathway inhibitor LY 294002. PGD2 also enhances Akt and CREB/ATF-1 phosphorylation. Our results provide evidence for a role of PGD2 in the regulation of the oxidant/antioxidant status in Sertoli cells and, more importantly, in the modulation of LDH expression which takes place through ROS generation and the Akt-CREB/ATF-1 pathway. PMID:27329155

  6. ROS mediated crosstalk between endoplasmic reticulum and mitochondria by Phloxine B under environmental UV irradiation.

    Science.gov (United States)

    Goyal, Shruti; Amar, Saroj Kumar; Srivastav, Ajeet Kumar; Chopra, Deepti; Pal, Manish Kumar; Arjaria, Nidhi; Ray, Ratan Singh

    2016-08-01

    Phloxine B (PhB) is a most commonly used dye in cosmetic products throughout the world. It shows an absorption in visible and ultraviolet radiations. PhB was photodegraded within 4h of UV exposure. It generates reactive oxygen species (ROS) photochemically and intracellularly. Photosensitized PhB caused dose dependent cell viability reduction of human keratinocyte cell line (HaCaT) which was measured through MTT (75.4%) and NRU (77.3%) assays. It also induces cell cycle arrest and DNA damage. Photosensitized PhB induces Ca(2+) release from endoplasmic reticulum (ER). It causes the upregulation of ER stress marker genes ATF6 (1.79 fold) and CHOP (1.93 fold) at transcription levels. The similar response of ATF6 (3.6 fold) and CHOP (2.38 fold) proteins was recorded at translation levels. CHOP targeted the mitochondria and reduced the mitochondrial membrane potential analyzed through JC-1 staining. It further increases Bax/Bcl2 ratio (3.58 fold) and promotes the release of cytochrome c, finally leads to caspase-dependent apoptosis. Upregulation of APAF1 (1.79 fold) in PhB treated cells under UV B exposure supports the mitochondrial-mediated apoptotic cell death. The results support the involvement of ER and mitochondria in ROS mediated PhB phototoxicity. Therefore, the use of PhB in cosmetic products may be deleterious to users during sunlight exposure. PMID:27288659

  7. Research progress of genomic alterations and treatment of Ph-like acute lymphoblastic leukemia%费城染色体样急性淋巴细胞白血病基因改变及治疗研究进展

    Institute of Scientific and Technical Information of China (English)

    顾姗姗

    2015-01-01

    Ph-like acute lymphoblastic leukemia (Ph-like ALL) involves various genomic alterations associated with high risk factors and poor clinical outcome, such as IKZF1, CRLF2, JAK1/2, EBF1-PDGFRB, ATF7IP, EPOR, SH2B3.JAK/STAT pathway and PI3K/mTOR pathway are likely to be the targets of Ph-like ALL.Here,the above genomic alterations and treatment progress are reviewed.%费城染色体样急性淋巴细胞白血病(Ph-like ALL)涉及与其高危特点和预后不良相关的多种基因组改变,如IKZF1 、CRLF2、JAK1/2、EBF1-PDGFRB、ATF7IP、EPOR、SH2B3等.JAK/STAT途径和PI3K/mTOR途径已被证实很可能是某些Ph-like ALL的相关靶点,文章重点综述以上基因组改变及治疗进展.

  8. Strengthening of Zircaloy-4 using Oxide Particles by Laser Beam Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Yang-Il; Park, Dong-Jun; Park, Jung-Hwan; Park, Jeong-Yong; Kim, Hyun-Gil; Koo, Yang-Hyun [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-10-15

    Oxide particles such as Y{sub 2}O{sub 3} and CeO{sub 2} were dispersed homogeneously in a Zircaloy-4 plate surface using an LBS method. From the tensile test at 380 .deg. C, the strength of laser ODS alloying on the Zircaloy-4 sheet was increased more than 50% when compared to the initial state of the sheet, although the ODS alloyed layer was less than 20% of the specimen thickness. This technology showed a good opportunity to increase the strength without major changes in the substrates of zirconium-based alloys. Accident tolerant fuel (ATF) cladding is being developed globally after the Fukushima accident with the demands for the nuclear fuel having higher safety at normal operation conditions as well as even in a severe accident conditions. Korea Atomic Energy Research Institute (KAERI) is one of the leading organizations for developing ATF claddings. One concept is to form an oxidation-resistant layer on Zr cladding surface. The other is to increase high-temperature mechanical strength of Zr tube. The oxide dispersion strengthened (ODS) zirconium was proposed to increase the strength of the Zr-based alloy up to high temperatures.

  9. Superficial paramucosal clear cell sarcoma of the soft parts resembling melanoma in a 13-year-old boy.

    Science.gov (United States)

    Sidiropoulos, Michael; Busam, Klaus; Guitart, Joan; Laskin, William B; Wagner, Annette M; Gerami, Pedram

    2013-02-01

    Clear cell sarcoma (CCS) of tendons and aponeuroses, also known as melanoma of soft parts, represents an aggressive rare malignancy that is characterized by a nested or fascicular pattern of spindled cells and a pathognomonic reciprocal translocation, t(12;22)(q13;q12), that results in the fusion of EWSR1 and ATF1 genes. Numerous recent studies have recognized the importance of a cutaneous CCS variant that can mimic a broad spectrum of entities, including spindle cell melanoma, spindle cell squamous carcinoma, cutaneous leiomyosarcoma and atypical fibroxanthoma. We report a case of a 13-year-old boy with cutaneous CCS who presented with a few months history of an asymptomatic papule on the lower lip that was suggestive of a mucocele. Biopsy of the lesion showed a wedge shaped neoplasm arranged in nests and fascicles of epithelioid- to oval-shaped cells with pale cytoplasm, open chromatin and prominent nucleolus. The superficial component was closely opposed to the basal epithelium resembling the junctional nests of a melanocytic neoplasm. The process extended into and involved the striated muscle of the lip. The cells expressed S-100, CD99 and synaptophysin by immunohistochemistry, and there was focal HMB-45 and microphthalmia transcription factor (MiTF) positivity as well. Fluorescence in situ hybridization confirmed the presence of the t(12;22) (ESWR1-ATF1) translocation. PMID:23228147

  10. The LACARA Vacuum Laser Accelerator Experiment: Beam Positioning and Alignment in a Strong Magnetic Field

    International Nuclear Information System (INIS)

    LACARA (laser cyclotron auto-resonance accelerator) is a vacuum laser accelerator of electrons that is under construction at the Accelerator Test Facility (ATF), Brookhaven National Laboratory. It is expected that the experiment will be assembled by September 2006; this paper presents progress towards this goal. According to numerical studies, as an electron bunch moves along the LACARA solenoidal magnetic field (∼5.2 T, length ∼1 m), it will be accelerated from 50 to ∼75 MeV by interacting with a 0.8 TW Gaussian-mode circularly polarized optical pulse provided by the ATF CO2 10.6μm laser system. The LACARA laser transport optics must handle 10 J and be capable of forming a Gaussian beam inside the solenoid with a 1.4 mm waist and a Rayleigh range of 60 cm. The electron optics must transport a bunch having input emittance of 0.015 mm-mrad and 100 μm waist through the magnet. Precision alignment between the electron beam and the solenoid magnetic axis is required, and a method to achieve this is described in detail. Emittance- filtering may be necessary to yield an accelerated bunch having a narrow (∼1%) energy-spread

  11. Coordinated Regulation of the Neutral Amino Acid Transporter SNAT2 and the Protein Phosphatase Subunit GADD34 Promotes Adaptation to Increased Extracellular Osmolarity*

    Science.gov (United States)

    Krokowski, Dawid; Jobava, Raul; Guan, Bo-Jhih; Farabaugh, Kenneth; Wu, Jing; Majumder, Mithu; Bianchi, Massimiliano G.; Snider, Martin D.; Bussolati, Ovidio; Hatzoglou, Maria

    2015-01-01

    Cells respond to shrinkage induced by increased extracellular osmolarity via programmed changes in gene transcription and mRNA translation. The immediate response to this stress includes the induction of expression of the neutral amino acid transporter SNAT2. Increased SNAT2-mediated uptake of neutral amino acids is an essential adaptive mechanism for restoring cell volume. In contrast, stress-induced phosphorylation of the α subunit of the translation initiation factor eIF2 (eIF2α) can promote apoptosis. Here we show that the response to mild hyperosmotic stress involves regulation of the phosphorylation of eIF2α by increased levels of GADD34, a regulatory subunit of protein phosphatase 1 (PP1). The induction of GADD34 was dependent on transcriptional control by the c-Jun-binding cAMP response element in the GADD34 gene promoter and posttranscriptional stabilization of its mRNA. This mechanism differs from the regulation of GADD34 expression by other stresses that involve activating transcription factor 4 (ATF4). ATF4 was not translated during hyperosmotic stress despite an increase in eIF2α phosphorylation. The SNAT2-mediated increase in amino acid uptake was enhanced by increased GADD34 levels in a manner involving decreased eIF2α phosphorylation. It is proposed that the induction of the SNAT2/GADD34 axis enhances cell survival by promoting the immediate adaptive response to stress. PMID:26041779

  12. Genome structure and organization of a member of a novel and distinct species of the genus Caulimovirus associated with dahlia mosaic.

    Science.gov (United States)

    Pahalawatta, V; Druffel, K L; Wyatt, S D; Eastwell, K C; Pappu, H R

    2008-01-01

    The genome structure and organization of a new and distinct caulimovirus that is widespread in dahlia (Dahlia variabilis) was determined. The double-stranded DNA genome was ca. 7.0 kb in size and shared many of the features of the members of the genus Caulimovirus, such as the presence of genes potentially coding for the movement protein, the inclusion body protein, and the reverse transcriptase (RT), and an intergenic region consisting of a potential 35S promoter. However, the virus differed from the previously described dahlia mosaic caulimovirus and other known caulimoviruses in that the aphid transmission factor (ATF) was absent and the putative coat protein contained a C-terminal deletion and was fused in-frame with the RT. Sequence identity at the amino acid level with known caulimoviruses including a previously reported caulimovirus from dahlia was low and ranged from 32 to 72%. The absence of an ATF and the highly divergent nature of the genomic sequence are characteristics of this new caulimovirus that is widely associated with dahlia. PMID:18253696

  13. Prmt7 Deficiency Causes Reduced Skeletal Muscle Oxidative Metabolism and Age-Related Obesity.

    Science.gov (United States)

    Jeong, Hyeon-Ju; Lee, Hye-Jin; Vuong, Tuan Anh; Choi, Kyu-Sil; Choi, Dahee; Koo, Sung-Hoi; Cho, Sung Chun; Cho, Hana; Kang, Jong-Sun

    2016-07-01

    Maintenance of skeletal muscle function is critical for metabolic health and the disruption of which exacerbates many chronic diseases such as obesity and diabetes. Skeletal muscle responds to exercise or metabolic demands by a fiber-type switch regulated by signaling-transcription networks that remains to be fully defined. Here, we report that protein arginine methyltransferase 7 (Prmt7) is a key regulator for skeletal muscle oxidative metabolism. Prmt7 is expressed at the highest levels in skeletal muscle and decreased in skeletal muscles with age or obesity. Prmt7(-/-) muscles exhibit decreased oxidative metabolism with decreased expression of genes involved in muscle oxidative metabolism, including PGC-1α. Consistently, Prmt7(-/-) mice exhibited significantly reduced endurance exercise capacities. Furthermore, Prmt7(-/-) mice exhibit decreased energy expenditure, which might contribute to the exacerbated age-related obesity of Prmt7(-/-) mice. Similarly to Prmt7(-/-) muscles, Prmt7 depletion in myoblasts also reduces PGC-1α expression and PGC-1α-promoter driven reporter activities. Prmt7 regulates PGC-1α expression through interaction with and activation of p38 mitogen-activated protein kinase (p38MAPK), which in turn activates ATF2, an upstream transcriptional activator for PGC-1α. Taken together, Prmt7 is a novel regulator for muscle oxidative metabolism via activation of p38MAPK/ATF2/PGC-1α. PMID:27207521

  14. Density functional theory calculations of defect and fission gas properties in U-Si fuels

    Energy Technology Data Exchange (ETDEWEB)

    Andersson, Anders David [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-02-03

    Accident tolerant fuels (ATF) are being developed in response to the Fukushima Daiichi accident in Japan. One of the options being pursued is U-Si fuels, such as the U3Si2 and U3Si5 compounds, which benefit from high thermal conductivity (metallic) compared to the UO2 fuel (insulator or semi-conductor) used in current Light Water Reactors (LWRs). The U-Si fuels also have higher fissile density. In order to perform meaningful engineering scale nuclear fuel performance simulations, the material properties of the fuel, including the response to irradiation environments, must be known. Unfortunately, the data available for U-Si fuels are rather limited, in particular for the temperature range where LWRs would operate. The ATF HIP is using multi-scale modeling and simulations to address this knowledge gap. The present study investigates point defect and fission gas properties in U3Si2, which is one of the main fuel candidates, using density functional theory (DFT) calculations. Based on a few assumption regarding entropy contributions, defect and fission diffusivities are predicted. Even though uranium silicides have been shown to amorphize easily at low temperature, we assume that U3Si2 remains crystalline under the conditions expected in Light Water Reactors (LWRs). The temperature and dose where amorphization occurs has not yet been well established.

  15. Pheromone synthesis in a biomicroreactor coated with anti-adsorption polyelectrolyte multilayer

    Science.gov (United States)

    Dimov, Nikolay; Muñoz, Lourdes; Carot-Sans, Gerard; Verhoeven, Michel L. P. M.; Bula, Wojciech P.; Kocer, Gülistan; Guerrero, Angel; Gardeniers, Han J. G. E.

    2011-01-01

    To prepare a biosynthetic module in an infochemical communication project, we designed a silicon/glass microreactor with anti-adsorption polyelectrolyte multilayer coating and immobilized alcohol acetyl transferase (atf), one of the key biosynthetic enzymes of the pheromone of Spodoptera littoralis, on agarose beads inside. The system reproduces the last step of the biosynthesis in which the precursor diene alcohol (Z,E)-9,11-tetradecadienol is transformed into the major component (Z,E)-9,11-tetradecadienyl acetate. The scope of this study was to analyze and implement a multilayer, anti-adsorption coating based on layer-by-layer deposition of polyethylenimine/dextransulfate sodium salt (PEI/DSS). The multilayers were composed of two PEI with molecular weights 750 and 1.2 kDa at pH 9.2 or 6.0. Growth, morphology, and stability of the layers were analyzed by ellipsometry and atomic force microscopy (AFM). The anti-adsorption functionality of the multilayer inside the microreactor was validated. The activity of His6-(atf) was measured by gas chromatography coupled to mass spectrometer (GC-MS). PMID:22662033

  16. A gene transfer comparative study of HSA-conjugated antiangiogenic factors in a transgenic mouse model of metastatic ocular cancer.

    Science.gov (United States)

    Frau, E; Magnon, C; Opolon, P; Connault, E; Opolon, D; Beermann, F; Beerman, F; Abitbol, M; Perricaudet, M; Bouquet, C

    2007-03-01

    Different antiangiogenic and antimetastatic recombinant adenoviruses were tested in a transgenic mouse model of metastatic ocular cancer (TRP1/SV40 Tag transgenic mice), which is a highly aggressive tumor, developed from the pigmented epithelium of the retina. These vectors, encoding amino-terminal fragments of urokinase plasminogen activator (ATF), angiostatin Kringles (K1-3), endostatin (ES) and canstatin (Can) coupled to human serum albumin (HSA) were injected to assess their metastatic and antiangiogenic activities in our model. Compared to AdCO1 control group, AdATF-HSA did not significantly reduce metastatic growth. In contrast, mice treated with AdK1-3-HSA, AdES-HSA and AdCan-HSA displayed significantly smaller metastases (1.19+/-1.19, 0.87+/-1.5, 0.43+/-0.56 vs controls 4.04+/-5.12 mm3). Moreover, a stronger inhibition of metastatic growth was obtained with AdCan-HSA than with AdK1-3-HSA (P=0.04). Median survival was improved by 4 weeks. A close correlation was observed between the effects of these viruses on metastatic growth and their capacity to inhibit tumor angiogenesis. Our study indicates that systemic antiangiogenic factors production by recombinant adenoviruses, particularly Can, might represent an effective way of delaying metastatic growth via inhibition of angiogenesis. PMID:17082795

  17. Legionella suppresses the host unfolded protein response via multiple mechanisms

    Science.gov (United States)

    Treacy-Abarca, Sean; Mukherjee, Shaeri

    2015-01-01

    The intracellular pathogen, Legionella pneumophila, secretes ∼300 effector proteins to modulate the host environment. Given the intimate interaction between L. pneumophila and the endoplasmic reticulum, we investigated the role of the host unfolded protein response (UPR) during L. pneumophila infection. Interestingly, we show that the host identifies L. pneumophila infection as a form of endoplasmic reticulum stress and the sensor pATF6 is processed to generate pATF6(N), a transcriptional activator of downstream UPR genes. However, L. pneumophila is able to suppress the UPR and block the translation of prototypical UPR genes, BiP and CHOP. Furthermore, biochemical studies reveal that L. pneumophila uses two effectors (Lgt1 and Lgt2) to inhibit the splicing of XBP1u mRNA to spliced XBP1 (XBP1s), an UPR response regulator. Thus, we demonstrate that L. pneumophila is able to inhibit the UPR by multiple mechanisms including blocking XBP1u splicing and causing translational repression. This observation highlights the utility of L. pneumophila as a powerful tool for studying a critical protein homeostasis regulator. PMID:26219498

  18. The protective effect of the earthworm active ingredients on hepatocellular injury induced by endoplasmic reticulum stress.

    Science.gov (United States)

    Wang, Qi; Duan, Leng-Xin; Xu, Zheng-Shun; Wang, Jian-Gang; Xi, Shou-Min

    2016-08-01

    The earthworm is a widely used Chinese herbal medicine. There are more than 40 prescriptions including earthworms in the "Compendium of Materia Medica". TCM theory holds that earthworms exert antispasmodic and antipyretic effects through the liver meridian to calm the liver. However, the clinical effect of earthworms on liver injury has not been clearly demonstrated. We have previously established a method to extract the active ingredients from earthworms (hereinafter referred to as EWAs) [1]. In the present study, we observed protective effect of the EWAs on tunicamycin-induced ERS (endoplasmic reticulum stress) model in human hepatic L02 cells. The results showed that the EWAs promote proliferation and reduced apoptosis of ERS model in L02 cells (P<0.01). The up-regulation of ERS-related proteins, including PERK (protein kinase RNA-like endoplasmic reticulum kinase), eIF2a (eukaryotic translation initiation factor 2a), ATF4 (activating transcription factor 4) and CHOP (CCAAT/enhancer binding protein homologous protein), in L02 cell under ERS was inhibited by treatment of the EWAs (P<0.01). In summary, our data suggest the EWAs can significant attenuate ERS-induced hepatocyte injury via PERK-eIF2a-ATF4 pathway. PMID:27470367

  19. Calcium Homeostasis and ER Stress in Control of Autophagy in Cancer Cells

    Directory of Open Access Journals (Sweden)

    Elżbieta Kania

    2015-01-01

    Full Text Available Autophagy is a basic catabolic process, serving as an internal engine during responses to various cellular stresses. As regards cancer, autophagy may play a tumor suppressive role by preserving cellular integrity during tumor development and by possible contribution to cell death. However, autophagy may also exert oncogenic effects by promoting tumor cell survival and preventing cell death, for example, upon anticancer treatment. The major factors influencing autophagy are Ca2+ homeostasis perturbation and starvation. Several Ca2+ channels like voltage-gated T- and L-type channels, IP3 receptors, or CRAC are involved in autophagy regulation. Glucose transporters, mainly from GLUT family, which are often upregulated in cancer, are also prominent targets for autophagy induction. Signals from both Ca2+ perturbations and glucose transport blockage might be integrated at UPR and ER stress activation. Molecular pathways such as IRE 1-JNK-Bcl-2, PERK-eIF2α-ATF4, or ATF6-XBP 1-ATG are related to autophagy induced through ER stress. Moreover ER molecular chaperones such as GRP78/BiP and transcription factors like CHOP participate in regulation of ER stress-mediated autophagy. Autophagy modulation might be promising in anticancer therapies; however, it is a context-dependent matter whether inhibition or activation of autophagy leads to tumor cell death.

  20. A Breast Tissue Protein Expression Profile Contributing to Early Parity-Induced Protection Against Breast Cancer

    Directory of Open Access Journals (Sweden)

    Christina Marie Gutierrez

    2015-11-01

    Full Text Available Background/Aims: Early parity reduces breast cancer risk, whereas, late parity and nulliparity increase breast cancer risk. Despite substantial efforts to understand the protective effects of early parity, the precise molecular circuitry responsible for these changes is not yet fully defined. Methods: Here, we have conducted the first study assessing protein expression profiles in normal breast tissue of healthy early parous, late parous, and nulliparous women. Breast tissue biopsies were obtained from 132 healthy parous and nulliparous volunteers. These samples were subjected to global protein expression profiling and immunohistochemistry. GeneSpring and MetaCore bioinformatics analysis software were used to identify protein expression profiles associated with early parity (low risk versus late/nulliparity (high risk. Results: Early parity reduces expression of key proteins involved in mitogenic signaling pathways in breast tissue through down regulation of EGFR1/3, ESR1, AKT1, ATF, Fos, and SRC. Early parity is also characterized by greater genomic stability and reduced tissue inflammation based on differential expression of aurora kinases, p53, RAD52, BRCA1, MAPKAPK-2, ATF-1, ICAM1, and NF-kappaB compared to late and nulli parity. Conclusions: Early parity reduces basal cell proliferation in breast tissue, which translates to enhanced genomic stability, reduced cellular stress/inflammation, and thus reduced breast cancer risk.