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Sample records for atf-1 torsatron

ATF-1 torsatron studies

International Nuclear Information System (INIS)

Lyon, J.F.; Carreras, B.A.; Charlton, L.A.

1983-01-01

The main advances in the ORNL Stellarator Program since the 1982 IAEA Conference have been: (1) engineering design of the ATF-1 torsatron; (2) extension of 3-D MHD equilibrium and stability studies and calculations of helical axis configurations; (3) study of stable equilibria with greater than or equal to 8% and direct access to the second stability regime; (4) 3-D Monte Carlo and analytic transport calculations which show a large reduction in transport at low collisionality for the absolute value of e phi'/T' greater than or equal to 1; (5) calculation of ambipolar electric fields; and (b) calculation of well confined ion drift surfaces in the ergodic field region outside the last closed flux surface
Overview of results from the ATF torsatron

International Nuclear Information System (INIS)

Colchin, R.J.; Murakami, M.; Anabitarte, E.; Anderson, F.S.B.; Bell, G.L.; Bell, J.D.; Bigelow, T.S.; Crume, E.C.; Dunlap, J.L.; Dyer, G.R.; England, A.C.; Fisher, P.W.; Gabbard, W.A.; Glowienka, J.C.; Goulding, R.H.; Halliwell, J.W.; Hanson, G.R.; Harris, J.H.; Haste, G.R.; Hidalgo-Vera, C.; Hillis, D.L.; Hiroe, S.; Horton, L.D.; Howe, H.C.; Hutchinson, D.P.; Isler, R.C.; Jernigan, T.C.; Kwon, M.; Langley, R.A.; Lee, D.K.; Lyon, J.F.; Lue, J.W.; Ma, C.H.; Menon, M.M.; Morris, R.N.; Mioduszewski, P.K.; Neilson, G.H.; Qualls, A.L.; Rasmussen, D.A.; Rogers, P.S.; Shaw, P.L.; Shepard, T.D.; Simpkins, J.E.; Sudo, S.; Thomas, C.E.; Uckan, T.; Wade, M.R.; Wilgen, J.B.; Wing, W.R.; Yamada, H.; Zielinski, J.J.

1990-01-01

Experiments involving plasma improvement, confinement scaling, bootstrap currents, and edge fluctuations have been carried out in the Advanced Toroidal Facility (ATF) torsatron [Fusion Technol. 10, 179 (1986)]. Average densities bar n e ≤9x10 19 m -3 have been obtained, with global energy confinement times τ * E ≤20 msec. Confinement times generally follow the stellarator/torsatron empirical scaling law, τ SL =0.17xP -0.58 n 0.69 e B 0.84 a 2 R 0.75 (with τ SL in seconds, power P in megawatts, density n e in 10 20 m -3 , and plasma radius a and major radius R in meters). Gas injection during neutral beam injection (NBI) causes increases in n e , so that τ * E does not decrease during NBI. Edge plasma fluctuations are found to exhibit a mode change near the peak of the energy confinement time. Plasma currents observed during electron cyclotron heating have been identified as bootstrap currents
Measurements of flux surfaces in the ATF torsatron

International Nuclear Information System (INIS)

England, A.C.; Colchin, R.J.; Harris, J.H.; Hillis, D.L.; Jernigan, T.C.; Anderson, F.S.B.

1989-01-01

Flux surfaces in the advanced toroidal facility (ATF) torsatron have been measured using electron-beam techniques. The beam was injected toroidally and impinged on a phosphor-coated screen located ∼ 180 degrees from the gun. The gun was mounted on a drive mechanism that enabled the beam to scan the entire cross section of the last closed flux surface in ATF. The screen material was st. steel, coated with ZnO:Zn (P-15 or P-24) phosphor, and the transparency was ∼ 90%. The emitted light was detected with an image-intensified CCD camera that viewed the mesh through a nearby port. The images were displayed directly on a TV monitor and stored on video tape. Frames from the video tape were transferred to a computer, where the image was enhanced and transformed to remove spatial distortions due to the lens and the viewing angle of the camera
Fluctuations and stability in the Advanced Toroidal Facility (ATF) torsatron

International Nuclear Information System (INIS)

Harris, J.H.; Charlton, L.A.; Bell, J.D.; Bigelow, T.S.; Carreras, B.A.; Colchin, R.J.; Crume, E.C.; Dominguez, N.; Dunlap, J.L.; Dyer, G.R.; England, A.C.; Glowienka, J.C.; Hillis, D.L.; Hiroe, S.; Horton, L.D.; Howe, H.C.; Isler, R.C.; Jernigan, T.C.; Leboeuf, J.N.; Lee, D.K.; Lynch, V.E.; Lyon, J.F.; Menon, M.M.; Murakami, M.; Rasmussen, D.A.; Uckan, T.; Wilgen, J.B.; Wing, W.R.; Bell, G.L.; Crocker, N.A.; Hanson, G.R.; Thomas, C.E.; Wade, M.R.; Ritz, C.P.

1990-01-01

We present the results of experimental and theoretical studies of fluctuations and instabilities in the ATF torsatron, a type of stellarator. Measurements of globally coherent magnetic fluctuations in high-β plasmas with narrow pressure profiles produced by a field error show evidence of self-stabilization ('second stability'); the trends are compatible with theoretical analysis of self-stabilization of resistive curvature-driven instabilities, but there are discrepancies between the absolute experimental and theoretical fluctuation amplitudes. Fluctuation measurements in plasma with broad pressure profiles reveal new phenomena--specifically, toroidally localized magnetic fluctuations, whose amplitudes increase with plasma pressure, and coherent density fluctuations with significant radial width
Effects of limiter biasing on the ATF torsatron

International Nuclear Information System (INIS)

Uckan, T.; Baylor, L.R.; Bell, J.D.; Bigelow, T.S.; England, A.C.; Harris, J.H.; Isler, R.C.; Jernigan, T.C.; Lyon, J.F.; Ma, C.H.; Mioduszewski, P.K.; Murakami, M.; Rasmussen, D.A.; Wilgen, J.B.; Aceto, S.C.; Zielinski, J.J.

1992-09-01

Positive limiter biasing on the currentless Advanced Toroidal Facility (ATF) torsatron produces a significant increase in the particle confinement with no improvement in the energy confinement. Experiments have been carried out in 1-T plasmas with ∼400 kill of electron cyclotron heating ECM. Two rail limiters located at the last closed flux surface (LCFS), one at the top and one at the bottom of the device, are biased at positive and negative potentials with respect to the vessel. When the limiters are positively biased at up to 300 V, the density increases sharply to the ECH cutoff value. At the same time, the H α radiation drops, indicating that the particle confinement improves. When the density is kept constant, the H α radiation is further reduced and there is almost no change in the plasma stored energy. Under these conditions, the density profile becomes peaked and the electric field becomes outward-pointing outside the LCFS and more negative inside the LCFS. In contrast, negative biasing yields some reduction of the density and stored energy at constant gas feed, and the plasma potential profile remains the same. Biasing has almost no effect on the intrinsic impurity levels in the plasma
Novel method of aligning ATF-1 coils

International Nuclear Information System (INIS)

Rome, J.A.; Harris, J.H.; Neilson, G.H.; Jernigan, T.C.

1983-08-01

The coils for the Advanced Toroidal Facility (ATF-1) torsatron may be easily aligned before the machine is placed under vacuum. This is done by creating nulls in the magnetic field by energizing the coils in various configurations. All of the nulls in vertical bar B vector vertical bar occur on the z-axis. When the nulls coincide, the coils are properly aligned
Advanced Toroidal Facility (ATF)

International Nuclear Information System (INIS)

Thompson, P.B.

1985-01-01

The Advanced Toroidal Facility (ATF) is a new magnetic plasma confinement device, under construction at Oak Ridge National Laboratory (ORNL), which will lead to improvements in toroidal magnetic fusion reactors. ATF is a type of stellarator known as a torsatron which theoretically has the capability at greater than or equal to8% beta in steady state. The ATF plasma has a major radius of 2.1 m, an average minor radius of 0.3 m, and a field of 2 T for a 5-s duration or 1 T steady state. The ATF device consists of a helical field (HF) coil set, a set of poloidal field (PF) coils, an exterior shell structure to support the coils, and a thin helically contoured vacuum vessel inside the coils. The ATF replaces the ISX-B tokamak at ORNL and will use the ISX-B auxiliary systems including 4 MW of neutral injection heating and 0.2 MW of electron cyclotron heating. ATF device is scheduled to start operation in the fall of 1986. An overview of the ATF device is presented including details of the construction process envisioned
ATFSR: a small torsatron reactor

International Nuclear Information System (INIS)

Houlberg, W.A.; Lacatski, J.T.; Uckan, N.A.

1985-01-01

A small (average minor radius anti a approx. = 1 m), moderate-aspect-ratio torsatron reactor based on the Advanced Toroidal Facility (ATF) is proposed as a starting point for improved stellarator reactor designs. The major limitation of the compact size is the lack of space under the helical coils for the blanket and shield. Neoclassical confinement models for helically trapped particles show that a large electric potential (radial electric field) is necessary to achieve ignition in a device of this size, although high-Q operation is still attainable with more modest potentials
Edge turbulence and transport: Text and ATF modeling

International Nuclear Information System (INIS)

Ritz, C.P.; Rhodes, T.L.; Lin, H.; Rowan, W.L.; Bengtson, R.; Wootton, A.J.; Diamond, P.H.; Ware, A.S.; Thayer, D.R.

1990-01-01

We present experimental results on edge turbulence and transport from the tokamak TEXT and the torsatron ATF. The measured electrostatic fluctuations can explain the edge transport of particles and energy. Certain drive (radiation) and stabilizing (velocity shear) terms are suggested by the results. The experimental fluctuation levels and spectral widths can be reproduced by considering the nonlinear evolution of the reduced MHD equations, incorporating a thermal drive from line radiation. In the tokamak limit (with toroidal electric field) the model corresponds to the resistivity gradient mode, while in the currentless torsatron or stellarator limit it corresponds to a thermally driven drift wave
MHD instabilities in heliotron/torsatron

International Nuclear Information System (INIS)

Wakatani, Masahiro; Nakamura, Yuji; Ichiguchi, Katsuji

1992-01-01

Recent theoretical results on MHD instabilities in heliotron/torsatron are reviewed. By comparing the results with experimental data in Heliotron E, Heliotron DR and ATF, it is pointed out that resistive interchange modes are the most crucial instabilities, since the magnetic hill occupies a substantial region of the plasma column. Development of three-dimensional MHD equilibrium codes has made significant progress. By applying the local stability criteria shown by D 1 (ideal MHD mode) and D R (resistive MHD mode) to the equilibria given by the three-dimensional codes such as BETA and VMEC, stability thresholds for the low n ideal modes or the low n resistive modes may be estimated with resonable accuracy, where n is a toroidal mode number. (orig.)
ATF [Advanced Toroidal Facility]-2 studies

International Nuclear Information System (INIS)

Lyon, J.F.; Carreras, B.A.; Dominguez, N.

1989-10-01

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
Helical magnetic axis configuration combined with l = 1 and weak l = -1 torsatron fields

International Nuclear Information System (INIS)

Kikuchi, Hitoshi; Saito, Katsunori; Gesso, Hirokazu; Shiina, Shoichi

1989-01-01

The superposition of a relatively weak l = -1 torsatron field on a main l = 1 torsatron field leads to the improvement of the confinement properties due to the formation of a local magnetic well, which results from the local curvature of the helical magnetic axis with a larger excursion in the major radius direction. This l±1 helical magnetic axis system has a comparatively simple, compact coil structure. Here the vacuum configuration properties of l = ±1 system are described. (author)
Symmetric modular torsatron

Science.gov (United States)

Rome, J.A.; Harris, J.H.

1984-01-01

A fusion reactor device is provided in which the magnetic fields for plasma confinement in a toroidal configuration is produced by a plurality of symmetrical modular coils arranged to form a symmetric modular torsatron referred to as a symmotron. Each of the identical modular coils is helically deformed and comprise one field period of the torsatron. Helical segments of each coil are connected by means of toroidally directed windbacks which may also provide part of the vertical field required for positioning the plasma. The stray fields of the windback segments may be compensated by toroidal coils. A variety of magnetic confinement flux surface configurations may be produced by proper modulation of the winding pitch of the helical segments of the coils, as in a conventional torsatron, winding the helix on a noncircular cross section and varying the poloidal and radial location of the windbacks and the compensating toroidal ring coils.
Compact torsatron reactors

International Nuclear Information System (INIS)

Lyon, J.F.; Carreras, B.A.; Lynch, V.E.; Tolliver, J.S.; Sviatoslavsky, I.N.

1988-05-01

Low-aspect-ratio torsatron configurations could lead to compact stellarator reactors with R 0 = 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 (R 0 ≅ 4 m,/bar a/ /approx lt/ 1 m) copper-coil ignition experiment. 26 refs., 11 figs., 7 tabs
Experimental studies on the Auburn Torsatron: Annual progress report

International Nuclear Information System (INIS)

Gandy, R.F.; Swanson, D.G.

1988-10-01

This paper discusses research programs in progress on the Auburn Torsatron. Topic areas covered are: ICR heating results; Compact Auburn Torsatron design; Compact Auburn Torsatron construction; and collaborations
Initial high-power testing of the ATF [Advanced Toroidal Facility] ECH [electron cyclotron heating] system

International Nuclear Information System (INIS)

White, T.L.; Bigelow, T.S.; Kimrey, H.D. Jr.

1987-01-01

The Advanced Toroidal Facility (ATF) is a moderate aspect ratio torsatron that will utilize 53.2 GHz 200 kW Electron Cyclotron Heating (ECH) to produce nearly current-free target plasmas suitable for subsequent heating by strong neutral beam injection. The initial configuration of the ECH system from the gyrotron to ATF consists of an optical arc detector, three bellows, a waveguide mode analyzer, two TiO 2 mode absorbers, two 90 0 miter bends, two waveguide pumpouts, an insulating break, a gate valve, and miscellaneous straight waveguide sections feeding a launcher radiating in the TE 02 mode. Later, a focusing Vlasov launcher will be added to beam the ECH power to the saddle point in ATF magnetic geometry for optimum power deposition. The ECH system has several unique features; namely, the entire ECH system is evacuated, the ECH system is broadband, forward power is monitored by a newly developed waveguide mode analyzer, phase correcting miter bends will be employed, and the ECH system will be capable of operating short pulse to cw. Initial high-power tests show that the overall system efficiency is 87%. The waveguide mode analyzer shows that the gyrotron mode output consists of 13% TE 01 , 82.6% TE 02 , 2.5% TE 03 , and 1.9% TE 04 . 4 refs
Neoclassical transport in a multiple-helicity torsatron in the low-collisionality (1/#betta#) regime

International Nuclear Information System (INIS)

Shaing, K.C.; Hokin, S.A.

1983-02-01

For a sufficiently high number of field periods (m/iota > l), the magnetic field of a multiple helicity torsatron can be reduced to a simple form such that the second adiabatic invariant J can be calculated. It is found that the particle and the heat fluxes for a multiple helicity torsatron in the low collisionality (1/#betta#) regime have the same geometric dependences. An optimization of both quantities is carried out for a given equilibrium constraint. It is shown that the transport fluxes can be smaller than those of the conventional stellarator by an order of magnitude. The effect of finite plasma beta on the neoclassical fluxes is also studied
Evaluation of Torsatrons as reactors

International Nuclear Information System (INIS)

Lyon, J.F.; Gulec, K.; Miller, R.L.; El-Guebaly, L.

1994-03-01

Stellarators have significant operational advantages over tokamaks as ignited steady-state reactors. This scoping study, which uses an integrated cost-minimization code that incorporates costing and reactor component models self-consistently with a 1-D energy transport calculation, shows that a torsatron reactor could also be economically competitive with a tokamak reactor. The projected cost of electricity (COE) estimated using the Advanced Reactor Innovation and Evaluation Studies (ARIES) costing algorithms is 65.6 mill/kW(e)h in constant 1992 dollars for a reference 1-GW(e) Compact Torsatron reactor case. The COE is relatively insensitive (<10% variation) over a wide range of assumptions, including variations in the maximum field allowed on the coils, the coil elongation, the shape of the density profile, the beta limit, the confinement multiplier, and the presence of a large loss region for alpha particles. The largest variations in the COE occur for variations in the electrical power output demanded and the plasma-coil separation ratio
High-mode-number ballooning modes in a heliotron/torsatron system: 1, Local magnetic shear

International Nuclear Information System (INIS)

Nakajima, N.

1996-05-01

The characteristics of the local magnetic shear, a quantity associated with high-mode-number ballooning mode stability, are considered in heliotron/torsatron devices that have a large Shafranov shift. The local magnetic shear is shown to vanish even in the stellarator-like region in which the global magnetic shear is positive. The reason for this is that the degree of the local compression of the poloidal magnetic field on the outer side of the torus, which maintains the toroidal force balance, is reduced in the stellarator-like region of global magnetic shear because the global rotational transform in heliotron/torsatron systems is a radially increasing function. This vanishing of the local magnetic shear is a universal property in heliotron/torsatron systems with a large Shafranov shift since it results from toroidal force balance in the stellarator-like global shear regime that is inherent to such systems
Assessment of torsatrons as reactors

International Nuclear Information System (INIS)

Lyon, J.F.; Painter, S.L.

1992-12-01

Stellarators have significant operational advantages over tokamaks as ignited steady-state reactors because stellarators have no dangerous disruptions and no need for continuous current drive or power recirculated to the plasma, both easing the first wall, blanket, and shield design; less severe constraints on the plasma parameters and profiles; and better access for maintenance. This study shows that a reactor based on the torsatron configuration (a stellarator variant) could also have up to double the mass utilization efficiency (MUE) and a significantly lower cost of electricity (COE) than a conventional tokamak reactor (ARIES-I) for a range of assumptions. Torsatron reactors can have much smaller coil systems than tokamak reactors because the coils are closer to the plasma and they have a smaller cross section (higher average current density because of the lower magnetic field). The reactor optimization approach and the costing and component models are those used in the current stage of the ARIES-I tokamak reactor study. Typical reactor parameters for a 1-GW(e) Compact Torsatron reactor example are major radius R 0 = 6.6-8.8 m, on-axis magnetic field B 0 = 4.8-7.5 T, B max (on coils) = 16 T, MUE 140-210 kW(e)/tonne, and COE (in constant 1990 dollars) = 67-79 mill/kW(e)h. The results are relatively sensitive to assumptions on the level of confinement improvement and the blanket thickness under the inboard half of the helical windings but relatively insensitive to other assumptions

ATF3 inhibits adipocyte differentiation of 3T3-L1 cells

International Nuclear Information System (INIS)

Jang, Min Kyung; Kim, Cho Hee; Seong, Je Kyung; Jung, Myeong Ho

2012-01-01

Highlights: ► Overexpression of ATF3 inhibits adipocyte differentiation in 3T3-L1 cells. ► Overexpression of ATF3 represses C/EBPα expression. ► ATF3 directly binds to mouse C/EBPα promoter spanning from −1928 to −1907. ► ATF3 may play a role in hypoxia-mediated inhibition of adipocyte differentiation. -- Abstract: ATF3 is a stress-adaptive gene that regulates proliferation or apoptosis under stress conditions. However, the role of ATF3 is unknown in adipocyte cells. Therefore, in this study, we investigated the functional role of ATF3 in adipocytes. Both lentivirus-mediated overexpression of ATF3 and stably-overexpressed ATF3 inhibited adipocyte differentiation in 3T3-L1 cells, as revealed by decreased lipid staining with oil red staining and reduction in adipogenic genes. Thapsigargin treatment and overexpression of ATF3 decreased C/EBPα transcript and repressed the activity of the 3.6-kb mouse C/EBPα promoter, demonstrating that ATF3 downregulates C/EBPα expression. Transfection studies using mutant constructs containing 5′-deletions in the C/EBPα promoter revealed that a putative ATF/CRE element, GGATGTCA, is located between −1921 and −1914. Electrophoretic mobility shift assay and chromatin immunoprecipitation assay demonstrated that ATF3 directly binds to mouse C/EBPα promoter spanning from −1928 to −1907. Both chemical hypoxia-mimetics or physical hypoxia led to reduce the C/EBPα mRNA and repress the promoter activity of the C/EBPα gene, whereas increase ATF3 mRNA, suggesting that ATF3 may contribute to the inhibition of adipocyte differentiation in hypoxia through downregulation of C/EBPα expression. Collectively, these results demonstrate that ATF3 represses the C/EBPα gene, resulting in inhibition of adipocyte differentiation, and thus plays a role in hypoxia-mediated inhibition of adipocyte differentiation.
TOREX-4: a torsatron proof of principle experiment

International Nuclear Information System (INIS)

Politzer, P.A.; Lidsky, L.M.; Montgomery, D.B.

1979-03-01

TOREX-4 is a torsatron Proof of Principle experiment designed to simultaneously achieve ntau approx. = to 5 x 10 13 , n approx. = to 5 x 10 14 /cm 3 , 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
Magnetic surfaces, particle orbits and neutral injection in conventional and ultimate torsatrons

International Nuclear Information System (INIS)

Anderson, D.T.; Derr, J.A.; Kruckewitt, T.; Shohet, J.L.; Rehker, S.; Tataronis, J.A.

1979-01-01

Capabilities in fully non-axisymmetric numerical methods have resulted in a parametric study of various conventional and ultimate torsatron configurations. No superbananas are found in torsatrons without local magnetic wells. Neutral injection calculations show that, if the vacuum magnetic surfaces are well defined, tangential injection is very efficient
Wisconsin torsatron/stellarator program, FY 1989

International Nuclear Information System (INIS)

Shohet, J.L.; Anderson, D.T.; Anderson, F.S.B.; Talmadge, J.N.

1988-07-01

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
Equipotential surfaces in the Proto-Cleo Torsatron

International Nuclear Information System (INIS)

Trost, P.K.; Shohet, J.L.

1986-01-01

Plasma potential measurements are made in electron cyclotron resonance plasmas in the Proto-Cleo Torsatron with an emissive probe. Plots of equipotential surfaces are presented and compared with the numerical calculated vacuum magnetic surfaces
Proceedings of US-Japan heliotron-stellarator workshop: Volume 4

International Nuclear Information System (INIS)

1987-01-01

This paper is the fourth of four volumes on the US-Japan Heliotron-Stellarator workshop. It contains talks on the following: Compact torsatron studies; Low aspect ratio torsatron design; Optimized small stellarator designs; Currents in ATF; Computations of 3-D equilibria with islands; and Magnetic surface mapping studies
Deciphering the role of the signal- and Sty1 kinase-dependent phosphorylation of the stress-responsive transcription factor Atf1 on gene activation.

Science.gov (United States)

Salat-Canela, Clàudia; Paulo, Esther; Sánchez-Mir, Laura; Carmona, Mercè; Ayté, José; Oliva, Baldo; Hidalgo, Elena

2017-08-18

Adaptation to stress triggers the most dramatic shift in gene expression in fission yeast ( Schizosaccharomyces pombe ), and this response is driven by signaling via the MAPK Sty1. Upon activation, Sty1 accumulates in the nucleus and stimulates expression of hundreds of genes via the nuclear transcription factor Atf1, including expression of atf1 itself. However, the role of stress-induced, Sty1-mediated Atf1 phosphorylation in transcriptional activation is unclear. To this end, we expressed Atf1 phosphorylation mutants from a constitutive promoter to uncouple Atf1 activity from endogenous, stress-activated Atf1 expression. We found that cells expressing a nonphosphorylatable Atf1 variant are sensitive to oxidative stress because of impaired transcription of a subset of stress genes whose expression is also controlled by another transcription factor, Pap1. Furthermore, cells expressing a phospho-mimicking Atf1 mutant display enhanced stress resistance, and although expression of the Pap1-dependent genes still relied on stress induction, another subset of stress-responsive genes was constitutively expressed in these cells. We also observed that, in cells expressing the phospho-mimicking Atf1 mutant, the presence of Sty1 was completely dispensable, with all stress defects of Sty1-deficient cells being suppressed by expression of the Atf1 mutant. We further demonstrated that Sty1-mediated Atf1 phosphorylation does not stimulate binding of Atf1 to DNA but, rather, establishes a platform of interactions with the basal transcriptional machinery to facilitate transcription initiation. In summary, our results provide evidence that Atf1 phosphorylation by the MAPK Sty1 is required for oxidative stress responses in fission yeast cells by promoting transcription initiation. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
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...
ATF2 Commissioning

Energy Technology Data Exchange (ETDEWEB)

Seryi, A.; /SLAC; Christian, G.; /KLTE-ATOMKI; Parker, B.; /BNL; Schulte, D.; Delahaye, J.-P.; Tomas, R.; Zimmermann, F.; /CERN; Wolski, A.; Elsen, E.; /Cockcroft Inst. /DESY; Sanuki, T.; /Tohoku U.; Gianfelice-Wendt, E.; Ross, M.; Wendt, M.; /Fermilab; Takahashi, T.; /Hiroshima U.; Bai, S.; Gao, J.; /Beijing, Inst. High Energy Phys.; Bolzon, B.; Geffroy, N.; Jeremie, A.; /Annecy, LAPP; Apsimon, R.; Burrows, P.; /Oxford U., JAI /Kyoto U., Inst. Chem. Res. /Kyungpook Natl. U. /Orsay, LAL /Phang Accelerator Lab /Royal Holloway, U. of London /SLAC /Daresbury /University Coll. London /Manchester U. /Univ. of Tokyo U.

2009-10-30

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.
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.
Analysis list: Atf4 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Atf4 Blood,Embryonic fibroblast,Epidermis + mm9 http://dbarchive.biosciencedbc.jp/k...yushu-u/mm9/target/Atf4.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Atf4.5.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/target/Atf4.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Atf...4.Blood.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Atf4.Embryonic_fi...broblast.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Atf4.Epidermis.tsv http://dbarchive.bioscience
Experimental studies on the Auburn Torsatron: Progress report

International Nuclear Information System (INIS)

Gandy, R.F.; Swanson, D.G.

1987-10-01

Progress on the Auburn Torsatron is discussed in this report. In particular, experiments are described dealing with methods of surface mapping the magnetic configuration, plasma confinement studies, ion cyclotron heating and modification to the device
Construction and initial operation of the Advanced Toroidal Facility

International Nuclear Information System (INIS)

Bell, G.L.; Bell, J.D.; Benson, R.D.

1989-08-01

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
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
Saccharomyces cerevisiae Atf1p is an alcohol acetyltransferase and a thioesterase in vitro.

Science.gov (United States)

Nancolas, Bethany; Bull, Ian D; Stenner, Richard; Dufour, Virginie; Curnow, Paul

2017-06-01

The alcohol-O-acyltransferases are bisubstrate enzymes that catalyse the transfer of acyl chains from an acyl-coenzyme A (CoA) donor to an acceptor alcohol. In the industrial yeast Saccharomyces cerevisiae this reaction produces acyl esters that are an important influence on the flavour of fermented beverages and foods. There is also a growing interest in using acyltransferases to produce bulk quantities of acyl esters in engineered microbial cell factories. However, the structure and function of the alcohol-O-acyltransferases remain only partly understood. Here, we recombinantly express, purify and characterize Atf1p, the major alcohol acetyltransferase from S. cerevisiae. We find that Atf1p is promiscuous with regard to the alcohol cosubstrate but that the acyltransfer activity is specific for acetyl-CoA. Additionally, we find that Atf1p is an efficient thioesterase in vitro with specificity towards medium-chain-length acyl-CoAs. Unexpectedly, we also find that mutating the supposed catalytic histidine (H191) within the conserved HXXXDG active site motif only moderately reduces the thioesterase activity of Atf1p. Our results imply a role for Atf1p in CoA homeostasis and suggest that engineering Atf1p to reduce the thioesterase activity could improve product yields of acetate esters from cellular factories. © 2017 The Authors. Yeast published by John Wiley & Sons, Ltd. © 2017 The Authors. Yeast published by John Wiley & Sons, Ltd.
ATF1 Modulates the Heat Shock Response by Regulating the Stress-Inducible Heat Shock Factor 1 Transcription Complex

Science.gov (United States)

Takii, Ryosuke; Fujimoto, Mitsuaki; Tan, Ke; Takaki, Eiichi; Hayashida, Naoki; Nakato, Ryuichiro; Shirahige, Katsuhiko

2014-01-01

The heat shock response is an evolutionally conserved adaptive response to high temperatures that controls proteostasis capacity and is regulated mainly by an ancient heat shock factor (HSF). However, the regulation of target genes by the stress-inducible HSF1 transcription complex has not yet been examined in detail in mammalian cells. In the present study, we demonstrated that HSF1 interacted with members of the ATF1/CREB family involved in metabolic homeostasis and recruited them on the HSP70 promoter in response to heat shock. The HSF1 transcription complex, including the chromatin-remodeling factor BRG1 and lysine acetyltransferases p300 and CREB-binding protein (CBP), was formed in a manner that was dependent on the phosphorylation of ATF1. ATF1-BRG1 promoted the establishment of an active chromatin state and HSP70 expression during heat shock, whereas ATF1-p300/CBP accelerated the shutdown of HSF1 DNA-binding activity during recovery from acute stress, possibly through the acetylation of HSF1. Furthermore, ATF1 markedly affected the resistance to heat shock. These results revealed the unanticipated complexity of the primitive heat shock response mechanism, which is connected to metabolic adaptation. PMID:25312646
Chondrocytic Atf4 regulates osteoblast differentiation and function via Ihh.

Science.gov (United States)

Wang, Weiguang; Lian, Na; Ma, Yun; Li, Lingzhen; Gallant, Richard C; Elefteriou, Florent; Yang, Xiangli

2012-02-01

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 osteogenesis during development and bone remodeling postnatally. Atf4 overexpression in chondrocytes of the Atf4(-/-);Col2a1-Atf4 double mutants corrects the reduction in stature and limb in Atf4(-/-) embryos and rectifies the decrease in Ihh expression, Hh signaling, proliferation and accelerated hypertrophy that characterize the Atf4(-/-) developing growth plate cartilages. Unexpectedly, this genetic manipulation also restores the expression of osteoblastic marker genes, namely Ocn and bone sialoprotein, in Atf4(-/-) developing bones. In Atf4(-/-);Col2a1-Atf4 adult mice, all the defective bone parameters found in Atf4(-/-) mice, including bone volume, trabecular number and thickness, and bone formation rate, are rescued. In addition, the conditioned media of ex vivo cultures from wild-type or Atf4(-/-);Col2a1-Atf4, but not Atf4(-/-) cartilage, corrects the differentiation defects of Atf4(-/-) bone marrow stromal cells and Ihh-blocking antibody eliminates this effect. Together, these data indicate that Atf4 in chondrocytes is required for normal Ihh expression and for its paracrine effect on osteoblast differentiation. Therefore, the cell-autonomous role of Atf4 in chondrocytes dominates the role of Atf4 in osteoblasts during development for the control of early osteogenesis and skeletal growth.
Analysis list: Atf3 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Atf3 Blood,Pancreas + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Atf3.1.tsv http:...//dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Atf3.5.tsv http://dbarchive.biosciencedbc.jp/k...yushu-u/mm9/target/Atf3.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Atf3.Blood.tsv,http://dba...rchive.biosciencedbc.jp/kyushu-u/mm9/colo/Atf3.Pancreas.tsv http://dbarchive.bios...ciencedbc.jp/kyushu-u/mm9/colo/Blood.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Pancreas.gml ...
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/ATF...4.1.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.bioscience...dbc.jp/kyushu-u/hg19/colo/ATF4.Others.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/Blood.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/Others.gml ...
Structural design and analysis for the ISX-C/ATF tokamak of the vacuum vessel, coil joints, and supports

International Nuclear Information System (INIS)

Mayhall, J.A.; Cain, W.D.; Hammonds, C.J.; Johnson, R.L.; Gray, W.H.

1981-01-01

The ISX-C/ATF is being designed as a test bed for advanced toroidal concepts. Because of numerous design concepts being evaluated, a flexible, easily changeable structural-design math-model was needed to afford quick evalution of the structural feasibility of the many proposed concepts. To satisfy this need, the NASTRAN Automated Multi-Stage Substructures technique was used to build a quick-changeable math model. This technique was especially needed because all the coils, first wall and diagnostic devices are to be supported by the vacuum vessel, requiring the entire structure to be analyzed as a system. Without the use of the substructuring technique, the required man hours and computer core would have made timely design analysis impossible. To illustrate the technique, the detailed design analysis of the concept Torsatron (with helical coils and T.F. coils) is presented

Isoproterenol Increases RANKL Expression in a ATF4/NFATc1-Dependent Manner in Mouse Osteoblastic Cells

Directory of Open Access Journals (Sweden)

Kyunghwa Baek

2017-10-01

Full Text Available Sympathetic nervous system stimulation-induced β-adrenergic signal transduction is known to induce bone loss and increase of osteoclast activity. Although isoproterenol, a nonspecific β-adrenergic receptor agonist, has been shown to increase receptor activator of NF-κB ligand (RANKL, the details of the regulatory mechanisms remain unclear. In the present study, we investigated the role of the nuclear factor of activated T-cells (NFAT in isoproterenol-induced RANKL expression in C2C12 and in primary cultured mouse calvarial cells. Isoproterenol increased nuclear factor of activated T-cells cytoplasmic 1 (NFATc1 and RANKL expressions at both mRNA and protein levels and increased NFAT reporter activity. NFATc1 knockdown blocked isoproterenol-mediated RANKL expression. Isoproterenol also promoted cAMP response element-binding protein 1 (CREB1 and activating transcription factor 4 (ATF4 phosphorylation. Isoproterenol-mediated transcriptional activation of NFAT was blocked by protein kinase A (PKA inhibitor H89. Isoproterenol-induced CREB1, ATF4, NFATc1, and RANKL expressions were suppressed by H89. Mutations in cAMP response element-like or NFAT-binding element suppressed isoproterenol-induced RANKL promoter activity. Chromatin immunoprecipitation analysis demonstrated that isoproterenol increased NFAT-binding and ATF4-binding activities on the mouse RANKL promoter, but did not increase CREB1-binding activity. Association of NFATc1 and ATF4 was not observed in a co-immunoprecipitation study. ATF4 knockdown suppressed isoproterenol-induced NFAT binding to the RANKL promoter, whereas NFATc1 knockdown did not suppress isoproterenol-induced ATF4 binding to the RANKL promoter. ATF4 knockdown suppressed isoproterenol-induced expressions of NFATc1 and RANKL. These results suggest that isoproterenol increases RANKL expression in an ATF4/NFATc1-dependent manner.
ATF3, an HTLV-1 bZip factor binding protein, promotes proliferation of adult T-cell leukemia cells

Directory of Open Access Journals (Sweden)

Ohshima Koichi

2011-03-01

Full Text Available Abstract Background Adult T-cell leukemia (ATL is an aggressive malignancy of CD4+ T-cells caused by human T-cell leukemia virus type 1 (HTLV-1. The HTLV-1 bZIP factor (HBZ gene, which is encoded by the minus strand of the viral genome, is expressed as an antisense transcript in all ATL cases. By using yeast two-hybrid screening, we identified activating transcription factor 3 (ATF3 as an HBZ-interacting protein. ATF3 has been reported to be expressed in ATL cells, but its biological significance is not known. Results Immunoprecipitation analysis confirmed that ATF3 interacts with HBZ. Expression of ATF3 was upregulated in ATL cell lines and fresh ATL cases. Reporter assay revealed that ATF3 could interfere with the HTLV-1 Tax's transactivation of the 5' proviral long terminal repeat (LTR, doing so by affecting the ATF/CRE site, as well as HBZ. Suppressing ATF3 expression inhibited proliferation and strongly reduced the viability of ATL cells. As mechanisms of growth-promoting activity of ATF3, comparative expression profiling of ATF3 knockdown cells identified candidate genes that are critical for the cell cycle and cell death, including cell division cycle 2 (CDC2 and cyclin E2. ATF3 also enhanced p53 transcriptional activity, but this activity was suppressed by HBZ. Conclusions Thus, ATF3 expression has positive and negative effects on the proliferation and survival of ATL cells. HBZ impedes its negative effects, leaving ATF3 to promote proliferation of ATL cells via mechanisms including upregulation of CDC2 and cyclin E2. Both HBZ and ATF3 suppress Tax expression, which enables infected cells to escape the host immune system.
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.
ATF edge plasma turbulence studies using a fast reciprocating Langmuir probe

International Nuclear Information System (INIS)

Uckan, T.; Hidalgo, C.; Bell, J.D.; Harris, J.H.; Dunlap, J.L.; Dyer, G.R.; Mioduszewski, P.K.; Wilgen, J.B.; Ritz, C.P.; Wootton, A.J.; Rhodes, T.L.; Carter, K.

1991-01-01

Electrostatic turbulence on the edge of the Advanced Toroidal Facility (ATF) torsatron is investigated experimentally with a fast reciprocating Langmuir probe (FRLP) array. Initial measurements of plasma electron density n e and temperature T e and fluctuations in density (n e ) and plasma floating potential (φ f ) are made in electron cyclotron heated plasmas at 1 T. At the last closed flux surface (LCFS, r√a ∼ 1), T e ∼ 20--40 eV and n e ∼ 10 12 cm -3 for a line-averaged electron density bar n e = (3--6) x 10 12 cm -3 . Relative fluctuation levels, as the FRLP is moved into core plasma where T e > 20 eV, are n e /n e ∼ 5% and eφ f /T e ∼ 2n e /n e about 2 cm inside the LCFS. The observed fluctuation spectra are broadband (40--300 kHz) with bar kρ s ≤ 0.1, where bar k is the wavenumber of the fluctuations and ρ s is the ion Larmor radius at the sound speed. The propagation direction of the fluctuations reverses to the electron diamagnetic direction around r√a ph ∼ v de ). The fluctuation-induced particle flux is comparable to fluxes estimated from the particle balance using the H α spectroscopic measurements. Many of the features seen in these experiments resemble the features of ohmically heated plasmas in the Texas Experimental Tokamak (TEXT). 18 refs., 10 figs
RF plasma production and heating below ion-cyclotron frequencies in Uragan torsatrons

International Nuclear Information System (INIS)

Moiseenko, V.E.; Berezhnyj, V.L.; Bondarenko, V.N.; Burchenko, P.Ya.; Chechkin, V.V.; Chernyshenko, V.Ya.; Dreval, M.B.; Garkusha, I.E.; Glazunov, G.P.; Grigor'eva, L.I.; Konovalov, V.G.; Kotsubanov, V.D.; Kramskoi, Ye.D.; Kulaga, A.E.; Lozin, A.V.; Castejon, F.; Hidalgo, C.; Hartmann, D.; Koch, R.; Lyssoivan, A.I.

2011-01-01

In the IPP-Kharkiv there are two torsatrons (stellarators) in operation, and in both of them Alfven resonance heating under high-k || conditions is used. This method of heating is advantageous for small-size devices, since in contrast to the minority and second-harmonic heating it can be realized at lower plasma densities. A series of experiments has been performed at the Uragan-3M torsatron with an aim to investigate the features of the discharge with a three-half-turn antenna. Electron temperatures in the T-bar = 0.2-0.5 keV range are achieved at plasma densities n-bar e approx. (0.5-1.5) x 10 13 cm -3 . The plasma energy content has increased by a factor of 2 with respect to the plasma produced with the frame antenna. A new four-strap shielded antenna has been manufactured and installed in the Uragan-2M. A high-frequency discharge for wall conditioning is introduced in the Uragan-2M torsatron. The discharge is sustained by a specially designed small frame antenna, and efficient hydrogen dissociation is achieved. A self-consistent model has been developed for simulation of plasma production in ICRF. The model includes a set of particle and energy-balance equations for the electrons, and the boundary problem for the Maxwell equations. The first calculation results on RF plasma production in the Uragan-2M stellarator with the frame-type antenna are presented.
Investigation of a washer-stack plasma gun on the Auburn torsatron

International Nuclear Information System (INIS)

Austin, M.E. Jr.

1986-01-01

A pulsed device for producing a highly-ionized plasma in the Auburn Torsatron is described and construction details given. A plasma is formed by discharging a 14 uF capacitor charged to 6 to 12 kV through a titanium washer impregnated with hydrogen. The ions and electrons are injected transversely into the Torsatron confinement field and the plasma is studied with an x-band microwave interferometer and H-alpha spectral-line detectors. The results of initial measurements to determine the optimal performance parameters for the gun, such as discharge voltage and position, are presented. Also, peak electron density and decay time of the guns plasma are given for different machine and souce conditions
ATF1 and RAS in exosomes are potential clinical diagnostic markers for cervical cancer.

Science.gov (United States)

Shi, Yanhua; Wang, Wei; Yang, Baozhi; Tian, Hongge

2017-10-01

Cervical cancer is one of the most common cancers among women worldwide. It is highly lethal yet can be treated when found in early stage. Thus, early detection is of significant important for early diagnosis of cervical cancer. Exosomes have been used as biomarkers in clinical diagnosis. It is unknown that whether blood exosomes associated with cervical cancer can be detected and if these exosomes can accurately represent the developmental stage of cervical cancer. Mouse models were made out of a relapsed cervical cancer patient's tumour sample for original and recurrent cervical cancer, and gene analysis in both tumours and exosomes in these mouse models were performed. We found that activating transcription factor 1 (ATF1) and RAS genes were significantly up-regulated in tumours of both primary and recurrent cervical cancer mouse model, and they can also be detected in the blood exosomes of the mouse model. Our results indicated that ATF1 and RAS could be potential candidate biomarkers for cervical cancer in early diagnosis. ATF1 and RAS genes were found significantly elevated in tumours of primary and recurrent cervical cancer mouse model, and they were also detected in the blood exosomes. Therefore, ATF1 and RAS could be used as a diagnostic marker for cervical cancer in the future. Copyright © 2017 John Wiley & Sons, Ltd.
ATF data management

International Nuclear Information System (INIS)

Kannan, K.L.; Baylor, L.R.

1988-01-01

Data management for the Advanced Toroidal Facility (ATF), a stellarator located at Oak Ridge National Laboratory, is provided by DMG, a locally developed, VAX-based software system. DMG is a data storage and retrieval software system that provides the user interface to ATF raw and analyzed data. Data are described in terms of data models and data types and are organized as signals into files, which are internally documented. The system was designed with user accessibility, software maintainability, and extensibility as primary goals. Extensibility features include compatibility with ATF as it moves from pulsed to steady-state operation and capability for use of the DMG system with experiments other than ATF. DMG is implemented as a run-time library of routines available as a shareable image. General-purpose and specialized data acquisition and analysis applications have been developed using the DMG system. This article describes the DMG system and the interfaces to it
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.
ATF [Advanced Toroidal Facility] edge plasma turbulence studies using a fast reciprocating Langmuir probe

International Nuclear Information System (INIS)

Uckan, T.; Hidalgo, C.; Bell, J.D.; Harris, J.H.; Dunlap, J.L.; Dyer, G.R.; Mioduszewski, P.K.; Wilgen, J.B.; Ritz, C.P.; Wootton, A.J.; Rhodes, T.L.; Carter, K.

1990-01-01

Electrostatic turbulence on the edge of the Advanced Torodial Facility (ATF) torsatron is investigated experimentally with a fast reciprocating Langmuir probe (FRLP) array. Initial measurements of plasma electron density n e and temperature T e and fluctuations in density (n e ) and plasma floating potential (φ f ) are made in ECH plasmas at 1 T. At the last closed flux surface (LCFS, r/bar a ∼1), T e ∼ 20--40 eV and n e ∼ 10 12 cm -3 for a line-averaged electron density bar n e = (3--6) x 10 12 cm -3 . Relative fluctuation levels, as the FRLP is moved into core plasma where T e > 20 eV, are n e /n e ∼ 5%, and e φ f /T e ∼ 2n e /n e about 2 cm inside the LCFS. The observed fluctuation spectra are broadband (40--300 kHz) with bar kρ s ≤ 0.1, where bar k is the wavenumber of the fluctuations and ρ s is the ion Larmor radius at the sound speed. The propagation direction of the fluctuations reverses to the electron diamagnetic direction around r/bar a ph ∼ v de ). The fluctuation-induced particle flux is comparable to fluxes estimated from the particle balance using the H α spectroscopic measurements. Many of the features seen in these experiments resemble the features of ohmically heated plasmas in the Texas Experimental Tokamak (TEXT). 17 refs., 10 figs
VEGF-A isoforms differentially regulate ATF-2-dependent VCAM-1 gene expression and endothelial-leukocyte interactions.

Science.gov (United States)

Fearnley, Gareth W; Odell, Adam F; Latham, Antony M; Mughal, Nadeem A; Bruns, Alexander F; Burgoyne, Nicholas J; Homer-Vanniasinkam, Shervanthi; Zachary, Ian C; Hollstein, Monica C; Wheatcroft, Stephen B; Ponnambalam, Sreenivasan

2014-08-15

Vascular endothelial growth factor A (VEGF-A) regulates many aspects of vascular physiology. VEGF-A stimulates signal transduction pathways that modulate endothelial outputs such as cell migration, proliferation, tubulogenesis, and cell-cell interactions. Multiple VEGF-A isoforms exist, but the biological significance of this is unclear. Here we analyzed VEGF-A isoform-specific stimulation of VCAM-1 gene expression, which controls endothelial-leukocyte interactions, and show that this is dependent on both ERK1/2 and activating transcription factor-2 (ATF-2). VEGF-A isoforms showed differential ERK1/2 and p38 MAPK phosphorylation kinetics. A key feature of VEGF-A isoform-specific ERK1/2 activation and nuclear translocation was increased phosphorylation of ATF-2 on threonine residue 71 (T71). Using reverse genetics, we showed ATF-2 to be functionally required for VEGF-A-stimulated endothelial VCAM-1 gene expression. ATF-2 knockdown blocked VEGF-A-stimulated VCAM-1 expression and endothelial-leukocyte interactions. ATF-2 was also required for other endothelial cell outputs, such as cell migration and tubulogenesis. In contrast, VCAM-1 was essential only for promoting endothelial-leukocyte interactions. This work presents a new paradigm for understanding how soluble growth factor isoforms program complex cellular outputs and responses by modulating signal transduction pathways. © 2014 Fearnley et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
The transcription factor ATF3 is upregulated during chondrocyte differentiation and represses cyclin D1 and A gene transcription

Directory of Open Access Journals (Sweden)

James Claudine G

2006-09-01

Full Text Available Abstract Background Coordinated chondrocyte proliferation and differentiation are required for normal endochondral bone growth. Transcription factors binding to the cyclicAMP response element (CRE are known to regulate these processes. One member of this family, Activating Tanscription Factor 3 (ATF3, is expressed during skeletogenesis and acts as a transcriptional repressor, but the function of this protein in chondrogenesis is unknown. Results Here we demonstrate that Atf3 mRNA levels increase during mouse chondrocyte differentiation in vitro and in vivo. In addition, Atf3 mRNA levels are increased in response to cytochalasin D treatment, an inducer of chondrocyte maturation. This is accompanied by increased Atf3 promoter activity in cytochalasin D-treated chondrocytes. We had shown earlier that transcription of the cell cycle genes cyclin D1 and cyclin A in chondrocytes is dependent on CREs. Here we demonstrate that overexpression of ATF3 in primary mouse chondrocytes results in reduced transcription of both genes, as well as decreased activity of a CRE reporter plasmid. Repression of cyclin A transcription by ATF3 required the CRE in the cyclin A promoter. In parallel, ATF3 overexpression reduces the activity of a SOX9-dependent promoter and increases the activity of a RUNX2-dependent promoter. Conclusion Our data suggest that transcriptional induction of the Atf3 gene in maturing chondrocytes results in down-regulation of cyclin D1 and cyclin A expression as well as activation of RUNX2-dependent transcription. Therefore, ATF3 induction appears to facilitate cell cycle exit and terminal differentiation of chondrocytes.
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.
A superconducting magnet upgrade of the ATF2 final focus

CERN Document Server

Parker, B; Escallier, J; He, P; Jain, P; Marone, A; Wanderer, P; Wu, KC; 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; Bambade, P; Coe, P; Urner, D; Seryi, A; Spencer, C; White, G

2010-01-01

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 [1]. But the ATF2 FF uses water cooled magnets and the ILC baseline has a superconducting (SC) FF [2]. 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 [3]. 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 [4]. 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 perfo...
Ripple transport in helical-axis advanced stellarators - a comparison with classical stellarator/torsatrons

International Nuclear Information System (INIS)

Beidler, C.D.; Hitchon, W.N.G.

1993-08-01

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.)
mTORC1 Balances Cellular Amino Acid Supply with Demand for Protein Synthesis through Post-transcriptional Control of ATF4

Directory of Open Access Journals (Sweden)

Yeonwoo Park

2017-05-01

Full Text Available The mammalian target of rapamycin complex 1 (mTORC1 is a master regulator of cell growth that is commonly deregulated in human diseases. Here we find that mTORC1 controls a transcriptional program encoding amino acid transporters and metabolic enzymes through a mechanism also used to regulate protein synthesis. Bioinformatic analysis of mTORC1-responsive mRNAs identified a promoter element recognized by activating transcription factor 4 (ATF4, a key effector of the integrated stress response. ATF4 translation is normally induced by the phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α through a mechanism that requires upstream open reading frames (uORFs in the ATF4 5′ UTR. mTORC1 also controls ATF4 translation through uORFs, but independently of changes in eIF2α phosphorylation. mTORC1 instead employs the 4E-binding protein (4E-BP family of translation repressors. These results link mTORC1-regulated demand for protein synthesis with an ATF4-regulated transcriptional program that controls the supply of amino acids to the translation machinery.
Function and regulation of ATF 3 expression induced by ionizing radiation

International Nuclear Information System (INIS)

Fan, Feiyue; Wang, Yong; Du, Liqin; Zhan, Qimin

2008-01-01

Full text: Ionizing radiation results in a series of damages of mammalian cells as a genotoxic stress. There are some genes expressed after cells damaged, in which ATF 3, a member of ATF/CREB family of transcription factors, is one of them. In this report, we demonstrate that ATF 3 can be induced by ionizing radiation. The induction of ATF 3 protein requires normal status of p53 function in cells. There are some quantitative relationships between ATF 3 induction and dosages of radiation or time post-irradiation. In another word, ATF 3 expression induced by ionizing radiation present dose- and time-dependent. The regulation of ATF 3 expression refers to program of promoter and transcription. Radiation induces ATF 3 expression by activating the promoter and RNA transcription. In method of tetracycline-inducible system (tet-off), we have found that over-expression of ATF 3 protein brings caspase/PARP proteins into cleavage, which induces cell programmed death, and suppresses cell growth. Meanwhile, it was found that ATF 3 expression could slow down progression of cell from G 1 to S phase. It indicates ATF 3 protein might play a negative role in the control of cell cycle progression. It is very excited that expression of ATF 3 protein did not only suppress cell growth, but also demonstrated protecting effect of cell growth suppression resulting from ionizing radiation. It is suggested that ATF 3 protein might take part in the damage repair process of cells. (author)
Magnetic surface mapping with highly transparent screens on the Auburn Torsatron

International Nuclear Information System (INIS)

Hartwell, G.J.; Gandy, R.F.; Henderson, M.A.; Hanson, J.D.; Swanson, D.G.; Bush, C.J.; Colchin, R.J.; England, A.C.; Lee, D.K.

1987-01-01

In stellarator-type magnetic confinement devices (of which the torsatron is one), the magnetic field is produced entirely by external, current-carrying coils. Two methods for mapping magnetic surfaces in the Auburn Torsatron were tested and compared, both of which involve the use of highly transparent screens. The first method consists of coating the screen with a phosphor that emits light when struck by electrons emitted by an electron gun. A pattern representative of a magnetic surface is formed on the screen, and this pattern is recorded photographically. The second method uses an uncoated screen to collect electrons emitted from an emissive probe, which is scanned over a poloidal cross section of the torus. Under certain conditions, the collected current is a constant over a particular magnetic surface so that a contour plot of the current versus position is equivalent to a plot of the magnetic surfaces. Parametric studies of the two methods are presented, and the effectiveness of each technique is discussed
Brain-Derived Neurotrophic Factor Elevates Activating Transcription Factor 4 (ATF4 in Neurons and Promotes ATF4-Dependent Induction of Sesn2

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Jin Liu

2018-03-01

Full Text Available Activating transcription factor 4 (ATF4 plays important physiologic roles in the brain including regulation of learning and memory as well as neuronal survival and death. Yet, outside of translational regulation by the eIF2α-dependent stress response pathway, there is little information about how its levels are controlled in neurons. Here, we show that brain-derived neurotrophic factor (BDNF promotes a rapid and sustained increase in neuronal ATF4 transcripts and protein levels. This increase is dependent on tropomyosin receptor kinase (TrkB signaling, but independent of levels of phosphorylated eIF2α. The elevation in ATF4 protein occurs both in nuclei and processes. Transcriptome analysis revealed that ATF4 mediates BDNF-promoted induction of Sesn2 which encodes Sestrin2, a protector against oxidative and genotoxic stresses and a mTor complex 1 inhibitor. In contrast, BDNF-elevated ATF4 did not affect expression of a number of other known ATF4 targets including several with pro-apoptotic activity. The capacity of BDNF to elevate neuronal ATF4 may thus represent a means to maintain this transcription factor at levels that provide neuroprotection and optimal brain function without risk of triggering neurodegeneration.
Proceedings of the SLAC/KEK ATF lattice workshop

International Nuclear Information System (INIS)

Urakawa, Junji

1993-04-01

The SLAC/KEK ATF Lattice Workshop was held on December 8-11, 1992 at KEK, National Laboratory for High Energy Physics. The purpose of this workshop is to critically review the ATF lattice design for any possible improvements, and also to bring SLAC colleagues up to date on recent progress at KEK. At KEK studies on intense multi-bunch beam acceleration and emittance reduction have been actively pursued, evolving into the ATF project since 1990. In 1991 we have launched a large scale reconstruction of the experimental hall. This is to build the shielded housing for the 1.54 GeV injector linac and the test damping ring. Our plan is to begin construction of the linac in March 1993. Some results from the discussions during the Workshop have been already incorporated in the revised ATF lattice design. (J.P.N.)

Atf4 regulates chondrocyte proliferation and differentiation during endochondral ossification by activating Ihh transcription.

Science.gov (United States)

Wang, Weiguang; Lian, Na; Li, Lingzhen; Moss, Heather E; Wang, Weixi; Perrien, Daniel S; Elefteriou, Florent; Yang, Xiangli

2009-12-01

Activating transcription factor 4 (Atf4) is a leucine-zipper-containing protein of the cAMP response element-binding protein (CREB) family. Ablation of Atf4 (Atf4(-/-)) in mice leads to severe skeletal defects, including delayed ossification and low bone mass, short stature and short limbs. Atf4 is expressed in proliferative and prehypertrophic growth plate chondrocytes, suggesting an autonomous function of Atf4 in chondrocytes during endochondral ossification. In Atf4(-/-) growth plate, the typical columnar structure of proliferative chondrocytes is disturbed. The proliferative zone is shortened, whereas the hypertrophic zone is transiently expanded. The expression of Indian hedgehog (Ihh) is markedly decreased, whereas the expression of other chondrocyte marker genes, such as type II collagen (Col2a1), PTH/PTHrP receptor (Pth1r) and type X collagen (Col10a1), is normal. Furthermore, forced expression of Atf4 in chondrocytes induces endogenous Ihh mRNA, and Atf4 directly binds to the Ihh promoter and activates its transcription. Supporting these findings, reactivation of Hh signaling pharmacologically in mouse limb explants corrects the Atf4(-/-) chondrocyte proliferation and short limb phenotypes. This study thus identifies Atf4 as a novel transcriptional activator of Ihh in chondrocytes that paces longitudinal bone growth by controlling growth plate chondrocyte proliferation and differentiation.
Advanced Toroidal Facility

International Nuclear Information System (INIS)

Johnson, R.L.

1985-01-01

The Advanced Toroidal Facility (ATF) is a new magnetic confinement plasma device under construction at the Oak Ridge National Laboratory (ORNL) that will lead to improvements in toroidal magnetic fusion reactors. The ATF is a type of stellerator, known as a ''torsatron'' which theoretically has the capability to operate at greater than or equal to8% beta in steady state. The ATF plasma has a major radius of 2.1 m, an average minor radius of 0.3 m, and a field of 2 T for a 2 s duration or 1 T steady state. The ATF device consists of a helical field (HF) coil set, a set of poloidal field (PF) coils, an exterior shell structure to support the coils, and a thin, helically contoured vacuum vessel inside the coils. The ATF replaces the Impurities Studies Experiment (ISX-B) tokamak at ORNL and will use the ISX-B auxiliary systems including 4 MW of electron cyclotron heating. The ATF is scheduled to start operation in late 1986. An overview of the ATF device is presented, including details of the construction process envisioned. 9 refs., 7 figs., 3 tabs
Beta limit of resistive plasma in Torsatron / Heliotron

International Nuclear Information System (INIS)

Itoh, K.; Ichiguchi, K.; Itoh, S.I.

1992-02-01

Stability against the interchange mode in the Torsatron / Heliotron device is investigated, taking into account the effects of the resistivity, current diffusivity, ion viscosity and thermal diffusivity. Critical beta for the low-mode-number stability is found at the finite beta value. For the range of plasma parameters of the present experiments, the resistive mode and current diffusive mode set comparable critical beta values, which are consistent with experimental observations. In future high temperature plasmas, the current diffusive mode determines the stability limit for the global mode. (author)
The cellular transcription factor CREB corresponds to activating transcription factor 47 (ATF-47) and forms complexes with a group of polypeptides related to ATF-43.

Science.gov (United States)

Hurst, H C; Masson, N; Jones, N C; Lee, K A

1990-12-01

Promoter elements containing the sequence motif CGTCA are important for a variety of inducible responses at the transcriptional level. Multiple cellular factors specifically bind to these elements and are encoded by a multigene family. Among these factors, polypeptides termed activating transcription factor 43 (ATF-43) and ATF-47 have been purified from HeLa cells and a factor referred to as cyclic AMP response element-binding protein (CREB) has been isolated from PC12 cells and rat brain. We demonstrated that CREB and ATF-47 are identical and that CREB and ATF-43 form protein-protein complexes. We also found that the cis requirements for stable DNA binding by ATF-43 and CREB are different. Using antibodies to ATF-43 we have identified a group of polypeptides (ATF-43) in the size range from 40 to 43 kDa. ATF-43 polypeptides are related by their reactivity with anti-ATF-43, DNA-binding specificity, complex formation with CREB, heat stability, and phosphorylation by protein kinase A. Certain cell types vary in their ATF-43 complement, suggesting that CREB activity is modulated in a cell-type-specific manner through interaction with ATF-43. ATF-43 polypeptides do not appear simply to correspond to the gene products of the ATF multigene family, suggesting that the size of the ATF family at the protein level is even larger than predicted from cDNA-cloning studies.
Energy confinement in the torsatron URAGAN-3M during the rf-heating mode

International Nuclear Information System (INIS)

Pashnev, V.K.; Burchenko, P.Ya.; Lozin, A.V. and others

2008-01-01

Energy confinement time of plasma in torsatron U-3M was measured both during quasi-stationary study of RF-discharge and after RF-power cut-off. Power absorbed by plasma in the confinement region was estimated. A mechanism which explain the plasma density behavior in the confinement region is proposed
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
Design and high order optimization of the ATF2 lattices

CERN Document Server

Marin, E; Woodley, M; Kubo, K; Okugi, T; Tauchi, T; Urakawa, J; Tomas, R

2013-01-01

The next generation of future linear colliders (LC) demands nano-meter beam sizes at the interaction point (IP) in order to reach the required luminosity. The final focus system (FFS) of a LC is meant to deliver such small beam sizes. The Accelerator Test Facility (ATF) aims to test the feasibility of the new local chromaticity correction scheme which the future LCs are based on. To this end the ATF2 nominal and ultra-low beta* lattices are design to vertically focus the beam at the IP to 37nm and 23nm, respectively if error-free lattices are considered. However simulations show that the measured field errors of the ATF2 magnets preclude to reach the mentioned spot sizes. This paper describes the optimization of high order aberrations of the ATF2 lattices in order to minimize the detrimental effect of the measured multipole components for both ATF2 lattices. Specifically three solutions are studied, the replacement of the last focusing quadrupole (QF1FF), insertion of octupole magnets and optics modification....
ATF [Advanced Toroidal Facility] data management

International Nuclear Information System (INIS)

Kannan, K.L.; Baylor, L.R.

1988-01-01

Data management for the Advanced Toroidal Facility (ATF), a stellarator located at Oak Ridge National Laboratory (ORNL), is provided by DMG, a locally developed, VAX-based software system. DMG is a data storage and retrieval software system that provides the user interface to ATF raw and analyzed data. Data are described in terms of data models and data types and are organized as signals into files, which are internally documented. The system was designed with user accessibility, software maintainability, and extensibility as primary goals. Extensibility features include compatibility with ATF as it moves from pulsed to steady-state operation and capability for use of the DMG system with experiments other than ATF. DMG is implemented as a run-time library of routines available as a shareable image. General-purpose and specialized data acquisition and analysis applications have been developed using the DMG system. This paper describes the DMG system and the interfaces to it. 4 refs., 2 figs
Azimuthal electric fields and ambipolarity in a multiple-helicity torsatron

International Nuclear Information System (INIS)

Hastings, D.E.; Shaing, K.C.

1985-01-01

In a torsatron there are multiple solutions to the ambipolarity relationship for the electric field. If the electric field is small over some region of space then the self-consistent poloidal electric field can be important and lead to potential islands. If the plasma is in the superbanana plateau regime, then slow resonant particles limit the rate of change of the electric field and, hence, give a minimum width for the spatial zone where the plasma is changing roots of the ambipolarity relationship
Damping Wiggler Study at KEK-ATF

CERN Document Server

Naito, Takashi; Honda, Yosuke; Korostelev, Maxim S; Kubo, Kiyoshi; Kuriki, Masao; Kuroda, Shigeru; Muto, Toshiya; Nakamura, Norio; Ross, Marc; Sakai, Hiroshi; Terunuma, Nobuhiro; Urakawa, Junji; Zimmermann, Frank

2005-01-01

The effects by damping wiggler magnets have been studied at KEK-ATF. The damping ring of the KEK-ATF is a 1.3 GeV storage ring capable of producing ultra-low emittance electron beams. It is significant issue to realize fast damping in the damping ring. The tuning method with 4 sets of wiggler was investigated for the ultra-low emittance beam. The performance on the beam quality, which is related to the transverse (x and y) and the longitudinal (z and dp/p), has been measured by the SR monitor, the laser wire, the streak camera and the energy spread monitor at the extraction line. We report on the operation condition and the measurement results.
Trapped particle confinement studies in L = 2 torsatrons for additional helical coils, radial electric field and finite beta effect

International Nuclear Information System (INIS)

Kato, A.; Nakamura, Y.; Wakatani, M.

1990-07-01

L = 2 torsatrons are studied to improve the high energy trapped particle confinement with additional l = 1 and/or l = 3 helical coils. The winding laws are selected in two ways. One is to realize 'σ - optimization' by the additional helical coils, but this approach loses magnetic well region. The other selection is to produce or deepen the magnetic well by the additional helical coils. L=3 helical coils are usable to this end. In this case the improvement of the trapped particle confinement depends on magnetic axis position. Radial electric field producing sheared rotational motion is also considered to improve the trapped particle confinement in a standard l = 2 torsatron. By excluding cancellation between E x B and ΔB drift motion occurred for the parabolic potential profiles, all deeply trapped particles can be confined in the central region. Degradation of the trapped particle confinement by the Shafranov shift is mitigated by shifting the magnetic axis inside in the vacuum configuration. (author)
Development of a conception of the stellarator based on torsatron and modular systems

International Nuclear Information System (INIS)

Georgiyevskiy, A.V.; Rudakov, V.A.; Tolok, V.T.

2003-01-01

The paper presents the historical review of the stellarator conception development on the example of thermonuclear research at the Kharkov Institute of Physics and Technology. The given material covers a period from the time of the large-scale stellarator 'Ukraine' offered by I.V.Kurchatov up to the present. The main attention put to torsatron and modular systems
Measured thermal and fast neutron fluence rates for ATF-1 holders during ATR cycle 160A

International Nuclear Information System (INIS)

Walker, B. J.; Miller, D. T.

2017-01-01

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 160A which were measured by the Radiation Measurements Laboratory (RML).
Measured thermal and fast neutron fluence rates for ATF-1 holders during ATR cycle 160A

Energy Technology Data Exchange (ETDEWEB)

Walker, B. J. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Miller, D. T. [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2017-06-06

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 160A which were measured by the Radiation Measurements Laboratory (RML).
The ATF [Advanced Toroidal Facility] Data Management System: [Final report

International Nuclear Information System (INIS)

Kannan, K.L.; Baylor, L.R.

1987-01-01

The Advanced Toroidal Facility (ATF) Data Management System (DMG) is a VAX-based software system that provides unified data access for ATF data acquisition and analysis. The system was designed with user accessibility, software maintainability, and extensibility as primary goals. This paper describes the layered architecture of the system design, the system implementation, use, and the data file structure. 3 refs., 1 fig
Larval hemolymph of rhinoceros beetle, Allomyrina dichotoma, enhances insulin secretion through ATF3 gene expression in INS-1 pancreatic β-cells.

Science.gov (United States)

Kim, Seung-Whan; Suh, Hyun-Woo; Yoo, Bo-Kyung; Kwon, Kisang; Yu, Kweon; Choi, Ji-Young; Kwon, O-Yu

2018-05-22

In this study, we show that INS-1 pancreatic β-cells treated for 2 h with hemolymph of larvae of rhinoceros beetle, Allomyrina dichotoma, secreted about twice as much insulin compared to control cells without such treatment. Activating transcription factor 3 (ATF3) was the highest upregulated gene in DNA chip analysis. The A. dichotoma hemolymph dose-dependently induced increased expression levels of genes encoding ATF3 and insulin. Conversely, treatment with ATF3 siRNA inhibited expression levels of both genes and curbed insulin secretion. These results suggest that the A. dichotoma hemolymph has potential for treating and preventing diabetes or diabetes-related complications.
Topics on MHD equilibrium and stability in heliotron / torsatron

International Nuclear Information System (INIS)

Ichiguchi, Katsuji; Nakajima, Noriyoshi; Okamoto, Masao.

1996-10-01

Recent topics on the MHD properties with and without bootstrap current in Heliotron / Torsatron configurations are presented. In a currentless equilibrium with a large Shafranov shift, a high-n ballooning mode can be unstable even in the region with positive gradient of the rotational transform. This is because the local shear in the field line bending term can be reduced by the fact that the local enhancement of the poloidal field varies in the radial direction. Since the local curvature of the field lines depends on the label of the magnetic field line, α, in Heliotron / Torsatron, the eigenvalue ω 2 also depends on α. In the Mercier stable region, the level surfaces of ω 2 of unstable modes form spheroids in the (ψ, θ k , α) space, where ψ and θ k are the label of the flux surface and the radial wave number, while they form cylinders in tokamaks. Such high-n modes cannot be related to low-n modes in this case. In the LHD configuration, bootstrap current depends on the collisionality of the plasma. When the beta value is raised by increasing the temperature with the density fixed, the plasma becomes less collisional and the bootstrap current grows in the direction where the rotational transform is increased. On the contrary, when the beta value is raised by increasing the density with the temperature fixed, the plasma becomes more collisional. While a small amount of the current flows in the same direction as in the above sequence at low beta in this case, the direction of the current reverses at high beta equilibrium. This is because the geometrical factor in the expression of the bootstrap current in the plateau regime has opposite signature to that in the 1/ν regime. The latter equilibrium sequence is more stable in the Mercier criterion than the former one. Thus, the beta should be raised by increasing the density rather than the temperature to obtain stable high beta plasma. (author)
Adenoviral gene transfer of angiostatic ATF-BPTI inhibits tumour growth

International Nuclear Information System (INIS)

Lefesvre, Pierre; Attema, Joline; Bekkum, Dirk van

2002-01-01

The outgrowth of new vessels – angiogenesis – in the tumour mass is considered to be a limiting factor of tumour growth. To inhibit the matrix lysis that is part of the tumour angiogenesis, we employed the chimeric protein mhATF-BPTI, composed of the receptor binding part of the urokinase (ATF) linked to an inhibitor of plasmin (BPTI). For delivery, recombinant adenovirus encoding the transgene of interest was injected intravenously or locally into the tumour. The anti tumour effect of this compound was compared to that of human endostatin and of mhATF alone in two different rat bronchial carcinomas growing either as subcutaneous implants or as metastases. Significant inhibition of the tumour growth and decrease of the number of lung metastasis was achieved when the concentration of mhATF-BPTI at the tumour site was above 400 of ng / g tissue. This concentration could be achieved via production by the liver, only if permissive to the recombinant adenovirus. When the tumour cells could be transduced, local delivery of the vector was enough to obtain a response. In the case of metastasis, the capacity of the lung tissue to concentrate the encoded protein was essential to reach the required therapeutic levels. Further, endostatin or mhATF could not reproduce the effects of mhATF-BPTI, at similar concentrations (mhATF) and even at 10-fold higher concentration (endostatin). The ATF-BPTI was shown to inhibit tumour growth of different rat lung tumours when critical concentration was reached. In these tumour models, endostatin or ATF induce almost no tumour response
Global MHD modes excited by energetic ions in heliotron/torsatron plasmas

International Nuclear Information System (INIS)

Toi, K.; Takechi, M.; Takagi, S.

1999-01-01

In the CHS heliotron/torsatron, fishbone instabilities (FBs) and toroidal Alfven eigenmodes(TAEs) are observed for the first time, in NBI heated plasmas where small beam driven current is induced. Pulsed increase in energetic ion loss flux is detected by an escaping ion probe during the m=3/n=2 FBs(m,n:poloidal and toroidal mode numbers). The sawtooth crash is often induced by the m=2/n=1 FBs. The current driven internal kink mode and pressure driven interchange modes are thought to be relevant MHD instabilities to FBs. TAEs with n=1 and n=2 are identified, and localized near the plasma core region where fairly low magnetic shear would be realized by the small net plasma current. So far, the observed TAEs do not lead to enhanced loss of energetic ions because of low magnetic fluctuation level. (author)
Global MHD modes excited by energetic ions in heliotron/torsatron plasmas

International Nuclear Information System (INIS)

Toi, K.; Takechi, M.; Takagi, S.

2001-01-01

In the CHS heliotron/torsatron, fishbone instabilities (FBs) and toroidal Alfven eigenmodes (TAEs) are observed for the first time, in NBI heated plasmas where small beam driven current is induced. Pulsed increase in energetic ion loss flux is detected by an escaping ion probe during the m=3/n=2 FBs (m,n: poloidal and toroidal mode numbers). The sawtooth crash is often induced by the m=2/n=1 FBs. The current driven internal kink mode and pressure driven interchange modes are thought to be relevant MHD instabilities to FBs. TAEs with n=1 and n=2 are identified, and localized near the plasma core region where fairly low magnetic shear would be realized by the small net plasma current. So far, the observed TAEs do not lead to enhanced loss of energetic ions because of low magnetic fluctuation level. (author)

Proto-CIRCUS tilted-coil tokamak–torsatron hybrid: Design and construction

Energy Technology Data Exchange (ETDEWEB)

Clark, A.W.; Doumet, M.; Hammond, K.C. [Department of Applied Physics and Applied Mathematics, Columbia University, New York, NY 10027 (United States); Kornbluth, Y. [Yeshiva University, New York, NY 10033 (United States); Spong, D.A. [Oak Ridge National Laboratory, Oak Ridge, TN 37830 (United States); Sweeney, R. [Department of Applied Physics and Applied Mathematics, Columbia University, New York, NY 10027 (United States); Volpe, F.A., E-mail: fvolpe@columbia.edu [Department of Applied Physics and Applied Mathematics, Columbia University, New York, NY 10027 (United States)

2014-11-15

Highlights: • A tokamak-like device with tilted toroidal field (TF) coils needs less plasma current than a conventional tokamak. • Rotational transform is partly generated by external coils. Device can be considered a tokamak–torsatron hybrid. • We designed and constructed the first device of this type. • Tilted TF coils are interlinked to each other, which helps to reduce aspect ratio of plasma. • This is a six-coil generalization of CNT stellarator, also at Columbia University, which features two interlinked coils. - Abstract: 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 measurements. Such comparisons will reveal whether this relatively simple concept can generate the expected rotational transform.
A special correcting winding for the l = 2 torsatron with split-type helical coils

International Nuclear Information System (INIS)

Kotenko, V.G.

2012-01-01

A split-type special correcting winding (split-type SCW) for the l = 2 torsatron toroidal magnetic system with split-type helical coils is considered. The split-type SCW gives the possibility of controlling the position of the magnetic surface configuration in the direction perpendicular to the torus equatorial plane. Numerical simulations were carried out to investigate the influence of the split-type SCW magnetic field on centered and distant relative to the torus surface magnetic surface configuration with a plane magnetic axis, being promising for the fusion reactor. The configuration is realized in the l = 2 torsatron with split-type helical coils and with the coils of an additional toroidal magnetic field. The calculations show that the split-type SCW magnetic field influence on the initial magnetic surface configuration leads mainly to the magnetic surface configuration displacement along the straight z axis of torus rotation. The displacement of ∼0.1a, a is the minor radius of the torus, has no critical effect on the magnetic surface parameters. An idea on the split-type SCW magnetic field structure is obtained by numerical simulations of the effect of this field as a minority magnetic field imposed on the magnetic field of a well-known configuration. The split-type SCW magnetic field is directed, predominantly along the major radius of the torus within its volume. The displacement range of the closed magnetic surface configuration depends on the split-type SCW magnetic field value.
Plasma engineering analysis of a small torsatron reactor

International Nuclear Information System (INIS)

Lacatski, J.T.; Houlberg, W.A.; Uckan, N.A.

1985-10-01

This study examines the plasma physics and reactor engineering feasibility of a small, medium aspect ratio, high-beta, l = 2, D-T torsatron power reactor, based on the magnetic configuration of the Advanced Toroidal Facility, Oak Ridge National Laboratory. Plasma analyses are performed to assess whether confinement in a small, average radius plasma is sufficient to yield an ignited or high-Q driven device. Much of the physics assessment focuses on an evaluation of the radial electric field created by the nonambipolar particle flux. Detailed transport simulations are done with both fixed and self-consistent evolution of the radial electric field. Basic reactor engineering considerations taken into account are neutron wall loading, maximum magnetic field at the helical coils, coil shield thickness, and tritium breeding blanket-shield thickness
R and D status of the ATF damping ring

International Nuclear Information System (INIS)

Urakawa, Junji

1994-01-01

The KEK accelerator test facility (ATF) is under construction. This paper gives the status of the design studies, the various R and D works and the construction for the damping ring of the ATF. (author)
CAVITY BEAM POSITION MONITOR SYSTEM FOR ATF2

CERN Document Server

Boogert, S T; Cullinan, F; Joshi, N; Lyapin, A; Aryshev, A; Honda, Y; Naito, T; Terunuma, N; Urakara, J; Heo, A; Kim, E-S; Kim, Y I; McCormick, D; Frisch, J; Nelson, J; Smith, T; White, G R

2011-01-01

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 41 high resolution C and S band resonant cavity beam position monitors (BPM) with associated mixer electronics and digitisers. In addition 4 high resolution BPMs have been recently installed at the interaction point, we briefly describe the first operational experience of these cavities in the ATF2 beam-line. The current status of the overall BPM system is also described, with a focus on operational techniques and performance.
Loss of ATF2 function leads to cranial motoneuron degeneration during embryonic mouse development.

Directory of Open Access Journals (Sweden)

Julien Ackermann

2011-04-01

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

International Nuclear Information System (INIS)

Swanson, D.G.

1985-01-01

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
Measured thermal and fast neutron fluence rates for ATF-1 holders during ATR cycle 158B/159A

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); Walker, Billy Justin [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2016-11-01

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 158B/159A which were measured by the Radiation Measurements Laboratory (RML).
Intervention of electroacupuncture on spinal p38 MAPK/ATF-2/VR-1 pathway in treating inflammatory pain induced by CFA in rats.

Science.gov (United States)

Fang, Jian-Qiao; Du, Jun-Ying; Liang, Yi; Fang, Jun-Fan

2013-03-22

Previous studies have demonstrated that p38 MAPK signal transduction pathway plays an important role in the development and maintenance of inflammatory pain. Electroacupuncture (EA) can suppress the inflammatory pain. However, the relationship between EA effect and p38 MAPK signal transduction pathway in inflammatory pain remains poorly understood. It is our hypothesis that p38 MAPK/ATF-2/VR-1 and/or p38 MAPK/ATF-2/COX-2 signal transduction pathway should be activated by inflammatory pain in CFA-injected model. Meanwhile, EA may inhibit the activation of p38 MAPK signal transduction pathway. The present study aims to investigate that anti-inflammatory and analgesic effect of EA and its intervention on the p38 MAPK signal transduction pathway in a rat model of inflammatory pain. EA had a pronounced anti-inflammatory and analgesic effect on CFA-induced chronic inflammatory pain in rats. EA could quickly raise CFA-rat's paw withdrawal thresholds (PWTs) and maintain good and long analgesic effect, while it subdued the ankle swelling of CFA rats only at postinjection day 14. EA could down-regulate the protein expressions of p-p38 MAPK and p-ATF-2, reduced the numbers of p-p38 MAPK-IR cells and p-ATF-2-IR cells in spinal dorsal horn in CFA rats, inhibited the expressions of both protein and mRNA of VR-1, but had no effect on the COX-2 mRNA expression. The present study indicates that inhibiting the activation of spinal p38 MAPK/ATF-2/VR-1 pathway may be one of the main mechanisms via central signal transduction pathway in the process of anti-inflammatory pain by EA in CFA rats.
Application of the Ball-Pen Probe in Two Low-Temperature Magnetised Plasma Devices and in Torsatron TJ-K

Czech Academy of Sciences Publication Activity Database

Adámek, Jiří; Peterka, M.; Gyergyek, T.; Kudrna, P.; Ramisch, M.; Stroth, U.; Cavalier, Jordan; Tichý, M.

2013-01-01

Roč. 53, č. 1 (2013), s. 39-44 ISSN 0863-1042. [International Workshop on Electric Probes in Magnetized Plasmas/9./. Iasi, 21.09.2011-23.09.2011] R&D Projects: GA AV ČR KJB100430901; GA ČR GA202/07/0044 Institutional support: RVO:61389021 Keywords : Ball- pen probe * magnetron * torsatron * CASTOR tokamak * coefficient Subject RIV: BL - Plasma and Gas Discharge Physics Impact factor: 0.983, year: 2013 http://onlinelibrary.wiley.com/doi/10.1002/ctpp.201310007/pdf
A first glance at the initial ATF experimental results

International Nuclear Information System (INIS)

Carreras, B.A.; Dominguez, N.; Leboeuf, J.N.; Lynch, V.E.; Charlton, L.A.

1989-05-01

In the initial phase of ATF operation, the plasma minor radius and the edge rotational transform were reduced by field errors. This caused an effective change of the magnetic configuration: it improved the stability properties but worsened the equilibrium properties. The threshold for the second stability regime was lowered to β 0 /approximately/ 1.5%. Experimental profile data are compatible with operation in the second stability regime, and the achieved beta values, β 0 /approximately/ 3%, are well beyond the theoretically calculated threshold. Magnetic fluctuation measurements showed the effects of beta self-stabilization. They are in reasonable agreement with the predictions of the theory and support the evidence that ATF has already operated in the second stability regime. 24 refs., 20 figs., 1 tab
Forecasting parameters of a the monuclear power plant with a torsatron reactor

International Nuclear Information System (INIS)

Artyugina, I.M.; Semenov, A.A.; Smirnov, A.N.

1982-01-01

A number of problems related to forecasting technical economical factors of thermonuclear electric plant (TNPP) based on the torsatron reactor is considered. Possible methodic approaches to the estimation of TNPP nonstandard equipment construction-mounting works and the results of forecasting the investment structure in TNPP are analysed. The influence of TP basic systems on the total investment value depending on accepted price level is shown. Quantitative estimations of specific investments and electric energy production cost permit to estimate rather optimistically the considered TNPP type and to draw a conclusion on advisability of the further study
PcToll2 positively regulates the expression of antimicrobial peptides by promoting PcATF4 translocation into the nucleus.

Science.gov (United States)

Lan, Jiang-Feng; Zhao, Li-Juan; Wei, Shun; Wang, Yuan; Lin, Li; Li, Xin-Cang

2016-11-01

Drosophila Toll and mammalian Toll-like receptors (TLRs) are a family of evolutionarily conserved immune receptors that play a crucial role in the first-line defense against intruded pathogens. Activating transcription factor 4 (ATF4), a member of the ATF/CREB transcription factor family, is an important factor that participates in TLR signaling and other physiological processes. However, in crustaceans, whether ATF4 homologs were involved in TLR signaling remains unclear. In the current study, we identified a Toll homolog PcToll2 and a novel ATF4 homolog PcATF4 from Procambarus clarkii, and analyzed the likely regulatory activity of PcATF4 in PcToll2 signaling. The complete cDNA sequence of PcToll2 was 4175 bp long containing an open reading frame of 2820 bp encoding a 939-amino acid protein, and the cDNA sequence of PcATF4 was 2027 bp long with an open reading frame of 1296 bp encoding a 431-amino acid protein. PcToll2 and human TLR4 shared the high identity and they were grouped into a cluster. Furthermore, PcToll2 had a close relationship with other shrimp TLRs that possessed potential antibacterial activity. PcToll2 was highly expressed in the hemocytes, heart and gills, while PcATF4 mainly distributed in gills. Upon challenge with Vibrio parahemolyticus, PcToll2 and PcATF4 together with the antimicrobial peptides of ALF1 and ALF2 were significantly up-regulated in the hemocytes, and the PcATF4 was translocated into the nucleus. After PcToll2 silencing and challenge with Vibrio, the translocation of PcATF4 into the nucleus was inhibited and the expression of ALF1 and ALF2 was reduced, but the expression of PcDorsal and PcSTAT was not affected. Furthermore, after PcATF4 knockdown and challenge with or without Vibrio, the expression of ALF1 and ALF2 was also decreased while the expression of PcToll2 was upregulated. These results suggested that PcToll2 might regulate the expression of ALF1 and ALF2 by promoting the import of PcATF4, instead of the routine
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. Published by Elsevier Inc.
The Loss of Activating Transcription Factor 4 (ATF4) Reduces Bone Toughness and Fracture Toughness

Science.gov (United States)

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

2014-01-01

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 the seimportant 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 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, ν1 Phosphate 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 maintaining bone toughness and fracture toughness. PMID:24509412
ATF5 polymorphisms influence ATF function and response to treatment in children with childhood acute lymphoblastic leukemia

OpenAIRE

Rousseau, Julie; Gagné, Vincent; Labuda, Malgorzata; Beaubois, Cyrielle; Sinnett, Daniel; Laverdière, Caroline; Moghrabi, Albert; Sallan, Stephen E.; Silverman, Lewis B.; Neuberg, Donna; Kutok, Jeffery L.; Krajinovic, Maja

2011-01-01

Asparaginase is a standard and critical component in the therapy of childhood acute lymphoblastic leukemia. Asparagine synthetase (ASNS) and the basic region leucine zipper activating transcription factor 5 (ATF5) and arginosuccinate synthase 1 (ASS1) have been shown to mediate the antileukemic effect of asparaginase and to display variable expression between leukemia cells that are resistant and sensitive to treatment. Fourteen polymorphisms in the regulatory and coding regions of these gene...
Improving the Organoleptic Properties of a Craft Mezcal Beverage by Increasing Fatty Acid Ethyl Ester Contents through ATF1 Expression in an Engineered Kluyveromyces marxianus UMPe-1 Yeast.

Science.gov (United States)

Campos-García, Jesús; Vargas, Alejandra; Farías-Rosales, Lorena; Miranda, Ana L; Meza-Carmen, Víctor; Díaz-Pérez, Alma L

2018-05-02

Mezcal, a traditional beverage that originated in Mexico, is produced from species of the Agavaceae family. The esters associated with the yeasts utilized during fermentation are important for improving the organoleptic properties of the beverage. We improved the ester contents in a mezcal beverage by using the yeast Kluyveromyces marxianus, which was engineered with the ATF1 gene. ATF1 expression in the recombinant yeast significantly increased compared with that in the parental yeast, but its fermentative parameters were unchanged. Volatile-organic-compound-content analysis showed that esters had significantly increased in the mezcal produced with the engineered yeast. In a sensory-panel test, 48% of the panelists preferred the mezcal produced from the engineered yeast, 30% preferred the mezcal produced from the wild type, and 15 and 7% preferred the two mezcal types produced following the routine procedure. Correlation analysis showed that the fruitiness/sweetness description of the mezcal produced using the ATF1-engineered K. marxianus yeast correlated with the content of the esters, whose presence improved the organoleptic properties of the craft mezcal beverage.
ATF6α/β-mediated adjustment of ER chaperone levels is essential for development of the notochord in medaka fish.

Science.gov (United States)

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

2013-05-01

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 knockout, but not ATF6α- or ATF6β single knockout, causes embryonic lethality, as in mice. Analyses of ER stress reporters reveal that ER stress occurs physiologically during medaka early embryonic development, particularly in the brain, otic vesicle, and notochord, resulting in ATF6α- and ATF6β-mediated induction of BiP, and that knockdown of the α1 chain of type VIII collagen reduces such ER stress. The absence of transcriptional induction of several ER chaperones in ATF6α/β double knockout causes more profound ER stress and impaired notochord development, which is partially rescued by overexpression of BiP. Thus ATF6α/β-mediated adjustment of chaperone levels to increased demands in the ER is essential for development of the notochord, which synthesizes and secretes large amounts of extracellular matrix proteins to serve as the body axis before formation of the vertebra.
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
Pharmacologic inhibition of S1P attenuates ATF6 expression, causes ER stress and contributes to apoptotic cell death.

Science.gov (United States)

Lebeau, Paul; Byun, Jae Hyun; Yousof, Tamana; Austin, Richard C

2018-04-22

Mammalian cells express unique transcription factors embedded in the endoplasmic reticulum (ER) membrane, such as the sterol regulatory element-binding proteins (SREBPs), that promote de novo lipogenesis. Upon their release from the ER, the SREBPs require proteolytic activation in the Golgi by site-1-protease (S1P). As such, inhibition of S1P, using compounds such as PF-429242 (PF), reduces cholesterol synthesis and may represent a new strategy for the management of dyslipidemia. In addition to the SREBPs, the unfolded protein response (UPR) transducer, known as the activating transcription factor 6 (ATF6), is another ER membrane-bound transcription factor that requires S1P-mediated activation. ATF6 regulates ER protein folding capacity by promoting the expression of ER chaperones such as the 78-kDa glucose-regulated protein (GRP78). ER-resident chaperones like GRP78 prevent and/or resolve ER polypeptide accumulation and subsequent ER stress-induced UPR activation by folding nascent polypeptides. Here we report that pharmacological inhibition of S1P reduced the expression of ATF6 and GRP78 and induced the activation of UPR transducers inositol-requiring enzyme-1α (IRE1α) and protein kinase RNA-like ER kinase (PERK). As a consequence, S1P inhibition also increased the susceptibility of cells to ER stress-induced cell death. Our findings suggest that S1P plays a crucial role in the regulation of ER folding capacity and also identifies a compensatory cross-talk between UPR transducers in order to maintain adequate ER chaperone expression and activity. Copyright © 2018. Published by Elsevier Inc.

Lifetime measurement of ATF damping ring

International Nuclear Information System (INIS)

Okugi, T.; Hayano, H.; Kubo, K.; Naito, T.; Terunuma, N.; Urakawa, J.; Zimmermann, F.

1998-06-01

The purpose of the ATF damping ring is the development of technologies for producing a low emittance beam required in future linear colliders such as JLC. The lifetime of the damping ring is very short (typically a few minutes). It is limited by elastic beam-gas scattering along with a small dynamic aperture, and by single intra-beam scattering (Touschek effect). The Touschek lifetime strongly depends upon the charge density of the beam, especially, the size of the vertical emittance. In this paper, the authors report the results of beam lifetime measurements in the ATF damping ring and the estimation of the vertical emittance from these measurements
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.
Equilibrium, stability and transport in L=1 compact helical axis configuration

International Nuclear Information System (INIS)

Kikuchi, Hitoshi; Ueno, Hikaru; Aizawa, Masamitsu; Suzuki, Kiyomitsu; Gesso, Hirokazu; Saito, Katsunori; Kawakami, Ichiro; Shiina, Shoichi

1990-01-01

The L=1 torsatron is modified by two methods to improve the plasma stability. First one is the negative pitch modulation of coil winding. Second is the superposition of a relatively weak L=-1 torsatron field. These modification give rise to a local magnetic well keeping a positive magnetic shear. The equilibrium, stability and transport of plasma in these modified L=1 torsatrons are described and discussed. (author)
Formation and termination of High ion temperature mode in Heliotron/torsatron plasmas

International Nuclear Information System (INIS)

Ida, K.; Kondo, K.; Nagasaki, K.

1997-01-01

Physics of the formation and termination of High ion temperature mode (high T i mode) are studied by controlling density profiles and radial electric field. High ion temperature mode is observed for neutral beam heated plasmas in Heliotron/torsatron plasmas (Heliotron-E). This high T i mode plasma is characterized by a peaked ion temperature profile and is associated with a peaked electron density profile produced by neutral beam fueling with low wall recycling. This high T i mode is terminated by flattening the electron density caused by either gas puffing or second harmonic ECH (core density 'pump-out'). (author)
Stabilisation of ballooning modes in torsatrons with an externally applied toroidal current

International Nuclear Information System (INIS)

Cooper, W.A.

1996-01-01

It has been found that ideal ballooning modes can impose very restrictive volume average β 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 β* from 2% to 5%. (author) 3 figs., 10 refs
Experimental approach for adhesion strength of ATF cladding

Energy Technology Data Exchange (ETDEWEB)

Kim, Donghyun; Kim, Hyochan; Yang, Yongsik; In, Wangkee [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Kim, Haksung [Hanyang University, Seoul (Korea, Republic of)

2016-10-15

The quality of a coating depends on the quality of its adhesion bond strength between the coating and the underlying substrate. Therefore, it is essential to evaluate the adhesion properties of the coating. There are many available test methods for the evaluation of coatings adhesion bond strength. Considering these restrictions of the coated cladding, the scratch test is useful for evaluation of adhesion properties compared to other methods. The purpose of the present study is to analyze the possibility of adhesion bond strength evaluation of ATF coated cladding by scratch testing on coatings cross sections. Experimental approach for adhesion strength of ATF coated cladding was investigated in the present study. The scratch testing was chosen as a testing method. Uncoated zircaloy-4 tube was employed as a reference and plasma spray and arc ion coating were selected as a ATF coated claddings for comparison. As a result, adhesion strengths of specimens affect the measured normal and tangential forces. For the future, the test will be conducted for CrAl coated cladding by laser coating, which is the most promising ATF cladding. Computational analysis with finite element method will also be conducted to analyze a stress distribution in the cladding tube.
Multi Optical Transition Radiation System for ATF2

International Nuclear Information System (INIS)

Alabau-Gonzalvo, Javier

2012-01-01

In this paper we describe the design, installation and first calibration tests of a Multi Optical Transition Radiation System in the beam diagnostic section of the Extraction (EXT) line of ATF2, close to the multi wire scanner system. This system will be a valuable tool for measuring beam sizes and emittances coming from the ATF Damping Ring. With an optical resolution of about 2 (micro)m an original OTR design (OTR1X) located after the septum at the entrance of the EXT line demonstrated the ability to measure a 5.5 (micro)m beam size in one beam pulse and to take many fast measurements. This gives the OTR the ability to measure the beam emittance with high statistics, giving a low error and a good understanding of emittance jitter. Furthermore the nearby wire scanners will be a definitive test of the OTR as a beam emittance diagnostic device. The multi-OTR system design proposed here is based on the existing OTR1X.
Equipotential surfaces in the Proto-Cleo Torsatron

International Nuclear Information System (INIS)

Trost, P.; Shohet, J.L.

1984-01-01

Space potential measurements have been made with the use of an emissive probe in the Proto-Cleo Torsatron. The emissive probe surface is heated to a temperature at which thermionic emission of electrons can occur. When the potential of the probe is less than the space potential, the probe predominately emits electrons, thus raising its potential. If the potential of the probe becomes greater than the space potential, the probe emits electrons at a much lower rate than it collects electrons, and thus the probe drops in potential. The dependence of the emitted and collected electron currents on the potential difference provides an accurate method to determine the space potential in the plasma. Space potential measurements have been made with this probe. The data are plotted as equipotential contours. A good correlation is seen between the equipotential measurements and the numerically predicted E.C.R.H. absorption layer, while the E.C.R.H. is on. During the time after the E.C.R.H. has been turned off, there is good correspondence between numerically calculated magnetic surfaces and the equipotential plots
CAVITY BEAM POSITION MONITOR SYSTEM FOR ATF2

CERN Document Server

Boogert, S T; Boorman, G; Molloy, S; Ross, M; Aryshev, A; Honda, Y; Terunuma, N; Urakawa, J; Kim, E S; Kim, Y I; Heo, A E; Lyapin, A; Swinson, C J; Frisch, J; McCormick, D M; Nelson, J; Smith, T; White, G R

2010-01-01

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.
Vibration measurement of accelerator tube table in ATF

International Nuclear Information System (INIS)

Nakayama, Y.; Sugahara, R.; Yamaoka, H.; Masuzawa, M.; Yamashita, S.

2004-01-01

Acceleration tube fixed to the table should not be a structure to amplify the vibration. Stability of ground is preferable for accelerator beam operation, and the beam control by extremely high resolution is especially demanded in GLC. Then, we have measured ground motion and table vibration in ATF at KEK. In this paper, some of analyzed results are shown, and we show the characteristics of vibration about the accelerator tube table in ATF. (author)
ICRH studies in TJ-IU torsatron

International Nuclear Information System (INIS)

Castejon, F.; Longinov, A.V.; Rodriguez R, L.

1993-01-01

Preliminary studies for Ion Cyclotron Resonance Heating (ICRH) in the frequency range f=3-150 MHz are presented for TJ-IU torsatron. This wide range implies the use of two different theoretical models. The first valid for high frequency, where the WKB approximation is applicable, and the second one which solves the full wave equation in one dimension. The high frequency calculations have been made using a ray tracing code and taking into account the magnetic field and plasma 3-D inhomogeneity. The results obtained in this case are presented in the first paper of this report, being the most important the criterion to avoid Fast Wave (fw)-slow wave (SW) coupling at Lower Hybrid Resonance, near the plasma edge, and the existence of so called Localized Modes. for the low frequency range wave-length is of the size of the plasma radius, therefore, the WKB approximation cannot be used. In this case a 1-D model is used which disregards toroidal effects, to study the main available heating scenarios which are presented in the second work of this report. the studies are made for hydrogen, deuterium and mixed plasmas with and without He 3 minority. Finally, the antenna designs to reach these several scenarios are presented in the third paper. Two different antenna models are provided for SW excitation, one of the current type and the other one of potential type. A third antenna is designed to excite FW which is similar to the current type antenna for SW, but rotated 90 degree Celsius
ICRH studies in TJ-IU torsatron

International Nuclear Information System (INIS)

Castejon, F.

1993-01-01

Preliminary studies for ion Cyclotron Resonance Heating (ICRH) in the frequency range f=3-150 MHz are presented for TJ-IU torsatron. This wide range implies the use of two different theoretical models. The first valid for high frequency, where the WKB approximation is applicable, and the second one which solves the full wave equation in one dimension. The high frequency calculations have been made using a ray tracing code and taking into account the magnetic field and plasma 3-D inhomogeneity. The results obtained in this case are presented in the first paper of this report, being the most important the criterion to avoid Fast Wave (FW)-Slow Wave (SW) coupling at Lower Hybrid Resonance, near the plasma edge, and the existence of so called Localized Modes. For the low frequency range wave-length is of the size of the plasma radius, there fore, the WKB approximation cannot be used. In this case a 1-D model is used which disregards toroidal effects, to study the main available heating scenarios which are presented in the second work of this report. The studies are made for hydrogen, deuterium and mixed plasmas with and without He3 majority. Finally, the antenna designs to reach these several scenarios are presented in the third paper. Two different antenna models are provided for SW excitation, one of the current type and the other one of potential type. A third antenna is designed to excite FW which is similar to the current type antenna for SW, but rotated 90 degree centigree. (Author)11 refs
Cardiac glycoside ouabain induces activation of ATF-1 and StAR expression by interacting with the α4 isoform of the sodium pump in Sertoli cells.

Science.gov (United States)

Dietze, Raimund; Konrad, Lutz; Shihan, Mazen; Kirch, Ulrike; Scheiner-Bobis, Georgios

2013-03-01

Sertoli cells express α1 and α4 isoforms of the catalytic subunit of Na(+),K(+)-ATPase (sodium pump). Our recent findings demonstrated that interactions of the α4 isoform with cardiotonic steroids (CTS) like ouabain induce signaling cascades that resemble the so-called non-classical testosterone pathway characterized by activation of the c-Src/c-Raf/Erk1/2/CREB signaling cascade. Here we investigate a possible physiological significance of the activated cascade. The results obtained in the current investigation show that the ouabain-induced signaling cascade also leads to the activation of the CREB-related activating transcription factor 1 (ATF-1) in the Sertoli cell line 93RS2 in a concentration- and time-dependent manner, as demonstrated by detection of ATF-1 phosphorylated on Ser63 in western blots. The ouabain-activated ATF-1 protein was found to localize to the cell nuclei. The sodium pump α4 isoform mediates this activation, as it is ablated when cells are incubated with siRNA to the α4 isoform. Ouabain also leads to increased expression of steroidogenic acute regulator (StAR) protein, which has been shown to be a downstream consequence of CREB/ATF-1 activation. Taking into consideration that CTS are most likely produced endogenously, the demonstrated induction of StAR expression by ouabain establishes a link between CTS, the α4 isoform of the sodium pump, and steroidogenesis crucial for male fertility and reproduction. Copyright © 2012 Elsevier B.V. All rights reserved.
ATF3 activates Stat3 phosphorylation through inhibition of p53 expression in skin cancer cells.

Science.gov (United States)

Hao, Zhen-Feng; Ao, Jun-Hong; Zhang, Jie; Su, You-Ming; Yang, Rong-Ya

2013-01-01

ATF3, a member of the ATF/CREB family of transcription factors, has been found to be selectively induced by calcineurin/NFAT inhibition and to enhance keratinocyte tumor formation, although the precise role of ATF3 in human skin cancer and possible mechanisms remain unknown. In this study, clinical analysis of 30 skin cancer patients and 30 normal donors revealed that ATF3 was accumulated in skin cancer tissues. Functional assays demonstrated that ATF3 significantly promoted skin cancer cell proliferation. Mechanically, ATF3 activated Stat3 phosphorylation in skin cancer cell through regulation of p53 expression. Moreover, the promotion effect of ATF3 on skin cancer cell proliferation was dependent on the p53-Stat3 signaling cascade. Together, the results indicate that ATF3 might promote skin cancer cell proliferation and enhance skin keratinocyte tumor development through inhibiting p53 expression and then activating Stat3 phosphorylation.
An ATF4-ATG5 signaling in hypothalamic POMC neurons regulates obesity.

Science.gov (United States)

Xiao, Yuzhong; Deng, Yalan; Yuan, Feixiang; Xia, Tingting; Liu, Hao; Li, Zhigang; Chen, Shanghai; Liu, Zhixue; Ying, Hao; Liu, Yi; Zhai, Qiwei; Guo, Feifan

2017-06-03

ATF4 (activating transcription factor 4) is an important transcription factor that has many biological functions, while its role in hypothalamic POMC (pro-opiomelanocortin-α) neurons in the regulation of energy homeostasis has not been explored. We recently discovered that mice with an Atf4 deletion specific to POMC neurons (PAKO mice) are lean and have higher energy expenditure. Furthermore, these mice are resistant to high-fat diet (HFD)-induced obesity and obesity-related metabolic disorders. Mechanistically, we found the expression of ATG5 (autophagy-related 5) is upregulated in POMC neurons of PAKO mice, and ATF4 regulates ATG5 expression by binding directly to its promoter. Mice with Atf4 and Atg5 double knockout in POMC neurons have reduced energy expenditure and gain more fat mass compared with PAKO mice under a HFD. Finally, the effect of Atf4 knockout in POMC neurons is possibly mediated by enhanced ATG5-dependent macroautophagy/autophagy and α-melanocyte-stimulating hormone (α-MSH) production in the hypothalamus. Together, this work not only identifies a beneficial role for ATF4 in hypothalamic POMC neurons in the regulation of obesity, but also provides a new potential therapeutic target for obesity and obesity-related metabolic diseases.
Lipopolysaccharide preconditioning protects hepatocytes from ischemia/reperfusion injury (IRI through inhibiting ATF4-CHOP pathway in mice.

Directory of Open Access Journals (Sweden)

Jianhua Rao

Full Text Available BACKGROUND: Low-dose lipopolysaccharide (LPS preconditioning-induced liver protection has been demonstrated during ischemia-reperfusion injury (IRI in several organs but has not been sufficiently elucidated underlying causal mechanism. This study investigated the role of low-dose LPS preconditioning on ATF4-CHOP pathway as well as the effects of the pathway on tissue injury and inflammation in a mouse model of liver partial-warm IRI. METHODS: LPS (100 µg/kg/d was injected intraperitoneally two days before ischemia. Hepatic injury was evaluated based on serum alanine aminotransferase levels, histopathology, and caspase-3 activity. The ATF4-CHOP pathway and its related apoptotic molecules were investigated after reperfusion. The role of LPS preconditioning on apoptosis and ATF4-CHOP pathway was examined in vitro. Moreover, the effects of the ATF4-CHOP pathway on apoptosis, Caspase-12, and Caspase-3 were determined with ATF4 small interfering RNA (siRNA. Inflammatory cytokine expression was also checked after reperfusion. Inflammatory cytokines and related signaling pathways were analyzed in vitro in macrophages treated by LPS preconditioning or ATF4 siRNA. RESULTS: LPS preconditioning significantly attenuated liver injury after IRI. As demonstrated by in vitro experiments, LPS preconditioning significantly reduced the upregulation of the ATF4-CHOP pathway and inhibited Caspase-12 and Caspase-3 activation after IRI. Later experiments showed that ATF4 knockdown significantly suppressed CHOP, cleaved caspase-12 and caspase-3 expression, as well as inhibited hepatocellular apoptosis. In addition, in mice pretreated with LPS, TNF-α and IL-6 were inhibited after reperfusion, whereas IL-10 was upregulated. Similarly, low-dose LPS significantly inhibited TNF-α, IL-6, ATF4-CHOP pathway, NF-κB pathway, and ERK1/2 in high-dose LPS-stimulated macrophages, whereas IL-10 and cytokine signaling (SOCS-3 suppressor were induced. Importantly, ATF4 siRNA is
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 ...
Inverse Cerenkov laser acceleration experiment at ATF

International Nuclear Information System (INIS)

Wang, X.J.; Pogorelsky, I.; Fernow, R.; Kusche, K.P.; Liu, Y.; Kimura, W.D.; Kim, G.H.; Romea, R.D.; Steinhauer, L.C.

1994-01-01

Inverse Cerenkov laser acceleration was demonstrated using an axicon optical system at the Brookhaven Accelerator Test Facility (ATF). The ATF S-band linac and a high power 10.6 μm CO 2 laser were used for the experiment. Experimental arrangement and the laser and the electron beams synchronization are discussed. The electrons were accelerated more than 0.7 MeV for a 34 MW CO 2 laser power. More than 3.7 MeV acceleration was measured with 0.7 GW CO 2 laser power, which is more than 20 times of the previous ICA experiment. The experimental results are compared with computer program TRANSPORT simulations
Frontline Science: ATF3 is responsible for the inhibition of TNF-α release and the impaired migration of acute ethanol-exposed monocytes and macrophages.

Science.gov (United States)

Hu, Chaojie; Meng, Xiaoming; Huang, Cheng; Shen, Chenlin; Li, Jun

2017-03-01

Binge drinking represses host innate immunity and leads to a high risk of infection. Acute EtOH-pretreated macrophages exhibit a decreased production of proinflammatory mediators in response to LPS. ATF3 is induced and counter-regulates the LPS/TLR4 inflammatory cascade. Here, we investigated the potential role of ATF3 in LPS tolerance in acute ethanol-pretreated macrophages. We found that there was an inverse correlation between ATF3 and LPS-induced TNF-α production in acute ethanol-pretreated murine monocytes and macrophages. The knockdown of ATF3 attenuated the inhibitory effects of acute ethanol treatment on LPS-induced TNF-α production. Furthermore, ChIP assays and co-IP demonstrated that ATF3, together with HDAC1, negatively modulated the transcription of TNF-α. In binge-drinking mice challenged with LPS, an up-regulation of ATF3 and HDAC1 and a concomitant decrease in TNF-α were observed. Given that HDAC1 was concomitantly induced in acute ethanol-exposed monocytes and macrophages, we used the HDACi TSA or silenced HDAC1 to explore the role of HDAC1 in acute ethanol-treated macrophages. Our results revealed that TSA treatment and HDAC1 knockdown prevented acute ethanol-induced ATF3 expression and the inhibition of TNF-α transcription. These data indicated a dual role for HDAC1 in acute ethanol-induced LPS tolerance. Furthermore, we showed that the induction of ATF3 led to the impaired migration of BM monocytes and macrophages. Overall, we present a novel role for ATF3 in the inhibition of LPS-induced TNF-α and in the impairment of monocyte and macrophage migration. © Society for Leukocyte Biology.
p53 and ATF4 mediate distinct and additive pathways to skeletal muscle atrophy during limb immobilization

Science.gov (United States)

Fox, Daniel K.; Ebert, Scott M.; Bongers, Kale S.; Dyle, Michael C.; Bullard, Steven A.; Dierdorff, Jason M.; Kunkel, Steven D.

2014-01-01

Immobilization causes skeletal muscle atrophy via complex signaling pathways that are not well understood. To better understand these pathways, we investigated the roles of p53 and ATF4, two transcription factors that mediate adaptations to a variety of cellular stresses. Using mouse models, we demonstrate that 3 days of muscle immobilization induces muscle atrophy and increases expression of p53 and ATF4. Furthermore, muscle fibers lacking p53 or ATF4 are partially resistant to immobilization-induced muscle atrophy, and forced expression of p53 or ATF4 induces muscle fiber atrophy in the absence of immobilization. Importantly, however, p53 and ATF4 do not require each other to promote atrophy, and coexpression of p53 and ATF4 induces more atrophy than either transcription factor alone. Moreover, muscle fibers lacking both p53 and ATF4 are more resistant to immobilization-induced atrophy than fibers lacking only p53 or ATF4. Interestingly, the independent and additive nature of the p53 and ATF4 pathways allows for combinatorial control of at least one downstream effector, p21. Using genome-wide mRNA expression arrays, we identified p21 mRNA as a skeletal muscle transcript that is highly induced in immobilized muscle via the combined actions of p53 and ATF4. Additionally, in mouse muscle, p21 induces atrophy in a manner that does not require immobilization, p53 or ATF4, and p21 is required for atrophy induced by immobilization, p53, and ATF4. Collectively, these results identify p53 and ATF4 as essential and complementary mediators of immobilization-induced muscle atrophy and discover p21 as a critical downstream effector of the p53 and ATF4 pathways. PMID:24895282

Fluctuations and confinement in ATF

International Nuclear Information System (INIS)

Isler, R.C.; Harris, J.H.; Murakami, M.

1993-01-01

In the period immediately prior to the suspension of ATF operation in November, 1991, a great deal of emphasis was palced on investigations of the fundamental mechanisms controlling confinement in this device. At that time, measurements of the density fluctuations throughout the plasma volume indicated the existence of theoretically predicted dissipative trapped electron and resistive interchange instabilities. These identifications were supported by results of dynamic configuration scans of the magnetic fields during which the extent of the magnetic well, shear, and fraction of confined trapped particles were changed continuously. Interpretation of the data from these experiments has been an ongoing exercise. Most recently, analysis of discharges employing strong gas puffing to change density gradients and fluctuation levels have strengthened the view that dissipative trapped electron modes may be present but do not play a significant direct role in energy transport. The present paper summarizes the current understanding concerning the identification of instabilities and their relationship to confinement in ATF
Bolometric measurements in ATF

International Nuclear Information System (INIS)

Hiroe, S.; Wilgen, J.B.; Batchelor, D.B.; Bigelow, T.S.; Wing, W.R.; Bell, G.L.; Gandy, R.F.; Goldfinger, R.C.; Kindsfather, R.R.

1989-01-01

Bolometer measurements are made under various plasma conditions in ATF. Each bolometer module includes four pairs of detectors; each pair consists of a sensor and a reference detector. Two or three detector pairs in each module were installed with various types of aperture masks to serve as radiation detectors. The rest were completely shielded from plasma emissions and used as blind detectors to measure background levels. When electron cyclotron heating (ECH) power was applied to ATF, the radiation signal was more than 10 times higher than that expected for 100 kW of radiated power. Surprisingly, similar signal levels were observed on the blind detectors. It is hypothesized that the bolometers are sensitive to ECH power at 53 GHz. (This problem may be general in near-term fusion experiments, in which microwave power will be an important tool for plasma heating.) In this paper, experiments aimed at proving this hypothesis are reported; bolometric signals before and after chromium gettering are discussed; and measurements of the microwave power deposition profile around the torus, made by using the observed microwave interference with the blind detectors, are presented. 4 refs., 4 figs
Electron cyclotron heating calculations for ATF

International Nuclear Information System (INIS)

Goldfinger, R.C.; Batchelor, D.B.

1986-03-01

The RAYS geometrical optics code has been used to calculate electron cyclotron wave propagation and heating in the Advanced Toroidal Facility (ATF) device under construction at Oak Ridge National Laboratory (ORNL). The intent of this work is to predict the outcome of various heating scenarios and to give guidance in designing an optimum heating system. Particular attention is paid to the effects of wave polarization and antenna location. We investigate first and second harmonic cyclotron heating with the parameters predicted for steady-state ATF operation. We also simulate the effect of wall reflections by calculating a uniform, isotropic flux of power radiating from the wall. These results, combined with the first-pass calculations, give a qualitative picture of the heat deposition profiles. From these results we identify the compromises that represent the optimum heating strategies for the ATF model considered here. Our basic conclusions are that second harmonic heating with the extraordinary mode (X-mode) gives the best result, with fundamental ordinary mode (O-mode) heating being slightly less efficient. Assuming the antenna location is restricted to the low magnetic field side, the antenna should be placed at phi = 0 0 (the toroidal angle where the helical coils are at the sides) for fundamental heating and at phi = 15 0 (where the helical coils are at the top and bottom) for second harmonic heating. These recommendations come directly from the ray tracing results as well as from a theoretical identification of the relevant factors affecting the heating
Review of the Advanced Toroidal Facility program

International Nuclear Information System (INIS)

Lyon, J.F.; Murakami, M.

1987-01-01

This report summarizes the history and design goals of the Advanced Toroidal Facility (ATF). The ATF is nearing completion at ORNL with device completion expected in May 1987 and first useful plasma operation in June/July 1987. ATF is a moderate-aspect-ratio torsatron, the world's largest stellarator facility with R = 2.1 m, α bar = 0.3 m and B = 2 T (5-s pulse) or 1 T (steady-state capability). It has been specifically designed to support the US tokamak program by studying important toroidal confinement issues in a similar magnetic geometry that allows external control of the magnetic configuration properties and their radial profiles: transform, shear, well depth, shaping, axis topology, etc. ATF will operate in a current-free model which allows separation of current-driven and pressure-driven plasma behavior. It also complements the world stellarator program in its magnetic configuration (between Heliotron-E and W VII-AS) and its capabilities (large size, good access, steady state capability, second stability access, etc.). For both roles ATF will require high-power long-pulse heating to carry out its physics goals since the high power NBI pulse is limited to 0.3 s. The ATF program focuses on demonstrating the principles of high-beta, steady-state operation in toroidal geometry through its study of: (1) scaling of beta limits with magnetic configuration properties and the plasma behavior in the second stability regime; (2) transport scaling at low collisionality and the role/control of electric field; (3) control of plasma density and impurities using divertors; (4) plasma heating with NBI, ECH, ICH, and plasma fueling with gas puffing and pellet injection; and (5) optimization of the magnetic configuration
Choice of cooling regime of the superconducting magnetic system of the ''Crystal-2'' torsatron

International Nuclear Information System (INIS)

Glasov, B.V.; Druj, O.S.; Kurnosov, V.I.; Skibenko, E.I.; Yuferov, V.B.

1981-01-01

General requirements to a system of cryogenic cooling of superconducting magnetic systems (SMS) are formulated. Distributions of the value of thermal stresses about the temperature range are obtained for basic construction materials of SMS ''Crystal-2'' torsatron. Concrete circuits of SMS cryoprovision are considered. Values of specific and total heat capacity of the system, specific consumption of liquid are determined taking into consideration constructional peculiarities of SMS of''Crystal-2'' plant. Efficiency of different ways of SMS cooling are estimated, dynamical dependences of cooling and heating of SMS of the ''Crystal-2'' plant are obtained taking this into consideration [ru
Determination of the electronic temperature in the torsatron TJ-I Upgrade by the two filters

Energy Technology Data Exchange (ETDEWEB)

Medina, F.; Ochando, M.

1994-07-01

A Te monitor for the TJ-IU torsatron, based on the two-filters method, has been designed. It will consist of two surface-barrier silicon detectors looking at the same plasma region through berylium filters of different thickness. Plasma electron temperature is deduced from the ratio of the soft-x-ray fluxes transmitted through the two filters. The flexibility in magnetic configuration of TJ-IU plasmas has been taken into account in the mechanical design of this diagnostic. It will be attached to an upper 1 port of the vacuum vessel and the whole system will be movable both, to change the spatial resolution when needed and to enable the scan of the full plasma cross-section to obtain the radial profile of electron temperature in a shot-to-shot basis. (Author) 7 refs.
Determination of the electronic temperature in the torsatron TJ-I Upgrade by the two filters

International Nuclear Information System (INIS)

Medina, F.; Ochando, M.

1994-01-01

A Te monitor for the TJ-IU torsatron, based on the two-filters method, has been designed. It will consist of two surface-barrier silicon detectors looking at the same plasma region through berylium filters of different thickness. Plasma electron temperature is deduced from the ratio of the soft-x-ray fluxes transmitted through the two filters. The flexibility in magnetic configuration of TJ-IU plasmas has been taken into account in the mechanical design of this diagnostic. It will be attached to an upper 1 port of the vacuum vessel and the whole system will be movable both, to change the spatial resolution when needed and to enable the scan of the full plasma cross-section to obtain the radial profile of electron temperature in a shot-to-shot basis. (Author) 7 refs
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.
Experimental results of the ATF in-line injection system

International Nuclear Information System (INIS)

Wang, X.J.; Srinivasan-Rao, T.; Batchelor, K.

1995-01-01

The initial experimental results of the Brookhaven accelerator test facility (ATF) in-line injector is presented. The ATF in-line injector employed a full copper RF gun with a pair of solenoid magnets for emittance compensation. The maximum acceleration field of the RF gun was measured to be 130 MV/m. The electron yield from the copper cathode was maximized using p- polarized laser and the Schottky effect. The quantum efficiency under optimum conditions was measured to be 0.04%. The measured electron bunch length was less than 11 ps, which agreed with the laser pulse length measurement using a streak camera. The normalized rms. emittance for 0.25 nC charge is 0.9 ± 0.1 mm-mrad, which is almost four times smaller than the emittance predicted by the space-charge effect for a non-emittance compensation photocathode RF gun. The normalized rms for 0.6 nC charge was measured range from 1 to 3 mm-mrad. This measurement was first experimental demonstration of emittance compensation in a high-gradient, S-band photocathode RF gun
Solve: a non linear least-squares code and its application to the optimal placement of torsatron vertical field coils

International Nuclear Information System (INIS)

Aspinall, J.

1982-01-01

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
ATF2 spot size tuning using the rotation matrix

CERN Document Server

Scarfe, A; Jones, J K; Angal-Kalinin, D

2010-01-01

The Accelerator Test Facility (ATF2) at KEK aims to experimentally verify the local chromaticity correction scheme to achieve a vertical beam size of 37nm. The facility is a scaled down version of the final focus design proposed for the future linear colliders. In order to achieve this goal, high precision tuning methods are being developed. One of the methods proposed for ATF2 is a novel method known as the ‘rotation matrix’ method. Details of the development and testing of this method, including orthogonality optimisation and simulation methods, are presented.
The FONT5 Bunch-by-Bunch Position and Angle Feedback System at ATF2

Science.gov (United States)

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

The FONT5 upstream beam-based feedback system at ATF2 is designed to correct the position and angle jitter at the entrance to the ATF2 final-focus system, and also to demonstrate a prototype intra-train feedback system for the International Linear Collider interaction point. We discuss the hardware, from stripline BPMs to kickers, and RF and digital signal processing, as well as presenting results from the latest beam tests at ATF2.
Dynamic behavior associated with electric field transitions in CHS Heliotron/Torsatron

International Nuclear Information System (INIS)

Fujisawa, A.; Iguchi, H.; Lee, S.

2001-01-01

A new kind of oscillatory steady state is discovered in observation of potential with a heavy ion beam probe in Compact Helical System Heliotron/Torsatron. Bulk plasma parameters, such as electron temperature and density profile, change being synchronized with the pulsation of potential. The phenomenon can be regarded as successive transitions between two bifurcative states of the plasma. The pulsation can be self-sustained and create a dynamic steady state in low density plasma with electron cyclotron heating. The cause of phenomenon is associated with the bifurcation nature of radial electric field, that is inherent with toroidal helical plasmas. This paper presents two examples of the phenomenon in different density regimes. Dependence of pulsation characteristics on several parameters is described. The bifurcation property predicted by a neoclassical theory is presented for comparison with the experimental observations. (author)
The cellular transcription factor CREB corresponds to activating transcription factor 47 (ATF-47) and forms complexes with a group of polypeptides related to ATF-43.

OpenAIRE

Hurst, H C; Masson, N; Jones, N C; Lee, K A

1990-01-01

Promoter elements containing the sequence motif CGTCA are important for a variety of inducible responses at the transcriptional level. Multiple cellular factors specifically bind to these elements and are encoded by a multigene family. Among these factors, polypeptides termed activating transcription factor 43 (ATF-43) and ATF-47 have been purified from HeLa cells and a factor referred to as cyclic AMP response element-binding protein (CREB) has been isolated from PC12 cells and rat brain. We...
A beam-profile monitor for the BNL Accelerator Test Facility (ATF)

International Nuclear Information System (INIS)

Russell, D.P.; McDonald, K.T.

1989-01-01

A beam-profile monitor has been designed to diagnose the 5-MeV high-brightness electron beam from the rf gun of the BNL Accelerator Test Facility (ATF). The monitor consists of a phosphor screen viewed by a CCD camera. The video images are digitized and stored by a framegrabber and analyzed by an IBM PC-AT to extract the emittance. Details of the hardware configuration are presented, along with the spatial resolution of the system measured as a function of phosphor-screen thickness. The strategies which will be used to measure the transverse and longitudinal emittances are briefly mentioned. The system should be capable of measuring a transverse geometric emittance of around 1 mm-mrad, as will be typical of the ATF beam. 6 refs., 2 figs
Operational Experiences Tuning the ATF2 Final Focus Optics Towards Obtaining a 37nm Electron Beam IP Spot Size

CERN Document Server

White, Glen; Woodley, Mark; Bai, Sha; Bambade, Philip; Renier, Yves; Bolzon, Benoit; Kamiya, Yoshio; Komamiya, Sachio; Oroku, Masahiro; Yamaguchi, Yohei; Yamanaka, Takashi; Kubo, Kiyoshi; Kuroda, Shigeru; Okugi, Toshiyuki; Tauchi, Toshiaki; Marin, Eduardo

2010-01-01

The primary aim of the ATF2 research accelerator is to test a scaled version of the final focus optics planned for use in next-generation linear lepton colliders. ATF2 consists of a 1.3 GeV linac, damping ring providing lowemittance electron beams (<12pm in the vertical plane), extraction line and final focus optics. The design details of the final focus optics and implementation at ATF2 are presented elsewhere. The ATF2 accelerator is currently being commissioned, with a staged approach to achieving the design IP spot size. It is expected that as we implement more demanding optics and reduce the vertical beta function at the IP, the tuning becomes more difficult and takes longer. We present here a description of the implementation of the tuning procedures and describe operational experiences and performances
Transition from L mode to high ion temperature mode in CHS heliotron/torsatron plasmas

International Nuclear Information System (INIS)

Ida, K.; Osakabe, M.; Tanaka, K.

2001-01-01

A high ion temperature mode (high T i mode) is observed for neutral beam heated plasmas in the Compact Helical System (CHS) Heliotron/torsatron. The high T i mode plasma is characterized by a high central ion temperature, T i (0), and is associated with a peaked electron density profile produced by neutral beam fueling with low wall recycling. Transition from L mode to high T i mode has been studied in CHS. The central ion temperature in the high T i mode discharges reaches to 1 keV which is 2.5 times higher than that in the L mode discharges. The ion thermal diffusivity is significantly reduced by a factor of more than 2-3 in the high T i mode plasma. The ion loss cone is observed in neutral particle flux in the energy range of 1-6 keV with a narrow range of pitch angle (90±10 degree) in the high T i mode. However, the degradation of ion energy confinement due to this loss cone is negligible. (author)
Development of the C-Band BPM System for ATF2

CERN Document Server

Lyapin, A; Wing, M; Shin, S; Honda, Y; Tauchi, T; Terunuma, N; Heo, A; Kim, E; Kim, K; Ainsworth, R C E; Boogert, S T; Boorman, G; Molloy, S; McCormick, D; Nelson, J; White, G; Ward, D

2010-01-01

The ATF2 international collaboration is intending to demonstrate nanometre beam sizes required for the future Linear Colliders. An essential part of the beam diagnostics needed to achieve that goal is the high resolution cavity beam position monitors (BPMs). In this paper we report on the C-band system consisting of 32 BPMs spread over the whole length of the new ATF2 extraction beamline. We discuss the design of the BPMs and electronics, main features of the DAQ system, and the first operational experience with these BPMs.
ATF4, A Novel Mediator of the Anabolic Actions of PTH on Bone

Science.gov (United States)

2008-07-01

pathways. Lastly, PTH stimulation of Ocn expres- sion was lost by silent interfering RNA down-regulation of ATF4 in MC-4 cells and Atf4/ bone marrow...M 2000 Para- thyroid hormone-related protein downregulates bone sialoprotein gene ex- pression in cementoblasts: role of the protein kinase A pathway
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.

2015-01-01

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. PMID:26667036

Social isolation stress induces ATF-7 phosphorylation and impairs silencing of the 5-HT 5B receptor gene

Science.gov (United States)

Maekawa, Toshio; Kim, Seungjoon; Nakai, Daisuke; Makino, Chieko; Takagi, Tsuyoshi; Ogura, Hiroo; Yamada, Kazuyuki; Chatton, Bruno; Ishii, Shunsuke

2010-01-01

Many symptoms induced by isolation rearing of rodents may be relevant to neuropsychiatric disorders, including depression. However, identities of transcription factors that regulate gene expression in response to chronic social isolation stress remain elusive. The transcription factor ATF-7 is structurally related to ATF-2, which is activated by various stresses, including inflammatory cytokines. Here, we report that Atf-7-deficient mice exhibit abnormal behaviours and increased 5-HT receptor 5B (Htr5b) mRNA levels in the dorsal raphe nuclei. ATF-7 silences the transcription of Htr5B by directly binding to its 5′-regulatory region, and mediates histone H3-K9 trimethylation via interaction with the ESET histone methyltransferase. Isolation-reared wild-type (WT) mice exhibit abnormal behaviours that resemble those of Atf-7-deficient mice. Upon social isolation stress, ATF-7 in the dorsal raphe nucleus is phosphorylated via p38 and is released from the Htr5b promoter, leading to the upregulation of Htr5b. Thus, ATF-7 may have a critical role in gene expression induced by social isolation stress. PMID:19893493
Beam-based alignment at the KEK-ATF damping ring

International Nuclear Information System (INIS)

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

2004-01-01

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
FIR interferometer and scattering measurements of ATF

International Nuclear Information System (INIS)

Ma, C.H.; Hutchinson, D.P.; Fockedey, Y.; Vander Sluis, K.L.; Bennett, C.A.

1989-01-01

A 15-channel far-infrared (FIR) interferometer system has been constructed to measure the electron densities on the ATF plasmas. The system consists of a pair of cw 214-μm difluoromethane (CH 2 F 2 ) lasers, optically pumped by separate CO 2 lasers. The large number of channels is achieved by the use of reflective beam expansion optics to create a beam of 2 cm /times/ 45 cm. After passing through the plasma discharge, the elongated beam produced by the cylindrical mirrors is dissected by an array of 15 off-axis paraboloid reflectors, each of which illuminates a single Schottky-diode detector. The use of the beam expanding optics system reduces the number of optical elements required for the interferometer to approximately 2-3 per channel. The FIR laser beams are transported from the laser room to the experimental area by 25 mm i.d. dielectric waveguides purged with dry nitrogen. The system can also be operated at a wavelength of 119-μm by changing the gas in FIR laser cavities to methanol for high density experiments. Details of the system are described. A study is underway to determine the optimum design of a FIR scattering system for the ATF. This scattering system will be used to investigate density fluctuations with scale lengths from 0.1 cm to the plasma radius. The laser for this scattering system may be operated at wavelengths of 447, 307, 214, 184, and 119 μm with power levels of 100 to 500 mW. A summary of the study is presented. 6 refs., 1 fig
The CDK inhibitor p21 is a novel target gene of ATF4 and contributes to cell survival under ER stress.

Science.gov (United States)

Inoue, Yasumichi; Kawachi, Shiori; Ohkubo, Tsubasa; Nagasaka, Mai; Ito, Shogo; Fukuura, Keishi; Itoh, Yuka; Ohoka, Nobumichi; Morishita, Daisuke; Hayashi, Hidetoshi

2017-11-01

Activating transcription factor 4 (ATF4) is well known for its role in the endoplasmic reticulum (ER) stress response. ATF4 also transcriptionally induces multiple effectors that determine cell fate depending on cellular context. In addition, ATF4 can communicate both pro-apoptotic and pro-survival signals. How ATF4 mediates its prosurvival roles, however, requires further investigation. Here, we report that the CDK inhibitor p21 is a novel target gene of ATF4. We identified two ATF4-responsive elements, one of which directly binds ATF4, within the first intron of the p21 gene. Importantly, overexpression of p21 enhances cell survival following ER stress induction, while p21 knockdown increases cell death. These results suggest that p21 induction plays a vital role in the cellular response to ER stress and indicate that p21 is a prosurvival effector of ATF4. © 2017 Federation of European Biochemical Societies.
Functional analysis of atfA gene to stress response in pathogenic thermal dimorphic fungus Penicillium marneffei.

Directory of Open Access Journals (Sweden)

Panjaphorn Nimmanee

Full Text Available 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.
High-brightness electron beam diagnostics at the ATF

International Nuclear Information System (INIS)

Wang, X.J.; Ben-Zvi, I.

1996-01-01

The Brookhaven Accelerator Test Facility (ATF) is a dedicated user facility for accelerator physicists. Its design is optimized to explore laser acceleration and coherent radiation production. To characterize the low-emittance, picoseconds long electron beam produced by the ATF's photocathode RF gun, we have installed electron beam profile monitors for transverse emittance measurement, and developed a new technique to measure electron beam pulse length by chirping the electron beam energy. We have also developed a new technique to measure the ps slice emittance of a 10 ps long electron beam. Stripline beam position monitors were installed along the beam to monitor the electron beam position and intensity. A stripline beam position monitor was also used to monitor the timing jitter between the RF system and laser pulses. Transition radiation was used to measure electron beam energy, beam profile and electron beam bunch length
Transcriptome-Based Modeling Reveals that Oxidative Stress Induces Modulation of the AtfA-Dependent Signaling Networks in Aspergillus nidulans

Directory of Open Access Journals (Sweden)

Erzsébet Orosz

2017-01-01

Full Text Available To better understand the molecular functions of the master stress-response regulator AtfA in Aspergillus nidulans, transcriptomic analyses of the atfA null mutant and the appropriate control strains exposed to menadione sodium bisulfite- (MSB-, t-butylhydroperoxide- and diamide-induced oxidative stresses were performed. Several elements of oxidative stress response were differentially expressed. Many of them, including the downregulation of the mitotic cell cycle, as the MSB stress-specific upregulation of FeS cluster assembly and the MSB stress-specific downregulation of nitrate reduction, tricarboxylic acid cycle, and ER to Golgi vesicle-mediated transport, showed AtfA dependence. To elucidate the potential global regulatory role of AtfA governing expression of a high number of genes with very versatile biological functions, we devised a model based on the comprehensive transcriptomic data. Our model suggests that an important function of AtfA is to modulate the transduction of stress signals. Although it may regulate directly only a limited number of genes, these include elements of the signaling network, for example, members of the two-component signal transduction systems. AtfA acts in a stress-specific manner, which may increase further the number and diversity of AtfA-dependent genes. Our model sheds light on the versatility of the physiological functions of AtfA and its orthologs in fungi.
Equilibrium and stability studies for high beta plasmas in torsatron/heliotron devices

International Nuclear Information System (INIS)

Carreras, B.A.; Cooper, W.A.; Charlton, L.A.

1983-01-01

The equilibrium and stability properties of high β plasmas in torsatron/heliotron devices have been investigated. Three numerical approaches have been used to study plasma equilibria for a range of coil configurations. The method of averaging permits fast equilibrium and stability calculations. Two fully 3-D codes, namely the Chodura-Schluter code, and the NEAR code recently developed at ORNL, are used to explore selected regions of parameter space. The resulting equilibria calculated with different methods are in good agreement. This validates the average method approach and enhances its usefulness. Results are presented for configurations with different aspect ratios and number of field periods. The role of the vertical field has also been studied in detail. The main conclusion is that for moderate aspect ratios (Asub(p) <= 8), the self-stabilizing effect of the magnetic axis shift is large enough to open a direct path to the second stability regime. (author)
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.
Ku70 acetylation and modulation of c-Myc/ATF4/CHOP signaling axis by SIRT1 inhibition lead to sensitization of HepG2 cells to TRAIL through induction of DR5 and down-regulation of c-FLIP

DEFF Research Database (Denmark)

Kim, Mi-Ju; Hong, Kyung-Soo; Kim, Hak-Bong

2013-01-01

In this study, we investigated the role of c-Myc/ATF4/CHOP signaling pathway in sensitization of human hepatoma HepG2 cells to TRAIL. Knockdown of SIRT1 or treatment with SIRT1 inhibitor caused the up-regulation of DR5 and down-regulation of c-FLIP through modulation of c-Myc/ATF4/CHOP pathway, a...
Metformin-induced inhibition of the mitochondrial respiratory chain increases FGF21 expression via ATF4 activation

International Nuclear Information System (INIS)

Kim, Kook Hwan; Jeong, Yeon Taek; Kim, Seong Hun; Jung, Hye Seung; Park, Kyong Soo; Lee, Hae-Youn; Lee, Myung-Shik

2013-01-01

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
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.
Essential role of eIF5-mimic protein in animal development is linked to control of ATF4 expression

Science.gov (United States)

Translational control of ATF4 through upstream ORFs (uORFs) plays an important role in eukaryotic gene regulation. While ATF4 translation is typically induced by inhibitory phosphorylation of eIF2, ATF4 translation can be also induced by expression of a new translational inhibitor protein, eIF5-mimi...
SAMS: The synchronization and monitoring system for ATF [Advanced Toroidal Facility] data acquisition

International Nuclear Information System (INIS)

Greenwood, D.E.

1987-01-01

SAMS performs much of the synchronization of the distributed data acquisition system for the Advanced Toroidal Facility (ATF). SAMS is responsible for propagating shot information and managing te data system directories and logical names. This paper describes how SAMS communicates with other processes, both within the VAX cluster that supports most of the ATF data acquisition and on VAXes that are connected to the cluster via DECnet. 3 refs
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

2016-10-14

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. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.
Equilibrium and stability studies for high-beta plasmas in torsatron/heliotron devices

International Nuclear Information System (INIS)

Carreras, B.A.; Charlton, L.A.; Cooper, W.A.

1983-01-01

The equilibrium and stability properties of high-#betta# plasmas in torsatron/heliotron devices have been investigated. Three numerical approaches have been used to study plasma equilibria for a range of coil configurations. The method of averaging permits fast equilibrium and stability calculations. Two fully 3-D codes, namely the Chodura-Schluter code, and the NEAR code recently developed at ORNL, are used to explore selected regions of parameter space. The resulting equilibria calculated with different methods are in good agreement. This validates the average method approach and enhances its usefulness. Results are presented for configurations with different aspect ratios and number of field periods. The role of the vertical field has also been studied in detail. The main conclusion is that for moderate aspect ratios (A/sub p/ less than or equal to 8), the self-stabilizing effect of the magnetic-axis shift is large enough to open a direct path to the second-stability regime
The first terawatt picosecond CO2 laser for advanced accelerator studies at the Brookhaven ATF

International Nuclear Information System (INIS)

Pogorelsky, I.V.; Ben-Zvi, I.; Skaritka, J.

1996-10-01

The first terawatt picosecond C0 2 laser system is under development at the Brookhaven Accelerator Test Facility. Presently operational 1 Joule 100-ps ATF laser will be upgraded with a 10 atm amplifier capable of delivery ∼ 15 Joules of laser energy in a 3 ps pulse. We describe the design of the x-ray preionized 10 atm amplifier of a 10 liter active volume energized by a 1 MV, 200 kA transverse electric discharge. The amplifier, equipped with internal optics, permits the accommodation of a regenerative stage and a multi-pass booster in a relatively compact single discharge volume. The ATF terawatt C0 2 laser shall become operational in 1997 to serve for laser acceleration, x-ray generation and other strong-field physics experiments
Fast wave heating experiments in the ion cyclotron range of frequencies on ATF

Energy Technology Data Exchange (ETDEWEB)

Kwon, M; Shepard, T D; Goulding, R H [Oak Ridge National Lab., TN (United States); and others

1992-07-01

Fast wave heating experiments in the ion cyclotron range of frequencies (ICRF) were performed on target plasmas produced by 350 kW of electron cyclotron heating at 53 GHz and also by neutral beam injection in the Advanced Toroidal Facility (ATF). Various heating regimes were investigated in the frequency range between 9.2 MHz and 28.8 MHz with magnetic fields of 0.95 T and 1.9 T on axis. The nominal pulse lengths of up to 200 kW RF power were in the range between 100 and 400 ms. Data from spectroscopy, loading measurements, and edge RF and Langmuir probes were used to characterize the RF induced effects on the ATF plasma. In the hydrogen minority regime at low plasma density, large suprathermal ion tails were observed with a neutral particle analyser. At high density (n-bar{sub e} {>=} 5.0 x 10{sup 13} cm{sup -3}) substantial increases in antenna loading were observed, but ICRF power was insufficient to produce definitive heating results. A two-dimensional RF heating code, ORION, and a Fokker-Planck code, RFTRANS, were used to simulate these experiments. A simulation of future high power, higher density experiments in ATF indicates improved bulk heating results due to the improved loading and more efficient thermalization of the minority tail. (author). 29 refs, 16 figs, 3 tabs.
RIA simulation tests using driver tube for ATF cladding

Energy Technology Data Exchange (ETDEWEB)

Cinbiz, Mahmut N. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Brown, N. R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Lowden, R. R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Linton, K. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Terrani, K. A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

2017-07-01

Pellet-cladding mechanical interaction (PCMI) is a potential failure mechanism for accident-tolerant fuel (ATF) cladding candidates during a reactivity-initiated accident (RIA). This report summarizes Fiscal Year (FY) 2017 research activities that were undertaken to evaluate the PCMI-like hoop-strain-driven mechanical response of ATF cladding candidates. To achieve various RIA-like conditions, a modified-burst test (MBT) device was developed to produce different mechanical pulses. The calibration of the MBT instrument was accomplished by performing mechanical tests on unirradiated Generation-I iron-chromium-aluminum (FeCrAl) alloy samples. Shakedown tests were also conducted in both FY 2016 and FY 2017 using unirradiated hydrided ZIRLO™ tube samples. This milestone report focuses on testing of ATF materials, but the benchmark tests with hydrided ZIRLO™ tube samples are documented in a recent journal article.a For the calibration and benchmark tests, the hoop strain was monitored using strain gauges attached to the sample surface in the hoop direction. A novel digital image correlation (DIC) system composed of a single high-speed camera and an array of six mirrors was developed for the MBT instrument to better resolve the failure behavior of samples and to provide useful data for validation of high-fidelity modeling and simulation tools. The DIC system enable a 360° view of a sample’s outer surface. This feature was added to the instrument to determine the precise failure location on a sample’s surface for strain predictions. The DIC system was tested on several silicon carbide fiber/silicon carbide matrix (SiC/SiC) composite tube samples at various pressurization rates of the driver tube (which correspond to the strain rates for the samples). The hoop strains for various loading conditions were determined for the SiC/SiC composite tube samples. Future work is planned to enhance understanding of the failure behavior of the ATF cladding candidates of age
Processes arising in the edge and diverted plasmas during ITB formation in the U-3M torsatron

Energy Technology Data Exchange (ETDEWEB)

Chechkin, V V [Institute of Plasma Physics, National Science Center ' Kharkov Institute of Physics and Technology' , Akademicheskaya st. 1, 61108 Kharkov (Ukraine); Grigor' eva, L I [Institute of Plasma Physics, National Science Center ' Kharkov Institute of Physics and Technology' , Akademicheskaya st. 1, 61108 Kharkov (Ukraine); Sorokovoy, E L [Institute of Plasma Physics, National Science Center ' Kharkov Institute of Physics and Technology' , Akademicheskaya st. 1, 61108 Kharkov (Ukraine); Sorokovoy, Ye L [Institute of Plasma Physics, National Science Center ' Kharkov Institute of Physics and Technology' , Akademicheskaya st. 1, 61108 Kharkov (Ukraine); Slavnyj, A S [Institute of Plasma Physics, National Science Center ' Kharkov Institute of Physics and Technology' , Akademicheskaya st. 1, 61108 Kharkov (Ukraine); Volkov, Ye D [Institute of Plasma Physics, National Science Center ' Kharkov Institute of Physics and Technology' , Akademicheskaya st. 1, 61108 Kharkov (Ukraine); Beletskij, A A [Institute of Plasma Physics, National Science Center ' Kharkov Institute of Physics and Technology' , Akademicheskaya st. 1, 61108 Kharkov (Ukraine); Burchenko, P Ya [Institute of Plasma Physics, National Science Center ' Kharkov Institute of Physics and Technology' , Akademicheskaya st. 1, 61108 Kharkov (Ukraine); Tsybenko, S A [Institute of Plasma Physics, National Science Center ' Kharkov Institute of Physics and Technology' , Akademicheskaya st. 1, 61108 Kharkov (Ukraine); Lozin, A V [Institute of Plasma Physics, National Science Center ' Kharkov Institute of Physics and Technology' , Akademicheskaya st. 1, 61108 Kharkov (Ukraine); Kulaga, A Ye; Letvinov, A P [Institute of Plasma Physics, National Science Center ' Kharkov Institute of Physics and Technology' , Akademicheskaya st. 1, 61108 Kharkov (Ukraine); Masuzaki, S; Yamazaki, K [National Institute for Fusion Science, Oroshi-cho 322-6, Toki-shi 509-5292 (Japan)

2006-05-15

Spontaneous changes in confined plasma parameters have been observed recently in the l = 3/m = 9 Uragan-3M torsatron with an RF produced and heated plasma, these being interpreted as transition to an improved confinement mode due to ITB formation near the {iota} = 1/4 rational magnetic surface. In the work presented joint studies are carried out of changes in some edge and diverted plasma characteristics that accompany ITB formation. It is shown that ITB formation induces a hard E{sub r} bifurcation at the boundary presumably driven by the ion orbit loss. As a result, E{sub r} becomes more negative, and an E{sub r} shear layer occurs, where the low-frequency microturbulence and the turbulence-induced anomalous transport are suppressed, i.e. an ETB is formed. At the pre-bifurcation phase of transition a reduction of fast ion loss takes place. The bifurcation results in an improvement of electron confinement, while the ion loss increases.

Determination of the electronic temperature in the torsatron TJ-I Upgrade by the two filters

International Nuclear Information System (INIS)

Medina, F.; Ochando, M.

1994-01-01

A Te monitor for the TJ-IU torsatron, based on the two-filters method, has been designed. It will consist of two surface-barrier silicon detectors looking at the same plasma region through berilium filters of different thickness. Plasma electron temperature is deduced from the ratio of the soft-x-ray fluxes transmitted through the two filters. The flexibility in magnetic configuration of TJ-IU plasmas has been taken into account in the mechanical design of this diagnostic. It will be attached to an upper port of the vacuum vessel and the whole system will be movable both, to change the spatial resolution when needed and to enable the scan of the full plasma cross-section to obtain the radial profile of electron temperature in a shot-to-shot basis. (Author)
Zeff measurements in ATF using visible bremsstrahlung

International Nuclear Information System (INIS)

Morita, S.; Richards, R.K.; Horton, L.D.; Isler, R.C.; Crume, E.C. Jr.; Murakami, M.

1991-04-01

Measurements of the effective charge Z eff in plasmas with electron cyclotron heating (ECH) and neutral beam injection (NBI) in the Advanced Toroidal Facility (ATF) have been carried out using visible bremsstrahlung. The electron temperature needed for the analysis is calculated from the measured stored energy and electron density. The value of Z eff varies widely depending on experimental conditions. In ECH plasmas it is between 2 and 8. In NBI plasmas, which are subject to radiation collapse, Z eff is between 3 and 5 at the time the stored energy reaches a maximum. However, Z eff is less than 2.5 in quasi-steady medium-density plasmas and is close to 1.2 in the highest-density plasmas, where the average electron density bar n e is of the order of 10 14 cm -3 . 12 refs., 29 figs., 1 tab
The Effects of IGF-1 on TNF-α-Treated DRG Neurons by Modulating ATF3 and GAP-43 Expression via PI3K/Akt/S6K Signaling Pathway.

Science.gov (United States)

Zhang, Lei; Yue, Yaping; Ouyang, Meishuo; Liu, Huaxiang; Li, Zhenzhong

2017-05-01

Upregulation of the pro-inflammatory cytokine tumor necrosis factor α (TNF-α) is involved in the development and progression of numerous neurological disorders. Recent reports have challenged the concept that TNF-α exhibits only deleterious effects of pro-inflammatory destruction, and have raised the awareness that it may play a beneficial role in neuronal growth and function in particular conditions, which prompts us to further investigate the role of this cytokine. Insulin-like growth factor-1 (IGF-1) is a cytokine possessing powerful neuroprotective effects in promoting neuronal survival, neuronal differentiation, neurite elongation, and neurite regeneration. The association of IGF-1 with TNF-α and the biological effects, produced by interaction of IGF-1 and TNF-α, on neuronal outgrowth status of primary sensory neurons are still to be clarified. In the present study, using an in vitro model of primary cultured rat dorsal root ganglion (DRG) neurons, we demonstrated that TNF-α challenge at different concentrations elicited diverse biological effects. Higher concentration of TNF-α (10 ng/mL) dampened neurite outgrowth, induced activating transcription factor 3 (ATF3) expression, reduced growth-associated protein 43 (GAP-43) expression, and promoted GAP-43 and ATF3 coexpression, which could be reversed by IGF-1 treatment; while lower concentration of TNF-α (1 ng/mL) promoted neurite sprouting, decreased ATF3 expression, increased GAP-43 expression, and inhibited GAP-43 and ATF3 coexpression, which could be potentiated by IGF-1 supplement. Moreover, IGF-1 administration restored the activation of Akt and p70 S6 kinase (S6K) suppressed by higher concentration of TNF-α (10 ng/mL) challenge. In contrast, lower concentration of TNF-α (1 ng/mL) had no significant effect on Akt or S6K activation, and IGF-1 administration activated these two kinases. The effects of IGF-1 were abrogated by phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. These data
Studies of plasma performance and transport in the advanced toroidal facility (ATF)

International Nuclear Information System (INIS)

Neilson, G.H.; Bigelow, T.S.; Carreras, B.A.

1989-01-01

An overview of recent ATF experimental results and program plans is presented, with emphasis on the role of magnetic configuration controls in transport studies. The ATF operating space is bounded by a density limit that effectively sets a limit on the energy confinement time τ E . Although this limit is not solely due to impurities, it has recently been raised by improved cleanliness following titanium gettering. This has led to collapse-free neutral beam injection (NBI) discharges with global τ E ∼ 16 ms. Preliminary experiments show that stored energy and bootstrap current are sensitive to details of the magnetic configuration. 13 refs., 8 figs
ATF3 mediates inhibitory effects of ethanol on hepatic gluconeogenesis.

Science.gov (United States)

Tsai, Wen-Wei; Matsumura, Shigenobu; Liu, Weiyi; Phillips, Naomi G; Sonntag, Tim; Hao, Ergeng; Lee, Soon; Hai, Tsonwin; Montminy, Marc

2015-03-03

Increases in circulating glucagon during fasting maintain glucose balance by stimulating hepatic gluconeogenesis. Acute ethanol intoxication promotes fasting hypoglycemia through an increase in hepatic NADH, which inhibits hepatic gluconeogenesis by reducing the conversion of lactate to pyruvate. Here we show that acute ethanol exposure also lowers fasting blood glucose concentrations by inhibiting the CREB-mediated activation of the gluconeogenic program in response to glucagon. Ethanol exposure blocked the recruitment of CREB and its coactivator CRTC2 to gluconeogenic promoters by up-regulating ATF3, a transcriptional repressor that also binds to cAMP-responsive elements and thereby down-regulates gluconeogenic genes. Targeted disruption of ATF3 decreased the effects of ethanol in fasted mice and in cultured hepatocytes. These results illustrate how the induction of transcription factors with overlapping specificity can lead to cross-coupling between stress and hormone-sensitive pathways.
Variants near DMRT1, TERT and ATF7IP are associated with testicular germ cell cancer

Science.gov (United States)

Turnbull, Clare; Rapley, Elizabeth A.; Seal, Sheila; Pernet, David; Renwick, Anthony; Hughes, Deborah; Ricketts, Michelle; Linger, Rachel; Nsengimana, Jeremie; Deloukas, Panagiotis; Huddart, Robert A.; Bishop, D Timothy; Easton, Douglas F.; Stratton, Michael R.; Rahman, Nazneen

2013-01-01

We conducted a genome-wide association study for testicular germ cell tumor genotyping 298,782 SNPs in 979 cases and 4,947 controls from the UK and replicating associations in a further 664 cases and 3,456 controls. We identified three novel susceptibility loci, two of which include genes that are involved in telomere regulation. We identified two independent signals within the TERT-CLPTM1L locus on chromosome 5 which has been associated with multiple other cancers (rs4635969, OR=1.54 (95%CI 1.33-1.79), P=1.14×10−23 and rs2736100, OR 1.33 (1.18-1.50) P=7.55 ×10−15). We also identified a locus on chromosome 12 (rs2900333, OR=1.27 (95%CI 1.12-1.44), P=6.16×10−10) that contains ATF7IP, a regulator of TERT expression. Finally we identified a locus on chromosome 9 (rs755383, OR=1.37 (95%CI 1.21-1.55), P=1.12×10−23) containing the sex determination gene DMRT1, which has been linked with teratoma susceptibility in mice. PMID:20543847
Activating transcription factor-3 (ATF3) functions as a tumor suppressor in colon cancer and is up-regulated upon heat-shock protein 90 (Hsp90) inhibition

International Nuclear Information System (INIS)

Hackl, Christina; Stoeltzing, Oliver; Lang, Sven A; Moser, Christian; Mori, Akira; Fichtner-Feigl, Stefan; Hellerbrand, Claus; Dietmeier, Wolfgang; Schlitt, Hans J; Geissler, Edward K

2010-01-01

Activating transcription factor-3 (ATF3) is involved in the complex process of cellular stress response. However, its exact role in cancer is discussed controversially because both tumor suppressive and oncogenic effects have been described. Here we followed-up on our previous observation that inhibition of Hsp90 may increase ATF3 expression and sought to determine the role of ATF3 in colon cancer. Regulation of ATF3 was determined in cancer cells using signaling inhibitors and a heat-shock protein-90 (Hsp90) antagonist. Human HCT116 cancer cells were stably transfected with an ATF3-shRNA or a luciferase-shRNA expression plasmid and alterations in cell motility were assessed in migration assays. The impact of ATF3 down-regulation on cancer growth and metastasis were investigated in a subcutaneous tumor model, a model of hepatic tumor growth and in a model of peritoneal carcinomatosis. Human colon cancer tissues were analyzed for ATF3 expression. The results show that therapeutic Hsp90 inhibition substantially up-regulates the expression of ATF3 in various cancer cells, including colon, gastric and pancreatic cancer. This effect was evident both in vitro and in vivo. RNAi mediated knock-down of ATF3 in HCT116 colon cancer cells significantly increased cancer cell migration in vitro. Moreover, in xenogenic mouse models, ATF3 knock-down promoted subcutaneous tumor growth and hepatic metastasis, as well as peritoneal carcinomatosis. Importantly, ATF3 expression was lower in human colon cancer specimens, as compared to corresponding normal surrounding tissues, suggesting that ATF3 may represent a down-regulated tumor suppressor in colon cancer. In conclusion, ATF3 down-regulation in colon cancer promotes tumor growth and metastasis. Considering that blocking Hsp90 induces ATF3 expression, Hsp90 inhibition may represent a valid strategy to treat metastatic colon cancer by up-regulating this anti-metastatic transcription factor
Overview of the ATF [Advanced Toroidal Facility] Program

International Nuclear Information System (INIS)

Lyon, J.F.; Aceto, S.C.; Anderson, F.S.B.

1989-01-01

Initial operation of ATF showed narrow pressure profiles and second stability behavior at lower beta than expected and revealed uncompensated dipoles in the HF winding leads that have since been corrected. Energy confinement times obtained with neutral beam injection and electron cyclotron heating roughly follow the LHD scaling. However, a plasma collapse is observed with NBI 6 refs., 9 figs
Wire alignment system for ATF LINAC

International Nuclear Information System (INIS)

Hayano, H.; Takeda, S.; Matsumoto, H.; Matsui, T.

1994-01-01

A wire based alignment system is adopted to make less than 40μm precision alignment for injector linac of Accelerator Test Facility (ATF). The system consists of two stretched SUS wires, pickup coils and active mover stages. The position of pickup coils in a mount which will be installed into LINAC stages is set to the calculated wire position prior to installation. All of LINAC stages are then moved to keep the calculated position by the active mover. The test results of wire position detection in a long term are described. (author)
Self-consistent analysis of radial electric field and fast ion losses in CHS Torsatron/Heliotron

International Nuclear Information System (INIS)

Sanuki, H.; Itoh, K.; Itoh, S.

1992-09-01

A self-consistent analysis is developed to determine the radial electric field and loss cone boundary in Torsatron/Heliotron plasmas under the influence of non-classical ion losses such as the loss cone loss ans charge exchange loss of fast ions with neutrals. Analysis is applied to the NBI heated plasmas in the Compact Helical System (CHS) device. Comparison is made between theoretical results and experimental observations. The increased ion particle losses caused by the orbit loss and charge exchange loss with neutrals make the radial electric field more negative than the value of purely neoclassical calculation. The partition of the injection energy among the shine through, direct orbit loss, change exchange loss and bulk heating is evaluated by using the self-consistent electric field profile. On-going experiments in the CHS device are briefly introduced. (author)
Proposal for a study of laser acceleration of electrons using micrograting structures at ATF (Phase 1)

International Nuclear Information System (INIS)

Chen, W.; Claus, J.; Fernow, R.C.

1989-01-01

We propose to investigate new methods of particle acceleration using a short-pulse CO 2 laser as the power source and grating-like structures as accelerator ''cavities''. Phase I of this program is intended to demonstrate the principle of the method. We will focus the laser light to a 3 mm line on the surface of the microstructure. The structure is used to transform the electric field pattern of the incoming transversely polarized laser beam to a mode which has a component along the electron beam direction in the vicinity of the surface. With 6 mJ of laser energy and a 6 ps pulse length, the electric field in the spot will be around 1 GV/m. The electron beam from the Brookhaven Accelerator Test Facility (ATF) will be focused transversely within the few micron transverse dimension of the microstructure. The maximum expected acceleration for a 1 GV/m field and a 3 mm acceleration length is 3 MeV. 17 refs., 11 figs., 2 tabs
Performance Comparison of Different System Identification Algorithms for FACET and ATF2

CERN Document Server

Pfingstner, J; Schulte, D

2013-01-01

Good system knowledge is an essential ingredient for the operation of modern accelerator facilities. For example, beam-based alignment algorithms and orbit feedbacks rely strongly on a precise measurement of the orbit response matrix. The quality of the measurement of this matrix can be improved over time by statistically combining the effects of small system excitations with the help of system identification algorithms. These small excitations can be applied in a parasitic mode without stopping the accelerator operation (on-line). In this work, different system identification algorithms are used in simulation studies for the response matrix measurement at ATF2. The results for ATF2 are finally compared with the results for FACET, latter originating from an earlier work.
An analytical method for calculating stresses and strains of ATF cladding based on thick walled theory

Energy Technology Data Exchange (ETDEWEB)

Kim, Dong Hyun; Kim, Hak Sung [Hanyang University, Seoul (Korea, Republic of); Kim, Hyo Chan; Yang, Yong Sik; In, Wang kee [KAERI, Daejeon (Korea, Republic of)

2016-05-15

In this paper, an analytical method based on thick walled theory has been studied to calculate stress and strain of ATF cladding. In order to prescribe boundary conditions of the analytical method, two algorithms were employed which are called subroutine 'Cladf' and 'Couple' of FRACAS, respectively. To evaluate the developed method, equivalent model using finite element method was established and stress components of the method were compared with those of equivalent FE model. One of promising ATF concepts is the coated cladding, which take advantages such as high melting point, a high neutron economy, and low tritium permeation rate. To evaluate the mechanical behavior and performance of the coated cladding, we need to develop the specified model to simulate the ATF behaviors in the reactor. In particular, the model for simulation of stress and strain for the coated cladding should be developed because the previous model, which is 'FRACAS', is for one body model. The FRACAS module employs the analytical method based on thin walled theory. According to thin-walled theory, radial stress is defined as zero but this assumption is not suitable for ATF cladding because value of the radial stress is not negligible in the case of ATF cladding. Recently, a structural model for multi-layered ceramic cylinders based on thick-walled theory was developed. Also, FE-based numerical simulation such as BISON has been developed to evaluate fuel performance. An analytical method that calculates stress components of ATF cladding was developed in this study. Thick-walled theory was used to derive equations for calculating stress and strain. To solve for these equations, boundary and loading conditions were obtained by subroutine 'Cladf' and 'Couple' and applied to the analytical method. To evaluate the developed method, equivalent FE model was established and its results were compared to those of analytical model. Based on the
Observation and interpretation of topological structures in impurity ion radiation profiles from the hot plasma of a torsatron

International Nuclear Information System (INIS)

Zurro, B.; McCarthy, K.J.; Ascasibar, E.; Aragon, F.; Burgos, C.; Lopez, A.; Salas, A.

1997-01-01

Significant features have been observed in impurity ion ultraviolet line emission profiles measured on the TJ-I U torsatron using a fast-scanning detector system with good spatial resolution. These features, which consist of flats and humps, provide evidence for the existence of topological structure in the plasma interior. It is postulated that these structures arise as a result of perturbations in the electron temperature and ion density profiles caused by magnetic islands. We develop a model to show how these structures can give rise to such features in ultraviolet radiation profiles and we use theoretical iota profiles to correlate the positions of the more prominent features with rational iota values. (orig.)
v-src induction of the TIS10/PGS2 prostaglandin synthase gene is mediated by an ATF/CRE transcription response element.

Science.gov (United States)

Xie, W; Fletcher, B S; Andersen, R D; Herschman, H R

1994-10-01

We recently reported the cloning of a mitogen-inducible prostaglandin synthase gene, TIS10/PGS2. In addition to growth factors and tumor promoters, the v-src oncogene induces TIS10/PGS2 expression in 3T3 cells. Deletion analysis, using luciferase reporters, identifies a region between -80 and -40 nucleotides 5' of the TIS10/PGS2 transcription start site that mediates pp60v-src induction in 3T3 cells. This region contains the sequence CGTCACGTG, which includes overlapping ATF/CRE (CGTCA) and E-box (CACGTG) sequences. Gel shift-oligonucleotide competition experiments with nuclear extracts from cells stably transfected with a temperature-sensitive v-src gene demonstrate that the CGTCACGTG sequence can bind proteins at both the ATF/CRE and E-box sequences. Dominant-negative CREB and Myc proteins that bind DNA, but do not transactivate, block v-src induction of a luciferase reporter driven by the first 80 nucleotides of the TIS10/PGS2 promoter. Mutational analysis distinguishes which TIS10/PGS2 cis-acting element mediates pp60v-src induction. E-box mutation has no effect on the fold induction in response to pp60v-src. In contrast, ATF/CRE mutation attenuates the pp60v-src response. Antibody supershift and methylation interference experiments demonstrate that CREB and at least one other ATF transcription factor in these extracts bind to the TIS10/PGS2 ATF/CRE element. Expression of a dominant-negative ras gene also blocks TIS10/PGS2 induction by v-src. Our data suggest that Ras mediates pp60v-src activation of an ATF transcription factor, leading to induced TIS10/PGS2 expression via the ATF/CRE element of the TIS10/PGS2 promoter. This is the first description of v-src activation of gene expression via an ATF/CRE element.
The ATF [Advanced Toroidal Facility] Status and Control System

International Nuclear Information System (INIS)

Baylor, L.R.; Devan, W.R.; Sumner, J.N.; Alban, A.M.

1987-01-01

The Advanced Toroidal Facility (ATF) Status and Control System (SCS) is a programmable controller-based state monitoring and supervisory control system. This paper describes the SCS implementation and its use of a host computer to run a commercially available software package that provides color graphic interactive displays, alarm logging, and archiving of state data
Low-Intensity Extracorporeal Shock Wave Therapy Enhances Brain-Derived Neurotrophic Factor Expression through PERK/ATF4 Signaling Pathway

Directory of Open Access Journals (Sweden)

Bohan Wang

2017-02-01

Full Text Available Low-intensity extracorporeal shock wave therapy (Li-ESWT is used in the treatment of erectile dysfunction, but its mechanisms are not well understood. Previously, we found that Li-ESWT increased the expression of brain-derived neurotrophic factor (BDNF. Here we assessed the underlying signaling pathways in Schwann cells in vitro and in penis tissue in vivo after nerve injury. The result indicated that BDNF were significantly increased by the Li-ESWT after nerve injury, as well as the expression of BDNF in Schwann cells (SCs, RT4-D6P2T in vitro. Li-ESWT activated the protein kinase RNA-like endoplasmic reticulum (ER kinase (PERK pathway by increasing the phosphorylation levels of PERK and eukaryotic initiation factor 2a (eIF2α, and enhanced activating transcription factor 4 (ATF4 in an energy-dependent manner. In addition, GSK2656157—an inhibitor of PERK—effectively inhibited the effect of Li-ESWT on the phosphorylation of PERK, eIF2α, and the expression of ATF4. Furthermore, silencing ATF4 dramatically attenuated the effect of Li-ESWT on the expression of BDNF, but had no effect on hypoxia-inducible factor (HIF1α or glial cell-derived neurotrophic factor (GDNF in Schwann cells. In conclusion, our findings shed new light on the underlying mechanisms by which Li-ESWT may stimulate the expression of BDNF through activation of PERK/ATF4 signaling pathway. This information may help to refine the use of Li-ESWT to further improve its clinical efficacy.
ATF4-Induced Metabolic Reprograming Is a Synthetic Vulnerability of the p62-Deficient Tumor Stroma.

Science.gov (United States)

Linares, Juan F; Cordes, Thekla; Duran, Angeles; Reina-Campos, Miguel; Valencia, Tania; Ahn, Christopher S; Castilla, Elias A; Moscat, Jorge; Metallo, Christian M; Diaz-Meco, Maria T

2017-12-05

Tumors undergo nutrient stress and need to reprogram their metabolism to survive. The stroma may play a critical role in this process by providing nutrients to support the epithelial compartment of the tumor. Here we show that p62 deficiency in stromal fibroblasts promotes resistance to glutamine deprivation by the direct control of ATF4 stability through its p62-mediated polyubiquitination. ATF4 upregulation by p62 deficiency in the stroma activates glucose carbon flux through a pyruvate carboxylase-asparagine synthase cascade that results in asparagine generation as a source of nitrogen for stroma and tumor epithelial proliferation. Thus, p62 directly targets nuclear transcription factors to control metabolic reprogramming in the microenvironment and repress tumorigenesis, and identifies ATF4 as a synthetic vulnerability in p62-deficient tumor stroma. Copyright © 2017 Elsevier Inc. All rights reserved.
ATF3 expression improves motor function in the ALS mouse model by promoting motor neuron survival and retaining muscle innervation.

Science.gov (United States)

Seijffers, Rhona; Zhang, Jiangwen; Matthews, Jonathan C; Chen, Adam; Tamrazian, Eric; Babaniyi, Olusegun; Selig, Martin; Hynynen, Meri; Woolf, Clifford J; Brown, Robert H

2014-01-28

ALS is a fatal neurodegenerative disease characterized by a progressive loss of motor neurons and atrophy of distal axon terminals in muscle, resulting in loss of motor function. Motor end plates denervated by axonal retraction of dying motor neurons are partially reinnervated by remaining viable motor neurons; however, this axonal sprouting is insufficient to compensate for motor neuron loss. Activating transcription factor 3 (ATF3) promotes neuronal survival and axonal growth. Here, we reveal that forced expression of ATF3 in motor neurons of transgenic SOD1(G93A) ALS mice delays neuromuscular junction denervation by inducing axonal sprouting and enhancing motor neuron viability. Maintenance of neuromuscular junction innervation during the course of the disease in ATF3/SOD1(G93A) mice is associated with a substantial delay in muscle atrophy and improved motor performance. Although disease onset and mortality are delayed, disease duration is not affected. This study shows that adaptive axonal growth-promoting mechanisms can substantially improve motor function in ALS and importantly, that augmenting viability of the motor neuron soma and maintaining functional neuromuscular junction connections are both essential elements in therapy for motor neuron disease in the SOD1(G93A) mice. Accordingly, effective protection of optimal motor neuron function requires restitution of multiple dysregulated cellular pathways.
The response of the prostate to circulating cholesterol: activating transcription factor 3 (ATF3 as a prominent node in a cholesterol-sensing network.

Directory of Open Access Journals (Sweden)

Jayoung Kim

Full Text Available Elevated circulating cholesterol is a systemic risk factor for cardiovascular disease and metabolic syndrome, however the manner in which the normal prostate responds to variations in cholesterol levels is poorly understood. In this study we addressed the molecular and cellular effects of elevated and suppressed levels of circulating cholesterol on the normal prostate. Integrated bioinformatic analysis was performed using DNA microarray data from two experimental formats: (1 ventral prostate from male mice with chronically elevated circulating cholesterol and (2 human prostate cells exposed acutely to cholesterol depletion. A cholesterol-sensitive gene expression network was constructed from these data and the transcription factor ATF3 was identified as a prominent node in the network. Validation experiments confirmed that elevated cholesterol reduced ATF3 expression and enhanced proliferation of prostate cells, while cholesterol depletion increased ATF3 levels and inhibited proliferation. Cholesterol reduction in vivo alleviated dense lymphomononuclear infiltrates in the periprostatic adipose tissue, which were closely associated with nerve tracts and blood vessels. These findings open new perspectives on the role of cholesterol in prostate health, and provide a novel role for ATF3, and associated proteins within a large signaling network, as a cholesterol-sensing mechanism.

Energy confinement scaling from the international stellarator database

Energy Technology Data Exchange (ETDEWEB)

Stroth, U [Max-Planck-Institut fuer Plasmaphysik, Garching (Germany); Murakami, M; Dory, R A; Yamada, H; Okamura, S; Sano, F; Obiki, T

1995-09-01

An international stellarator database on global energy confinement is presented comprising data from the ATF, CHS and Heliotron E heliotron/torsatrons and the W7-A and W7-AS shearless stellarators. Regression expressions for the energy confinement time are given for the individual devices and the combined dataset. A comparison with tokamak L mode confinement is discussed on the basis of various scaling expressions. In order to make this database available to interested colleagues, the structure of the database and the parameter list are explained in detail. More recent confinement results incorporating data from enhanced confinement regimes such as H mode are reported elsewhere. (author).
Design of bunch compressing system with suppression of coherent synchrotron radiation for ATF upgrade

International Nuclear Information System (INIS)

Jing, Yichao; Fedurin, Mikhail; Stratakis, Diktys

2015-01-01

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.
Opportunities for the LWR ATF materials development program to contribute to the LBE-cooled ADS materials qualification program

Energy Technology Data Exchange (ETDEWEB)

Gong, Xing, E-mail: gongxingzfl@hotmail.com [Department of ATF R& D, Nuclear Fuel Research and Development Center, China Nuclear Power Technology Research Institute Co., Ltd., China General Nuclear Power Corporation (CGN), Shenzhen, 518026 (China); Li, Rui, E-mail: li-rui@cgnpc.com.cn [Department of ATF R& D, Nuclear Fuel Research and Development Center, China Nuclear Power Technology Research Institute Co., Ltd., China General Nuclear Power Corporation (CGN), Shenzhen, 518026 (China); Sun, Maozhou; Ren, Qisen [Department of ATF R& D, Nuclear Fuel Research and Development Center, China Nuclear Power Technology Research Institute Co., Ltd., China General Nuclear Power Corporation (CGN), Shenzhen, 518026 (China); Liu, Tong, E-mail: liutong@cgnpc.com.cn [Department of ATF R& D, Nuclear Fuel Research and Development Center, China Nuclear Power Technology Research Institute Co., Ltd., China General Nuclear Power Corporation (CGN), Shenzhen, 518026 (China); Short, Michael P., E-mail: hereiam@mit.edu [Department of Nuclear Science and Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, 02139 (United States)

2016-12-15

Accelerator-driven systems (ADS) are a promising approach for nuclear waste disposal. Nevertheless, the principal candidate materials proposed for ADS construction, such as the ferritic/martensitic steel, T91, and austenitic stainless steels, 316L and 15-15Ti, are not fully compatible with the liquid lead-bismuth eutectic (LBE) coolant. Under some operating conditions, liquid metal embrittlement (LME) or liquid metal corrosion (LMC) may occur in these steels when exposed to LBE. These environmentally-induced material degradation effects pose a threat to ADS reactor safety, as failure of the materials could initiate a severe accident, in which fission products are released into the coolant. Meanwhile, parallel efforts to develop accident-tolerant fuels (ATF) in light water reactors (LWRs) could provide both general materials design philosophies and specific material solutions to the ADS program. In this paper, the potential contributions of the ATF materials development program to the ADS materials qualification program are evaluated and discussed in terms of service conditions and materials performance requirements. Several specific areas where coordinated development may benefit both programs, including composite materials and selected coatings, are discussed. - Highlights: • ATF materials developed for LWRs could be candidate materials for the LBE-cooled ADS program. • Similar material design and protection philosophies are utilized in both programs. • Unique challenges of LBE-cooled ADS systems could possibly be addressed by LWR ATF materials. • More coordinated testing should be performed between the ATF and ADS programs.
Achievement of ultra-low emittance beam in the ATF damping ring

CERN Document Server

Honda, Y; Araki, S; Bane, Karl Leopold Freitag; Brachmann, A; Frisch, J; Fukuda, M; Hasegawa, K; Hayano, H; Hendrickson, L; Higashi, Y; Higo, T; Hirano, K; Hirose, T; Iida, K; Imai, T; Inoue, Y; Karataev, P; Kubo, K; Kurihara, Y; Kuriki, M; Kuroda, R; Kuroda, S; Luo, X; Matsuda, M; McCormick, D; Muto, T; Nakajima, K; Nelson, J; Nomura, M; Ohashi, A; Okugi, T; Omori, T; Ross, M; Sakai, H; Sakai, I; Sasao, N; Smith, S; Suzuki, T; Takano, M; Takashi, N; Taniguchi, T; Terunuma, N; Toge, N; Turner, J; Urakawa, J; Vogel, V; Wolski, A; Woodley, M; Yamazaki, I; Yamazaki, Y; Yocky, J; Young, A; Zimmermann, Frank

2003-01-01

We report on the smallest vertical emittance achieved in single-bunch-mode operation of the ATF. The emittances were measured with a laser-wire beam-profile monitor installed in the damping ring. The bunch length and the momentum spread of the beam were also recorded under the same conditions. The smallest vertical rms emittance measured is 4 pm in the limit of zero current. It increases by a factor of 1.5 for a bunch intensity of 10^10 electrons. There are no discrepancies between the measured data and the calculations of intra-beam scattering.
Studies of emittance growth in the ATF

International Nuclear Information System (INIS)

Zimmermann, F.

1997-03-01

Several different mechanisms of emittance growth in the Accelerator Test Facility (ATF) at KEK are investigated: the author calculates rise times of the fast beam-ion instability for the damping ring (DR), and discusses the emittance growth caused by coherent synchrotron radiation in the beam-transport line (BT), the effect of quadrupole wake fields in the injector linac, and, finally, a single-bunch head-tail ion effect that can occur in both the DR and the BT. A first attempt to measure the quadrupole wake on the real machine is also reported
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.
Down-regulation of ATF2 in the inhibition of T-2-toxin-induced chondrocyte apoptosis by selenium chondroitin sulfate nanoparticles

Science.gov (United States)

Han, Jing; Guo, Xiong

2013-12-01

Selenium chondroitin sulfate nanoparticles (SeCS) with a size range of 30-200 nm were obtained in our previous study. Meanwhile, the up-regulated expression of ATF2 mRNA and protein levels could be observed in the cartilage from Kashin-Beck disease (KBD) patients. In this paper, we investigated the inhibition effect of SeCS on T-2-toxin-induced apoptosis of chondrocyte from KBD patients. Here, we found that when the chondrocytes were treated with T-2 toxin, the chondrocyte apoptosis performed in a concentration-dependent manner. The apoptosis of chondrocyte induced by T-2 toxin involved the increased levels of ATF2, JNK and p38 mRNAs and related protein expression. SeCS could partly block the T-2-toxin-induced chondrocyte apoptosis by decreasing the expression of ATF2, JNK and p38 mRNAs and p-JNK, p-38, ATF2 and p-ATF2 proteins. JNK and p38 pathways involved in the apoptosis of chondrocyte induced by T-2 toxin, and SeCS was efficient in the inhibition of chondrocyte apoptosis by T-2 toxin. These results suggested that SeCS had a potential for further prevention and treatment for KBD as well as other selenium deficiency disease.
Characteristics of ICR-produced peripheral plasma in the URAGAN-3M torsatron

International Nuclear Information System (INIS)

Besedin, N.T.; Chechkin, V.V.; Fomin, I.P.

1991-01-01

Some plasma parameters outside the confinement volume near the last closed magnetic surface (LCMS) and in the divertor fluxes were studied by probe and microwave techniques during ICR production and heating of the plasma in the Uragan-3M torsatron (1=3, m=9, R o =100cm, a-bar≤11 cm, l (a-bar)≤0.29; B o ≤20kG, n-bar e ≅2x10 12 cm -3 , T i (0)=200-300 eV, T e (0)≅100 eV). When moving around the LCMS, the steepness of the radial density, electron temperature and potential profiles increases with the distance away from the ''rib'' of the LCMS. The quasi-steady radial electric field E r near the LCMS exceeds 100 V/cm and is directed outwards, opposite to the calculated ambipolar electric field inside the confinement volume. It is shown that the total flow of the diverted plasma in the spacing between two helical windings consists of (i) a weakly mobile non-resonant component which is presumably formed at the periphery due to ionization, and (ii) a component whose value and poloidal location are sensitive to resonance conditions for RF power absorption, this flow being apparently formed by a plasma diffusing through the LCMS and/or generated near the LCMS, where the filed E r is localized. Based on plasma parameters measurements after the RF pulse is switched off, a qualitative model of peripheral plasma dynamics after the end of the RF heating is constructed. 23 refs.; 13 figs. (author)
Distinct Residues Contribute to Motility Repression and Autoregulation in the Proteus mirabilis Fimbria-Associated Transcriptional Regulator AtfJ.

Science.gov (United States)

Bode, Nadine J; Chan, Kun-Wei; Kong, Xiang-Peng; Pearson, Melanie M

2016-08-01

Proteus mirabilis contributes to a significant number of catheter-associated urinary tract infections, where coordinated regulation of adherence and motility is critical for ascending disease progression. Previously, the mannose-resistant Proteus-like (MR/P) fimbria-associated transcriptional regulator MrpJ has been shown to both repress motility and directly induce the transcription of its own operon; in addition, it affects the expression of a wide range of cellular processes. Interestingly, 14 additional mrpJ paralogs are included in the P. mirabilis genome. Looking at a selection of MrpJ paralogs, we discovered that these proteins, which consistently repress motility, also have nonidentical functions that include cross-regulation of fimbrial operons. A subset of paralogs, including AtfJ (encoded by the ambient temperature fimbrial operon), Fim8J, and MrpJ, are capable of autoinduction. We identified an element of the atf promoter extending from 487 to 655 nucleotides upstream of the transcriptional start site that is responsive to AtfJ, and we found that AtfJ directly binds this fragment. Mutational analysis of AtfJ revealed that its two identified functions, autoregulation and motility repression, are not invariably linked. Residues within the DNA-binding helix-turn-helix domain are required for motility repression but not necessarily autoregulation. Likewise, the C-terminal domain is dispensable for motility repression but is essential for autoregulation. Supported by a three-dimensional (3D) structural model, we hypothesize that the C-terminal domain confers unique regulatory capacities on the AtfJ family of regulators. Balancing adherence with motility is essential for uropathogens to successfully establish a foothold in their host. Proteus mirabilis uses a fimbria-associated transcriptional regulator to switch between these antagonistic processes by increasing fimbrial adherence while simultaneously downregulating flagella. The discovery of multiple
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.
Intestinal DMBT1 expression is modulated by Crohn's disease-associated IL23R variants and by a DMBT1 variant which influences binding of the transcription factors CREB1 and ATF-2.

Directory of Open Access Journals (Sweden)

Julia Diegelmann

Full Text Available OBJECTIVES: DMBT is an antibacterial pattern recognition and scavenger receptor. In this study, we analyzed the role of DMBT1 single nucleotide polymorphisms (SNPs regarding inflammatory bowel disease (IBD susceptibility and examined their functional impact on transcription factor binding and downstream gene expression. METHODS: Seven SNPs in the DMBT1 gene region were analyzed in 2073 individuals including 818 Crohn's disease (CD patients and 972 healthy controls in two independent case-control panels. Comprehensive epistasis analyses for the known CD susceptibility genes NOD2, IL23R and IL27 were performed. The influence of IL23R variants on DMBT1 expression was analyzed. Functional analysis included siRNA transfection, quantitative PCR, western blot, electrophoretic mobility shift and luciferase assays. RESULTS: IL-22 induces DMBT1 protein expression in intestinal epithelial cells dependent on STAT3, ATF-2 and CREB1. IL-22 expression-modulating, CD risk-associated IL23R variants influence DMBT1 expression in CD patients and DMBT1 levels are increased in the inflamed intestinal mucosa of CD patients. Several DMBT1 SNPs were associated with CD susceptibility. SNP rs2981804 was most strongly associated with CD in the combined panel (p = 3.0 × 10(-7, OR 1.42; 95% CI 1.24-1.63. All haplotype groups tested showed highly significant associations with CD (including omnibus P-values as low as 6.1 × 10(-18. The most strongly CD risk-associated, non-coding DMBT1 SNP rs2981804 modifies the DNA binding sites for the transcription factors CREB1 and ATF-2 and the respective genomic region comprising rs2981804 is able to act as a transcriptional regulator in vitro. Intestinal DMBT1 expression is decreased in CD patients carrying the rs2981804 CD risk allele. CONCLUSION: We identified novel associations of DMBT1 variants with CD susceptibility and discovered a novel functional role of rs2981804 in regulating DMBT1 expression. Our data suggest an important
Intestinal DMBT1 expression is modulated by Crohn's disease-associated IL23R variants and by a DMBT1 variant which influences binding of the transcription factors CREB1 and ATF-2.

Science.gov (United States)

Diegelmann, Julia; Czamara, Darina; Le Bras, Emmanuelle; Zimmermann, Eva; Olszak, Torsten; Bedynek, Andrea; Göke, Burkhard; Franke, Andre; Glas, Jürgen; Brand, Stephan

2013-01-01

DMBT is an antibacterial pattern recognition and scavenger receptor. In this study, we analyzed the role of DMBT1 single nucleotide polymorphisms (SNPs) regarding inflammatory bowel disease (IBD) susceptibility and examined their functional impact on transcription factor binding and downstream gene expression. Seven SNPs in the DMBT1 gene region were analyzed in 2073 individuals including 818 Crohn's disease (CD) patients and 972 healthy controls in two independent case-control panels. Comprehensive epistasis analyses for the known CD susceptibility genes NOD2, IL23R and IL27 were performed. The influence of IL23R variants on DMBT1 expression was analyzed. Functional analysis included siRNA transfection, quantitative PCR, western blot, electrophoretic mobility shift and luciferase assays. IL-22 induces DMBT1 protein expression in intestinal epithelial cells dependent on STAT3, ATF-2 and CREB1. IL-22 expression-modulating, CD risk-associated IL23R variants influence DMBT1 expression in CD patients and DMBT1 levels are increased in the inflamed intestinal mucosa of CD patients. Several DMBT1 SNPs were associated with CD susceptibility. SNP rs2981804 was most strongly associated with CD in the combined panel (p = 3.0 × 10(-7), OR 1.42; 95% CI 1.24-1.63). All haplotype groups tested showed highly significant associations with CD (including omnibus P-values as low as 6.1 × 10(-18)). The most strongly CD risk-associated, non-coding DMBT1 SNP rs2981804 modifies the DNA binding sites for the transcription factors CREB1 and ATF-2 and the respective genomic region comprising rs2981804 is able to act as a transcriptional regulator in vitro. Intestinal DMBT1 expression is decreased in CD patients carrying the rs2981804 CD risk allele. We identified novel associations of DMBT1 variants with CD susceptibility and discovered a novel functional role of rs2981804 in regulating DMBT1 expression. Our data suggest an important role of DMBT1 in CD pathogenesis.
The Brookhaven ATF low-emittance beam line

International Nuclear Information System (INIS)

Wang, X.J.; Kirk, H.G.

1991-01-01

One component of the experimental program at the Brookhaven Accelerator Test Facility (ATF) consists of a class of experiments which will study the acceleration of electrons through micron-size structures which are exposed in coincidence to a 100 GW CO 2 laser beam. These experiments require the development and control of an electron beam with geometric emittances on the order of 10 -10 m-rad and intensities on the order of 10 6 electrons. In this paper, the authors describe the strategies for producing such beams and the effects of higher-order aberrations. Particle tracking results are presented for the final-focus system
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......-cells and human islet cells against pro-inflammatory mediators. These results were confirmed in genetically modified islets derived from Ubi-JunB transgenic mice. Our findings identify ATF3 as a novel downstream target of JunB in the survival mechanism of β-cells under inflammatory stress....
Plans for improvements to the ATF ECH system

International Nuclear Information System (INIS)

Bigelow, T.S.; Goldfinger, R.C.; Murakami, M.; Schaich, C.R.; Wilgen, J.B.

1993-01-01

The Advanced Toroidal Facility (ATF) stellarator experiment at Oak Ridge National Laboratory (ORNL) uses electron cyclotron waves for plasma formation and heating. Although the existing systems are quite reliable and produce acceptable plasmas, a few deficiencies should be corrected. Therefore, several possible upgrades to the electron cyclotron heating (ECH) systems have been planned. Some of the desirable changes are (1) improving the launcher to make power deposition in the plasma more centralized, (2) improving the gyrotron power waveform monitoring diagnostics, (3) building a high-field launch system for higher density operation at 53-GHz (4) building a separate transmission line for the 35-GHz gyrotron, and (5) installing a higher frequency, higher power (84- or 110-GHz) gyrotron system for improved plasma density and temperature capability. This paper discusses options for these improvements and conceptual designs. (orig.)
v-src Induction of the TIS10/PGS2 prostaglandin synthase gene is mediated by an ATF/CRE transcription response element

Energy Technology Data Exchange (ETDEWEB)

Xie, W.; Fletcher, B.S.; Andersen, R.D.; Herschman, H.R. [Univ. of California, Los Angeles, CA (United States)

1994-10-01

The authors recently reported the cloning of a mitogen-inducible prostaglandin synthase gene, TIS10/PGS2. In addition to growth factor and tumor promoters, the v-src oncogene induces TIS10/PGS2 expression in 3T3 cells. Deletion analysis, using luciferase reporters, identifies a region between -80 and -40 nucleotides 5{prime} of the TIS10/PGS2 transcription start site that mediates pp60{sup v-src} induction in 3T3 cells. This region contains the sequence CGTCACGTG, which includes overlapping ATF/CRE (CGTCA) and E-box (CACGTG) sequences. Gel shift-oligonucleotide competition experiments with nuclear extracts from cells stably transfected with a temperature-sensitive v-src gene demonstrate that the CGTCACGTG sequence can bind proteins at both the AFT/CRE and E-box sequences. Dominant-negative CREB and Myc proteins that bind DNA, but do not transactivate, block v-src induction of a luciferase reporter driven by the first 80 nucleotides of the TIS10/PGS2 promoter. Mutational analysis distinguishes which TIS10/PGS2 cis-acting element mediates pp60{sup v-src} induction. E-box mutation has no effect on the fold induction in response to pp60{sup v-src}. In contrast, ATF/CRE mutation attenuates the pp{sup v-src} response. Antibody supershift and methylation interference experiments demonstrate that CREB and at least one other ATF transcription factor in these extracts bind to the TIS10/PGS2 ATF/CRE element. Expression of a dominant-negative ras gene also blocks TIS10/PGS2 induction by v-src. The data suggest that Ras mediates pp60{sup v-src} activation of an ATF transcription factor, leading to induced TIS10/PGS2 expression via the ATF/CRE element of the TIS10/PGS2 promoter. This is the first description of v-src activation of gene expression via an ATF/CRE element. 64 refs., 8 figs.
The ATF two-frequency correlation reflectometer

International Nuclear Information System (INIS)

Hanson, G.R.; Wilgen, J.B.; Anabitarte, E.; Bell, J.D.; Harris, J.H.; Dunlap, J.L.; Thomas, C.E.

1990-01-01

The Advanced Toroidal Facility (ATF) density fluctuation reflectometer system consists of two individual reflectometers operating in the 30- to 40-GHz band. Each reflectometer consists of a tunable microwave source and a quadrature phase detector connected to the same antenna system. This arrangement allows two-frequency operation along the same radial chord for radial coherence measurements. The technique used in making radial coherence measurements is discussed and the results of such experiments are given. Initial experiments have shown high coherence when the frequencies of the two reflectometers are tuned close together and a clear loss of coherence as the radial separation of the cutoff layers is increased by increasing the frequency separation of the two reflectometers. Recent results have shown that local measurements of density fluctuations in plasmas with electron cyclotron heating (ECH) are possible and that detailed structure can be seen in the fluctuation spectra. In addition, radial correlation lengths have been found to be from 0.5 to 1.0 cm in ECH plasmas, with some frequency structures having correlation lengths up to 3 cm. In plasmas with neutral beam injection (NBI), the radial correlation lengths in the edge region have been found to be approximately 0.1--0.2 cm. 4 figs
The Brookhaven ATF low-emittance beam line

International Nuclear Information System (INIS)

Wang, X.J.

1991-01-01

One component of the experimental program at the Brookhaven Accelerator Test Facility (ATF) consists of a class of experiments which will study the acceleration of electrons through micron-size structures which are exposed in coincidence to a 100 GW CO 2 laser beam. These experiments require the development and control of an electron beam with geometric emittances on the order of 10 -10 m-rad and intensities on the order of 10 6 electrons. In this paper, we describe the strategies for producing such beams and the effects of high-order aberrations. Particle tracking results are presented for the final-focus system. 9 refs., 6 figs., 2 tabs
Loading, absorption, and Fokker-Planck calculations for upcoming ICRF experiments on ATF

International Nuclear Information System (INIS)

Shepard, T.D.; Carter, M.D.; Goulding, R.H.; Kwon, M.

1989-01-01

ICRF experiments on ATF at the 100-kW level are planned for the current 1989 operating period. These plans include the 2ω/sub cH/ regime at f/sub RF/ = 28.88 MHz, D(H) at 14.44 MHz, and 4 He( 3 He) and D( 3 He) at 9.63 MHz. ECH target plasmas have n/sub eO/ /approxreverse arrowlt/ 0.15 /times/ 10 20 m/sup /minus/3/ and B = 0.95 T. The density and temperature profiles obtained are broader than those from 1988, owing to recent field error corrections. The values used for target-plasma parameters in the calculations were taken from initial 1989 ATF data. Loading and absorption calculations have been performed using the 3D RF heating code ORION with a helically symmetric equilibrium, and Fokker-Planck calculations were performed using the steady-state code RFTRANS with two velocity dimensions and one spatial dimension. 6 refs., 3 figs
Cryptocephal, the Drosophila melanogaster ATF4, is a specific coactivator for ecdysone receptor isoform B2.

Directory of Open Access Journals (Sweden)

Sebastien A Gauthier

Full Text Available The ecdysone receptor is a heterodimer of two nuclear receptors, the Ecdysone receptor (EcR and Ultraspiracle (USP. In Drosophila melanogaster, three EcR isoforms share common DNA and ligand-binding domains, but these proteins differ in their most N-terminal regions and, consequently, in the activation domains (AF1s contained therein. The transcriptional coactivators for these domains, which impart unique transcriptional regulatory properties to the EcR isoforms, are unknown. Activating transcription factor 4 (ATF4 is a basic-leucine zipper transcription factor that plays a central role in the stress response of mammals. Here we show that Cryptocephal (CRC, the Drosophila homolog of ATF4, is an ecdysone receptor coactivator that is specific for isoform B2. CRC interacts with EcR-B2 to promote ecdysone-dependent expression of ecdysis-triggering hormone (ETH, an essential regulator of insect molting behavior. We propose that this interaction explains some of the differences in transcriptional properties that are displayed by the EcR isoforms, and similar interactions may underlie the differential activities of other nuclear receptors with distinct AF1-coactivators.

ONC201 kills solid tumor cells by triggering an integrated stress response dependent on ATF4 activation by specific eIF2α kinases.

Science.gov (United States)

Kline, C Leah B; Van den Heuvel, A Pieter J; Allen, Joshua E; Prabhu, Varun V; Dicker, David T; El-Deiry, Wafik S

2016-02-16

ONC201 (also called TIC10) is a small molecule that inactivates the cell proliferation- and cell survival-promoting kinases Akt and ERK and induces cell death through the proapoptotic protein TRAIL. ONC201 is currently in early-phase clinical testing for various malignancies. We found through gene expression and protein analyses that ONC201 triggered an increase in TRAIL abundance and cell death through an integrated stress response (ISR) involving the transcription factor ATF4, the transactivator CHOP, and the TRAIL receptor DR5. ATF4 was not activated in ONC201-resistant cancer cells, and in ONC201-sensitive cells, knockdown of ATF4 or CHOP partially abrogated ONC201-induced cytotoxicity and diminished the ONC201-stimulated increase in DR5 abundance. The activation of ATF4 in response to ONC201 required the kinases HRI and PKR, which phosphorylate and activate the translation initiation factor eIF2α. ONC201 rapidly triggered cell cycle arrest, which was associated with decreased abundance of cyclin D1, decreased activity of the kinase complex mTORC1, and dephosphorylation of the retinoblastoma (Rb) protein. The abundance of X-linked inhibitor of apoptosis protein (XIAP) negatively correlated with the extent of apoptosis in response to ONC201. These effects of ONC201 were independent of whether cancer cells had normal or mutant p53. Thus, ONC201 induces cell death through the coordinated induction of TRAIL by an ISR pathway. Copyright © 2016, American Association for the Advancement of Science.
Endoplasmic reticulum stress-responsive transcription factor ATF6α directs recruitment of the Mediator of RNA polymerase II transcription and multiple histone acetyltransferase complexes.

Science.gov (United States)

Sela, Dotan; Chen, Lu; Martin-Brown, Skylar; Washburn, Michael P; Florens, Laurence; Conaway, Joan Weliky; Conaway, Ronald C

2012-06-29

The basic leucine zipper transcription factor ATF6α functions as a master regulator of endoplasmic reticulum (ER) stress response genes. Previous studies have established that, in response to ER stress, ATF6α translocates to the nucleus and activates transcription of ER stress response genes upon binding sequence specifically to ER stress response enhancer elements in their promoters. In this study, we investigate the biochemical mechanism by which ATF6α activates transcription. By exploiting a combination of biochemical and multidimensional protein identification technology-based mass spectrometry approaches, we have obtained evidence that ATF6α functions at least in part by recruiting to the ER stress response enhancer elements of ER stress response genes a collection of RNA polymerase II coregulatory complexes, including the Mediator and multiple histone acetyltransferase complexes, among which are the Spt-Ada-Gcn5 acetyltransferase (SAGA) and Ada-Two-A-containing (ATAC) complexes. Our findings shed new light on the mechanism of action of ATF6α, and they outline a straightforward strategy for applying multidimensional protein identification technology mass spectrometry to determine which RNA polymerase II transcription factors and coregulators are recruited to promoters and other regulatory elements to control transcription.
Feedback system of the RF phase in KEK-ATF linac

Energy Technology Data Exchange (ETDEWEB)

Okugi, T.; Hayano, H.; Kuriki, M.; Naito, T. [Accelerator Laboratory, High Energy Accelerator Research Organization, Tsukuba, Ibaraki (Japan)

2000-07-01

KEK-ATF linac is built in the Assembly Hall for TRISTAN project in 1991. The thermal condition of the hall is not good enough for a stable linac operation, because the temperature of the klystron gallery is drifted by 1degC within one day. RF phase is also drifted by 3-5deg of the S-band frequency in day and night. In order to control the RF phase, we installed RF phase detectors, which have S/H circuit in order to use for pulsed RF. By using the phase detector, an RF phase feedback system was tested. It was found that a stable klystron operation could be performed within the phase drift of {+-}0.5deg in a day. (author)
Transition to the improved confinement mode in torsatron U-3M in range of rare collision frequencies

International Nuclear Information System (INIS)

Pashnev, V.K.; Sorokovov, E.L.; Berezhnyj, V.L. and others

2010-01-01

Transition to the mode of improved plasma confinement in U-3M facility earlier was discussed in works [1-3]. In these studies discussed the various processes in the confinement volume and in the peripheral plasma that accompany the transition process. Study of plasma confinement and process of transition into the mode of improved confinement just at rare collisions between plasma particles is very important because future fusion reactor based on a toroidal magnetic trap will operate under plasma parameters with rare collision frequencies ('banana' mode). The peculiarity of experiments on torsatron U-3M is that they are conducted at small density n-bar e ≤ 2 lover case x 10 12 cm -3 and, thereby, the frequency of collisions in the confinement area is in the 'banana' mode [4]. And herewith, time of collisions is essentially smaller (up to several orders for electrons and up to the order for ions) than the lifetime of plasma particles. It ensures maxwellization of distribution function and possibility to compare the obtained results with data from other experiments. The objective of this work is to study the main regularity of transition into the mode of improved confinement. Also it is interesting to compare the results with data from other facilities.
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.
Induction of Liver Steatosis and Lipid Droplet Formation in ATF6α-Knockout Mice Burdened with Pharmacological Endoplasmic Reticulum Stress

OpenAIRE

Harada, Akihiro; Okada, Tetsuya; Sato, Takashi; Mori, Kazutoshi; Yamamoto, Keisuke; Takahara, Kazuna; Oyadomari, Seiichi

2010-01-01

Accumulation of unfolded proteins in the endoplasmic reticulum (ER) activates homeostatic responses collectively termed the unfolded protein response. Among the three principal signaling pathways operating in mammals, activating transcription factor (ATF)6? plays a pivotal role in transcriptional induction of ER-localized molecular chaperones and folding enzymes as well as components of ER-associated degradation, and thereby mouse embryonic fibroblasts deficient in ATF6? are sensitive to ER s...
MicroRNA-214 Suppresses Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Targeting ATF4

Directory of Open Access Journals (Sweden)

Siqi Yao

2017-01-01

Full Text Available Periodontitis is the main cause of adult tooth loss. Stem cell-based tissue engineering has become a promising therapy for periodontitis treatment. To date, human periodontal ligament stem cells (hPDLSCs have been shown to be a favorable source for tissue engineering, but modulatory mechanisms of hPDLSCs remain unclear. Approximately 60% of mammalian genes are the targets of over 2000 miRNAs in multiple human cell types, and miRNAs are able to influence various biological processes in the human body, including bone formation. In this study, we found that after osteogenic induction, miR-214 was significantly decreased in hPDLSCs; therefore, we examined the effects of miR-214 on osteogenic differentiation. Computational miRNA target prediction analyses and luciferase reporter assays revealed that activating transcription factor 4 (ATF4 is a direct target of miR-214. We prepared cells overexpressing miR-214 and found that miR-214 negatively regulates osteogenic differentiation of hPDLSCs. For the target of miR-214, ATF4 protein expression level was decreased after induction. In conclusion, we found that miR-214-ATF4 axis is a novel pathway for regulating hPDLSC osteogenic differentiation.
Stimulation of p38 (HOG1) kinase pathway by ionizing radiation results in downstream modulation of ATF/CREB transcription factor activity in NIH-3T3 cells

International Nuclear Information System (INIS)

Stevenson, Mary Ann; Yao Jin

1997-01-01

Purpose/Objective:p38 kinase, a member of the MAP kinase family, is activated in response to stresses such as high osmolarity and UV irradiation as well exposure to cytokines such as IL1β and TNFα. The kinase is part of a signal transduction pathway that leads from receptor activation through a three kinase cascade resulting in the activation of p38. p38 activation then leads to the phosphorylation of target proteins that include transcription factors such as nuclear factor of interleukin 6 and members of the activating transcription factor (ATF) family, and in addition, the stress protein, HSP27, via activation of MAPKAP2 kinase. In the present report, we have investigated the potential role of p38 in the response of NIH-3T3 cells to ionizing radiation. Materials and Methods:NIH-3T3 cells were grown to confluence in DMEM+10%CS and then serum deprived for 24 hours in DMEM+0.1%CS. Radiation exposures were delivered using a Philips RT250 (250Kvp X-ray tube). Activated forms of p38 kinase and ATF/CREB transcription factors were identified using immunoblotting techniques employing activation specific antibodies raised against the phosphorylated forms of the kinases/transcription factors. Kinase activity was directly measured using immunokinase assays. DNA binding of transcription factors to their respective consensus sequences was assayed by EMSA. Results:We found that p38 becomes rapidly phosphorylated and activated by exposure to ionizing radiation. Significantly, p38 is activated to a similar degree and with a similar time course by serum derpviation and entry of cells into a non-proliferating G 0 state, suggesting a causal role for p38 in quiescence. Phosphorylation of p38 directly correlated with phosphorylation and activation of ATF/CREB family members as well as DNA binding by these activated factors. Conclusion:Activation of p38 kinase and downstream transcription factors may play an important role in the response of cells to ionizing radiation. We are
Development of the alternate entry port for the ATF

International Nuclear Information System (INIS)

Parsa, Z.

1993-05-01

We discussed a second entry port for the Accelerator Test Facility (ATF) injection system at Brookhaven National Laboratory, which consists of a photocathode rf gun and a straight - ahead beamline directly into the 50 MeV linac. The proposed second entry port should improve the beam quality and lower the emittance needed for FEL (Free Electron Laser), and laser - acceleration experiments. A discussion on the laser driven high brightness photoelectrons through the primary entry port (a low energy 180 degrees achromatic double bend transport line) now in operation, and a beam analysis for the proposed secondary port is also given
ATF4 induction through an atypical integrated stress response to ONC201 triggers p53-independent apoptosis in hematological malignancies.

Science.gov (United States)

Ishizawa, Jo; Kojima, Kensuke; Chachad, Dhruv; Ruvolo, Peter; Ruvolo, Vivian; Jacamo, Rodrigo O; Borthakur, Gautam; Mu, Hong; Zeng, Zhihong; Tabe, Yoko; Allen, Joshua E; Wang, Zhiqiang; Ma, Wencai; Lee, Hans C; Orlowski, Robert; Sarbassov, Dos D; Lorenzi, Philip L; Huang, Xuelin; Neelapu, Sattva S; McDonnell, Timothy; Miranda, Roberto N; Wang, Michael; Kantarjian, Hagop; Konopleva, Marina; Davis, R Eric; Andreeff, Michael

2016-02-16

The clinical challenge posed by p53 abnormalities in hematological malignancies requires therapeutic strategies other than standard genotoxic chemotherapies. ONC201 is a first-in-class small molecule that activates p53-independent apoptosis, has a benign safety profile, and is in early clinical trials. We found that ONC201 caused p53-independent apoptosis and cell cycle arrest in cell lines and in mantle cell lymphoma (MCL) and acute myeloid leukemia (AML) samples from patients; these included samples from patients with genetic abnormalities associated with poor prognosis or cells that had developed resistance to the nongenotoxic agents ibrutinib and bortezomib. Moreover, ONC201 caused apoptosis in stem and progenitor AML cells and abrogated the engraftment of leukemic stem cells in mice while sparing normal bone marrow cells. ONC201 caused changes in gene expression similar to those caused by the unfolded protein response (UPR) and integrated stress responses (ISRs), which increase the translation of the transcription factor ATF4 through an increase in the phosphorylation of the translation initiation factor eIF2α. However, unlike the UPR and ISR, the increase in ATF4 abundance in ONC201-treated hematopoietic cells promoted apoptosis and did not depend on increased phosphorylation of eIF2α. ONC201 also inhibited mammalian target of rapamycin complex 1 (mTORC1) signaling, likely through ATF4-mediated induction of the mTORC1 inhibitor DDIT4. Overexpression of BCL-2 protected against ONC201-induced apoptosis, and the combination of ONC201 and the BCL-2 antagonist ABT-199 synergistically increased apoptosis. Thus, our results suggest that by inducing an atypical ISR and p53-independent apoptosis, ONC201 has clinical potential in hematological malignancies. Copyright © 2016, American Association for the Advancement of Science.
Timing system for multi-bunch/multi-train operation at ATF

International Nuclear Information System (INIS)

Naito, T.; Hayano, H.; Urakawa, J.; Imai, T.

2000-01-01

A timing system has been constructed for multi-bunch/multi-train operation at KEK-ATF. The linac accelerates 20 bunches of multi-bunch with 2.8 ns spacing. The Damping Ring stores up to 5 trains of multi-bunch. The timing system is required to provide flexible operation mode and bucket selection. A personal computer is used for manipulating the timing. The performance of kicker magnets at the injection/extruction is key issue for multi-train operation. The hardware and the test results are presented. (author)
Heavy ion beam probe diagnostic system for ATF

International Nuclear Information System (INIS)

Carnevali, A.; Misium, J.; Lewis, J.F.; Connor, K.A.

1986-01-01

The potential structure in non-axisymmetric toroidal confinement devices is largely responsible for the particle drift surfaces. A heavy ion beam probe diagnostic, which can directly determine the potential, is thus planned for ATF. The most significant device characteristics affecting the implementation of such a system on this complex magnetic geometry that were not encountered on tokamaks are the large toroidal separation (15 degrees) of vertical and horizontal ports and substantial magnetic return fields in the region of the ion optics and energy analyzer electric fields. The status of the design is presented with particular emphasis on the choice of energy analyzer required by the large dispersion in ion trajectories produced by this field
High resolution upgrade of the ATF damping ring BPM system

International Nuclear Information System (INIS)

Terunuma, N.; Urakawa, J.; Frisch, J.; May, J.; McCormick, D.; Nelson, J.; Seryi, A.; Smith, T.; Woodley, M.; Briegel, C.; Dysert, R.

2008-01-01

A beam position monitor (BPM) upgrade at the KEK Accelerator Test Facility (ATF) damping ring has been accomplished in its first stage, carried out by a KEK/FNAL/SLAC collaboration under the umbrella of the global ILC R and D effort. The upgrade consists of a high resolution, high reproducibility read-out system, based on analog and digital downconversion techniques, digital signal processing, and also tests a new automatic gain error correction schema. The technical concept and realization, as well as preliminary results of beam studies are presented
A Project to Design and Build the Magnets for a New Test Beamline, the ATF2, at KEK

Energy Technology Data Exchange (ETDEWEB)

Spencer, Cherrill M.; /slac; Sugahara, Ryuhei; Masuzawa, Mika; /KEK, Tsukuba; Bolzon, Benoit; Jeremie, Andrea; /Annecy, LAPP

2011-02-07

In order to achieve the high luminosity required at the proposed International Linear Collider (ILC), it is critical to focus the beams to nanometer size with the ILC Beam Delivery System, and to maintain the beams collisions with a nanometer-scale stability. To establish the technologies associated with this ultra-high precision beam handling, a special beamline has been designed and built as an extension of the existing extraction beamline of the Accelerator Test Facility at KEK, Japan. The ATF provides an adequate ultra-low emittance electron beam that is comparable to the ILC requirements; the ATF2 mimics the ILC final focus system to create a tightly focused, stable beam. There are 37 magnets in the ATF2, 29 quadrupoles, 5 sextupoles and 3 bends. These magnets had to be acquired in a short time and at minimum cost, which led to various acquisition strategies; but nevertheless they had to meet strict requirements on integrated strength, physical dimensions, compatibility with existing magnet movers and beam position monitors, mechanical stability and field stability and quality. This paper will describe how 2 styles of quadrupoles, 2 styles of sextupoles, one dipole style and their supports were designed, fabricated, refurbished or modified, measured and aligned by a small team of engineers from 3 continents.
Implementation and validation of the linear collider final focus prototype: ATF2 at KEK (Japan); Implementation et validation de la focalisation finale du collisionneur lineaire: ATF2 at KEK (Japan)

Energy Technology Data Exchange (ETDEWEB)

Renier, Y.

2010-06-15

The two linear collider projects (ILC and CLIC) require beam delivery systems with the same local chromaticity correction scheme in the final focus. ATF2 at KEK (Japan), an implementation of this scheme scaled down in energy, uses the beam extracted from ATF, which is one of the most successful damping rings in the world. The ATF2 goals are to prove the feasibility and the stability of the linear collider final focus system and to define and test the experimental correction procedures. The nominal beam sizes at the interaction point are 3 {mu}m horizontally and 37 nm vertically. The work in this thesis was started before the commissioning and covered its first year at KEK. At the beginning, we observed that the stripline BPMs were not working properly so we investigated their behavior in detail. The problem was characterized and later solved in 2010 by upgrading the electronics. We then developed an efficient procedure to check the modeling of the beam line, comparing measurements of transfer matrices to model predictions calculated on line. After obtaining a good agreement, we were able to successfully test the trajectory correction algorithm which had been developed, reducing the difference between BPM measurements and the target values down to 0.5 mm horizontally and 0.2 mm vertically. We also successfully developed an algorithm to reconstruct pulse to pulse beam trajectory fluctuations with sub-micron precision. This reconstruction also gave a precise determination of the energy fluctuation, allowing a global fit of the dispersion function along the beam line with a precision of a few mm. A simple and robust IP beam size tuning method using sextupoles displacements was also studied in simulation, whose performance indicates that, given some assumptions on the error level of the beam, convergence within 20% of the nominal beam size should be possible in 8 hours with a 80% probability. (author)
Experimental and Theoretical Progress of Linear Collider Final Focus Design and ATF2 Facility

CERN Document Server

Seryi, Andrei; Zimmermann, Frank; Kubo, Kiyoshi; Kuroda, Shigeru; Okugi, Toshiyuki; Tauchi, Toshiaki; Terunuma, Nobuhiro; Urakawa, Junji; White, Glen; Woodley, Mark; Angal-Kalinin, Deepa

2014-01-01

In this brief overview we will reflect on the process of the design of the linear collider (LC) final focus (FF) optics, and will also describe the theoretical and experimental efforts on design and practical realisation of a prototype of the LC FF optics implemented in the ATF2 facility at KEK, Japan, presently being commissioned and operated.
Localisation of beam offset jitter sources at ATF2

CERN Document Server

Pfingstner, J; Patecki, M; Schulte, D; Tomás, R

2014-01-01

For the commissioning and operation of modern particle accelerators, automated error detection and diagnostics methods are becoming increasingly important. In this paper, we present two such methods, which are capable of localising sources of beam offset jitter with a combination of correlation studies and so called degree of freedom plots. The methods were applied to the ATF2 beam line at KEK, where one of the major goals is the reduction of the beam offset jitter. Results of this localisation are shown in this paper. A big advantage of the presented method is its high robustness especially to varying optics parameters. Therefore, we believe that the developed beam offset jitter localisation methods can be easily applied to other accelerators.
Development of an S-band cavity Beam Position Monitor for ATF2

Science.gov (United States)

Heo, A.; Kim, E.-S.; Kim, H.; Son, D.; Honda, Y.; Tauchi, T.

2013-04-01

We have developed an S-band cavity Beam Position Monitor (BPM) in order to measure the position of an electron beam in the final focus area at ATF2, which is the test facility for the final focus design for the International Linear Collider (ILC). The lattice of the ILC Beam Delivery System (BDS) has been modified, requiring a larger physical aperture of 40 mm in the final focus area. The beam orbit measurement in this area is now covered with high resolution S-Band cavity BPMs. In this paper we summarize the design of the cavity BPM and the first experimental results. The calibration slopes were measured as 0.87 counts/μm in the x-coordinate direction and 1.16 counts/μm in the y-coordinate direction.
Preliminary neutronic assessment for ATF (Accident Tolerant Fuel) based on iron alloy

International Nuclear Information System (INIS)

Abe, Alfredo; Carluccio, Thiago; Piovezan, Pamela; Giovedi, Claudia; Martins, Marcelo R.

2015-01-01

After Fukushima Daiichi nuclear accident in 2011, the nuclear fuel performance under accident condition became a very important issue and currently different research and development program are in progress toward to reliability and withstand under accident condition. These initiatives are known as ATF (Accident Tolerant Fuel) R and D program, which many countries with different research institutes, fuel vendors and others are nowadays involved. Accident Tolerant Fuel (ATF) can be defined as enhanced fuel which can tolerate loss of active cooling system capability for a considerably longer time period and the fuel/cladding system can be maintained without significant degradation and can also improve the fuel performance during normal operations and transients, as well as design-basis accident (DBA) and beyond design-basis (BDBA) accident. Different materials have being proposed as fuel cladding candidates considering thermo-mechanical properties and lower reaction kinetic with steam and slower hydrogen production. The aim of this work is to perform a neutronic assessment for several cladding candidates based on iron alloy considering a standard PWR fuel rod (fuel pellet and dimension). The purpose of the assessment is to address different parameters that might contribute for possible neutronic reactivity gain in order to overcome the penalty due to increase of neutron absorption in the cladding materials. All the neutronic assessment is performed using MCNP, Monte Carlo code. (author)
Avian metapneumovirus subgroup C induces autophagy through the ATF6 UPR pathway.

Science.gov (United States)

Hou, Lei; Wei, Li; Zhu, Shanshan; Wang, Jing; Quan, Rong; Li, Zixuan; Liu, Jue

2017-10-03

An increasing number of studies have demonstrated that macroautophagy/autophagy plays an important role in the infectious processes of diverse pathogens. However, it remains unknown whether autophagy is induced in avian metapneumovirus (aMPV)-infected host cells, and, if so, how this occurs. Here, we report that aMPV subgroup C (aMPV/C) induces autophagy in cultured cells. We demonstrated this relationship by detecting classical autophagic features, including the formation of autophagsomes, the presence of GFP-LC3 puncta and the conversation of LC3-I into LC3-II. Also, we used pharmacological regulators and siRNAs targeting ATG7 or LC3 to examine the role of autophagy in aMPV/C replication. The results showed that autophagy is required for efficient replication of aMPV/C. Moreover, infection with aMPV/C promotes autophagosome maturation and induces a complete autophagic process. Finally, the ATF6 pathway, of which one component is the unfolded protein response (UPR), becomes activated in aMPV/C-infected cells. Knockdown of ATF6 inhibited aMPV/C-induced autophagy and viral replication. Collectively, these results not only show that autophagy promotes aMPV/C replication in the cultured cells, but also reveal that the molecular mechanisms underlying aMPV/C-induced autophagy depends on regulation of the ER stress-related UPR pathway.

TPL2 (Therapeutic Targeting Tumor Progression Locus-2)/ATF4 (Activating Transcription Factor-4)/SDF1α (Chemokine Stromal Cell-Derived Factor-α) Axis Suppresses Diabetic Retinopathy.

Science.gov (United States)

Lai, De-Wei; Lin, Keng-Hung; Sheu, Wayne Huey-Herng; Lee, Maw-Rong; Chen, Chung-Yu; Lee, Wen-Jane; Hung, Yi-Wen; Shen, Chin-Chang; Chung, Tsung-Ju; Liu, Shing-Hwa; Sheu, Meei-Ling

2017-09-01

Diabetic retinopathy is characterized by vasopermeability, vascular leakage, inflammation, blood-retinal barrier breakdown, capillary degeneration, and neovascularization. However, the mechanisms underlying the association between diabetes mellitus and progression retinopathy remain unclear. TPL2 (tumor progression locus 2), a serine-threonine protein kinase, exerts a pathological effect on vascular angiogenesis. This study investigated the role of N ε -(carboxymethyl)lysine, a major advanced glycation end products, and the involved TPL2-related molecular signals in diabetic retinopathy using models of in vitro and in vivo and human samples. Serum N ε -(carboxymethyl)lysine levels and TPL2 kinase activity were significantly increased in clinical patients and experimental animals with diabetic retinopathy. Intravitreal administration of pharmacological blocker or neutralizing antibody inhibited TPL2 and effectively suppressed the pathological characteristics of retinopathy in streptozotocin-induced diabetic animal models. Intravitreal VEGF (vascular endothelial growth factor) neutralization also suppressed the diabetic retinopathy in diabetic animal models. Mechanistic studies in primary human umbilical vein endothelial cells and primary retinal microvascular endothelial cells from streptozotocin-diabetic rats, db/db mice, and samples from patients with diabetic retinopathy revealed a positive parallel correlation between N ε -(carboxymethyl)lysine and the TPL2/chemokine SDF1α (stromal cell-derived factor-α) axis that is dependent on endoplasmic reticulum stress-related molecules, especially ATF4 (activating transcription factor-4). This study demonstrates that inhibiting the N ε -(carboxymethyl)lysine-induced TPL2/ATF4/SDF1α axis can effectively prevent diabetes mellitus-mediated retinal microvascular dysfunction. This signaling axis may include the therapeutic potential for other diseases involving pathological neovascularization or macular edema. © 2017
Fuel licensing process for an industrial use. ATF licensing process for an industrial use - Utility's perspective

International Nuclear Information System (INIS)

Waeckel, Nicolas

2013-01-01

To develop and license a breakthrough nuclear fuel technology for commercial use is becoming challenging. All the former safety analysis design limits (SAFDLs) defined in the 1970's for the standard UO 2 -Zr fuels, might no longer be applicable. Identification of the appropriate safety analysis design limits For each type of innovative fuel, the developers will have to identify and investigate all the possible failure/ruins scenarios (not only those related to severe accidents but also those related to normal operation). In order to save time and to focus on the best options, those failure scenarios (which could be 'killers' for the ATF concept) have to be determined early enough in the development process. Based on the above failure scenarios, the developers will have to propose the licensing limits (and the experimental protocol to determine and to justify them). As mentioned earlier, the licensing limits should not be defined against the accidental conditions only. For the operators, the (good) in-reactor fuel behaviour is crucial. As an example, in the case of the new fuel concepts coming with an outer coating, it is important to include the analysis of the consequences of the loss of this protective outer layer in the licensing process due to a manufacturing defect or an inevitable in-reactor fretting wear. Obviously, the new/specific SAFDLs will have to be endorsed by the regulators (which could be a long process by itself). Identification of a commercial reactor to irradiate the first ATF A commercial NPP is not a material test reactor (MTR); irradiating lead test fuel rods (LTFRs) or lead test assemblies (LTAs) implies strict requirements regarding the manufacturing processes [which should not include chemicals (additives or solvents) potentially incompatible with the nuclear technical specifications], the compatibility with the hosting fuel core (in terms of geometry, enrichment, thermal hydraulic performances, etc.) and the robustness and
Summary of the U.S. National Workshop. Results for ATF Metrics Development

International Nuclear Information System (INIS)

Pasamehmetoglu, Kemal

2013-01-01

This presentation discussed the main outcomes of a recent US National Workshop on Accident-Tolerant Fuels, focusing on results for ATF metrics development. All thermal, mechanical and chemical properties are relevant in defining the metrics for accident tolerance, but considerable testing and analyses are needed to identify the dominant attributes and quantify the metrics. Current analysis tools are not fully adequate to complete the task, and a need was highlighted for strong collaborations to complete the experimental data to qualify the new tools
High-mode-number ballooning modes in a heliotron/torsatron system. II. Stability

International Nuclear Information System (INIS)

Nakajima, N.

1996-01-01

In heliotron/torsatron systems that have a large Shafranov shift, the local magnetic shear is found to have no stabilizing effect on high-mode-number ballooning modes at the outer side of the torus, even in the region where the global shear is stellarator-like in nature. The disappearance of this stabilization, in combination with the compression of the flux surfaces at the outer side of the torus, leads at relatively low values of the plasma pressure to significant modifications of the stabilizing effect due to magnetic field-line bending on high-mode-number ballooning modes-specifically, that the field-line bending stabilization can be remarkably suppressed or enhanced. In an equilibrium that is slightly Mercier-unstable or completely Mercier-stable due to peaked pressure profiles, such as those used in standard stability calculations, high-mode-number ballooning modes are destabilized due to these modified stability effects, with their eigenfunctions highly localized along the field line. Highly localized mode structures such as these cause the ballooning mode eigenvalues ω 2 to have a strong field line dependence (i.e., α-variation) through the strong dependence of the local magnetic curvature, such that the level surfaces of ω 2 (ψ,θ k ,α) (≤0) become spheroids in (ψ,θ k ,α) space, where ψ labels flux surfaces and θ k is the radial wave number. Because the spheroidal level surfaces for unstable eigenvalues are surrounded by level surfaces for stable eigenvalues of high-mode-number toroidal Alfvacute en eigenmodes, those high-mode-number ballooning modes never lead to low-mode-number modes. In configuration space, these high-mode-number modes are localized in a single toroidal pitch of the helical coils, and hence they may experience substantial stabilization due to finite Larmor radius effects. copyright 1996 American Institute of Physics
Torsion of surface plate of the active support table for the ATF damping ring

International Nuclear Information System (INIS)

Takeuchi, Yasunori; Takeda, Shigeru; Kudo, Kikuo; Funahashi, Yoshisato; Kanazawa, Yasunori.

1996-01-01

Distortion of the surface plate of active support table was measured using precise tiltmeters. It is found that the surface plate is twisted when the temperature changes. The effect of this phenomenon is much smaller than the alignment tolerance of the ATF damping ring if the room temperature is controlled within 0.4degC. However, it is not negligible in the linear collider case. (author)
High Resolution BPM Upgrade for the ATF Damping Ring at KEK

International Nuclear Information System (INIS)

Eddy, N.; Briegel, C.; Fellenz, B.; Gianfelice-Wendt, E.; Prieto, P.; Rechenmacher, R.; Semenov, A.; Voy, D.; Wendt, M.; Zhang, D.; Terunuma, N.

2011-01-01

A beam position monitor (BPM) upgrade at the KEK Accelerator Test Facility (ATF) damping ring has been accomplished, carried out by a KEK/FNAL/SLAC collaboration under the umbrella of the global ILC R and D effort. The upgrade consists of a high resolution, high reproducibility read-out system, based on analog and digital down-conversion techniques, digital signal processing, and also implements a new automatic gain error correction schema. The technical concept and realization as well as results of beam studies are presented. The next generation of linear colliders require ultra-low vertical emittance of <2 pm-rad. The damping ring at the KEK Accelerator Test Facility (ATF) is designed to demonstrate this mission critical goal. A high resolution beam position monitor (BPM) system for the damping ring is one of the key tools for realizing this goal. The BPM system needs to provide two distnict measurements. First, a very high resolution (∼100-200nm) closed-orbit measurement which is averaged over many turns and realized with narrowband filter techniques - 'narrowband mode'. This is needed to monitor and steer the beam along an optimum orbit and to facilitate beam-based alignment to minimize non-linear field effects. Second, is the ability to make turn by turn (TBT) measurements to support optics studies and corrections necessary to achieve the design performance. As the TBT measurement necessitates a wider bandwidth, it is often referred to as 'wideband mode'. The BPM upgrade was initiated as a KEK/SLAC/FNAL collaboration in the frame of the Global Design Initiative of the International Linear Collider. The project was realized and completed using Japan-US funds with Fermilab as the core partner.
Upgrade of MHD data acquisition system from ISX-B [Impurity Study Experiment] to ATF [Advanced Toroidal Facility

International Nuclear Information System (INIS)

Bell, J.D.; Pare, V.L.

1987-01-01

The data acquisition system assembled to study magnetohydrodynamic (MHD) activity on the Impurity Study Experiment (ISX-B) tokamak at Oak Ridge National Laboratory (ORNL) is being revised for use on the Advanced Toroidal Facility (ATF). The new hardware and software architectures are based on ISX-B experience and will feature different modes of operation for storing various subsets of available data, a user interface that requires less routine activity than the earlier system, and continued support of calibration and testing measurement used on ISX-B. The new hardware organization and software components are described in detail. 2 refs., 5 figs., 1 tab
The data acquisition and control system for Thomson Scattering on ATF [Advanced Toroidal Facility

International Nuclear Information System (INIS)

Stewart, K.A.; Kindsfather, R.R.; Rasmussen, D.A.

1989-01-01

The 2-dimensional Thomson Scattering System measuring electron temperatures and densities in the Advanced Toroidal Facility (ATF) is interfaced to a VAX-8700 computer system running in a clustered configuration. Calibration, alignment, and operation of this diagnostic is under computer control. Extensive CAMAC instrumentation is used for timing control, data acquisition, and laser alignment. This paper will discuss the computer hardware and software, system operations, and data storage and retrieval. 3 refs
Implementation and validation of the linear collider final focus prototype: ATF2 at KEK (Japan)

International Nuclear Information System (INIS)

Renier, Y.

2010-06-01

The two linear collider projects (ILC and CLIC) require beam delivery systems with the same local chromaticity correction scheme in the final focus. ATF2 at KEK (Japan), an implementation of this scheme scaled down in energy, uses the beam extracted from ATF, which is one of the most successful damping rings in the world. The ATF2 goals are to prove the feasibility and the stability of the linear collider final focus system and to define and test the experimental correction procedures. The nominal beam sizes at the interaction point are 3 μm horizontally and 37 nm vertically. The work in this thesis was started before the commissioning and covered its first year at KEK. At the beginning, we observed that the stripline BPMs were not working properly so we investigated their behavior in detail. The problem was characterized and later solved in 2010 by upgrading the electronics. We then developed an efficient procedure to check the modeling of the beam line, comparing measurements of transfer matrices to model predictions calculated on line. After obtaining a good agreement, we were able to successfully test the trajectory correction algorithm which had been developed, reducing the difference between BPM measurements and the target values down to 0.5 mm horizontally and 0.2 mm vertically. We also successfully developed an algorithm to reconstruct pulse to pulse beam trajectory fluctuations with sub-micron precision. This reconstruction also gave a precise determination of the energy fluctuation, allowing a global fit of the dispersion function along the beam line with a precision of a few mm. A simple and robust IP beam size tuning method using sextupoles displacements was also studied in simulation, whose performance indicates that, given some assumptions on the error level of the beam, convergence within 20% of the nominal beam size should be possible in 8 hours with a 80% probability. (author)
Experimental evidence of EDGE turbulence driven by multiple mechanisms in ATF

International Nuclear Information System (INIS)

Hidalgo, C.

1993-01-01

The scaling properties of edge fluctuations have been investigated using Langmuir probes in the edge region of the Advance Toroidal Facility (ATF). Fluctuations in the ion saturation current (ls/ls) and transport inferred from the fluctuations increase with increasing density gradient, while keeping unchanged local electron temperature. The modification of the electron temperature in the range (10-50) eV, Keeping constant the density profile, does not have any significant influence on ls/ ls. In regions were Er/B =0, the poloidal phase velocity of the fluctuations is given by vph 2Te/LnB. More then one of any so far proposed mechanisms must be invoked to explain all the experimental observations. (Author) 14 refs
Recent results on cleaning and conditioning the ATF vacuum system

International Nuclear Information System (INIS)

Langley, R.A.; Clark, T.L.; Glowienka, J.C.; Goulding, R.H.; Mioduszewski, P.K.; Rasmussen, D.A.; Rayburn, T.F.; Schaich, C.R.; Shepard, T.D.; Simpkins, J.E.; Yarber, J.L.

1990-01-01

Techniques for cleaning and conditioning the vacuum vessel of the Advanced Toroidal Facility (ATF) and its internal components are described. The vacuum vessel cleaning technique combines baking to 150 degree C and glow discharges with hydrogen gas. Chromium gettering is used to further condition the system. The major internal components are the anodized aluminum baffles in the Thomson scattering system, a graphite-shielded ICRF antenna, two graphite limiters, and a diagnostic graphite plate. Three independent heating systems are used to bake some of the major components of the system. The major characteristics used for assessing cleanliness and conditioning progress are the maximum pressure attained during bakeout, the results of gas analysis, and revelant plasma parameters (e.g., time to radiative decay). Details of the various cleaning and conditioning procedures and results are presented
Experimental Evidence of Edge turbulence driven by multiple mechanisms in ATF

International Nuclear Information System (INIS)

Hidalgo, C.; Harris, J.M.; Uckran, T.; Manson, G.R.; Bell, J.D.

1993-01-01

The scaling properties of edge fluctuations have been investigated using Langmuir probes in the edge region of the Advance Toroidal Facility (ATF). Fluctuations in the ion saturation current (I s /I s ) and transport inferred from the fluctuations increase with increasing density gradient, while keeping unchanged local electron temperature. The modification of the electron temperature in the range (10-50) eV, Keeping constant the density profile, does not have any significant influence on I s /I s . In regions were E r /B∼0, the poloidal phase velocity of the fluctuations is given by V p h∼ 2T e L n B. More then one of any so far proposed mechanisms must be invoked to explain all the experimental observations.(Author)
Recent results on cleaning and conditioning the ATF vacuum system

International Nuclear Information System (INIS)

Langley, R.A.; Clark, T.L.; Glowienka, J.C.

1989-01-01

Techniques for cleaning and conditioning the vacuum vessel of the Advanced Toroidal Facility (ATF) and its internal components are described. The vacuum vessel cleaning technique combines baking to 150/degree/C and glow discharges with hydrogen gas. Chromium gettering is used to further condition the system. The major internal components are the anodized aluminum baffles in the Thomson scattering system, a graphite-shielded ICRF antenna, two graphite limiters, and a diagnostic graphite plate. Three independent heating systems are used to bake some of the major components of the system. The major characteristics used for assessing cleanliness and conditioning progress are the maximum pressure attained during bakeout, the results of gas analysis, and relevant plasma parameters (e.g., time to radiative decay). Details of the various cleaning and conditioning procedures and results are presented. 5 refs., 8 figs., 3 tabs
Location and repair of air leaks in the ATF vacuum vessel

International Nuclear Information System (INIS)

Schwenterly, S.W.; Gabbard, W.A.; Schaich, C.R.; Yarber, J.L.

1989-01-01

On the basis of partial pressure rate-of-rise and base pressure measurements, it was determined that the Advanced Toroidal Facility (ATF) vacuum vessel had an air leak in the low 10 -4 mbarx ell/s range. Pinpointing this leak by conventional helium leak-checking procedures was not possible, because large portions of the outside of the vessel are covered by the helical field coils and a structural shell. Various alternative leak detection schemes that were considered are summarized and their advantages and disadvantages noted. In the method ultimately employed, gum-rubber patches of various sizes ranging from 12.7 by 12.7 cm to 20.3 by 30.5 cm were positioned on the inside surfaces of the vessel and evacuated by the leak detector (LD). After roughly 5% of the surface was inspected in this way, a leak of >10 -5 mbar xL/s was discovered and localized to an area of 5 by 5 cm. Dye penetrant applied to this area disclosed three pinholes. Two small slag pockets were discovered while these points were being ground out. After these were rewelded, no further leakage could be found in the repaired area. Global leak rates measured after the machine was reevacuated indicated that this leak was about 30% of the overall leak rate. 1 ref., 5 figs., 1 tab
Wolfram syndrome 1 gene negatively regulates ER stress signaling in rodent and human cells.

Science.gov (United States)

Fonseca, Sonya G; Ishigaki, Shinsuke; Oslowski, Christine M; Lu, Simin; Lipson, Kathryn L; Ghosh, Rajarshi; Hayashi, Emiko; Ishihara, Hisamitsu; Oka, Yoshitomo; Permutt, M Alan; Urano, Fumihiko

2010-03-01

Wolfram syndrome is an autosomal-recessive disorder characterized by insulin-dependent diabetes mellitus, caused by nonautoimmune loss of beta cells, and neurological dysfunctions. We have previously shown that mutations in the Wolfram syndrome 1 (WFS1) gene cause Wolfram syndrome and that WFS1 has a protective function against ER stress. However, it remained to be determined how WFS1 mitigates ER stress. Here we have shown in rodent and human cell lines that WFS1 negatively regulates a key transcription factor involved in ER stress signaling, activating transcription factor 6alpha (ATF6alpha), through the ubiquitin-proteasome pathway. WFS1 suppressed expression of ATF6alpha target genes and repressed ATF6alpha-mediated activation of the ER stress response element (ERSE) promoter. Moreover, WFS1 stabilized the E3 ubiquitin ligase HRD1, brought ATF6alpha to the proteasome, and enhanced its ubiquitination and proteasome-mediated degradation, leading to suppression of ER stress signaling. Consistent with these data, beta cells from WFS1-deficient mice and lymphocytes from patients with Wolfram syndrome exhibited dysregulated ER stress signaling through upregulation of ATF6alpha and downregulation of HRD1. These results reveal a role for WFS1 in the negative regulation of ER stress signaling and in the pathogenesis of diseases involving chronic, unresolvable ER stress, such as pancreatic beta cell death in diabetes.
Polysaccharide from Angelica sinensis protects H9c2 cells against oxidative injury and endoplasmic reticulum stress by activating the ATF6 pathway.

Science.gov (United States)

Niu, Xiaowei; Zhang, Jingjing; Ling, Chun; Bai, Ming; Peng, Yu; Sun, Shaobo; Li, Yingdong; Zhang, Zheng

2018-01-01

Objectives Angelica sinensis exerts various pharmacological effects, such as antioxidant and anti-apoptotic activity. This study aimed to investigate the active ingredients in A. sinensis with antioxidant properties and whether A. sinensis polysaccharide (ASP) protects H9c2 cells against oxidative and endoplasmic reticulum (ER) stress. Methods The ingredients of A. sinensis and their targets and related pathways were determined using web-based databases. Markers of oxidative stress, cell viability, apoptosis, and ER stress-related signalling pathways were measured in H9c2 cells treated with hydrogen peroxide (H 2 O 2 ) and ASP. Results The ingredient-pathway-disease network showed that A. sinensis exerted protective effects against oxidative injury through its various active ingredients on regulation of multiple pathways. Subsequent experiments showed that ASP pretreatment significantly decreased H 2 O 2 -induced cytotoxicity and apoptosis in H9c2 cells. ASP pretreatment inhibited H 2 O 2 -induced reactive oxygen species generation, lactic dehydrogenase release, and malondialdehyde production. ASP exerted beneficial effects by inducing activating transcription factor 6 (ATF6) and increasing ATF6 target protein levels, which in turn attenuated ER stress and increased antioxidant activity. Conclusions Our findings indicate that ASP, a major water-soluble component of A. sinensis, exerts protective effects against H 2 O 2 -induced injury in H9c2 cells by activating the ATF6 pathway, thus ameliorating ER and oxidative stress.
Hepatocyte DACH1 Is Increased in Obesity via Nuclear Exclusion of HDAC4 and Promotes Hepatic Insulin Resistance

Directory of Open Access Journals (Sweden)

Lale Ozcan

2016-06-01

Full Text Available Defective insulin signaling in hepatocytes is a key factor in type 2 diabetes. In obesity, activation of calcium/calmodulin-dependent protein kinase II (CaMKII in hepatocytes suppresses ATF6, which triggers a PERK-ATF4-TRB3 pathway that disrupts insulin signaling. Elucidating how CaMKII suppresses ATF6 is therefore essential to understanding this insulin resistance pathway. We show that CaMKII phosphorylates and blocks nuclear translocation of histone deacetylase 4 (HDAC4. As a result, HDAC4-mediated SUMOylation of the corepressor DACH1 is decreased, which protects DACH1 from proteasomal degradation. DACH1, together with nuclear receptor corepressor (NCOR, represses Atf6 transcription, leading to activation of the PERK-TRB3 pathway and defective insulin signaling. DACH1 is increased in the livers of obese mice and humans, and treatment of obese mice with liver-targeted constitutively nuclear HDAC4 or DACH1 small hairpin RNA (shRNA increases ATF6, improves hepatocyte insulin signaling, and protects against hyperglycemia and hyperinsulinemia. Thus, DACH1-mediated corepression in hepatocytes emerges as an important link between obesity and insulin resistance.
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 2^nd 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.
Measurements of the fast ion distribution during neutral beam injection and ion cyclotron heating in ATF [Advanced Toroidal Facility

International Nuclear Information System (INIS)

Wade, M.R.; Kwon, M.; Thomas, C.E.; Colchin, R.J.; England, A.C.; Gossett, J.M.; Horton, L.D.; Isler, R.C.; Lyon, J.F.; Rasmussen, D.A.; Rayburn, T.M.; Shepard, T.D.; Bell, G.L.; Fowler, R.H.; Morris, R.N.

1990-01-01

A neutral particle analyzer (NPA) with horizontal and vertical scanning capability has been used to make initial measurements of the fast ion distribution during neutral beam injection (NBI) and ion cyclotron heating (ICH) on the Advanced Toroidal Facility (ATF). These measurements are presented and compared with the results of modeling codes that predict the analyzer signals during these heating processes. 6 refs., 5 figs
Mitochondrial dysfunction enhances cisplatin resistance in human gastric cancer cells via the ROS-activated GCN2-eIF2α-ATF4-xCT pathway.

Science.gov (United States)

Wang, Sheng-Fan; Chen, Meng-Shian; Chou, Yueh-Ching; Ueng, Yune-Fang; Yin, Pen-Hui; Yeh, Tien-Shun; Lee, Hsin-Chen

2016-11-08

Mitochondrial DNA mutations and defects in mitochondrial enzymes have been identified in gastric cancers, and they might contribute to cancer progression. In previous studies, mitochondrial dysfunction was induced by oligomycin-enhanced chemoresistance to cisplatin. Herein, we dissected the regulatory mechanism for mitochondrial dysfunction-enhanced cisplatin resistance in human gastric cancer cells. Repeated cisplatin treatment-induced cisplatin-resistant cells exhibited high SLC7A11 (xCT) expression, and xCT inhibitors (sulfasalazine or erastin), xCT siRNA, or a GSH synthesis inhibitor (buthionine sulphoximine, BSO) could sensitize these cells to cisplatin. Clinically, the high expression of xCT was associated with a poorer prognosis for gastric cancer patients under adjuvant chemotherapy. Moreover, we found that mitochondrial dysfunction enhanced cisplatin resistance and up-regulated xCT expression, as well as intracellular glutathione (GSH). The xCT inhibitors, siRNA against xCT or BSO decreased mitochondrial dysfunction-enhanced cisplatin resistance. We further demonstrated that the upregulation of the eIF2α-ATF4 pathway contributed to mitochondrial dysfunction-induced xCT expression, and activated eIF2α kinase GCN2, but not PERK, stimulated the eIF2α-ATF4-xCT pathway in response to mitochondrial dysfunction-increased reactive oxygen species (ROS) levels. In conclusion, our results suggested that the ROS-activated GCN2-eIF2α-ATF4-xCT pathway might contribute to mitochondrial dysfunction-enhanced cisplatin resistance and could be a potential target for gastric cancer therapy.

Development of Electrical Capacitance Sensors for Accident Tolerant Fuel (ATF) Testing at the Transient Reactor Test (TREAT) Facility

Energy Technology Data Exchange (ETDEWEB)

Liu, Maolong; Ryals, Matthew; Ali, Amir; Blandford, Edward; Jensen, Colby; Condie, Keith; Svoboda, John; O' Brien, Robert

2016-08-01

A variety of instruments are being developed and qualified to support the Accident Tolerant Fuels (ATF) program and future transient irradiations at the Transient Reactor Test (TREAT) facility at Idaho National Laboratory (INL). The University of New Mexico (UNM) is working with INL to develop capacitance-based void sensors for determining the timing of critical boiling phenomena in static capsule fuel testing and the volume-averaged void fraction in flow-boiling in-pile water loop fuel testing. The static capsule sensor developed at INL is a plate-type configuration, while UNM is utilizing a ring-type capacitance sensor. Each sensor design has been theoretically and experimentally investigated at INL and UNM. Experiments are being performed at INL in an autoclave to investigate the performance of these sensors under representative Pressurized Water Reactor (PWR) conditions in a static capsule. Experiments have been performed at UNM using air-water two-phase flow to determine the sensitivity and time response of the capacitance sensor under a flow boiling configuration. Initial measurements from the capacitance sensor have demonstrated the validity of the concept to enable real-time measurement of void fraction. The next steps include designing the cabling interface with the flow loop at UNM for Reactivity Initiated Accident (RIA) ATF testing at TREAT and further characterization of the measurement response for each sensor under varying conditions by experiments and modeling.
Amino alcohol- (NPS-2143 and quinazolinone-derived calcilytics (ATF936 and AXT914 differentially mitigate excessive signalling of calcium-sensing receptor mutants causing Bartter syndrome Type 5 and autosomal dominant hypocalcemia.

Directory of Open Access Journals (Sweden)

Saskia Letz

Full Text Available Activating calcium sensing receptor (CaSR mutations cause autosomal dominant hypocalcemia (ADH characterized by low serum calcium, inappropriately low PTH and relative hypercalciuria. Four activating CaSR mutations cause additional renal wasting of sodium, chloride and other salts, a condition called Bartter syndrome (BS type 5. Until today there is no specific medical treatment for BS type 5 and ADH. We investigated the effects of different allosteric CaSR antagonists (calcilytics on activating CaSR mutants.All 4 known mutations causing BS type 5 and five ADH mutations were expressed in HEK 293T cells and receptor signalling was studied by measurement of intracellular free calcium in response to extracellular calcium ([Ca2+]o. To investigate the effect of calcilytics, cells were stimulated with 3 mM [Ca2+]o in the presence or absence of NPS-2143, ATF936 or AXT914.All BS type 5 and ADH mutants showed enhanced signalling activity to [Ca2+]o with left shifted dose response curves. In contrast to the amino alcohol NPS-2143, which was only partially effective, the quinazolinone calcilytics ATF936 and AXT914 significantly mitigated excessive cytosolic calcium signalling of all BS type 5 and ADH mutants studied. When these mutants were co-expressed with wild-type CaSR to approximate heterozygosity in patients, ATF936 and AXT914 were also effective on all mutants.The calcilytics ATF936 and AXT914 are capable of attenuating enhanced cytosolic calcium signalling activity of CaSR mutations causing BS type 5 and ADH. Quinazolinone calcilytics might therefore offer a novel treatment option for patients with activating CaSR mutations.
Comparison of ATF and TJ-II stellarator equilibria as computed by the 3-D VMEC and PIES codes

International Nuclear Information System (INIS)

Johnson, J.L.; Monticello, D.A.; Reiman, A.H.; Hirshman, S.P.

1992-01-01

A comparison is made of results from the PIES code, which determines the equilibrium properties of three-dimensional toroidal configurations by direct integration along the magnetic field lines, with those from the VMEC code, which uses an energy minimization in a flux representation to determine the equilibrium configuration, for two devices: the ATF stellarator at Oak Ridge and the TJ-11 heliac which is being built in Madrid. The results obtained from the two codes are in good agreement, providing additional validation for the codes
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
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”.
Analysis of the superconducting wiggler magnets for the ATF Harmonic Generation FEL experiment

International Nuclear Information System (INIS)

Zhang, X.; Ben-Zvi, I.; Ingold, G.; Krinsky, S.; Yu, L.H.

1992-01-01

In this paper, we consider the superconducting wiggler magnet under construction for the High Gain Harmonic Generation experiment (HGHG) at the Accelerator Test Facility (ATF) at BNL. This wiggler consists of an energy modulation section, a dispersion magnet and a radiator section. We present an analysis of the dispersion magnet and the end effects in the other wiggler sections. The purpose of the dispersion magnet is to convert energy modulation of the electron beam into spatial bunching. For the dispersion magnet, we discuss the physical requirements, analyze the magnetic design, determine the focusing properties, and consider the effect of departures from ideal behavior on the FEL gain. In the modulator and radiator wigglers we analyze the effects due to the ends of the wiggler and discuss their correction. In addition, the localized field produced by a trim coil for horizontal beam steering is investigated
Location and repair of air leaks in the ATF [Advanced Toroidal Facility] vacuum vessel

International Nuclear Information System (INIS)

Schwenterly, S.W.; Gabbard, W.A.; Schaich, C.R.; Yarber, J.L.

1989-01-01

On the basis of partial pressure rate-of-rise and base pressure measurements, it was determined that the Advanced Toroidal Facility (ATF) vacuum vessel had an air leak in the low 10 -4 mbar-ell/s range. Pinpointing this leak by conventional helium leak-checking procedures was not possible, because large portions of the outside of the vessel are covered by the helcial field coils and a structural shell. Various alternative leak-detection schemes that were considered are summarized and their advantages and disadvantages noted. In the method ultimately employed, gun-rubber patches of various sizes ranging from 12.7 by 12.7 cm to 20.3 by 30.5 cm were positioned on the inside surfaces of the vessel and evacuated by the leak detector (LD). After roughly 5% of the surface was inspected in this way, a leak of > 10 -5 mbar-ell/s was discovered and localized to an area of 5 by 5 cm. Dye penetrant applied to this area disclosed three pinholes. Two small slag pockets were discovered while these points were being ground out. After these were rewelded, no furthered leakage could be found in the repaired area. Global leak rates measured after the machine was reevacuated indicated that this leak was about 30% of the overall leak rate. 1 ref., 5 figs., 1 tab
Study of neoclassical transport in the 1/ν regime for a research fusion reactor

International Nuclear Information System (INIS)

Kalyuzhnyj, V.N.; Kasilov, S.V.; Nemov, V.V.

2005-01-01

In frame of the concept of a steady-state operated research fusion reactor (RFR) in papers [1-4] the RFR with an increased plasma-wall detachment was proposed with the purpose to enable not only the production but also a long-term confinement of a self-sustained plasma at the existing technology level. In connection with complication of the corresponding magnetic configuration an investigation of the neoclassical transport is desirable for such systems. In the present work neoclassical transport for a magnetic configuration of l=2 torsatron type variant of RFR system with an additional opposite toroidal magnetic field is investigated numerically. A so-called 1/ν transport regime, in which the transport coefficients are increased with reduction of particle collision frequency ν is considered. For calculating of transport coefficients a technique, based on integration along magnetic field lines in a given stellarator magnetic field is used. The magnetic field of helical windings is calculated by Biot-Savart law. The obtained transport coefficients are presented in a standard form containing a factor depending on the magnetic field geometry. From analysis of the received results follows that in respect of the neoclassical transport the proposed magnetic configuration turns out to be closer to configuration of the classical stellarator (with helical winding), than to configuration of the classical torsatron/geliotron. (author)
Ballooning Representation Approach to Low-Frequency Instabilities in Stellarators

International Nuclear Information System (INIS)

Dewar, R.L.; Gardner, H.J.; Lewandowski, J.; Persson, M.

1995-01-01

Local ideal MHD ballooning eigenvalues have been calculated on many field lines for heliac and torsatron cases using a parallel implementation of a ballooning code on a Thinking Machines Corporation CM-5 Global eigenvalues have been estimated for the torsatron test case using the ray tracing method of Dewar and Glasser and also by using the TERPSI-CHORE global eigenvalue code, with good agreement. As a preliminary to detailed study of H-1, 3-D visualizations of stability-related quantities have been produced. 6 refs
Non-destructive Preirradiation Assessment of UN / U-Si ''LANL1'' ATF formulation

International Nuclear Information System (INIS)

Vogel, Sven C.; Losko, Adrian Simon; Pokharel, Reeju; Ickes, Timothy Lee; Hunter, James F.; Brown, Donald William; Voit, Stewart Lancaster; Tremsin, Anton S.; Bourke, Mark Andrew; McClellan, Kenneth James

2016-01-01

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 U 3 Si 5 reference formulations (two enrichment levels), and two reject pellets with visible flaws (to qualify the technique). The 235 U 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 U 3 Si 5 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 handling. We demonstrated synchrotron-based 3D X
Emittance studies of the BNL/SLAC/UCLA 1.6 cell photocathode rf gun

International Nuclear Information System (INIS)

Palmer, D.T.; Miller, R.H.; Wang, X.J.

1997-01-01

The symmetrized 1.6 cell S-band photocathode gun developed by the BNL/SLAC/UCLA collaboration is in operation at the Brookhaven Accelerator Test Facility (ATF). A novel emittance compensation solenoid magnet has also been designed, built and is in operation at the ATF. These two subsystems form an emittance compensated photoinjector used for beam dynamics, advanced acceleration and free electron laser experiments at the ATF. The highest acceleration field achieved on the copper cathode is 150 MV/m, and the guns normal operating field is 130 MV/m. The maximum rf pulse length is 3 micros. The transverse emittance of the photoelectron beam were measured for various injection parameters. The 1 nC emittance results are presented along with electron bunch length measurements that indicated that at above the 400 pC, space charge bunch lengthening is occurring. The thermal emittance, ε o , of the copper cathode has been measured
Mechanical testing and development of the helical field coil joint for the Advanced Toroidal Facility

International Nuclear Information System (INIS)

Nelson, B.E.; Bryan, W.E.; Goranson, P.L.; Warwick, J.E.

1985-01-01

The helical field (HF) coil set for the Advanced Toroidal Facility (ATF) is an M = 12, l = 2, constant-ratio torsatron winding consisting of 2 coils, each with 14 turns of heavy copper conductor. The coils are divided into 24 identical segments to facilitate fabrication and minimize the assembly schedule. The segments are connected across through-bolted lap joints that must carry up to 124,000 A per turn for 5 s or 62,500 A steady-state. In addition, the joints must carry the high magnetic and thermal loads induced in the conductor and still fit within the basic 140- by 30-mm copper envelope. Extensive testing and development were undertaken to verify and refine the basic joint design. Tests included assembly force and clamping force for various types of misalignment; joint resistance as a function of clamping force; clamp bolt relaxation due to thermal cycling; fatigue testing of full-size, multiturn joint prototypes; and low-cycle fatigue and tensile tests of annealed CDA102 copper. The required performance parameters and actual test results, as well as the final joint configuration, are presented. 2 refs., 9 figs., 4 tabs
v-src induction of the TIS10/PGS2 prostaglandin synthase gene is mediated by an ATF/CRE transcription response element.

OpenAIRE

Xie, W; Fletcher, B S; Andersen, R D; Herschman, H R

1994-01-01

We recently reported the cloning of a mitogen-inducible prostaglandin synthase gene, TIS10/PGS2. In addition to growth factors and tumor promoters, the v-src oncogene induces TIS10/PGS2 expression in 3T3 cells. Deletion analysis, using luciferase reporters, identifies a region between -80 and -40 nucleotides 5' of the TIS10/PGS2 transcription start site that mediates pp60v-src induction in 3T3 cells. This region contains the sequence CGTCACGTG, which includes overlapping ATF/CRE (CGTCA) and E...
Preliminary Results on New Prototypes of Precision Rh-0.5at%Fe Resistance Thermometers of Chinese Production

Science.gov (United States)

Pavese, F.; Szmyrka-Grzebyk, A.; Lipinski, L.; Manuszkiewicz, H.; Qiu, Ping; Zhang, Jin Tao; Lin, Peng; Li, Xing Wei

2008-02-01

Given the practical impossibility of obtaining new precision Rh-0.5at%Fe resistance thermometers in recent years, the possible re-starting of the production of such thermometers in Yunnan (China) was explored by Istituto Nazionale di Ricerca Metrologica (INRIM). Ten prototypes of the new production were made available in early 2006. The paper reports the preliminary data from the testing performed to date on these prototypes at National Institute of Metrology (NIM) and Instytut Niskich Temperatur i Badan Strukturalnych (INTiBS). Although a problem with the alloy composition was detected, the reproducibility results on thermal cycling are very encouraging. Resistance-temperature ( R- T) characteristics below 30 K, though not identical with those of similar thermometers formerly available from Tinsley and VNIIFTRI, are still suitable for accurate metrology.
Beam emittance and the effects of the rf, space charge and wake fields: Application to the ATF photoelectron beam

International Nuclear Information System (INIS)

Parsa, Z.

1991-01-01

Laser driven photoelectron guns are of interest for use in new methods of accelerations, future development of Linear Colliders and new experiments such as Free Electron laser (IFEL). Such guns are potential source of low emittance-high current and short bunch length electron beams, where the emitted electrons are accelerated quickly to a relativistic energy by a strong rf, electric field in the cavity. We present a brief overview of the beam dynamic studies, e.g. emittance for the Brookhaven National Laboratory (BNL) ATF high brightness photocathode radio frequency gun (now in operation), and show the effects of the rf, Space Charge, and Wake fields on the photoelectrons. 4 refs., 7 figs
ONC201 kills solid tumor cells by triggering an integrated stress response dependent on ATF4 activation by specific eIF2α kinases

OpenAIRE

Kline, C. Leah B.; Van den Heuvel, A. Pieter J.; Allen, Joshua E.; Prabhu, Varun V.; Dicker, David T.; El-Deiry, Wafik S.

2016-01-01

ONC201 (also called TIC10) is a small molecule that inactivates the cell proliferation- and cell survival-promoting kinases AKT and ERK and induces cell death through the pro-apoptotic protein TRAIL. ONC201 is currently in early phase clinical testing for various malignancies. Here, we found through gene expression and protein analyses that ONC201 triggered an increase in TRAIL abundance and cell death through an integrated stress response (ISR) involving the transcription factor ATF4, the tr...
Two CGTCA motifs and a GHF1/Pit1 binding site mediate cAMP-dependent protein kinase A regulation of human growth hormone gene expression in rat anterior pituitary GC cells.

Science.gov (United States)

Shepard, A R; Zhang, W; Eberhardt, N L

1994-01-21

We established the cis-acting elements which mediate cAMP responsiveness of the human growth hormone (hGH) gene in transiently transfected rat anterior pituitary tumor GC cells. Analysis of the intact hGH gene or hGH 5'-flanking DNA (5'-FR) coupled to the hGh cDNA or chloramphenicol acetyltransferase or luciferase genes, indicated that cAMP primarily stimulated hGH promoter activity. Cotransfection of a protein kinase A inhibitory protein cDNA demonstrated that the cAMP response was mediated by protein kinase A. Mutational analysis of the hGH promoter identified two core cAMP response element motifs (CGTCA) located at nucleotides -187/-183 (distal cAMP response element; dCRE) and -99/-95 (proximal cAMP response element; pCRE) and a pituitary-specific transcription factor (GHF1/Pit1) binding site at nucleotides -123/-112 (dGHF1) which were required for cAMP responsiveness. GHF1 was not a limiting factor, since overexpression of GHF1 in cotransfections increased basal but not forskolin induction levels. Gel shift analyses indicated that similar, ubiquitous, thermostable protein(s) specifically bound the pCRE and dCRE motifs. The CGTCA motif-binding factors were cAMP response element binding protein (CREB)/activating transcription factor-1 (ATF-1)-related, since the DNA-protein complex was competed by unlabeled CREB consensus oligonucleotide, specifically supershifted by antisera to CREB and ATF-1 but not ATF-2, and was bound by purified CREB with the same relative binding affinity (pCRE < dCRE < CREB) and mobility as the GC nuclear extract. UV cross-linking and Southwestern blot analyses revealed multiple DNA-protein interactions of which approximately 100- and approximately 45-kDa proteins were predominant; the approximately 45-kDa protein may represent CREB. These results indicate that CREB/ATF-1-related factors act coordinately with the cell-specific factor GHF1 to mediate cAMP-dependent regulation of hGH-1 gene transcription in anterior pituitary somatotrophs.
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.
SB203580 Modulates p38 MAPK Signaling and Dengue Virus-Induced Liver Injury by Reducing MAPKAPK2, HSP27, and ATF2 Phosphorylation.

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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.
A Low-Protein, High-Carbohydrate Diet Stimulates Thermogenesis in the Brown Adipose Tissue of Rats via ATF-2.

Science.gov (United States)

de França, Suélem A; dos Santos, Maísa P; Przygodda, Franciele; Garófalo, Maria Antonieta R; Kettelhut, Isis C; Magalhães, Diego A; Bezerra, Kalinne S; Colodel, Edson M; Flouris, Andreas D; Andrade, Cláudia M B; Kawashita, Nair H

2016-03-01

The aim of this study was to evaluate thermogenesis in the interscapular brown adipose tissue (IBAT) of rats submitted to low-protein, high-carbohydrate (LPHC) diet and the involvement of adrenergic stimulation in this process. Male rats (~100 g) were submitted to LPHC (6%-protein; 74%-carbohydrate) or control (C; 17%-protein; 63%-carbohydrate) isocaloric diets for 15 days. The IBAT temperature was evaluated in the rats before and after the administration of noradrenaline (NA) (20 µg 100 g b w(-1) min(-1)). The expression levels of uncoupling protein 1 (UCP1) and other proteins involved in the regulation of UCP1 expression were determined by Western blot (Student's t test, P ≤ 0.05). The LPHC diet promoted a 1.1 °C increase in the basal temperature of IBAT when compared with the basal temperature in the IBAT of the C group. NA administration promoted a 0.3 °C increase in basal temperature in the IBAT of the C rats and a 0.5 °C increase in the IBAT of the LPHC group. The level of UCP1 increased 60% in the IBAT of LPHC-fed rats, and among the proteins involved in its expression, such as β3-AR and α1-AR, there was a 40% increase in the levels of p38-MAPK and a 30% decrease in CREB when compared to the C rats. The higher sympathetic flux to IBAT, which is a consequence of the administration of the LPHC diet to rats, activates thermogenesis and increases the expression of UCP1 in the tissue. Our results suggest that the increase in UCP1 content may occur via p38 MAPK and ATF2.

Physical mechanism determining the radial electric field and its radial structure in a toroidal plasma

International Nuclear Information System (INIS)

Ida, Katsumi; Miura, Yukitoshi; Itoh, Sanae

1994-10-01

Radial structures of plasma rotation and radial electric field are experimentally studied in tokamak, heliotron/torsatron and stellarator devices. The perpendicular and parallel viscosities are measured. The parallel viscosity, which is dominant in determining the toroidal velocity in heliotron/torsatron and stellarator devices, is found to be neoclassical. On the other hand, the perpendicular viscosity, which is dominant in dictating the toroidal rotation in tokamaks, is anomalous. Even without external momentum input, both a plasma rotation and a radial electric field exist in tokamaks and heliotrons/torsatrons. The observed profiles of the radial electric field do not agree with the theoretical prediction based on neoclassical transport. This is mainly due to the existence of anomalous perpendicular viscosity. The shear of the radial electric field improves particle and heat transport both in bulk and edge plasma regimes of tokamaks. (author) 95 refs
Dual N- and C-terminal helices are required for endoplasmic reticulum and lipid droplet association of alcohol acetyltransferases in Saccharomyces cerevisiae.

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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.
Regulation of Saccharomyces cerevisiae genetic engineering on the production of acetate esters and higher alcohols during Chinese Baijiu fermentation.

Science.gov (United States)

Li, Wei; Wang, Jian-Hui; Zhang, Cui-Ying; Ma, Hong-Xia; Xiao, Dong-Guang

2017-06-01

Acetate esters and higher alcohols greatly influence the quality and flavor profiles of Chinese Baijiu (Chinese liquor). Various mutants have been constructed to investigate the interactions of ATF1 overexpression, IAH1 deletion, and BAT2 deletion on the production of acetate esters and higher alcohols. The results showed that the overexpression of ATF1 under the control of the PGK1 promoter with BAT2 and IAH1 double-gene deletion led to a higher production of acetate esters and a lower production of higher alcohols than the overexpression of ATF1 with IAH1 deletion or overexpression of ATF1 with BAT2 deletion. Moreover, deletion of IAH1 in ATF1 overexpression strains effectively increased the production of isobutyl acetate and isoamyl acetate by reducing the hydrolysis of acetate esters. The decline in the production of higher alcohol by the ATF1 overexpression strains with BAT2 deletion is due to the interaction of ATF1 overexpression and BAT2 deletion. Mutants with varying abilities of producing acetate esters and higher alcohols were developed by genetic engineering. These strains have great potential for industrial application.
Ankaferd Blood Stopper induces apoptosis and regulates PAR1 and ...

African Journals Online (AJOL)

Mine Mumcuoglu

2014-12-16

Dec 16, 2014 ... investigated for its properties. However there are no ... types of proteins and factors acting on cellular functions such as protein-2 (AP2), ... ATF1), cyclic AMP response element binding protein (CREB),. E2F1–5, E2F6, EGR, ...
Transition from resistive-g to eta-i driven turbulence in stellarator systems

International Nuclear Information System (INIS)

Hong, B.-G.; Horton, W.; Hamaguchi, S.; Wakantani, M.; Yagi, M.; Sugama, H.

1990-02-01

By an electromagnetic incompressible two fluid model describing both ion temperature gradient drift modes (η i modes) and resistive interchange modes (g modes), a new type of η i mode is studied in cylindrical geometry including magnetic shear and an averaged curvature of Heliotron/Torsatron. This η i mode is destabilized by the coupling to the unstable g mode. Finite plasma pressure beta increases the growth rate of this mode and the radial mode width also increases with plasma pressure beta indicating large anomalous transport in the Heliotron/Torsatron configuration. The transport from η i mode exceeds that from resistive g when the mean-free-path exceeds the machine circumference. For plasma beta above two to three times the Suydam limit the m = 1/n = 1 growth rate increases from the η i mode value to the MHD value. 13 refs., 5 figs
Beam-driven currents in the 1/ν regime in a helical system

International Nuclear Information System (INIS)

Nakajima, Noriyoshi; Okamoto, Masao.

1990-04-01

Beam currents driven by a neutral particle injection in a helical system (stellarator, heliotron/torsatron) are studied in the 1/ν collisionality regime. The general expression for the beam-driven current is obtained for arbitrary magnetic field configurations by solving the drift kinetic equation for electrons. It is found that F = J(net)/J(b) (J(net) is the net current and J(b) is the fast ion beam current) increases as f(t) and Zeff where f(t) is the fraction of trapped electrons and Zeff is the effective ionic charge number. Especially, for Zeff ≅ 1 the effect of trapped electrons is large and F is roughly proportional to f(t). On the other hand, if Zeff > or approx 3 the effect of trapped electrons becomes small. (author)
Superbanana orbits in stellarator geometries

International Nuclear Information System (INIS)

Derr, J.A.; Shohet, J.L.

1979-04-01

The presence of superbanana orbit types localized to either the interior or the exterior of stellarators and torsatrons is numerically investigated for 3.5 MeV alpha particles. The absence of the interior superbanana in both geometries is found to be due to non-conservation of the action. Exterior superbananas are found in the stellarator only, as a consequence of the existence of closed helical magnetic wells. No superbananas of either type are found in the torsatron
FOXO1 orchestrates the bone-suppressing function of gut-derived serotonin

Science.gov (United States)

Kode, Aruna; Mosialou, Ioanna; Silva, Barbara C.; Rached, Marie-Therese; Zhou, Bin; Wang, Ji; Townes, Tim M.; Hen, Rene; DePinho, Ronald A.; Guo, X. Edward; Kousteni, Stavroula

2012-01-01

Serotonin is a critical regulator of bone mass, fulfilling different functions depending on its site of synthesis. Brain-derived serotonin promotes osteoblast proliferation, whereas duodenal-derived serotonin suppresses it. To understand the molecular mechanisms of duodenal-derived serotonin action on osteoblasts, we explored its transcriptional mediation in mice. We found that the transcription factor FOXO1 is a crucial determinant of the effects of duodenum-derived serotonin on bone formation We identified two key FOXO1 complexes in osteoblasts, one with the transcription factor cAMP-responsive element–binding protein 1 (CREB) and another with activating transcription factor 4 (ATF4). Under normal levels of circulating serotonin, the proliferative activity of FOXO1 was promoted by a balance between its interaction with CREB and ATF4. However, high circulating serotonin levels prevented the association of FOXO1 with CREB, resulting in suppressed osteoblast proliferation. These observations identify FOXO1 as the molecular node of an intricate transcriptional machinery that confers the signal of duodenal-derived serotonin to inhibit bone formation. PMID:22945629
Phase decomposition in a mechanically alloyed Cu-44.5 at%Ni-22.5 at%Fe alloy during isothermal aging

International Nuclear Information System (INIS)

Lopez-Hirata, Victor M.; Saucedo-Munoz, Maribel L.; Diaz-Barriga-Arceo, Lucia G.

2006-01-01

A supersaturated solid solution of Cu-44.5 at%Ni-22.5 at%Fe alloy was produced by ball milling of a pure chemical elemental mixture for 1080 ks. An fcc supersaturated solid solution with a grain size of about 20 nm was obtained after milling. This alloy was subsequently aged at 803, 898 and 1003 K for different times. The growth kinetics of the modulation wavelength was determined from the X-ray diffraction results and followed the Lifshitz-Slyozov-Wagner theory for a diffusion-controlled coarsening in the MA alloy after aging. The growth kinetics of composition modulation wavelength for the MA alloy was faster at 803 and 898 K than that for the same alloy composition obtained by a conventional processing and then aged at the same temperatures. The activation energy for the decomposed phase coarsening process in the MA alloy was lower than that corresponding to the conventionally-processed alloy. (author)
Status of the US stellarator reactor study

International Nuclear Information System (INIS)

Lyon, J.F.; Gulec, K.; Miller, R.L.; El-Guebaly, L.

1994-01-01

Stellarators have significant operational advantages over tokamaks as ignited steady-state reactors. This scoping study, which uses an integrated cost-minimization code that incorporates costing and reactor component models self-consistently with a 1-D energy transport calculation, shows that a torsatron reactor could also be competitive with a tokamak reactor. The projected cost of electricity (COE) estimated using the ARIES costing algorithms is 62.5 mill/kW(e)h in constant 1992 dollars for a 1-GW(e) Compact Torsatron reactor reference case. The COE is relatively insensitive (< 10% variation) over a wide range of assumptions including variations in the maximum field allowed on the coils, the coil elongation, the shape of the density profile, the beta limit, the confinement multiplier, and the presence of a large loss region for alpha particles. The largest variations in the COE occur for variations in the electrical power output demanded and the plasma-coil separation ratio
Neutron Characterization of Encapsulated ATF-1/LANL-1 Mockup Fuel Capsules

Energy Technology Data Exchange (ETDEWEB)

Vogel, Sven C. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Borges, Nicholas Paul [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Losko, Adrian Simon [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Mosby, Shea Morgan [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Voit, Stewart Lancaster [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); White, Joshua Taylor [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Byler, Darrin David [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Dunwoody, John Tyler [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Nelson, Andrew Thomas [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Mcclellan, Kenneth James [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2017-09-28

Twenty pellets of mock-up accident tolerant fuels UN-U3Si5 were produced at LANL and loaded in two rodlet/capsule assemblies. Tomographic imaging and diffraction measurements were performed to characterize these samples at the Flight-Path 5 and HIPPO beam lines at LANSCE/LANL between November 2016 and January 2017 as well as in August 2017. The entire ~10 cm long, ~1 cm diameter fuel volume could be characterized, however due to time constraints only 2 mm slices in 4mm increments were characterized with neutron diffraction and a 28mm subset of the entire sample was characterized with energy-resolved neutron imaging. The double encapsulation of the fuel into two steel containers does not pose a problem for the neutron analysis and the methods could be applied to enriched as well irradiated fuels.
Skeletal Complications in Neurofibromatosis Type 1: the Role of Neurofibromin Haploinsufficiency in Defective Skeletal Remodeling and Bone Healing in NF1

Science.gov (United States)

2009-01-01

pathogenesis of pseudoarthrosis of the tibia (1). Health reports from the Vanderbilt mouse colony indicated exposure to mouse parvo virus (MPV) and...facility following the quarantine period and two, clean, consecutive monthly health reports, consistent with BIDMC Animal Research Facility animal...M.D., Sowa, H., Starbuck , M., Liu, X., Ron, D., Parada, L.F., and Karsenty, G. 2006. ATF4 mediation of NF1 functions in osteoblast reveals a
Cyclin D3 interacts with human activating transcription factor 5 and potentiates its transcription activity

International Nuclear Information System (INIS)

Liu Wenjin; Sun Maoyun; Jiang Jianhai; Shen Xiaoyun; Sun Qing; Liu Weicheng; Shen Hailian; Gu Jianxin

2004-01-01

The Cyclin D3 protein is a member of the D-type cyclins. Besides serving as cell cycle regulators, D-type cyclins have been reported to be able to interact with several transcription factors and modulate their transcriptional activations. Here we report that human activating transcription factor 5 (hATF5) is a new interacting partner of Cyclin D3. The interaction was confirmed by in vivo coimmunoprecipitation and in vitro binding analysis. Neither interaction between Cyclin D1 and hATF5 nor interaction between Cyclin D2 and hATF5 was observed. Confocal microscopy analysis showed that Cyclin D3 could colocalize with hATF5 in the nuclear region. Cyclin D3 could potentiate hATF5 transcriptional activity independently of its Cdk4 partner. But Cyclin D1 and Cyclin D2 had no effect on hATF5 transcriptional activity. These data provide a new clue to understand the new role of Cyclin D3 as a transcriptional regulator
Role of TLR4/NADPH oxidase/ROS-activated p38 MAPK in VCAM-1 expression induced by lipopolysaccharide in human renal mesangial cells

Directory of Open Access Journals (Sweden)

Lee I-Ta

2012-11-01

Full Text Available Abstract Background In bacteria-induced glomerulonephritis, Toll-like receptor 4 (TLR4 activation by lipopolysaccharide (LPS, a key component of the outer membranes of Gram-negative bacteria can increase oxidative stress and the expression of vascular cell adhesion molecule-1 (VCAM-1, which recruits leukocytes to the glomerular mesangium. However, the mechanisms underlying VCAM-1 expression induced by LPS are still unclear in human renal mesangial cells (HRMCs. Results We demonstrated that LPS induced VCAM-1 mRNA and protein levels associated with an increase in the promoter activity of VCAM-1, determined by Western blot, RT-PCR, and promoter assay. LPS-induced responses were inhibited by transfection with siRNAs of TLR4, myeloid differentiation factor 88 (MyD88, Nox2, Nox4, p47phox, c-Src, p38 MAPK, activating transcription factor 2 (ATF2, and p300 or pretreatment with the inhibitors of reactive oxygen species (ROS, edaravone, NADPH oxidase [apocynin (APO or diphenyleneiodonium chloride (DPI], c-Src (PP1, p38 MAPK (SB202190, and p300 (GR343. LPS induced NADPH oxidase activation, ROS production, and p47phox translocation from the cytosol to the membrane, which were reduced by PP1 or c-Src siRNA. We observed that LPS induced TLR4, MyD88, c-Src, and p47phox complex formation determined by co-immunoprecipitation and Western blot. We further demonstrated that LPS stimulated ATF2 and p300 phosphorylation and complex formation via a c-Src/NADPH oxidase/ROS/p38 MAPK pathway. Up-regulation of VCAM-1 led to enhancing monocyte adhesion to HRMCs challenged with LPS, which was inhibited by siRNAs of c-Src, p47phox, p38 MAPK, ATF2, and p300 or pretreatment with an anti-VCAM-1 neutralizing antibody. Conclusions In HRMCs, LPS-induced VCAM-1 expression was, at least in part, mediated through a TLR4/MyD88/ c-Src/NADPH oxidase/ROS/p38 MAPK-dependent p300 and ATF2 pathway associated with recruitment of monocyte adhesion to kidney. Blockade of these pathways may
PGC-1α in aging and lifelong exercise training-mediated regulation of UPR in mouse liver

DEFF Research Database (Denmark)

Maag Kristensen, Caroline; Brandt, Christina Tingbjerg; Jørgensen, Stine Ringholm

2017-01-01

of specific UPR pathways and increased activity of the ATF6 pathway in the liver with aging. Lifelong exercise training prevented the age-associated change in BiP and IRE1α protein, but not cleaved ATF6 protein and resulted in further decreased PERK protein. Taken together, the present study provides evidence...... that the capacity and activity of the three UPR pathways are differentially regulated in the liver with aging and lifelong exercise training. In addition, PGC-1α does not seem to regulate the activity of hepatic UPR in response to exercise training, but to influence the capacity of the liver to induce UPR......Aging is associated with changes in several metabolic pathways affecting liver function including the adaptive unfolded protein response (UPR). On the other hand, exercise training has been shown to exert beneficial effects on metabolism in the liver and exercise training has been reported...
Transcription of human resistin gene involves an interaction of Sp1 with peroxisome proliferator-activating receptor gamma (PPARgamma.

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Anil K Singh

2010-03-01

Full Text Available Resistin is a cysteine rich protein, mainly expressed and secreted by circulating human mononuclear cells. While several factors responsible for transcription of mouse resistin gene have been identified, not much is known about the factors responsible for the differential expression of human resistin.We show that the minimal promoter of human resistin lies within approximately 80 bp sequence upstream of the transcriptional start site (-240 whereas binding sites for cRel, CCAAT enhancer binding protein alpha (C/EBP-alpha, activating transcription factor 2 (ATF-2 and activator protein 1 (AP-1 transcription factors, important for induced expression, are present within sequences up to -619. Specificity Protein 1(Sp1 binding site (-276 to -295 is also present and an interaction of Sp1 with peroxisome proliferator activating receptor gamma (PPARgamma is necessary for constitutive expression in U937 cells. Indeed co-immunoprecipitation assay demonstrated a direct physical interaction of Sp1 with PPARgamma in whole cell extracts of U937 cells. Phorbol myristate acetate (PMA upregulated the expression of resistin mRNA in U937 cells by increasing the recruitment of Sp1, ATF-2 and PPARgamma on the resistin gene promoter. Furthermore, PMA stimulation of U937 cells resulted in the disruption of Sp1 and PPARgamma interaction. Chromatin immunoprecipitation (ChIP assay confirmed the recruitment of transcription factors phospho ATF-2, Sp1, Sp3, PPARgamma, chromatin modifier histone deacetylase 1 (HDAC1 and the acetylated form of histone H3 but not cRel, C/EBP-alpha and phospho c-Jun during resistin gene transcription.Our findings suggest a complex interplay of Sp1 and PPARgamma along with other transcription factors that drives the expression of resistin in human monocytic U937 cells.
Cisplatin Induces Cytotoxicity through the Mitogen-Activated Protein Kinase Pathways ana Activating Transcription Factor 3

Directory of Open Access Journals (Sweden)

Carly St. Germain

2010-07-01

Full Text Available The mechanisms underlying the proapoptotic effect of the chemotherapeutic agent, cisplatin, are largely undefined. Understanding the mechanisms regulating cisplatin cytotoxicity may uncover strategies to enhance the efficacy of this important therapeutic agent. This study evaluates the role of activating transcription factor 3 (ATF3 as a mediator of cisplatin-induced cytotoxicity. Cytotoxic doses of cisplatin and carboplatin treatments consistently induced ATF3 expression in five tumor-derived cell lines. Characterization of this induction revealed a p53, BRCA1, and integrated stress response-independent mechanism, all previously implicated in stress-mediated ATF3 induction. Analysis of mitogenactivated protein kinase (MAPK pathway involvement in ATF3 induction by cisplatin revealed a MAPK-dependent mechanism. Cisplatin treatment combined with specific inhibitors to each MAPK pathway (c-Jun N-terminal kinase, extracellularsignal-regulated kinase, and p38 resulted in decreasedATF3 induction at the protein level. MAPK pathway inhibition led to decreased ATF3 messenger RNA expression and reduced cytotoxic effects of cisplatin as measured by the 3-(4,5-dimethylthiazol-2-ylF2,5-diphenyltetrazolium bromide cell viability assay. In A549 lung carcinoma cells, targeting ATF3 with specific small hairpin RNA also attenuated the cytotoxic effects of cisplatin. Similarly, ATF3-/murine embryonic fibroblasts (MEFs were shown to be less sensitive to cisplatin-induced cytotoxicity compared with ATF3+/+ MEFs. This study identifies cisplatin as a MAPK pathway-dependent inducer of ATF3, whose expression influences cisplatin’s cytotoxic effects.
100 MeV laser accelerator demonstration and 1 GeV baseline design development. 1992 Annual report

International Nuclear Information System (INIS)

1992-01-01

The acceleration of relativistic electrons using the inverse Cerenkov effect was first demonstrated at Stanford University in 1981. Later, Fontana and Pantell developed an improved configuration for the inverse Cerenkov acceleration (ICA) process. A radially polarized laser beam is focused by an axicon onto the e-beam traveling through a gas-filled interaction region. The light intersects the e-beam at the Cerenkov angle θ c , where θ c = cos -1 (1/nβ), n is the index of refraction of the gas, and β is the ratio of the electron velocity to the speed of light. The goal of the present program is to demonstrate improved laser acceleration using the Fontana and Pantell configuration. The experiments will be performed on the Accelerator Test Facility (ATF) located at Brookhaven National Laboratory (BNL). This facility features a 50 MeV linac fed by a Nd:YAG (4ω) laser-driven photocathode e-gun. It will be upgraded to 65 MeV in the near future. The ATF also has a high peak power CO 2 laser, which was developed for laser acceleration studies. The present ICA experiment was divided into two phases. Phase 1 was to examine certain experimental issues in preparation for Phase 2. Phase 1 was successfully completed in the spring of 1992. Phase 2 is to perform the actual laser acceleration experiments on the ATF e-beam. The authors are currently waiting for the availability of the e-beam so that they can begin the Phase 2 experiments. In this section, the theory and experimental hardware for the present program are described. The results of the Phase 1 experiments are presented, and an update on the Phase 2 experiment is given
PGC-1α in the exercise training-mediated regulation of hepatic UPR in mice

DEFF Research Database (Denmark)

Maag Kristensen, Caroline

not be elucidated, because exercise training only had minor effects in the control mice. Study II demonstrated that aging mice had elevated hepatic triglyceride content, a tendency for increased BiP protein, decreased PERK protein content as well as increased IRE1α and cleaved ATF6 protein level in the liver...
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

2009-12-01

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.

Activating transcription factor 4 underlies the pathogenesis of arsenic trioxide-mediated impairment of macrophage innate immune functions

Energy Technology Data Exchange (ETDEWEB)

Srivastava, Ritesh K.; Li, Changzhao [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Wang, Yong [Department of Medicine, University of Alabama at Birmingham, Birmingham, AL (United States); Weng, Zhiping; Elmets, Craig A. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Harrod, Kevin S. [Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, AL (United States); Deshane, Jessy S., E-mail: treena@uab.edu [Department of Medicine, University of Alabama at Birmingham, Birmingham, AL (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States)

2016-10-01

Chronic arsenic exposure to humans is considered immunosuppressive with augmented susceptibility to several infectious diseases. The exact molecular mechanisms, however, remain unknown. Earlier, we showed the involvement of unfolded protein response (UPR) signaling in arsenic-mediated impairment of macrophage functions. Here, we show that activating transcription factor 4 (ATF4), a UPR transcription factor, regulates arsenic trioxide (ATO)-mediated dysregulation of macrophage functions. In ATO-treated ATF4{sup +/+} wild-type mice, a significant down-regulation of CD11b expression was associated with the reduced phagocytic functions of peritoneal and lung macrophages. This severe immuno-toxicity phenotype was not observed in ATO-treated ATF4{sup +/−} heterozygous mice. To confirm these observations, we demonstrated in Raw 264.7 cells that ATF4 knock-down rescues ATO-mediated impairment of macrophage functions including cytokine production, bacterial engulfment and clearance of engulfed bacteria. Sustained activation of ATF4 by ATO in macrophages induces apoptosis, while diminution of ATF4 expression protects against ATO-induced apoptotic cell death. Raw 264.7 cells treated with ATO also manifest dysregulated Ca{sup ++} homeostasis. ATO induces Ca{sup ++}-dependent calpain-1 and caspase-12 expression which together regulated macrophage apoptosis. Additionally, apoptosis was also induced by mitochondria-regulated pathway. Restoring ATO-impaired Ca{sup ++} homeostasis in ER/mitochondria by treatments with the inhibitors of inositol 1,4,5-trisphosphate receptor (IP3R) and voltage-dependent anion channel (VDAC) attenuate innate immune functions of macrophages. These studies identify a novel role for ATF4 in underlying pathogenesis of macrophage dysregulation and immuno-toxicity of arsenic. - Highlights: • ATF4 regulates arsenic-mediated impairment in macrophage functions. • Arsenic-mediated alterations in pulmonary macrophage are diminished in ATF4{sup +/−} mice
Activating transcription factor 4 underlies the pathogenesis of arsenic trioxide-mediated impairment of macrophage innate immune functions

International Nuclear Information System (INIS)

Srivastava, Ritesh K.; Li, Changzhao; Wang, Yong; Weng, Zhiping; Elmets, Craig A.; Harrod, Kevin S.; Deshane, Jessy S.; Athar, Mohammad

2016-01-01

Chronic arsenic exposure to humans is considered immunosuppressive with augmented susceptibility to several infectious diseases. The exact molecular mechanisms, however, remain unknown. Earlier, we showed the involvement of unfolded protein response (UPR) signaling in arsenic-mediated impairment of macrophage functions. Here, we show that activating transcription factor 4 (ATF4), a UPR transcription factor, regulates arsenic trioxide (ATO)-mediated dysregulation of macrophage functions. In ATO-treated ATF4 +/+ wild-type mice, a significant down-regulation of CD11b expression was associated with the reduced phagocytic functions of peritoneal and lung macrophages. This severe immuno-toxicity phenotype was not observed in ATO-treated ATF4 +/− heterozygous mice. To confirm these observations, we demonstrated in Raw 264.7 cells that ATF4 knock-down rescues ATO-mediated impairment of macrophage functions including cytokine production, bacterial engulfment and clearance of engulfed bacteria. Sustained activation of ATF4 by ATO in macrophages induces apoptosis, while diminution of ATF4 expression protects against ATO-induced apoptotic cell death. Raw 264.7 cells treated with ATO also manifest dysregulated Ca ++ homeostasis. ATO induces Ca ++ -dependent calpain-1 and caspase-12 expression which together regulated macrophage apoptosis. Additionally, apoptosis was also induced by mitochondria-regulated pathway. Restoring ATO-impaired Ca ++ homeostasis in ER/mitochondria by treatments with the inhibitors of inositol 1,4,5-trisphosphate receptor (IP3R) and voltage-dependent anion channel (VDAC) attenuate innate immune functions of macrophages. These studies identify a novel role for ATF4 in underlying pathogenesis of macrophage dysregulation and immuno-toxicity of arsenic. - Highlights: • ATF4 regulates arsenic-mediated impairment in macrophage functions. • Arsenic-mediated alterations in pulmonary macrophage are diminished in ATF4 +/− mice. • Changes in macrophage
Activation of the unfolded protein response during anoxia exposure in the turtle Trachemys scripta elegans.

Science.gov (United States)

Krivoruchko, Anastasia; Storey, Kenneth B

2013-02-01

Red-eared slider turtles, Trachemys scripta elegans, can survive for several weeks without oxygen when submerged in cold water. We hypothesized that anaerobiosis is aided by adaptive up-regulation of the unfolded protein response (UPR), a stress-responsive pathway that is activated by accumulation of unfolded proteins in the endoplasmic reticulum (ER) and functions to restore ER homeostasis. RT-PCR, western immunoblotting and DNA-binding assays were used to quantify the responses and/or activation status of UPR-responsive genes and proteins in turtle tissues after animal exposure to 5 or 20 h of anoxic submergence at 4 °C. The phosphorylation state of protein kinase-like ER kinase (PERK) (a UPR-regulated kinase) and eukaryotic initiation factor 2 (eIF2α) increased by 1.43-2.50 fold in response to anoxia in turtle heart, kidney, and liver. Activation of the PERK-regulated transcription factor, activating transcription factor 4 (ATF4), during anoxia was documented by elevated atf4 transcripts and total ATF4 protein (1.60-2.43 fold), increased nuclear ATF4 content, and increased DNA-binding activity (1.44-2.32 fold). ATF3 and GADD34 (downstream targets of ATF4) also increased by 1.38-3.32 fold in heart and liver under anoxia, and atf3 transcripts were also elevated in heart. Two characteristic chaperones of the UPR, GRP78, and GRP94, also responded positively to anoxia with strong increases in both the transcript and protein levels. The data demonstrate that the UPR is activated in turtle heart, kidney, and liver in response to anoxia, suggesting that this pathway mediates an integrated stress response to protect tissues during oxygen deprivation.
Effect of quercetin on apoptosis of PANC-1 cells.

Science.gov (United States)

Lee, Joo Hyun; Lee, Han-Beom; Jung, Gum O; Oh, Jung Taek; Park, Dong Eun; Chae, Kwon Mook

2013-12-01

To investigate the chemotherapeutic effect of quercetin against cancer cells, signaling pathway of apoptosis was explored in human pancreatic cells. Various anticancer drugs including adriamycin, cisplatin, 5-fluorouracil (5-FU) and gemcitabine were used. Cell viability was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphe-nyltetra zolium bromide assay. Apoptosis was determined by 4'-6-diamidino-2-phenylindole nuclei staining and flow cytometry in PANC-1 cells treated with 50 µg/mL quercetin for 24 hours. Expression of endoplas mic reticulum (ER) stress mediators including, Grp78/Bip, p-PERK, PERK, ATF4, ATF6 and GADD153/CHOP proteins were measured by Western blot analysis. Mitochondrial membrane potential was measured by fluorescence staining with JC-1, rhodamine 123. Quercetin induced the apoptosis of PANC-1, which was characterized as nucleic acid and genomic DNA fragmentation, chromatin condensation, and sub-G0/G1 fraction of cell cycle increase. But not adriamycin, cisplatin, gemcitabine, and 5-FU. PANC-1 cells were markedly sensitive to quercetin. Treatment with quercetin resulted in the increased accumulation of intracellular Ca(2+) ion. Treatment with quercetin also increased the expression of Grp78/Bip and GADD153/CHOP protein and induced mitochondrial dysfunction. Quercetin exerted cytotoxicity against human pancreatic cancer cells via ER stress-mediated apoptotic signaling including reactive oxygen species production and mitochondrial dysfunction. These data suggest that quercetin may be an important modulator of chemosensitivity of cancer cells against anticancer chemotherapeutic agents.
Comprehensive Behavioral Analysis of Activating Transcription Factor 5-Deficient Mice

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Mariko Umemura

2017-07-01

Full Text Available Activating transcription factor 5 (ATF5 is a member of the CREB/ATF family of basic leucine zipper transcription factors. We previously reported that ATF5-deficient (ATF5-/- mice demonstrated abnormal olfactory bulb development due to impaired interneuron supply. Furthermore, ATF5-/- mice were less aggressive than ATF5+/+ mice. Although ATF5 is widely expressed in the brain, and involved in the regulation of proliferation and development of neurons, the physiological role of ATF5 in the higher brain remains unknown. Our objective was to investigate the physiological role of ATF5 in the higher brain. We performed a comprehensive behavioral analysis using ATF5-/- mice and wild type littermates. ATF5-/- mice exhibited abnormal locomotor activity in the open field test. They also exhibited abnormal anxiety-like behavior in the light/dark transition test and open field test. Furthermore, ATF5-/- mice displayed reduced social interaction in the Crawley’s social interaction test and increased pain sensitivity in the hot plate test compared with wild type. Finally, behavioral flexibility was reduced in the T-maze test in ATF5-/- mice compared with wild type. In addition, we demonstrated that ATF5-/- mice display disturbances of monoamine neurotransmitter levels in several brain regions. These results indicate that ATF5 deficiency elicits abnormal behaviors and the disturbance of monoamine neurotransmitter levels in the brain. The behavioral abnormalities of ATF5-/- mice may be due to the disturbance of monoamine levels. Taken together, these findings suggest that ATF5-/- mice may be a unique animal model of some psychiatric disorders.
Thermal hydraulic-Mechanic Integrated Simulation for Advanced Cladding Thermal Shock Fracture Analysis during Reflood Phase in LBLOCA

Energy Technology Data Exchange (ETDEWEB)

Son, Seong Min; Lee, You Ho; Cho, Jae Wan; Lee, Jeong Ik [KAERI, Daejeon (Korea, Republic of)

2016-05-15

This study suggested thermal hydraulic-mechanical integrated stress based methodology for analyzing the behavior of ATF type claddings by SiC-Duplex cladding LBLOCA simulation. Also, this paper showed that this methodology could predict real experimental result well. That concept for enhanced safety of LWR called Advanced Accident-Tolerance Fuel Cladding (ATF cladding, ATF) is researched actively. However, current nuclear fuel cladding design criteria for zircaloy cannot be apply to ATF directly because those criteria are mainly based on limiting their oxidation. So, the new methodology for ATF design criteria is necessary. In this study, stress based analysis methodology for ATF cladding design criteria is suggested. By simulating LBLOCA scenario of SiC cladding which is the one of the most promising candidate of ATF. Also we'll confirm our result briefly through comparing some facts from other experiments. This result is validating now. Some of results show good performance with 1-D failure analysis code for SiC fuel cladding that already developed and validated by Lee et al,. It will present in meeting. Furthermore, this simulation presented the possibility of understanding the behavior of cladding deeper. If designer can predict the dangerous region and the time precisely, it may be helpful for designing nuclear fuel cladding geometry and set safety criteria.
Cytokines downregulate the sarcoendoplasmic reticulum pump Ca2+ ATPase 2b and deplete endoplasmic reticulum Ca2+, leading to induction of endoplasmic reticulum stress in pancreatic beta-cells

DEFF Research Database (Denmark)

Cardozo, Alessandra K; Ortis, Fernanda; Storling, Joachim

2005-01-01

-requiring ER-to-nucleus signal kinase 1alpha (IRE1alpha) and PRK (RNA-dependent protein kinase)-like ER kinase (PERK)/activating transcription factor 4 (ATF4), but not ATF6. In contrast, the ER stress-inducing agent thapsigargin triggered these four pathways in parallel. In conclusion, our results suggest...
Induction of Activating Transcription Factor 3 Is Associated with Cisplatin Responsiveness in Non–Small Cell Lung Carcinoma Cells

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Jair Bar

2016-09-01

Full Text Available Non–small cell lung carcinoma (NSCLC is the most common cause of cancer deaths, with platin-based combination chemotherapy the most efficacious therapies. Gains in overall survival are modest, highlighting the need for novel therapeutic approaches including the development of next-generation platin combination regimens. The goal of this study was to identify novel regulators of platin-induced cytotoxicity as potential therapeutic targets to further enhance platin cytotoxicity. Employing RNA-seq transcriptome analysis comparing two parental NSCLC cell lines Calu6 and H23 to their cisplatin-resistant sublines, Calu6cisR1 and H23cisR1, activating transcription factor 3 (ATF3 was robustly induced in cisplatin-treated parental sensitive cell lines but not their resistant sublines, and in three of six tumors evaluated, but not in their corresponding normal adjacent lung tissue (0/6. Cisplatin-induced JNK activation was a key regulator of this ATF3 induction. Interestingly, in both resistant sublines, this JNK induction was abrogated, and the expression of an activated JNK construct in these cells enhanced both cisplatin-induced cytotoxicity and ATF3 induction. An FDA-approved drug compound screen was employed to identify enhancers of cisplatin cytotoxicity that were dependent on ATF3 gene expression. Vorinostat, a histone deacetylase inhibitor, was identified in this screen and demonstrated synergistic cytotoxicity with cisplatin in both the parental Calu6 and H23 cell lines and importantly in their resistant sublines as well that was dependent on ATF3 expression. Thus, we have identified ATF3 as an important regulator of cisplatin cytotoxicity and that ATF3 inducers in combination with platins are a potential novel therapeutic approach for NSCLC.
Obesity challenges the hepatoprotective function of the integrated stress response to asparaginase exposure in mice.

Science.gov (United States)

Nikonorova, Inna A; Al-Baghdadi, Rana J T; Mirek, Emily T; Wang, Yongping; Goudie, Michael P; Wetstein, Berish B; Dixon, Joseph L; Hine, Christopher; Mitchell, James R; Adams, Christopher M; Wek, Ronald C; Anthony, Tracy G

2017-04-21

Obesity increases risk for liver toxicity by the anti-leukemic agent asparaginase, but the mechanism is unknown. Asparaginase activates the integrated stress response (ISR) via sensing amino acid depletion by the eukaryotic initiation factor 2 (eIF2) kinase GCN2. The goal of this work was to discern the impact of obesity, alone versus alongside genetic disruption of the ISR, on mechanisms of liver protection during chronic asparaginase exposure in mice. Following diet-induced obesity, biochemical analysis of livers revealed that asparaginase provoked hepatic steatosis that coincided with activation of another eIF2 kinase PKR-like endoplasmic reticulum kinase (PERK), a major ISR transducer to ER stress. Genetic loss of Gcn2 intensified hepatic PERK activation to asparaginase, yet surprisingly, mRNA levels of key ISR gene targets such as Atf5 and Trib3 failed to increase. Instead, mechanistic target of rapamycin complex 1 (mTORC1) signal transduction was unleashed, and this coincided with liver dysfunction reflected by a failure to maintain hydrogen sulfide production or apolipoprotein B100 (ApoB100) expression. In contrast, obese mice lacking hepatic activating transcription factor 4 ( Atf4 ) showed an exaggerated ISR and greater loss of endogenous hydrogen sulfide but normal inhibition of mTORC1 and maintenance of ApoB100 during asparaginase exposure. In both genetic mouse models, expression and phosphorylation of Sestrin2, an ATF4 gene target, was increased by asparaginase, suggesting mTORC1 inhibition during asparaginase exposure is not driven via eIF2-ATF4-Sestrin2. In conclusion, obesity promotes a maladaptive ISR during asparaginase exposure. GCN2 functions to repress mTORC1 activity and maintain ApoB100 protein levels independently of Atf4 expression, whereas hydrogen sulfide production is promoted via GCN2-ATF4 pathway. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
Overview of the US stellarator reactor study

International Nuclear Information System (INIS)

Lyon, J.F.; Gulec, K.; Miller, R.L.; El-Guebaly, L.

1993-01-01

This study, which uses a cost-minimization code that incorporates the ARIES costing and reactor component models with a I-D energy transport calculation, shows that a torsatron reactor could be competitive with a tokamak reactor
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
Evolution of magnetic order in mechanically alloyed Al-1 at%Fe

International Nuclear Information System (INIS)

Sebastian, Varkey; Lakshmi, N.; Venugopalan, K.

2007-01-01

The evolution of ferromagnetic order in high-energy ball-milled Al-1 at% Fe before the onset of a considerable Fe-Al solid solution phase has been investigated using 57 Fe Moessbauer and bulk magnetization studies. The unmilled sample does not exhibit bulk magnetic properties and an onset of bulk magnetization is observed only after 30 min of milling, when the grain size becomes comparable to the ferromagnetic exchange length. The Curie temperatures of all the samples are less than that of pure iron. The reduction in grain size is accompanied by an increase in coercivity and reduced remanence and a decrease in T C . The effective magnetic moment per iron atom decreases with the development of a non-magnetic, Al-rich Fe-Al solution on longer milling. The clustering of Fe at grain boundaries is responsible for the observed bulk magnetic ordering. The systematic variation of the magnetic properties has been qualitatively correlated with the evolution of microstructure, reduction in grain size and enhanced inter-granular exchange coupling
Activating Transcription Factor 3 regulates in part the enhanced tumour cell cytotoxicity of the histone deacetylase inhibitor M344 and cisplatin in combination

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St Germain Carly

2010-09-01

Full Text Available Abstract Background Activating Transcription Factor (ATF 3 is a key regulator of the cellular integrated stress response whose expression has also been correlated with pro-apoptotic activities in tumour cell models. Combination treatments with chemotherapeutic drugs, such as cisplatin, and histone deacetylase (HDAC inhibitors have been demonstrated to enhance tumour cell cytotoxicity. We recently demonstrated a role for ATF3 in regulating cisplatin-induced apoptosis and others have shown that HDAC inhibition can also induce cellular stress. In this study, we evaluated the role of ATF3 in regulating the co-operative cytotoxicity of cisplatin in combination with an HDAC inhibitor. Results The HDAC inhibitor M344 induced ATF3 expression at the protein and mRNA level in a panel of human derived cancer cell lines as determined by Western blot and quantitative RT-PCR analyses. Combination treatment with M344 and cisplatin lead to increased induction of ATF3 compared with cisplatin alone. Utilizing the MTT cell viability assay, M344 treatments also enhanced the cytotoxic effects of cisplatin in these cancer cell lines. The mechanism of ATF3 induction by M344 was found to be independent of MAPKinase pathways and dependent on ATF4, a known regulator of ATF3 expression. ATF4 heterozygote (+/- and knock out (-/- mouse embryonic fibroblast (MEF as well as chromatin immunoprecipitation (ChIP assays were utilized in determining the mechanistic induction of ATF3 by M344. We also demonstrated that ATF3 regulates the enhanced cytotoxicity of M344 in combination with cisplatin as evidenced by attenuation of cytotoxicity in shRNAs targeting ATF3 expressing cells. Conclusion This study identifies the pro-apoptotic factor, ATF3 as a novel target of M344, as well as a mediator of the co-operative effects of cisplatin and M344 induced tumour cell cytotoxicity.
Thermal and electrical joint test for the helical field coils in the Advanced Toroidal Facility

International Nuclear Information System (INIS)

Brown, R.L.; Johnson, R.L.

1985-01-01

Initial feasibility studies of a number of configurations for the Advanced Toroidal Facility (ATF) resulted in the selection of a resistive copper continuous-coil torsatron as the optimum device considering the physics program, cost, and schedule. Further conceptual design work was directed toward optimization of this configuration and, if possible, a shorter schedule. It soon became obvious that in order to shorten the schedule, a number of design and fabrication activities should proceed in parallel. This was most critical for the vacuum vessel and the helical field (HF) coils. If the HF coils were wound in place on a completed vacuum vessel, the overall schedule would be significantly (greater than or equal to12 months) longer. The approach of parallel scheduel paths requires that the HF coils be segmented into parts of less than or equal to180 0 of poloidal angle and that joints be made on a turn-by-turn basis when the segments are installed. It was obvious from the outset that the compact and complex geometry of the joint design presented a special challenge in the areas of reliability, assembly, maintenance, disassembly, and cost. Also, electrical, thermal, and force excursions are significant for these joints. A number of soldered, welded, brazed, electroplated, and bolted joints were evaluated. The evaluations examined fabrication feasibility and complexity, thermal-electrical performance at approximately two-thirds of the steady-state design conditions, and installation and assembly processes. Results of the thermal-electrical tests were analyzed and extrapolated to predict performance at peak design parameters. The final selection was a lap-type joint clamped with insulated bolts that pass through the winding packing. 3 refs., 4 figs
27 CFR 24.110 - Organizational documents.

Science.gov (United States)

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Organizational documents..., DEPARTMENT OF THE TREASURY LIQUORS WINE Establishment and Operations Application § 24.110 Organizational... under control number 1512-0058) [T.D. ATF-299, 55 FR 24989, June 19, 1990, as amended by T.D. ATF-409...
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

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...
Diallyl trisulfide ameliorates myocardial ischemia-reperfusion injury by reducing oxidative stress and endoplasmic reticulum stress-mediated apoptosis in type 1 diabetic rats: role of SIRT1 activation.

Science.gov (United States)

Yu, Liming; Li, Shu; Tang, Xinlong; Li, Zhi; Zhang, Jian; Xue, Xiaodong; Han, Jinsong; Liu, Yu; Zhang, Yuji; Zhang, Yong; Xu, Yinli; Yang, Yang; Wang, Huishan

2017-07-01

Diallyl trisulfide (DATS) protects against apoptosis during myocardial ischemia-reperfusion (MI/R) injury in diabetic state, although the underlying mechanisms remain poorly defined. Previously, we and others demonstrated that silent information regulator 1 (SIRT1) activation inhibited oxidative stress and endoplasmic reticulum (ER) stress during MI/R injury. We hypothesize that DATS reduces diabetic MI/R injury by activating SIRT1 signaling. Streptozotocin (STZ)-induced type 1 diabetic rats were subjected to MI/R surgery with or without perioperative administration of DATS (40 mg/kg). We found that DATS treatment markedly improved left ventricular systolic pressure and the first derivative of left ventricular pressure, reduced myocardial infarct size as well as serum creatine kinase and lactate dehydrogenase activities. Furthermore, the myocardial apoptosis was also suppressed by DATS as evidenced by reduced apoptotic index and cleaved caspase-3 expression. However, these effects were abolished by EX527 (the inhibitor of SIRT1 signaling, 5 mg/kg). We further found that DATS effectively upregulated SIRT1 expression and its nuclear distribution. Additionally, PERK/eIF2α/ATF4/CHOP-mediated ER stress-induced apoptosis was suppressed by DATS treatment. Moreover, DATS significantly activated Nrf-2/HO-1 antioxidant signaling pathway, thus reducing Nox-2/4 expressions. However, the ameliorative effects of DATS on oxidative stress and ER stress-mediated myocardial apoptosis were inhibited by EX527 administration. Taken together, these data suggest that perioperative DATS treatment effectively ameliorates MI/R injury in type 1 diabetic setting by enhancing cardiac SIRT1 signaling. SIRT1 activation not only upregulated Nrf-2/HO-1-mediated antioxidant signaling pathway but also suppressed PERK/eIF2α/ATF4/CHOP-mediated ER stress level, thus reducing myocardial apoptosis and eventually preserving cardiac function.
77 FR 5735 - Importation of Arms, Ammunition and Implements of War and Machine Guns, Destructive Devices, and...

Science.gov (United States)

2012-02-06

... benefit for ATF. ATF employs data entry contractors who spend an average of 2 hours completing quality... per hour. ATF examiners typically spend 4 hours processing an ATF Form 6 application. The average... members of the United States military returning to the United States from abroad with firearms and for non...
Control of radial electric field in torus plasma

International Nuclear Information System (INIS)

Ida, K.; Idei, H.; Sanuki, H.

1994-09-01

The radial electric fields is controlled by changing the direction of neutral beam from co to counter to plasma current in tokamak, while it is controlled by the 2nd harmonic ECH and NBI and pellet injection in heliotron/torsatron. (author)
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.

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

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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.
The Role of Activator Protein-1 (AP-1) Family Members in CD30-Positive Lymphomas

Science.gov (United States)

Garces de los Fayos Alonso, Ines; Lagger, Sabine; Merkel, Olaf; Kenner, Lukas

2018-01-01

The Activator Protein-1 (AP-1) transcription factor (TF) family, composed of a variety of members including c-JUN, c-FOS and ATF, is involved in mediating many biological processes such as proliferation, differentiation and cell death. Since their discovery, the role of AP-1 TFs in cancer development has been extensively analysed. Multiple in vitro and in vivo studies have highlighted the complexity of these TFs, mainly due to their cell-type specific homo- or hetero-dimerization resulting in diverse transcriptional response profiles. However, as a result of the increasing knowledge of the role of AP-1 TFs in disease, these TFs are being recognized as promising therapeutic targets for various malignancies. In this review, we focus on the impact of deregulated expression of AP-1 TFs in CD30-positive lymphomas including Classical Hodgkin Lymphoma and Anaplastic Large Cell Lymphoma. PMID:29597249
Carbon monoxide protects against hepatic steatosis in mice by inducing sestrin-2 via the PERK-eIF2α-ATF4 pathway.

Science.gov (United States)

Kim, Hyo Jeong; Joe, Yeonsoo; Kim, Seul-Ki; Park, Se-Ung; Park, Jeongmin; Chen, Yingqing; Kim, Jin; Ryu, Jinhyun; Cho, Gyeong Jae; Surh, Young-Joon; Ryter, Stefan W; Kim, Uh-Hyun; Chung, Hun-Taeg

2017-09-01

Nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, has emerged as one of the most common causes of chronic liver disease in developed countries over the last decade. NAFLD comprises a spectrum of pathological hepatic changes, including steatosis, steatohepatitis, advanced fibrosis, and cirrhosis. Autophagy, a homeostatic process for protein and organelle turnover, is decreased in the liver during the development of NAFLD. Previously, we have shown that carbon monoxide (CO), a reaction product of heme oxygenase (HO) activity, can confer protection in NAFLD, though the molecular mechanisms remain unclear. We therefore investigated the mechanisms underlying the protective effect of CO on methionine/choline-deficient (MCD) diet-induced hepatic steatosis. We found that CO induced sestrin-2 (SESN2) expression through enhanced mitochondrial ROS production and protected against MCD-induced NAFLD progression through activation of autophagy. SESN2 expression was increased by CO or CO-releasing molecule (CORM2), in a manner dependent on signaling through the protein kinase R-like endoplasmic reticulum kinase (PERK), eukaryotic initiation factor-2 alpha (eIF2α)/ activating transcription factor-4 (ATF4)-dependent pathway. CO-induced SESN2 upregulation in hepatocytes contributed to autophagy induction through activation of 5'-AMP-activated protein kinase (AMPK) and inhibition of mechanistic target of rapamycin (mTOR) complex I (mTORC1). Furthermore, we demonstrate that CO significantly induced the expression of SESN2 and enhanced autophagy in the livers of MCD-fed mice or in MCD-media treated hepatocytes. Conversely, knockdown of SESN2 abrogated autophagy activation and mTOR inhibition in response to CO. We conclude that CO ameliorates hepatic steatosis through the autophagy pathway induced by SESN2 upregulation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Concentration of remote-handled, transuranic, sodium nitrate-based sludge using agitated thin-film evaporators

International Nuclear Information System (INIS)

Walker, J.F. Jr.; Youngblood, E.L.; Berry, J.B.; Pen, Ben-Li

1991-01-01

The Waste Handling and Packaging Plant (WHPP) is being designed at Oak Ridge National Laboratory (ORNL) to prepared transuranic waste for final disposal. Once operational, this facility will process, package, and certify remote-handled transuranic waste for ultimate shipment and disposal at the Waste Isolation Pilot Plant (WIPP) in Carlsbad, New Mexico. One of the wastes that will be handled at WHIPP is the transuranic sludge currently stored at ORNL in eight 50,000-gal underground tanks. The use of an Agitated Thin-Film Evaporator (ATFE) for concentration of this waste is being investigated. Tests have shown that the ATFE can be used to produce a thick slurry, a powder, or a fused salt. A computer model developed at the Savannah River Plant (SRP) to simulate the operation of ATFE's on their waste is being modified for use on the ORNL transuranic sludge. This paper summarizes the results of the test with the ATFEs to date, discusses the changes in the SRP model necessary to use this model with the ORNL waste, and compares the results of the model with the actual data taken from the operation of ATFEs at vendors' test facilities. 8 refs., 1 fig., 3 tabs
Brookhaven National Laboratory's Accelerator Test Facility: research highlights and plans

Science.gov (United States)

Pogorelsky, I. V.; Ben-Zvi, I.

2014-08-01

The Accelerator Test Facility (ATF) at Brookhaven National Laboratory has served as a user facility for accelerator science for over a quarter of a century. In fulfilling this mission, the ATF offers the unique combination of a high-brightness 80 MeV electron beam that is synchronized to a 1 TW picosecond CO2 laser. We unveil herein our plan to considerably expand the ATF's floor space with an upgrade of the electron beam's energy to 300 MeV and the CO2 laser's peak power to 100 TW. This upgrade will propel the ATF even further to the forefront of research on advanced accelerators and radiation sources, supporting the most innovative ideas in this field. We discuss emerging opportunities for scientific breakthroughs, including the following: plasma wakefield acceleration studies in research directions already active at the ATF; laser wakefield acceleration (LWFA), where the longer laser wavelengths are expected to engender a proportional increase in the beam's charge while our linac will assure, for the first time, the opportunity to undertake detailed studies of seeding and staging of the LWFA; proton acceleration to the 100-200 MeV level, which is essential for medical applications; and others.
Engineered zinc-finger transcription factors inhibit the replication and transcription of HBV in vitro and in vivo.

Science.gov (United States)

Luo, Wei; Wang, Junxia; Xu, Dengfeng; Bai, Huili; Zhang, Yangli; Zhang, Yuhong; Li, Xiaosong

2018-04-01

In the present study, an artificial zinc-finger transcription factor eukaryotic expression vector specifically recognizing and binding to the hepatitis B virus (HBV) enhancer (Enh) was constructed, which inhibited the replication and expression of HBV DNA. The HBV EnhI‑specific pcDNA3.1‑artificial transcription factor (ATF) vector was successfully constructed, and then transformed or injected into HepG2.2.15 cells and HBV transgenic mice, respectively. The results demonstrated that the HBV EnhI (1,070‑1,234 bp)‑specific ATF significantly inhibited the replication and transcription of HBV DNA in vivo and in vitro. The HBV EnhI‑specific ATF may be a meritorious component of progressive combination therapies for eliminating HBV DNA in infected patients. A radical cure for chronic HBV infection may become feasible by using this bioengineering technology.
Activating Transcription Factor 3 Regulates Immune and Metabolic Homeostasis

Science.gov (United States)

Rynes, Jan; Donohoe, Colin D.; Frommolt, Peter; Brodesser, Susanne; Jindra, Marek

2012-01-01

Integration of metabolic and immune responses during animal development ensures energy balance, permitting both growth and defense. Disturbed homeostasis causes organ failure, growth retardation, and metabolic disorders. Here, we show that the Drosophila melanogaster activating transcription factor 3 (Atf3) safeguards metabolic and immune system homeostasis. Loss of Atf3 results in chronic inflammation and starvation responses mounted primarily by the larval gut epithelium, while the fat body suffers lipid overload, causing energy imbalance and death. Hyperactive proinflammatory and stress signaling through NF-κB/Relish, Jun N-terminal kinase, and FOXO in atf3 mutants deregulates genes important for immune defense, digestion, and lipid metabolism. Reducing the dose of either FOXO or Relish normalizes both lipid metabolism and gene expression in atf3 mutants. The function of Atf3 is conserved, as human ATF3 averts some of the Drosophila mutant phenotypes, improving their survival. The single Drosophila Atf3 may incorporate the diversified roles of two related mammalian proteins. PMID:22851689
Activating transcription factor 3 regulates immune and metabolic homeostasis.

Science.gov (United States)

Rynes, Jan; Donohoe, Colin D; Frommolt, Peter; Brodesser, Susanne; Jindra, Marek; Uhlirova, Mirka

2012-10-01

Integration of metabolic and immune responses during animal development ensures energy balance, permitting both growth and defense. Disturbed homeostasis causes organ failure, growth retardation, and metabolic disorders. Here, we show that the Drosophila melanogaster activating transcription factor 3 (Atf3) safeguards metabolic and immune system homeostasis. Loss of Atf3 results in chronic inflammation and starvation responses mounted primarily by the larval gut epithelium, while the fat body suffers lipid overload, causing energy imbalance and death. Hyperactive proinflammatory and stress signaling through NF-κB/Relish, Jun N-terminal kinase, and FOXO in atf3 mutants deregulates genes important for immune defense, digestion, and lipid metabolism. Reducing the dose of either FOXO or Relish normalizes both lipid metabolism and gene expression in atf3 mutants. The function of Atf3 is conserved, as human ATF3 averts some of the Drosophila mutant phenotypes, improving their survival. The single Drosophila Atf3 may incorporate the diversified roles of two related mammalian proteins.
Fermentation of Apple Juice with a Selected Yeast Strain Isolated from the Fermented Foods of Himalayan Regions and Its Organoleptic Properties

OpenAIRE

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, sugg...
Preliminary safety analysis of the PWR with accident-tolerant fuels during severe accident conditions

International Nuclear Information System (INIS)

Wu, Xiaoli; Li, Wei; Wang, Yang; Zhang, Yapei; Tian, Wenxi; Su, Guanghui; Qiu, Suizheng; Liu, Tong; Deng, Yongjun; Huang, Heng

2015-01-01

Highlights: • Analysis of severe accident scenarios for a PWR fueled with ATF system is performed. • A large-break LOCA without ECCS is analyzed for the PWR fueled with ATF system. • Extended SBO cases are discussed for the PWR fueled with ATF system. • The accident-tolerance of ATF system for application in PWR is illustrated. - Abstract: Experience gained in decades of nuclear safety research and previous nuclear accidents direct to the investigation of passive safety system design and accident-tolerant fuel (ATF) system which is now becoming a hot research point in the nuclear energy field. The ATF system is aimed at upgrading safety characteristics of the nuclear fuel and cladding in a reactor core where active cooling has been lost, and is preferable or comparable to the current UO 2 –Zr system when the reactor is in normal operation. By virtue of advanced materials with improved properties, the ATF system will obviously slow down the progression of accidents, allowing wider margin of time for the mitigation measures to work. Specifically, the simulation and analysis of a large break loss of coolant accident (LBLOCA) without ECCS and extended station blackout (SBO) severe accident are performed for a pressurized water reactor (PWR) loaded with ATF candidates, to reflect the accident-tolerance of ATF
Analysis of the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP-1) gene and promoter in Hodgkin's disease isolates

DEFF Research Database (Denmark)

Sandvej, K; Andresen, B S; Zhou, X G

2000-01-01

AIMS: To study the distribution of Epstein-Barr virus (EBV) variants containing mutations in the latent membrane protein 1 (LMP-1) oncogene and promoter in EBV associated Hodgkin's disease and infectious mononucleosis compared with previous findings in asymptomatic EBV carriers. METHODS: Sequence...... analysis of the EBV LMP-1 promoter and gene in isolates from Danish patients with Hodgkin's disease (n = 61) and infectious mononucleosis (n = 10). RESULTS: Viruses (previously designated group D) that contain two mutations in the activating transcription factor/cAMP response element (ATF/CRE) in the LMP-1...... promoter, which are known to decrease promoter activity greatly, were significantly less frequent in Hodgkin's disease than in both infectious mononucleosis (p = 0.0081) and asymptomatic EBV carriers (p = 0.0084). In some cases, the LMP-1 gene contained mutations in a recently identified cytotoxic T cell...
Intravenous Lipid Infusion Induces Endoplasmic Reticulum Stress in Endothelial Cells and Blood Mononuclear Cells of Healthy Adults.

Science.gov (United States)

Tampakakis, Emmanouil; Tabit, Corey E; Holbrook, Monika; Linder, Erika A; Berk, Brittany D; Frame, Alissa A; Bretón-Romero, Rosa; Fetterman, Jessica L; Gokce, Noyan; Vita, Joseph A; Hamburg, Naomi M

2016-01-11

Endoplasmic reticulum (ER) stress and the subsequent unfolded protein response may initially be protective, but when prolonged, have been implicated in atherogenesis in diabetic conditions. Triglycerides and free fatty acids (FFAs) are elevated in patients with diabetes and may contribute to ER stress. We sought to evaluate the effect of acute FFA elevation on ER stress in endothelial and circulating white cells. Twenty-one healthy subjects were treated with intralipid (20%; 45 mL/h) plus heparin (12 U/kg/h) infusion for 5 hours. Along with increased triglyceride and FFA levels, intralipid/heparin infusion reduced the calf reactive hyperemic response without a change in conduit artery flow-mediated dilation consistent with microvascular dysfunction. To investigate the short-term effects of elevated triglycerides and FFA, we measured markers of ER stress in peripheral blood mononuclear cells (PBMCs) and vascular endothelial cells (VECs). In VECs, activating transcription factor 6 (ATF6) and phospho-inositol requiring kinase 1 (pIRE1) proteins were elevated after infusion (both P<0.05). In PBMCs, ATF6 and spliced X-box-binding protein 1 (XBP-1) gene expression increased by 2.0- and 2.5-fold, respectively (both P<0.05), whereas CHOP and GADD34 decreased by ≈67% and 74%, respectively (both P<0.01). ATF6 and pIRE1 protein levels also increased (both P<0.05), and confocal microscopy revealed the nuclear localization of ATF6 after infusion, suggesting activation. Along with microvascular dysfunction, intralipid infusion induced an early protective ER stress response evidenced by activation of ATF6 and IRE1 in both leukocytes and endothelial cells. Our results suggest a potential link between metabolic disturbances and ER stress that may be relevant to vascular disease. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
Activating transcription factor 3 is a target molecule linking hepatic steatosis to impaired glucose homeostasis.

Science.gov (United States)

Kim, Ji Yeon; Park, Keon Jae; Hwang, Joo-Yeon; Kim, Gyu Hee; Lee, DaeYeon; Lee, Yoo Jeong; Song, Eun Hyun; Yoo, Min-Gyu; Kim, Bong-Jo; Suh, Young Ho; Roh, Gu Seob; Gao, Bin; Kim, Won; Kim, Won-Ho

2017-08-01

Non-alcoholic fatty liver disease (NAFLD) contributes to impaired glucose tolerance, leading to type 2 diabetes (T2D); however, the precise mechanisms and target molecules that are involved remain unclear. Activating transcription factor 3 (ATF3) is associated with β-cell dysfunction that is induced by severe stress signals in T2D. We aimed to explore the exact functional role of ATF3 as a mechanistic link between hepatic steatosis and T2D development. Zucker diabetic fatty (ZDF) rats were utilized for animal experiments. An in vivo-jetPEI siRNA delivery system against ATF3 was used for loss-of-function experiments. We analyzed the baseline cross-sectional data derived from the biopsy-proven NAFLD registry (n=322). Human sera and liver tissues were obtained from 43 patients with biopsy-proven NAFLD and from seven healthy participants. ATF3 was highly expressed in the livers of ZDF rats and in human participants with NAFLD and/or T2D. Insulin resistance and hepatic steatosis were associated with increased ATF3 expression and decreased fatty acid oxidation via mitochondrial dysfunction and were attenuated by in vivo ATF3 silencing. Knockdown of ATF3 also ameliorated glucose intolerance, impaired insulin action, and inflammatory responses in ZDF rats. In patients with NAFLD and/or T2D, a significant positive correlation was observed between hepatic ATF3 expression and surrogate markers of T2D, mitochondrial dysfunction, and macrophage infiltration. Increased hepatic ATF3 expression is closely associated with hepatic steatosis and incident T2D; therefore, ATF3 may serve as a potential therapeutic target for NAFLD and hepatic steatosis-induced T2D. Hepatic activating transcription factor 3 (ATF3) may play an important role in oxidative stress-mediated hepatic steatosis and the development of type 2 diabetes (T2D) in a Zucker diabetic fatty (ZDF) rat model and in human patients with non-alcoholic fatty liver disease (NAFLD). Therefore, ATF3 may be a useful biomarker for
Chaetocin induces endoplasmic reticulum stress response and leads to death receptor 5-dependent apoptosis in human non-small cell lung cancer cells.

Science.gov (United States)

Liu, Xianfang; Guo, Sen; Liu, Xiangguo; Su, Ling

2015-11-01

Epigenetic abnormalities are associated with non-small cell lung cancer (NSCLC) initiation and progression. Epigenetic drugs are being studied and in clinical trials. However, the molecular mechanism underlying the apoptosis by the epigenetic agents remains unclear. SUV39H1 is an important methyl-transferase for lysine 9 on histone H3 and usually related to gene transcriptional suppression, and chaetocin acts as the inhibitor of SUV39H1. We demonstrated here that chaetocin effectively suppressed the growth of multiple lung cancer cells through inducing apoptosis in a death receptor 5 (DR5)-dependent manner. Chaetocin treatment activated endoplasmic reticulum (ER) stress which gave rise to the up-regulation of ATF3 and CHOP. Furthermore, ATF3 and CHOP contributed to the induction of DR5 and subsequent apoptosis. When SUV39H1 was silenced with siRNA, the expression of ATF3, CHOP and DR5 was elevated. Thereafter, knockdown of SUV39H1 induced apoptosis in NSCLC cells. In summary, chaetocin pharmacologically inhibits the activity of SUV39H1 which provokes ER stress and results in up-regulation of ATF3 and CHOP, leading to DR5-dependent apoptosis eventually. These findings provide a novel interpretation on the anti-neoplastic activity of epigenetic drugs as a new therapeutic approach in NSCLC.
MicroRNA-214 Suppresses Gluconeogenesis by Targeting Activating Transcriptional Factor 4*

Science.gov (United States)

Li, Kai; Zhang, Jin; Yu, Junjie; Liu, Bin; Guo, Yajie; Deng, Jiali; Chen, Shanghai; Wang, Chunxia; Guo, Feifan

2015-01-01

Although the gluconeogenesis pathway is already a target for the treatment of type 2 diabetes, the potential role of microRNAs (miRNAs) in gluconeogenesis remains unclear. Here, we investigated the physiological functions of miR-214 in gluconeogenesis. The expression of miR-214 was suppressed by glucagon via protein kinase A signaling in primary hepatocytes, and miR-214 was down-regulated in the livers of fasted, high fat diet-induced diabetic and leptin receptor-mutated (db/db) mice. The overexpression of miR-214 in primary hepatocytes suppressed glucose production, and silencing miR-214 reversed this effect. Gluconeogenesis was suppressed in the livers of mice injected with an adenovirus expressing miR-214 (Ad-miR-214). Additionally, Ad-miR-214 alleviated high fat diet-induced elevation of gluconeogenesis and hyperglycemia. Furthermore, we found that activating transcription factor 4 (ATF4), a reported target of miR-214, can reverse the suppressive effect of miR-214 on gluconeogenesis in primary hepatocytes, and this suppressive effect was blocked in liver-specific ATF4 knock-out mice. ATF4 regulated gluconeogenesis via affecting forkhead box protein O1 (FOXO1) transcriptional activity. Finally, liver-specific miR-214 transgenic mice exhibited suppressed gluconeogenesis and reduced expression of ATF4, phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase in liver. Taken together, our results suggest that the miR-214-ATF4 axis is a novel pathway for the regulation of hepatic gluconeogenesis. PMID:25657009
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. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.
Electric field bifurcation and transition in the core plasma of CHS

International Nuclear Information System (INIS)

Fujisawa, A.; Iguchi, H.; Sanuki, H.; Itoh, K.; Okamura, S.; Matsuoka, K.; Hamada, Y.; Itoh, S.-I.

1997-01-01

In the CHS heliotron/torsatron, dynamic phenomena associated with transitions in radial electric field were observed during combined ECH+NBI heated plasmas. The observations with high temporal resolution confirmed a nonlinear relation between radial electric field and radial current to cause these phenomena associated with electric field bifurcation. (author)
Papers presented at the 6th H-mode workshop (Seeon, Germany)

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-10-01

The 6th H-mode workshop was held at Kloster Seeon (Germany) during the period of September 22-24, 1997. Contribution to this workshop is reported. Reports include. 1. Role of Nonuniform Superthermal Ions for Internal Transport Barriers. 2. Electric Field Bifurcation and Transition in the Core Plasma of CHS. 3. Formation and Termination of High Ion Temperature Mode in Heliotron/torsatron Plasmas. 4. Transition to an Enhanced Internal Transport Barrier. 5. Physics of Collapses - Probabilistic Occurrence of ELMs and Crashes -. (J.P.N.)
Acoustic transfer function of cavity and its application to rapid evaluation of sound field at low frequency band

Institute of Scientific and Technical Information of China (English)

YIN Gang; CHEN Hualing; HU Xuanli; HUANG Xieqing

2001-01-01

A new method to obtain numerical solution of Acoustic Transfer Function (ATF) by BEM is presented. For a simply supported panel backed by a rectangular cavity at low frequency band (0-200 Hz), the frequency property of ATF is analyzed. The relation between the accuracy of the rapid evaluation of sound field and the discretization schemes of the vibrational panel is discussed. The result shows that the method to obtain ATF and the rapid evaluation of sound field using the ATF is suitable to low frequency band. If an appropriate discretization scheme is choosed based on the frequency involved and the effort to obtain ATF, the accuracy of the rapid evaluation of sound field is acceptable.
A TAD further: exogenous control of gene activation.

Science.gov (United States)

Mapp, Anna K; Ansari, Aseem Z

2007-01-23

Designer molecules that can be used to impose exogenous control on gene transcription, artificial transcription factors (ATFs), are highly desirable as mechanistic probes of gene regulation, as potential therapeutic agents, and as components of cell-based devices. Recently, several advances have been made in the design of ATFs that activate gene transcription (activator ATFs), including reports of small-molecule-based systems and ATFs that exhibit potent activity. However, the many open mechanistic questions about transcriptional activators, in particular, the structure and function of the transcriptional activation domain (TAD), have hindered rapid development of synthetic ATFs. A compelling need thus exists for chemical tools and insights toward a more detailed portrait of the dynamic process of gene activation.

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.
MicroRNA-214 suppresses gluconeogenesis by targeting activating transcriptional factor 4.

Science.gov (United States)

Li, Kai; Zhang, Jin; Yu, Junjie; Liu, Bin; Guo, Yajie; Deng, Jiali; Chen, Shanghai; Wang, Chunxia; Guo, Feifan

2015-03-27

Although the gluconeogenesis pathway is already a target for the treatment of type 2 diabetes, the potential role of microRNAs (miRNAs) in gluconeogenesis remains unclear. Here, we investigated the physiological functions of miR-214 in gluconeogenesis. The expression of miR-214 was suppressed by glucagon via protein kinase A signaling in primary hepatocytes, and miR-214 was down-regulated in the livers of fasted, high fat diet-induced diabetic and leptin receptor-mutated (db/db) mice. The overexpression of miR-214 in primary hepatocytes suppressed glucose production, and silencing miR-214 reversed this effect. Gluconeogenesis was suppressed in the livers of mice injected with an adenovirus expressing miR-214 (Ad-miR-214). Additionally, Ad-miR-214 alleviated high fat diet-induced elevation of gluconeogenesis and hyperglycemia. Furthermore, we found that activating transcription factor 4 (ATF4), a reported target of miR-214, can reverse the suppressive effect of miR-214 on gluconeogenesis in primary hepatocytes, and this suppressive effect was blocked in liver-specific ATF4 knock-out mice. ATF4 regulated gluconeogenesis via affecting forkhead box protein O1 (FOXO1) transcriptional activity. Finally, liver-specific miR-214 transgenic mice exhibited suppressed gluconeogenesis and reduced expression of ATF4, phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase in liver. Taken together, our results suggest that the miR-214-ATF4 axis is a novel pathway for the regulation of hepatic gluconeogenesis. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
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. Copyright © 2013 Elsevier Ltd. All rights reserved.
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.
Measurement of impulse peak insertion loss from two acoustic test fixtures and four hearing protector conditions with an acoustic shock tube

Science.gov (United States)

Murphy, William J.; Fackler, Cameron J.; Berger, Elliott H.; Shaw, Peter B.; Stergar, Mike

2015-01-01

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. PMID:26356380
Advanced fusion concepts: project summaries

International Nuclear Information System (INIS)

1980-12-01

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
Thermal aging of melt-spun NdFeB magnetic powder in hydrogen

International Nuclear Information System (INIS)

Pinkerton, Frederick E.; Balogh, Michael P.; Ellison, Nicole; Foto, Aldo; Sechan, Martin; Tessema, Misle M.; Thompson, Margarita P.

2016-01-01

High energy product neodymium-iron-boron (NdFeB) magnets are the premier candidate for demanding electrified vehicle traction motor applications. Injection molded (IM) or compression molded (CM) magnets made using NdFeB powders are promising routes to improve motor efficiency, cost, and manufacturability. However, IM and CM NdFeB magnets are susceptible to substantial thermal aging losses at motor operating temperatures when exposed to the automatic transmission fluid (ATF) used as a lubricant and cooling medium. The intrinsic coercivity H ci of NdFeB IM and CM magnets degrades by as much as 18% when aged for 1000 h in ATF at 150 °C, compared to a 3% loss when aged in air. Here we report aging studies of rapidly quenched NdFeB powder in air, ATF, and H 2 gas. Expansion of the NdFeB crystal lattice in both ATF and H 2 identified hydrogen dissociated from the ATF during aging and diffused into the primary NdFeB phase as the probable cause of the coercivity loss of IM and CM magnets. - Highlights: • Injection molded NdFeB magnets age rapidly in automatic transmission fluid (ATF). • Coercivity loss is not due to direct chemical reaction between ATF and the powder. • Chemical reaction with the binder does not play a major role in aging. • Hydrogen dissociates from ATF and diffuses into Nd 2 Fe 14 B, reducing coercivity.
Thermal aging of melt-spun NdFeB magnetic powder in hydrogen

Energy Technology Data Exchange (ETDEWEB)

Pinkerton, Frederick E., E-mail: frederick.e.pinkerton@gm.com [Chemical and Materials Systems Laboratory, General Motors Research and Development Center, Warren, MI 48092 (United States); Balogh, Michael P.; Ellison, Nicole [Chemical and Materials Systems Laboratory, General Motors Research and Development Center, Warren, MI 48092 (United States); Foto, Aldo [Element Materials Technology Wixom, Inc (United States); Sechan, Martin; Tessema, Misle M.; Thompson, Margarita P. [Powertrain Materials/Fluids/AMPPD Engineering and Labs, GFL VE/PT Materials Engineering, General Motors LLC, Pontiac, MI 48340 (United States)

2016-11-01

High energy product neodymium-iron-boron (NdFeB) magnets are the premier candidate for demanding electrified vehicle traction motor applications. Injection molded (IM) or compression molded (CM) magnets made using NdFeB powders are promising routes to improve motor efficiency, cost, and manufacturability. However, IM and CM NdFeB magnets are susceptible to substantial thermal aging losses at motor operating temperatures when exposed to the automatic transmission fluid (ATF) used as a lubricant and cooling medium. The intrinsic coercivity H{sub ci} of NdFeB IM and CM magnets degrades by as much as 18% when aged for 1000 h in ATF at 150 °C, compared to a 3% loss when aged in air. Here we report aging studies of rapidly quenched NdFeB powder in air, ATF, and H{sub 2} gas. Expansion of the NdFeB crystal lattice in both ATF and H{sub 2} identified hydrogen dissociated from the ATF during aging and diffused into the primary NdFeB phase as the probable cause of the coercivity loss of IM and CM magnets. - Highlights: • Injection molded NdFeB magnets age rapidly in automatic transmission fluid (ATF). • Coercivity loss is not due to direct chemical reaction between ATF and the powder. • Chemical reaction with the binder does not play a major role in aging. • Hydrogen dissociates from ATF and diffuses into Nd{sub 2}Fe{sub 14}B, reducing coercivity.
Comparison of parallel viscosity with neoclassical theory

International Nuclear Information System (INIS)

Ida, K.; Nakajima, N.

1996-04-01

Toroidal rotation profiles are measured with charge exchange spectroscopy for the plasma heated with tangential NBI in CHS heliotron/torsatron device to estimate parallel viscosity. The parallel viscosity derived from the toroidal rotation velocity shows good agreement with the neoclassical parallel viscosity plus the perpendicular viscosity. (μ perpendicular = 2 m 2 /s). (author)
Dialogue between E. coli free radical pathways and the mitochondria of C. elegans.

Science.gov (United States)

Govindan, J Amaranath; Jayamani, Elamparithi; Zhang, Xinrui; Mylonakis, Eleftherios; Ruvkun, Gary

2015-10-06

The microbial world presents a complex palette of opportunities and dangers to animals, which have developed surveillance and response strategies to hints of microbial intent. We show here that the mitochondrial homeostatic response pathway of the nematode Caenorhabditis elegans responds to Escherichia coli mutations that activate free radical detoxification pathways. Activation of C. elegans mitochondrial responses could be suppressed by additional mutations in E. coli, suggesting that C. elegans responds to products of E. coli to anticipate challenges to its mitochondrion. Out of 50 C. elegans gene inactivations known to mediate mitochondrial defense, we found that 7 genes were required for C. elegans response to a free radical producing E. coli mutant, including the bZip transcription factor atfs-1 (activating transcription factor associated with stress). An atfs-1 loss-of-function mutant was partially resistant to the effects of free radical-producing E. coli mutant, but a constitutively active atfs-1 mutant growing on wild-type E. coli inappropriately activated the pattern of mitochondrial responses normally induced by an E. coli free radical pathway mutant. Carbonylated proteins from free radical-producing E. coli mutant may directly activate the ATFS-1/bZIP transcription factor to induce mitochondrial stress response: feeding C. elegans with H2O2-treated E. coli induces the mitochondrial unfolded protein response, and inhibition of a gut peptide transporter partially suppressed C. elegans response to free radical damaged E. coli.
Correlation of Meiotic DSB Formation and Transcription Initiation Around Fission Yeast Recombination Hotspots.

Science.gov (United States)

Yamada, Shintaro; Okamura, Mika; Oda, Arisa; Murakami, Hiroshi; Ohta, Kunihiro; Yamada, Takatomi

2017-06-01

Meiotic homologous recombination, a critical event for ensuring faithful chromosome segregation and creating genetic diversity, is initiated by programmed DNA double-strand breaks (DSBs) formed at recombination hotspots. Meiotic DSB formation is likely to be influenced by other DNA-templated processes including transcription, but how DSB formation and transcription interact with each other has not been understood well. In this study, we used fission yeast to investigate a possible interplay of these two events. A group of hotspots in fission yeast are associated with sequences similar to the cyclic AMP response element and activated by the ATF/CREB family transcription factor dimer Atf1-Pcr1. We first focused on one of those hotspots, ade6-3049 , and Atf1. Our results showed that multiple transcripts, shorter than the ade6 full-length messenger RNA, emanate from a region surrounding the ade6-3049 hotspot. Interestingly, we found that the previously known recombination-activation region of Atf1 is also a transactivation domain, whose deletion affected DSB formation and short transcript production at ade6-3049 These results point to a possibility that the two events may be related to each other at ade6-3049 In fact, comparison of published maps of meiotic transcripts and hotspots suggested that hotspots are very often located close to meiotically transcribed regions. These observations therefore propose that meiotic DSB formation in fission yeast may be connected to transcription of surrounding regions. Copyright © 2017 by the Genetics Society of America.
Antibiotic treatment failure when consulting patients with respiratory tract infections in general practice

DEFF Research Database (Denmark)

Bordado Sköld, Margrethe; Aabenhus, Rune; Guassora, Ann Dorrit

2017-01-01

as cases of antibiotic treatment failure (ATF). Objectives: We studied antibiotic treatment failure in patients with acute RTIs from a general practitioner (GP) perspective, aiming to explore (i) GPs’ views of ATF in primary care; (ii) how ATF influences the doctor-patient relationship; and (iii) GPs....... GPs used many communicative tools to maintain trust with patients in cases of ATF, but they did not consider such incidents to affect the doctor-patient relationship adversely. Conclusion: These findings suggest a possible communication gap between doctors and patients, partly due to a narrow medical...... definition of ATF. Studies describing patients’ views are still missing. General practitioners’ experiences and views on antibiotic treatment failure in acute respiratory infections or its effects on the doctor–patient relationship have not been studied previously....
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

/JNK) and their downstream transcription factors (ATF-2, Elk-1 and c-Jun) were examined. RESULTS: We observed that compared with control (DMSO-treated cerebral arteries), the cerebral arteries treated by DSP exhibited enhanced expression of MMP13 and AT(1) receptors, but not of AT(2) receptors, at both mRNA and protein...... 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...
Identification of the G13 (cAMP-response-element-binding protein-related protein) gene product related to activating transcription factor 6 as a transcriptional activator of the mammalian unfolded protein response.

Science.gov (United States)

Haze, K; Okada, T; Yoshida, H; Yanagi, H; Yura, T; Negishi, M; Mori, K

2001-04-01

Eukaryotic cells control the levels of molecular chaperones and folding enzymes in the endoplasmic reticulum (ER) by a transcriptional induction process termed the unfolded protein response (UPR). The mammalian UPR is mediated by the cis-acting ER stress response element consisting of 19 nt (CCAATN(9)CCACG), the CCACG part of which is considered to provide specificity. We recently identified the basic leucine zipper (bZIP) protein ATF6 as a mammalian UPR-specific transcription factor; ATF6 is activated by ER stress-induced proteolysis and binds directly to CCACG. Here we report that eukaryotic cells express another bZIP protein closely related to ATF6 in both structure and function. This protein encoded by the G13 (cAMP response element binding protein-related protein) gene is constitutively synthesized as a type II transmembrane glycoprotein anchored in the ER membrane and processed into a soluble form upon ER stress as occurs with ATF6. The proteolytic processing of ATF6 and the G13 gene product is accompanied by their relocation from the ER to the nucleus; their basic regions seem to function as a nuclear localization signal. Overexpression of the soluble form of the G13 product constitutively activates the UPR, whereas overexpression of a mutant lacking the activation domain exhibits a strong dominant-negative effect. Furthermore, the soluble forms of ATF6 and the G13 gene product are unable to bind to several point mutants of the cis-acting ER stress response element in vitro that hardly respond to ER stress in vivo. We thus concluded that the two related bZIP proteins are crucial transcriptional regulators of the mammalian UPR, and propose calling the ATF6 gene product ATF6alpha and the G13 gene product ATF6beta.
Modular Stellarator Reactor conceptual design study

International Nuclear Information System (INIS)

Miller, R.L.; Bathke, C.G.

1983-01-01

A conceptual design study of the Modular Stellarator Reactor is summarized. The physics basis of the approach is elucidated with emphasis on magnetics performance optimization. Key engineering features of the fusion power core are described. Comparisons with an analogous continuous-helical-coil (torsatron) system are made as the basis of a technical and economic assessment
Modular stellarator reactor conceptual design study

International Nuclear Information System (INIS)

Miller, R.L.; Krakowski, R.A.; Bathke, C.G.

1983-01-01

A conceptual design study of the Modular Stellarator Reactor is summarized. The physics basis of the approach is elucidated with emphasis on magnetics performance optimization. Key engineering features of the fusion power core are described. Comparisons with an analogous continuous-helical-coil (torsatron) system are made as the basis of a technical and economic assessment
Confinement physic study in a small low-aspect-ratio helical device CHS

International Nuclear Information System (INIS)

Okamura, S.; Matsuoka, K.; Akiyama, R.

1999-01-01

The configuration parameter of the plasma position relative to the center of the helical coil winding is very effective one for controlling the MHD stability and the trapped particle confinement in Heliotron/Torsatron systems. But these two characteristics are contradictory to each other in this parameter. The inward shifted configuration is favorable for the drift-orbit-optimization but it is predicted unstable with the Mercier criterion. Various physics problems, such as electric field structure, plasma rotation and MHD phenomena, have been studied in CHS with a compromising intermediate position. With this standard configuration, CHS has supplied experimental results for understanding general toroidal confinement physics and low-aspect-ratio helical systems. In the recent experiments, it was found that the wide range of inward shifted configurations gives stable plasma discharges without any restriction to the special pressure profile. Such enhanced range of operation made it possible to study experimentally the drift-orbit-optimized configuration in the Heliotron/Torsatron systems. The effect of configuration improvement was studied with plasmas in a low collisionality regime. (author)
Wendelstein VII-A in torsatron mode

International Nuclear Information System (INIS)

Harmeyer, E.; Kisslinger, J.; Rau, F.; Wobig, H.

1985-03-01

Variable shear - positive or negative, up to about 20 percent - can be introduced into the Wendelstein VII-A Stellarator vacuum field configuration by different currents in the two helix systems, and balancing the resulting vertical field. (orig.)
Gemcitabine treatment induces endoplasmic reticular (ER) stress and subsequently upregulates urokinase plasminogen activator (uPA) to block mitochondrial-dependent apoptosis in Panc-1 cancer stem-like cells (CSCs).

Science.gov (United States)

Wang, Li; Zhang, Yi; Wang, Weiguo; Zhu, Yunjie; Chen, Yang; Tian, Bole

2017-01-01

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor survival rates. The presence of cancer stem-like cells (CSCs) is believed to be among the underlying reasons for the aggressiveness of PDAC, which contributes to chemoresistance and recurrence. However, the mechanisms that induce chemoresistance and inhibit apoptosis remain largely unknown. We used serum-free medium to enrich CSCs from panc-1 human pancreatic cancer cells and performed sphere formation testing, flow cytometry, quantitative reverse transcription polymerase chain reaction (RT-qPCR) and semi-quantitative western blotting to confirm the stemness of panc-1 CSCs. Hallmarks of endoplasmic reticulum (ER) stress, including IRE1, PERK, ATF4, ATF6α, GRP78 and uPA expression, were detected after gemcitabine treatment. Effects of gemcitabine-induced uPA expression on cell invasion, sphere formation, colony formation and gemcitabine sensitivity were detected. Electrophoretic mobility shift assays (EMSAs) and RNA-immunoprecipitation (RIP) were performed to detect interaction between the uPA mRNA 3'-UTR and mutant p53-R273H expressed by panc-1 CSCs. The effects of upregulated uPA by gemcitabine on apoptosis were detected by Annexin V-FITC/PI staining, and the impact of uPA on small molecule CP-31398-restored mutant p53 transcriptional activity was measured by a luciferase reporter assay. Enriched panc-1 CSCs expressing high levels of CD44 and CD133 also produced significantly higher amounts of Oct4 and Nanog. Compared with panc-1 cells, panc-1 CSCs presented chemoresistance to gemcitabine. ER stress gene detections demonstrated effects of gemcitabine-induced ER stress on both the pro-apoptotic and pro-survival branches. ER stress-induced ATF6α upregulated level of uPA by transcriptionally activating GRP78. Gemcitabine-induced uPA promoted invasion, sphere formation and colony formation and attenuated apoptosis induced by gemcitabine in panc-1 CSCs, depending on interaction with mutant p53
ERalpha and AP-1 interact in vivo with a specific sequence of the F promoter of the human ERalpha gene in osteoblasts.

Science.gov (United States)

Lambertini, Elisabetta; Tavanti, Elisa; Torreggiani, Elena; Penolazzi, Letizia; Gambari, Roberto; Piva, Roberta

2008-07-01

Estrogen-responsive genes often have an estrogen response element (ERE) positioned next to activator protein-1 (AP-1) binding sites. Considering that the interaction between ERE and AP-1 elements has been described for the modulation of bone-specific genes, we investigated the 17-beta-estradiol responsiveness and the role of these cis-elements present in the F promoter of the human estrogen receptor alpha (ERalpha) gene. The F promoter, containing the sequence analyzed here, is one of the multiple promoters of the human ERalpha gene and is the only active promoter in bone tissue. Through electrophoretic mobility shift (EMSA), chromatin immunoprecipitation (ChIP), and re-ChIP assays, we investigated the binding of ERalpha and four members of the AP-1 family (c-Jun, c-fos, Fra-2, and ATF2) to a region located approximately 800 bp upstream of the transcriptional start site of exon F of the human ERalpha gene in SaOS-2 osteoblast-like cells. Reporter gene assay experiments in combination with DNA binding assays demonstrated that F promoter activity is under the control of upstream cis-acting elements which are recognized by specific combinations of ERalpha, c-Jun, c-fos, and ATF2 homo- and heterodimers. Moreover, ChIP and re-ChIP experiments showed that these nuclear factors bind the F promoter in vivo with a simultaneous occupancy stimulated by 17-beta-estradiol. Taken together, our findings support a model in which ERalpha/AP-1 complexes modulate F promoter activity under conditions of 17-beta-estradiol stimulation. (c) 2008 Wiley-Liss, Inc.

Energy transmittance predicts conductive hearing loss in older children and adults

Science.gov (United States)

Keefe, Douglas H.; Simmons, Jeffrey L.

2003-12-01

The test performance of a wideband acoustic transfer function (ATF) test and 226-Hz tympanometry was assessed in predicting the presence of conductive hearing loss, based on an air-bone gap of 20 dB or more. Two ATF tests were designed using an improved calibration method over a frequency range (0.25-8 kHz): an ambient-pressure test and a tympanometric test using an excess static pressure in the ear canal. Wideband responses were objectively classified using moment analyses of energy transmittance, which was a more appropriate test variable than energy reflectance. Subjects included adults and children of age 10 years and up, with 42 normal-functioning ears and 18 ears with a conductive hearing loss. Predictors were based on the magnitudes of the moment deviations from the 10th to 90th percentiles of the normal group. Comparing tests at a fixed specificity of 0.90, the sensitivities were 0.28 for peak-compensated static acoustic admittance at 226 Hz, 0.72 for ambient-pressure ATF, and 0.94 for pressurized ATF. Pressurized ATF was accurate at predicting conductive hearing loss with an area under the receiver operating characteristic curve of 0.95. Ambient-pressure ATF may have sufficient accuracy to use in some hearing-screening applications, whereas pressurized ATF has additional accuracy that may be appropriate for hearing-diagnostic applications.
Breakout Session B: Reactor Performance, R and D and Technological Issues. Breakout Session: Operation, R and D and technological issues

International Nuclear Information System (INIS)

Waeckel, Nicolas; Ott, Larry J.

2013-01-01

Three main outcomes resulted from this break-out session, as well as a few recommendations. Outcomes: 1 - The development of ATF is likely to be a long, stepwise/iterative approach, for which a broad consensus on the objectives is essential: - ATF should be as good as current fuels during normal operation ('first do no harm' principle), including good mechanical properties, and for DBA; - ATF should exhibit higher performances during severe accidents. 2 - For normal operation and DBA, the qualification path is well known and should follow the regulatory requirement: - the same as for an advanced fuel (properties characterisation, justification tests regarding SAFDLs of SRP4.2, etc.); - need to confirm though that the ATF candidate does not exhibit a specific behaviour or damage mechanisms that may require a specific justification (specific tests, specific SAFDL). 3 - For severe accidents, the recurrent questions are as follows: - What is the target? (in terms of expected performance); - What is the criterion for success? - Which tests should be run to justify the new fuel? Recommendations: 1 - In terms of organisation of the general development process: - identify the key factors or physical parameters that will really reduce the accident consequences; - calculate one BWR scenario (3-F) and one PWR (TMI-2) with the appropriate simulation tools; - run sensitivity analysis to scale the relative (beneficial) effect of various physical parameters (thermal conductivity, oxidation kinetics, H 2 production, exo-thermal reaction, FP retention, mechanical behaviour, etc.); - these calculations will be run with data progressively qualified on ad-hoc experience. 2 - International co-operation is recommended, especially during the feasibility phase: - no proprietary concern at this stage; - from utility point of view, it is better if all fuel vendors propose an ATF, to ensure the security of supply; - cross-irradiation of ATF candidates (ATR, HRP, JHR) can accelerate
Ergodization of magnetic surfaces due to finite beta effect in a helical system

International Nuclear Information System (INIS)

Hayashi, Takaya.

1989-04-01

Breaking of magnetic surfaces due to finite beta effect in a l=2 heliotron/torsatron configuration is studied by using a newly developed three dimensional equilibrium code. Breaking can be suppressed by a larger aspect ratio configuration, shaping of magnetic surface (inward shift or prolate shape), pitch modulation of helical coils, or pressure profile control. (author)
Fault-controlled development of shallow hydrothermal systems: Structural and mineralogical insights from the Southern Andes

Science.gov (United States)

Roquer, T.; Arancibia, G.; Rowland, J. V.; Iturrieta, P. C.; Morata, D.; Cembrano, J. M.

2017-12-01

Paleofluid-transporting systems can be recognized as meshes of fracture-filled veins in eroded zones of extinct hydrothermal systems. Here we conducted meso-microstructural analysis and mechanical modeling from two exhumed exposures of the faults governing regional tectonics of the Southern Andes: the Liquiñe-Ofqui Fault System (LOFS) and the Andean Transverse Faults (ATF). A total of 107 fractures in both exposures were analyzed. The ATF specific segment shows two tectonic solutions that can be modeled as Andersonian and non-Andersonian tectonic regimes: (1) shear (mode II/III) failure occurs at differential stresses > 28 MPa and fluid pressures 85-98% lithostatic in the non-Andersonian regime. Additionally, the LOFS exposure cyclically fails in extension (mode I) or extension + shear (modes I + II/III) in the Andersonian regime, at differential stresses 40-80% lithostatic. In areas of spatial interaction between ATF and LOFS, these conditions might favor: (1) the storage of overpressured fluids in hydrothermal systems associated with the ATF faults, and (2) continuous fluid flow through vertical conduits in the LOFS faults. These observations suggest that such intersections are highly probable locations for concentrated hydrothermal activity, which must be taken into consideration for further geothermal exploration. ACKNOWLEDGEMENTS. PhD CONICYT grants, Centro de Excelencia en Geotermia de los Andes (CEGA-FONDAP/CONICYT Project #15090013), FONDECYT Project #1130030 and Project CONICYT REDES #140036.
The effect of increased yeast alcohol acetyltransferase and esterase activity on the flavour profiles of wine and distillates.

Science.gov (United States)

Lilly, Mariska; Bauer, Florian F; Lambrechts, Marius G; Swiegers, Jan H; Cozzolino, Daniel; Pretorius, Isak S

2006-07-15

The fruity odours of wine are largely derived from the synthesis of esters and higher alcohols during yeast fermentation. The ATF1- and ATF2-encoded alcohol acetyltransferases of S. cerevisiae are responsible for the synthesis of ethyl acetate and isoamyl acetate esters, while the EHT1-encoded ethanol hexanoyl transferase is responsible for synthesizing ethyl caproate. However, esters such as these might be degraded by the IAH1-encoded esterase. The objectives of this study were: (a) to overexpress the genes encoding ester-synthesizing and ester-degrading enzymes in wine yeast; (b) to prepare Colombard table wines and base wines for distillation using these modified strains; and (c) to analyse and compare the ester concentrations and aroma profiles of these wines and distillates. The overexpression of ATF1 significantly increased the concentrations of ethyl acetate, isoamyl acetate, 2-phenylethyl acetate and ethyl caproate, while the overexpression of ATF2 affected the concentrations of ethyl acetate and isoamyl acetate to a lesser degree. The overexpression of IAH1 resulted in a significant decrease in ethyl acetate, isoamyl acetate, hexyl acetate and 2-phenylethyl acetate. The overexpression of EHT1 resulted in a marked increase in ethyl caproate, ethyl caprylate and ethyl caprate. The flavour profile of the wines and distillates prepared using the modified strains were also significantly altered as indicated by formal sensory analysis. This study offers prospects for the development of wine yeast starter strains with optimized ester-producing capability that could assist winemakers in their effort to consistently produce wine and distillates such as brandy to definable flavour specifications and styles.
Hypoxia induces cyclophilin B through the activation of transcription factor 6 in gastric adenocarcinoma cells.

Science.gov (United States)

Jeong, Kwon; Kim, Kiyoon; Kim, Hunsung; Oh, Yoojung; Kim, Seong-Jin; Jo, Yunhee; Choe, Wonchae

2015-06-01

Hypoxia is an important form of physiological stress that induces cell death, due to the resulting endoplasmic reticulum (ER) stress, particularly in solid tumors. Although previous studies have indicated that cyclophilin B (CypB) plays a role in ER stress, there is currently no direct information supporting the mechanism of CypB involvement under hypoxic conditions. However, it has previously been demonstrated that ER stress positively regulates the expression of CypB. In the present study, it was demonstrated that CypB is transcriptionally regulated by hypoxia-mediated activation of transcription factor 6 (ATF6), an ER stress transcription factor. Subsequently, the effects of ATF6 on CypB promoter activity were investigated and an ATF6-responsive region in the promoter was identified. Hypoxia and ATF6 expression each increased CypB promoter activity. Collectively, these results demonstrate that ATF6 positively regulates the expression of CypB by binding to an ATF6-responsive region in the promoter, which may play an important role in the attenuation of apoptosis in the adaption to hypoxia. These results suggest that CypB may be a key molecule in the adaptation of cells to hypoxic conditions.
A novel heterozygous mutation of the WFS1 gene leading to constitutive endoplasmic reticulum stress is the cause of Wolfram syndrome.

Science.gov (United States)

Morikawa, Shuntaro; Tajima, Toshihiro; Nakamura, Akie; Ishizu, Katsura; Ariga, Tadashi

2017-12-01

Wolfram syndrome (WS) is a disorder characterized by the association of insulin-dependent diabetes mellitus (DM), diabetes insipidus, deafness, and optic nerve atrophy. WS is caused by WFS1 mutations encoding WFS1 protein expressed in endoplasmic reticulum (ER). During ER protein synthesis, misfolded and unfolded proteins accumulate, known as "ER stress". This is attenuated by the unfolded protein response (UPR), which recovers and maintains ER functions. Because WFS1 is a UPR component, mutant WFS1 might cause unresolvable ER stress conditions and cell apoptosis, the major causes underlying WS symptoms. We encountered an 11-month-old Japanese female WS patient with insulin-dependent DM, congenital cataract and severe bilateral hearing loss. Analyze the WFS1 and functional consequence of the patient WFS1 in vitro. The patient WFS1 contained a heterozygous 4 amino acid in-frame deletion (p.N325_I328del). Her mutant WFS1 increased GRP78 and ATF6α promoter activities in the absence of thapsigargin, indicating constitutive ER stress and nuclear factor of activated T-cell reporter activity, reflecting elevated cytosolic Ca 2+ signals. Mutant transfection into cells reduced mRNA expression levels of sarcoplasmic/endoplasmic reticulum Ca 2+ transport ATPase 2b (SERCA2b) compared with wild type. Because SERCA2b is required for ER and cytoplasmic Ca 2+ homeostasis, decreased SERCA2b expression might affect ER Ca 2+ efflux, causing cell apoptosis. A novel heterozygous mutation of WFS1 induced constitutive ER stress through ATF6α activation and ER Ca 2+ efflux, resulting in cell apoptosis. These results provide new insights into the roles of WFS1 in UPR and mechanism of monogenic DM. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Simulations of the BNL/SLAC/UCLA 1.6 cell emittance compensated photocathode RF gun low energy beam line

International Nuclear Information System (INIS)

Palmer, D.T.; Miller, R.H.; Winick, H.

1995-01-01

A dedicated low energy (2 to 10 MeV) experimental beam line is now under construction at Brookhaven National Laboratories Accelerator Test Facility (BNL/ATF) for photocathode RF gun testing and photoemission experiments. The design of the experimental line, using the 1.6 cell photocathode RF gun developed by the BNL/SLAC/UCLA RF gun collaboration is presented. Detailed beam dynamics simulations were performed for the 1.6 cell RF gun injector using a solenoidal emittance compensation technique. An experimental program for testing the 1.6 cell RF gun is presented. This program includes beam loading caused by dark current, higher order mode field measurements, integrated and slice emittance measurements using a pepper-pot and RF kicker cavity
Modular coils: a promising toroidal-reactor-coil system

International Nuclear Information System (INIS)

Chu, T.K.; Furth, H.P.; Johnson, J.L.; Ludescher, C.; Weimer, K.E.

1981-04-01

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
Identification of a c-Jun N-terminal kinase-2-dependent signal amplification cascade that regulates c-Myc levels in ras transformation

DEFF Research Database (Denmark)

Mathiasen, D.P.; Egebjerg, C.; Andersen, S.H.

2012-01-01

are essential for ras transformation. Previous studies show that ERK-mediated serine 62 phosphorylation protects c-Myc from proteasomal degradation. ERK is, however, not alone sufficient to stabilize c-Myc but requires the cooperation of cancerous inhibitor of protein phosphatase 2A (CIP2A), an oncogene...... that counteracts protein phosphatase 2A-mediated dephosphorylation of c-Myc. Here we show that JNK2 regulates Cip2a transcription via ATF2. ATF2 and c-Myc cooperate to activate the transcription of ATF3. Remarkably, not only ectopic JNK2, but also ectopic ATF2, CIP2A, c-Myc and ATF3 are sufficient to rescue...... the defective ras transformation of JNK2-deficient cells. Thus, these data identify the key signal converging point of JNK2 and ERK pathways and underline the central role of CIP2A in ras transformation.Oncogene advance online publication, 27 June 2011; doi:10.1038/onc.2011.230....
Development Status of Accident-tolerant Fuel for Light Water Reactors in Korea

Directory of Open Access Journals (Sweden)

Hyun-Gil Kim

2016-02-01

Full Text Available For a long time, a top priority in the nuclear industry was the safe, reliable, and economic operation of light water reactors. However, the development of accident-tolerant fuel (ATF became a hot topic in the nuclear research field after the March 2011 events at Fukushima, Japan. In Korea, innovative concepts of ATF have been developing to increase fuel safety and reliability during normal operations, operational transients, and also accident events. The microcell UO2 and high-density composite pellet concepts are being developed as ATF pellets. A microcell UO2 pellet is envisaged to have the enhanced retention capabilities of highly radioactive and corrosive fission products. High-density pellets are expected to be used in combination with the particular ATF cladding concepts. Two concepts—surface-modified Zr-based alloy and SiC composite material—are being developed as ATF cladding, as these innovative concepts can effectively suppress hydrogen explosions and the release of radionuclides into the environment.
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.
Theory of anomalous transport in toroidal helical plasmas

International Nuclear Information System (INIS)

Itoh, K.; Itoh, S.; Fukuyama, A.

1992-03-01

Theoretical model of the anomalous transport in Torsatron/Heliotron plasmas is developed, based on the current-diffusive interchange instability which is destabilized due to the averaged magnetic hill near edge. Analytic formula of transport coefficient is derived. This model explains the high edge transport, the power degradation and energy confinement scaling law and the enhanced heat-pulse thermal conduction. (author)
Progress in modular-stellarator fusion-power-reactor conceptual designs

International Nuclear Information System (INIS)

Sviatoslavsky, I.N.; Van Sciver, S.W.; Kulcinski, G.L.

1982-01-01

Recent encouraging experimental results on stellarators/torsatrons/heliotrons (S/T/H) have revived interest in these concepts as possible fusion power reactors. The use of modular coils to generate the stellarator topology has added impetus to this renewed interest. Studies of the modular coil approach to stellarators by UW-Madison and Los Alamos National Laboratory are summarized in this paper
Poloidal rotation velocity measurement in toroidal plasmas via microwave reflectometry

International Nuclear Information System (INIS)

Pavlichenko, O.S.; Skibenko, A.I.; Fomin, I.P.; Pinos, I.B.; Ocheretenko, V.L.; Berezhniy, V.L.

2001-01-01

Results of experiment modeling backscattering of microwaves from rotating plasma layer perturbed by fluctuations are presented. It was shown that auto- and crosscorrelation of reflected power have a periodicity equal to rotation period. Such periodicity was observed by microwave reflectometry in experiments on RF plasma production on U-3M torsatron and was used for measurement of plasma poloidal rotation velocity. (author)
Role of paraoxonase-1 in bone anabolic effects of parathyroid hormone in hyperlipidemic mice

Energy Technology Data Exchange (ETDEWEB)

Lu, Jinxiu [Department of Physiology, University of California, Los Angeles (United States); Cheng, Henry [Department of Medicine, University of California, Los Angeles (United States); Atti, Elisa [Division of Diagnostic and Surgical Sciences, School of Dentistry, University of California, Los Angeles (United States); Shih, Diana M. [Department of Medicine, University of California, Los Angeles (United States); Demer, Linda L. [Department of Physiology, University of California, Los Angeles (United States); Department of Medicine, University of California, Los Angeles (United States); Department of Bioengineering, University of California, Los Angeles (United States); Tintut, Yin, E-mail: ytintut@mednet.ucla.edu [Department of Medicine, University of California, Los Angeles (United States)

2013-02-01

Highlights: ► Anabolic effects of PTH were tested in hyperlipidemic mice overexpressing PON1. ► Expression of antioxidant regulatory genes was induced in PON1 overexpression. ► Bone resorptive activity was reduced in PON1 overexpressing hyperlipidemic mice. ► PON1 restored responsiveness to intermittent PTH in bones of hyperlipidemic mice. -- Abstract: Hyperlipidemia blunts anabolic effects of intermittent parathyroid hormone (PTH) on cortical bone, and the responsiveness to PTH are restored in part by oral administration of the antioxidant ApoA-I mimetic peptide, D-4F. To evaluate the mechanism of this rescue, hyperlipidemic mice overexpressing the high-density lipoprotein-associated antioxidant enzyme, paraoxonase 1 (Ldlr{sup −/−}PON1{sup tg}) were generated, and daily PTH injections were administered to Ldlr{sup −/−}PON1{sup tg} and to littermate Ldlr{sup −/−} mice. Expression of bone regulatory genes was determined by realtime RT-qPCR, and cortical bone parameters of the femoral bones by micro-computed tomographic analyses. PTH-treated Ldlr{sup −/−}PON1{sup tg} mice had significantly greater expression of PTH receptor (PTH1R), activating transcription factor-4 (ATF4), and osteoprotegerin (OPG) in femoral cortical bone, as well as significantly greater cortical bone mineral content, thickness, and area in femoral diaphyses compared with untreated Ldlr{sup −/−}PON1{sup tg} mice. In contrast, in control mice (Ldlr{sup −/−}) without PON1 overexpression, PTH treatment did not induce these markers. Calvarial bone of PTH-treated Ldlr{sup −/−}PON1{sup tg} mice also had significantly greater expression of osteoblastic differentiation marker genes as well as BMP-2-target and Wnt-target genes. Untreated Ldlr{sup −/−}PON1{sup tg} mice had significantly greater expression of PTHR1 than untreated Ldlr{sup −/−} mice, whereas sclerostin expression was reduced. In femoral cortical bones, expression levels of transcription factors, Fox
Incorporating elements of social franchising in government health services improves the quality of infant and young child feeding counselling services at commune health centres in Vietnam.

Science.gov (United States)

Nguyen, Phuong H; Kim, Sunny S; Keithly, Sarah C; Hajeebhoy, Nemat; Tran, Lan M; Ruel, Marie T; Rawat, Rahul; Menon, Purnima

2014-12-01

Although social franchising has been shown to enhance the quality of reproductive health services in developing countries, its effect on nutrition services remains unexamined. This study assessed the effects of incorporating elements of social franchising on shaping the quality of infant and young child feeding (IYCF) counselling facilities and services in Vietnam. Process-related data collected 12 months after the launch of the first franchises were used to compare randomly assigned Alive & Thrive-supported health facilities (AT-F, n = 20) with standard facilities (SF, n = 12) across three dimensions of service quality: 'structure', 'process' and 'outcome' that capture the quality of facilities, service delivery, and client perceptions and use, respectively. Data collection included facility assessments (n = 32), staff surveys (n = 96), counselling observations (n = 137), client exit interviews (n = 137) and in-depth interviews with mothers (n = 48). Structure: AT-F were more likely to have an unshared, well-equipped room for nutrition counselling than SF (65.0% vs 10.0%). Compared with SF providers, AT-F staff had better IYCF knowledge (mean score 9.9 vs 8.8, range 0-11 for breastfeeding; mean score 3.6 vs 3.2, range 0-4 for complementary feeding). AT-F providers also demonstrated significantly better interpersonal communication skills (score 9.6 vs 5.1, range 0-13) and offered more comprehensive counselling sessions. Overall utilization of franchises was low (10%). A higher proportion of pregnant women utilized franchise services (48.9%), compared with mothers with children 6-23.9 months (1.4%). There was no quantitative difference in client satisfaction with counselling services between AT-F and SF, but franchise users praised the AT-F for problem solving related to child feeding. Incorporating elements of social franchising significantly enhances the quality of IYCF counselling services within government primary healthcare facilities, particularly their
Altered Expression of Endoplasmic Reticulum Stress Associated Genes in Hippocampus of Learned Helpless Rats: Relevance to Depression Pathophysiology

Directory of Open Access Journals (Sweden)

Matthew A. Timberlake

2016-01-01

Full Text Available The unfolded protein response (UPR is an evolutionarily conserved defensive mechanism that is used by cells to correct misfolded proteins that accumulate in the endoplasmic reticulum. These proteins are misfolded as a result of physical stress on a cell and initiate a host of downstream effects that govern processes ranging from inflammation to apoptosis. To examine whether UPR system plays a role in depression, we examined the expression of genes that are part of the three different pathways for UPR activation, namely GRP78, GRP94, ATF6, XBP-1, ATF4 and CHOP using an animal model system that distinguishes vulnerability (learned helpless, LH from resistance (non-learned helpless, NLH to develop depression. Rats were exposed to inescapable shock on day 1 and day 7 and were tested for escape latency on day 14. Rats not given shock but tested for escape latency were used as tested control (TC. Plasma corticosterone levels were measured. Expression levels of various UPR associated genes were determined in hippocampus using qPCR. We found that the corticosterone level was higher in LH rats compared with TC and NLH rats. Expression of GRP78, GRP94, ATF6 and XBP-1 were significantly upregulated in LH rats compared with TC or NLH rats, whereas NLH rats did not show such changes. Expression levels of ATF4 and CHOP showed trends towards upregulation but were not significantly altered in LH or NLH group. Our data show strong evidence of altered UPR system in depressed rats, which could be associated with development of depressive behavior.
Blimp-1 controls plasma cell function through regulation of immunoglobulin secretion and the unfolded protein response

Science.gov (United States)

Tellier, Julie; Shi, Wei; Minnich, Martina; Liao, Yang; Crawford, Simon; Smyth, Gordon K; Kallies, Axel; Busslinger, Meinrad; Nutt, Stephen L

2015-01-01

Plasma cell differentiation requires silencing of B cell transcription, while establishing antibody-secretory function and long-term survival. The transcription factors Blimp-1 and IRF4 are essential for plasma cell generation, however their function in mature plasma cells has remained elusive. We have found that while IRF4 was essential for plasma cell survival, Blimp-1 was dispensable. Blimp-1-deficient plasma cells retained their transcriptional identity, but lost the ability to secrete antibody. Blimp-1 regulated many components of the unfolded protein response (UPR), including XBP-1 and ATF6. The overlap of Blimp-1 and XBP-1 function was restricted to the UPR, with Blimp-1 uniquely regulating mTOR activity and plasma cell size. Thus, Blimp-1 is required for the unique physiological capacity of plasma cells that enables the secretion of protective antibody. PMID:26779600
78 FR 22773 - Regulation Strengthening Accountability of Attorneys and Non-Attorney Representatives Appearing...

Science.gov (United States)

2013-04-17

..., Firearms and Explosives (ATF). The commenter states that the ATF requires practitioners to satisfy minimum... the right to review and respond to evidence forming the basis of any potential disciplinary action...

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
Thermal aging of melt-spun NdFeB magnetic powder in hydrogen

Science.gov (United States)

Pinkerton, Frederick E.; Balogh, Michael P.; Ellison, Nicole; Foto, Aldo; Sechan, Martin; Tessema, Misle M.; Thompson, Margarita P.

2016-11-01

High energy product neodymium-iron-boron (NdFeB) magnets are the premier candidate for demanding electrified vehicle traction motor applications. Injection molded (IM) or compression molded (CM) magnets made using NdFeB powders are promising routes to improve motor efficiency, cost, and manufacturability. However, IM and CM NdFeB magnets are susceptible to substantial thermal aging losses at motor operating temperatures when exposed to the automatic transmission fluid (ATF) used as a lubricant and cooling medium. The intrinsic coercivity Hci of NdFeB IM and CM magnets degrades by as much as 18% when aged for 1000 h in ATF at 150 °C, compared to a 3% loss when aged in air. Here we report aging studies of rapidly quenched NdFeB powder in air, ATF, and H2 gas. Expansion of the NdFeB crystal lattice in both ATF and H2 identified hydrogen dissociated from the ATF during aging and diffused into the primary NdFeB phase as the probable cause of the coercivity loss of IM and CM magnets.
Serum levels of RBP4 and adipose tissue levels of PTP1B are increased in obese men resident in northeast Scotland without associated changes in ER stress response genes

Directory of Open Access Journals (Sweden)

Hoggard N

2012-05-01

Full Text Available Nigel Hoggard1, Abdelali Agouni2, Nimesh Mody2, Mirela Delibegovic21Rowett Institute of Nutrition and Health, 2Integrative Physiology, University of Aberdeen, Aberdeen, UKBackground: Retinol-binding protein 4 (RBP4 is an adipokine identified as a marker of insulin resistance in mice and humans. Protein tyrosine phosphatase 1B (PTP1B expression levels as well as other genes involved in the endoplasmic reticulum (ER stress response are increased in adipose tissue of obese, high-fat-diet-fed mice. In this study we investigated if serum and/or adipose tissue RBP4 protein levels and expression levels of PTP1B and other ER stress-response genes are altered in obese and obese/diabetic men resident in northeast Scotland.Methods: We studied three groups of male volunteers: (1 normal/overweight (body mass index [BMI] < 30, (2 obese (BMI > 30, and (3 obese/diabetic (BMI > 30 controlling their diabetes either by diet or the antidiabetic drug metformin. We analyzed their serum and adipose tissue RBP4 protein levels as well as adipose tissue mRNA expression of PTP1B, binding immunoglobulin protein (BIP, activated transcription factor 4 (ATF4, and glucose-regulated protein 94 (GRP94 alongside other markers of adiposity (percentage body fat, leptin, cholesterol, triglycerides and insulin resistance (oral glucose tolerance tests, insulin, homeostatic model assessment–insulin resistance, C-reactive protein, and adiponectin.Results: We found that obese Scottish subjects had significantly higher serum RBP4 protein levels in comparison to the normal/overweight subjects (P < 0.01. Serum RBP4 levels were normalized in obese/diabetic subjects treated with diet or metformin (P < 0.05. Adipose tissue RBP4 protein levels were comparable between all three groups of subjects as were serum and adipose transthyretin levels. Adipose tissue PTP1B mRNA levels were increased in obese subjects in comparison to normal/overweight subjects (P < 0.05; however diet and/or metformin
ATF experimental plans

International Nuclear Information System (INIS)

Murakami, M.

1987-01-01

The Program is directed at better understanding and improvement of toroidal confinement through studies of: β limit; 2nd stability region; low nu* transport; role of E-field; effects of magnetic configurations (externally controlled) on β and transport; and issues critical to steady state operation (energy and particle handling, ICRF)
Gas6 induces cancer cell migration and epithelial–mesenchymal transition through upregulation of MAPK and Slug

Energy Technology Data Exchange (ETDEWEB)

Lee, Yunhee [Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of); Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Lee, Mira [Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Kim, Semi, E-mail: semikim@kribb.re.kr [Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of); Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of)

2013-04-26

Highlights: •We investigated the molecular mechanisms underlying Gas6-mediated cancer cell migration. •Gas6 treatment and subsequent Axl activation induce cell migration and EMT via upregulation of Slug. •Slug expression mediated by Gas6 is mainly through c-Jun and ATF-2 in an ERK1/2 and JNK-dependent manner. •The Gas6/Axl-Slug axis may be exploited as a target for anti-cancer metastasis therapy. -- Abstract: Binding of Gas6 to Axl (Gas6/Axl axis) alters cellular functions, including migration, invasion, proliferation, and survival. However, the molecular mechanisms underlying Gas6-mediated cell migration remain poorly understood. In this study, we found that Gas6 induced the activation of JNK and ERK1/2 signaling in cancer cells expressing Axl, resulting in the phosphorylation of activator protein-1 (AP-1) transcription factors c-Jun and ATF-2, and induction of Slug. Depletion of c-Jun or ATF-2 by siRNA attenuated the Gas6-induced expression of Slug. Slug expression was required for cell migration and E-cadherin reduction/vimentin induction induced by Gas6. These results suggest that Gas6 induced cell migration via Slug upregulation in JNK- and ERK1/2-dependent mechanisms. These data provide an important insight into the molecular mechanisms mediating Gas6-induced cell migration.
Activating transcription factor 6 mediates oxidized LDL-induced cholesterol accumulation and apoptosis in macrophages by up-regulating CHOP expression.

Science.gov (United States)

Yao, Shutong; Zong, Chuanlong; Zhang, Ying; Sang, Hui; Yang, Mingfeng; Jiao, Peng; Fang, Yongqi; Yang, Nana; Song, Guohua; Qin, Shucun

2013-01-01

This study was to explore whether activating transcription factor 6 (ATF6), an important sensor to endoplasmic reticulum (ER) stress, would mediate oxidized low-density lipoprotein (ox-LDL)- induced cholesterol accumulation and apoptosis in cultured macrophages and the underlying molecular mechanisms. Intracellular lipid droplets and total cholesterol levels were assayed by oil red O staining and enzymatic colorimetry, respectively. Cell viability and apoptosis were determined using MTT assay and AnnexinV-FITC apoptosis detection kit, respectively. The nuclear translocation of ATF6 in cells was detected by immunofluorescence analysis. Protein and mRNA levels were examined by Western blot analysis and real time-PCR, respectively. ATF6 siRNA was transfected to RAW264.7 cells by lipofectamin. Exposure of cells to ox-LDL induced glucose-regulated protein 78 (GRP78). C/EBP homologous protein (CHOP), a key-signaling component of ER stress-induced apoptosis, was up-regulated in ox-LDL-treated cells. ATF6, a factor that positively regulates CHOP expression, was activated by ox-LDL in a concentration- and time- dependent manner. The role of the ATF6-mediated ER stress pathway was further confirmed through the siRNA-mediated knockdown of ATF6, which attenuated ox-LDL-induced upregulation of CHOP, cholesterol accumulation and apoptosis in macrophages. In addition, the phosphorylation of double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase (PERK), another factor that positively regulates CHOP expression, was induced in the presence of ox-LDL, and PERK-specific siRNA also inhibited the ox-LDL-induced upregulation of CHOP and apoptosis in RAW264.7 cells. These results demonstrate that ER stress-related proteins, particularly ATF6 and its downstream molecule CHOP, are involved in ox-LDL-induced cholesterol accumulation and apoptosis in macrophages.
Theoretical and experimental studies on electric field and confinement in helical systems

International Nuclear Information System (INIS)

Sanuki, H.; Itoh, K.; Todoroki, J.; Ida, K.; Idei, H.; Iguchi, H.; Yamada, H.

1994-06-01

The present study consists of two parts. The first part is oriented to a theoretical model of selfconsistent analysis to determine simultaneously the electric field and loss cone boundary in heliotron/torsatron configurations under the influence of nonclassical particle losses. The second part is referred to the analysis on NBI heated and ECH plasmas in Compact Helical System (CHS) device. A comparison is made between theoretical results and experimental observations. (author)
Active trajectory control for a heavy ion beam probe on the compact helical system

International Nuclear Information System (INIS)

Fujisawa, A.; Iguchi, H.; Lee, S.; Crowley, T.P.; Hamada, Y.; Hidekuma, S.; Kojima, M.

1996-05-01

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)
[Activation of endoplasmic reticulum stress and its effect on osteogenic differentiation induced by micropit/nanotube topography].

Science.gov (United States)

Shi, M Q; Song, W; Han, T X; Chang, B; Zhang, Y M

2017-02-09

Objective: To explore the activation of endoplasmic reticulum stress (ERS) in bone marrow mesenchymal stem cell (BMMSC) and its effect on osteogenic differentiation induced by micropit/nanotube topography (MNT), so as to provide guidance for the topography design of biomaterials. Methods: Four sample groups were fabricated: polishing control group (polished titanium, PT, no treatment), thapsigargin treatment (TG, 0.1 μmol/L TG treated for 9 h), MNT5 and MNT20 (anodized at 5 V and 20 V after acid etching). Scanning electron microscope (SEM) was used to observe the topography of Ti samples. The alkaline phosphatase (ALP) production, collagen secretion and extracellular matrix (ECM) mineralization of BMMSC (osteogenic induced for 7, 14 and 21 d) on Ti samples were detected to evaluate the osteogenic differentiation. After 12 h incubation, the shape and size of ER was examined using a transmission electron microscope (TEM), and ERS-related genes including immunoglobulin heavy chain binding protein (BiP), protein kinase RNA-like endoplasmic reticulum kinase (PERK) and activating transcription factor 4 (ATF4) were detected by quantitative real-time PCR (qRT-PCR). Results: After 7, 14 and 21 d of induction, the ALP production, collagen secretion and ECM mineralization in TG and MNT20 all significantly increased compared to PT ( P< 0.05). The cells grown on TG, MNT5 and MNT20 surfaces displayed gross distortions of the ER. Compared to PT, BiP, PERK, ATF4 mRNA expression in TG was respectively 1.87±0.10, 2.24±0.35, 1.85±0.14; BiP, ATF4 mRNA expression in MNT5 were respectively 1.27±0.09, 1.25±0.04; BiP, PERK, ATF4 mRNA expression in MNT20 were respectively 1.44±0.09, 2.40±0.60, 1.48±0.05 ( P< 0.05). Conclusions: MNT triggered different degree of ERS, and the activated ERS may promote MNT-induced osteogenic differentiation.
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)

2017-08-01

After the March 2011 accident at Fukushima Daiichi, Oak Ridge National Laboratory (ORNL) began conducting high temperature steam oxidation testing of candidate materials for accident tolerant fuel (ATF) cladding in August 2011 [1-11]. The ATF concept is to enhance safety margins in light water reactors (LWR) during severe accident scenarios by identifying materials with 100× slower steam oxidation rates compared to current Zr-based alloys. In 2012, the ORNL laboratory equipment was expanded and made available to the entire ATF community as the Severe Accident Test Station (SATS) [4,12]. Compared to the current UO2/Zr-based alloy fuel system, an ATF alternative would significantly reduce the rate of heat and hydrogen generation in the core during a coolant-limited severe accident [13-14]. The steam oxidation behavior of candidate materials is a key metric in the evaluation of ATF concepts and also an important input into models [15-17]. However, initial 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. Also, because many accident scenarios include steadily increasing temperatures, the required data are not traditional isothermal exposures but exposures with varying “ramp” rates. In some cases, the steam oxidation behavior has been surprising and difficult to interpret. Thus, more fundamental information continues to be collected. In addition, more work continues to focus on commercially-manufactured tube material. This report summarizes recent work to characterize the behavior of candidate alloys exposed to high temperature steam, evaluate steam oxidation behavior in various ramp scenarios and continue to collect integral data on FeCrAl compared to conventional Zr-based cladding.
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

and atf = 400Hz,J_{max} = 0.10T. Measurements are carried out on samples in a stress-relieved state and with magnetic anisotropies induced by stress or field annealing. Atf = 50Hz, a minimum m Ptversus σ is observed. The σ-value (sigma_{min}) corresponding to the minimum PTincreases with increasing |Ku......|. Atf = 400Hz, a minimum in PTversus σ is observed in the samples with induced magnetic anisotropy, whereassigma_{min} = 0in the stress-relieved samiales. However, no correlation between andsigma_{min}and Kuis possible from the present data....
An Active Trap Filter for Switching Harmonics Attenuation of Low-Pulse-Ratio Inverters

DEFF Research Database (Denmark)

Bai, Haofeng; Wang, Xiongfei; Loh, Poh Chiang

2017-01-01

method has also been proposed for the ATF to better enforce its active switching harmonic bypassing ability. Compared with conventional schemes for controlling active power filters, the proposed method is more readily implemented, since it requires neither current reference generation nor high......-bandwidth current control loop. Moreover, the use of a series LC-filter at its ac-side helps the ATF to reduce its inverter voltage and power ratings. Compensated frequency range of the ATF can hence be enlarged by using a comparably higher switching frequency and a proper step-by-step design procedure...
Co-activation of AMPK and mTORC1 Induces Cytotoxicity in Acute Myeloid Leukemia

Directory of Open Access Journals (Sweden)

Pierre Sujobert

2015-06-01

Full Text Available AMPK is a master regulator of cellular metabolism that exerts either oncogenic or tumor suppressor activity depending on context. Here, we report that the specific AMPK agonist GSK621 selectively kills acute myeloid leukemia (AML cells but spares normal hematopoietic progenitors. This differential sensitivity results from a unique synthetic lethal interaction involving concurrent activation of AMPK and mTORC1. Strikingly, the lethality of GSK621 in primary AML cells and AML cell lines is abrogated by chemical or genetic ablation of mTORC1 signaling. The same synthetic lethality between AMPK and mTORC1 activation is established in CD34-positive hematopoietic progenitors by constitutive activation of AKT or enhanced in AML cells by deletion of TSC2. Finally, cytotoxicity in AML cells from GSK621 involves the eIF2α/ATF4 signaling pathway that specifically results from mTORC1 activation. AMPK activation may represent a therapeutic opportunity in mTORC1-overactivated cancers.
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
Experiment list: SRX122485 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available antibody=Atf3 || treatment=LPS || time=120 min || chip antibody manufacturer 1=Santa Cruz || chip antibody ...catalog number 1=sc-188 || chip antibody manufacturer 2=Abcam || chip antibody catalog number 2=ab70005-100
Genome interrogation for novel salinity tolerant Arabidopsis mutants.

Science.gov (United States)

van Tol, Niels; Pinas, Johan; Schat, Henk; Hooykaas, Paul J J; van der Zaal, Bert J

2016-12-01

Soil salinity is becoming an increasingly large problem in agriculture. In this study, we have investigated whether a capacity to withstand salinity can be induced in the salinity sensitive plant species Arabidopsis thaliana, and whether it can be maintained in subsequent generations. To this end, we have used zinc finger artificial transcription factor (ZF-ATFs) mediated genome interrogation. Already within a relatively small collection Arabidopsis lines expressing ZF-ATFs, we found 41 lines that were tolerant to 100 mM NaCl. Furthermore, ZF-ATF encoding gene constructs rescued from the most strongly salinity tolerant lines were indeed found to act as dominant and heritable agents for salinity tolerance. Altogether, our data provide evidence that a silent capacity to withstand normally lethal levels of salinity exists in Arabidopsis and can be evoked relatively easily by in trans acting transcription factors like ZF-ATFs. © 2016 John Wiley & Sons Ltd.
Regulatory motifs for CREB-binding protein and Nfe2l2 transcription factors in the upstream enhancer of the mitochondrial uncoupling protein 1 gene.

Science.gov (United States)

Rim, Jong S; Kozak, Leslie P

2002-09-13

Thermogenesis against cold exposure in mammals occurs in brown adipose tissue (BAT) through mitochondrial uncoupling protein (UCP1). Expression of the Ucp1 gene is unique in brown adipocytes and is regulated tightly. The 5'-flanking region of the mouse Ucp1 gene contains cis-acting elements including PPRE, TRE, and four half-site cAMP-responsive elements (CRE) with BAT-specific enhancer elements. In the course of analyzing how these half-site CREs are involved in Ucp1 expression, we found that a DNA regulatory element for NF-E2 overlaps CRE2. Electrophoretic mobility shift assay and competition assays with the CRE2 element indicates that nuclear proteins from BAT, inguinal fat, and retroperitoneal fat tissue interact with the CRE2 motif (CGTCA) in a specific manner. A supershift assay using an antibody against the CRE-binding protein (CREB) shows specific affinity to the complex from CRE2 and nuclear extract of BAT. Additionally, Western blot analysis for phospho-CREB/ATF1 shows an increase in phosphorylation of CREB/ATF1 in HIB-1B cells after norepinephrine treatment. Transient transfection assay using luciferase reporter constructs also indicates that the two half-site CREs are involved in transcriptional regulation of Ucp1 in response to norepinephrine and cAMP. We also show that a second DNA regulatory element for NF-E2 is located upstream of the CRE2 region. This element, which is found in a similar location in the 5'-flanking region of the human and rodent Ucp1 genes, shows specific binding to rat and human NF-E2 by electrophoretic mobility shift assay with nuclear extracts from brown fat. Co-transfections with an Nfe2l2 expression vector and a luciferase reporter construct of the Ucp1 enhancer region provide additional evidence that Nfe2l2 is involved in the regulation of Ucp1 by cAMP-mediated signaling.
A new pumping strategy for petroleum product recovery from contaminated hydrogeologic systems: Laboratory and field evaluations

International Nuclear Information System (INIS)

Abdul, A.S.

1992-01-01

More than 200,000 gallons of automatic transmission fluid (ATF) leaked from an underground storage tank system and contaminated an area of about 64,000 ft 2 of a soil and ground water system. A pumping strategy for improved drainage and recovery of free oil was developed, tested in a laboratory model aquifer, and implemented (1) the oil recovery rate is carefully controlled to maximize the pumping rate while maintaining continuity between the oil layer in the soil and the recovery well, to avoid isolation of the oil in the subsurface; and (2) the rate of ground water pumping is controlled to maintain the depressed oil/water interface at its prepumped position. This approach prevents further spread of oil into the ground water, prevents reduction in the volume of recoverable oil due to residual retention, and maintains a gradient for oil flow toward the recovery well. In a model aquifer study, nearly 100% of the recoverable volume of ATF was pumped from the system, and about 56,000 gallons of the ATF has been recovered from the field site
Experiment list: SRX122493 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available antibody=Atf4 || treatment=LPS || time=120 min || chip antibody manufacturer 1=Abcam || chip antibody catal...og number 1=ab28830-100 || chip antibody manufacturer 2=Santa Cruz || chip antibody catalog number 2=sc-200
Proceedings of the SLAC/KEK linear collider workshop on damping ring

International Nuclear Information System (INIS)

Urakawa, J.; Yoshioka, M.

1992-07-01

Since the SLAC/KEK joint meeting was first held at SLAC in March 1987, we have had such a meeting annually with the present one the 6th. This meeting is planned to discuss the damping ring issue in particular. We have ever stressed the importance of study of damping rings and considered construction of a test damping ring as key issue for the ATF project, since we started construction of the ATF in 1987. In 1991 we had large-scale reconstruction of a building to make a shielded area where a 1.54 GeV injector linac for the ring is to be installed. (J.P.N.)

Integrating a Trust Framework with a Distributed Certificate Validation Scheme for MANETs

Directory of Open Access Journals (Sweden)

Marias Giannis F

2006-01-01

Full Text Available Many trust establishment solutions in mobile ad hoc networks (MANETs rely on public key certificates. Therefore, they should be accompanied by an efficient mechanism for certificate revocation and validation. Ad hoc distributed OCSP for trust (ADOPT is a lightweight, distributed, on-demand scheme based on cached OCSP responses, which provides certificate status information to the nodes of a MANET. In this paper we discuss the ADOPT scheme and issues on its deployment over MANETs. We present some possible threats to ADOPT and suggest the use of a trust assessment and establishment framework, named ad hoc trust framework (ATF, to support ADOPT's robustness and efficiency. ADOPT is deployed as a trust-aware application that provides feedback to ATF, which calculates the trustworthiness of the peer nodes' functions and helps ADOPT to improve its performance by rapidly locating valid certificate status information. Moreover, we introduce the TrustSpan algorithm to reduce the overhead that ATF produces, and the TrustPath algorithm to identify and use trusted routes for propagating sensitive information, such as third parties' accusations. Simulation results show that ATF adds limited overhead compared to its efficiency in detecting and isolating malicious and selfish nodes. ADOPT's reliability is increased, since it can rapidly locate a legitimate response by using information provided by ATF.
Experiment list: SRX122488 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available antibody=Atf3 || treatment=LPS || time=120 min || chip antibody manufacturer 1=Santa Cruz || chip antibody c...atalog number 1=sc-188 || chip antibody manufacturer 2=Abcam || chip antibody catalog number 2=ab70005-100 h
Experiment list: SRX122491 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ntibody=Atf3 || treatment=LPS || time=60 min || chip antibody manufacturer 1=Santa Cruz || chip antibody cat...alog number 1=sc-188 || chip antibody manufacturer 2=Abcam || chip antibody catalog number 2=ab70005-100 htt
Experiment list: SRX122487 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available antibody=Atf3 || treatment=LPS || time=120 min || chip antibody manufacturer 1=Santa Cruz || chip antibody c...atalog number 1=sc-188 || chip antibody manufacturer 2=Abcam || chip antibody catalog number 2=ab70005-100 h
Experiment list: SRX122490 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ntibody=Atf3 || treatment=LPS || time=30 min || chip antibody manufacturer 1=Santa Cruz || chip antibody cat...alog number 1=sc-188 || chip antibody manufacturer 2=Abcam || chip antibody catalog number 2=ab70005-100 htt
Experiment list: SRX122494 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available hip antibody=Atf4 || treatment=LPS || time=120 min || chip antibody manufacturer 1=Abcam || chip antibody ca...talog number 1=ab28830-100 || chip antibody manufacturer 2=Santa Cruz || chip antibody catalog number 2=sc-2
Experiment list: SRX122492 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ntibody=Atf3 || treatment=LPS || time=60 min || chip antibody manufacturer 1=Santa Cruz || chip antibody cat...alog number 1=sc-188 || chip antibody manufacturer 2=Abcam || chip antibody catalog number 2=ab70005-100 htt
Experiment list: SRX122484 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ntibody=Atf3 || treatment=LPS || time=0 min || chip antibody manufacturer 1=Santa Cruz || chip antibody cata...log number 1=sc-188 || chip antibody manufacturer 2=Abcam || chip antibody catalog number 2=ab70005-100 http
Activating transcription factor 6 polymorphisms and haplotypes are associated with impaired glucose homeostasis and type 2 diabetes in dutch Caucasians

NARCIS (Netherlands)

Meex, Steven J. R.; van Greevenbroek, Marleen M. J.; Ayoubi, Torik A.; Vlietinck, Robert; van Vliet-Ostaptchouk, Jana V.; Hofker, Martin H.; Vermeulen, Vicky M. M. -J.; Schalkwijk, Casper G.; Feskens, Edith J. M.; Boer, Jolanda M. A.; Stehouwer, Coen D. A.; van der Kallen, Carla J. H.; de Bruin, Tjerk W. A.

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
Effect of increased yeast alcohol acetyltransferase activity on flavor profiles of wine and distillates.

Science.gov (United States)

Lilly, M; Lambrechts, M G; Pretorius, I S

2000-02-01

The distinctive flavor of wine, brandy, and other grape-derived alcoholic beverages is affected by many compounds, including esters produced during alcoholic fermentation. The characteristic fruity odors of the fermentation bouquet are primarily due to a mixture of hexyl acetate, ethyl caproate (apple-like aroma), iso-amyl acetate (banana-like aroma), ethyl caprylate (apple-like aroma), and 2-phenylethyl acetate (fruity, flowery flavor with a honey note). The objective of this study was to investigate the feasibility of improving the aroma of wine and distillates by overexpressing one of the endogenous yeast genes that controls acetate ester production during fermentation. The synthesis of acetate esters by the wine yeast Saccharomyces cerevisiae during fermentation is ascribed to at least three acetyltransferase activities, namely, alcohol acetyltransferase (AAT), ethanol acetyltransferase, and iso-amyl AAT. To investigate the effect of increased AAT activity on the sensory quality of Chenin blanc wines and distillates from Colombar base wines, we have overexpressed the alcohol acetyltransferase gene (ATF1) of S. cerevisiae. The ATF1 gene, located on chromosome XV, was cloned from a widely used commercial wine yeast strain of S. cerevisiae, VIN13, and placed under the control of the constitutive yeast phosphoglycerate kinase gene (PGK1) promoter and terminator. Chromoblot analysis confirmed the integration of the modified copy of ATF1 into the genome of three commercial wine yeast strains (VIN7, VIN13, and WE228). Northern blot analysis indicated constitutive expression of ATF1 at high levels in these yeast transformants. The levels of ethyl acetate, iso-amyl acetate, and 2-phenylethyl acetate increased 3- to 10-fold, 3.8- to 12-fold, and 2- to 10-fold, respectively, depending on the fermentation temperature, cultivar, and yeast strain used. The concentrations of ethyl caprate, ethyl caprylate, and hexyl acetate only showed minor changes, whereas the acetic acid
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.
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.
Effects of lateral variations of crustal rheology on the occurrence of post-orogenic normal faults: The Alto Tiberina Fault (Northern Apennines, Central Italy)

Science.gov (United States)

Pauselli, Cristina; Ranalli, Giorgio

2017-11-01

The Northern Apennines (NA) are characterized by formerly compressive structures partly overprinted by subsequent extensional structures. The area of extensional tectonics migrated eastward since the Miocene. The youngest and easternmost major expression of extension is the Alto Tiberina Fault (ATF). We estimate 2D rheological profiles across the NA, and conclude that lateral rheological crustal variations have played an important role in the formation of the ATF and similar previously active faults to the west. Lithospheric delamination and mantle degassing resulted in an easterly-migrating extension-compression boundary, coinciding at present with the ATF, where (i) the thickness of the upper crust brittle layer reaches a maximum; (ii) the critical stress difference required to initiate faulting at the base of the brittle layer is at a minimum; and (iii) the total strengths of both the brittle layer and the whole lithosphere are at a minimum. Although the location of the fault is correlated with lithospheric rheological properties, the rheology by itself does not account for the low dip ( 20°) of the ATF. Two hypotheses are considered: (a) the low dip of the ATF is related to a rotation of the stress tensor at the time of initiation of the fault, caused by a basal shear stress ( 100 MPa) possibly related to corner flow associated with delamination; or (b) the low dip is associated to low values of the friction coefficient (≤ 0.5) coupled with high pore pressures related to mantle degassing. Our results establishing the correlation between crustal rheology and the location of the ATF are relatively robust, as we have examined various possible compositions and rheological parameters. They also provide possible general indications on the mechanisms of localized extension in post-orogenic extensional setting. The hypotheses to account for the low dip of the ATF, on the other hand, are intended simply to suggest possible solutions worthy of further study.
77 FR 67026 - Agency Information Collection Activities: Proposed Collection; Comments Requested: Report of...

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2012-11-08

... Lost ATF Form 5400.30, Intrastate Purchase of Explosives Coupon ACTION: 60-day notice. The Department... of information, including the validity of the methodology and assumptions used; --Enhance the quality... or Lost ATF F 5400.30, Intrastate Purchase Explosives Coupon. (3) Agency form number, if any, and the...
75 FR 67663 - Labeling Imported Wines With Multistate Appellations (2008R-265P)

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2010-11-03

.... ATF-53, multistate appellations were suggested by domestic wine industry members. ATF decided to allow...-2010-0007; Notice No. 110] RIN 1513-AB58 Labeling Imported Wines With Multistate Appellations (2008R.... SUMMARY: The Alcohol and Tobacco Tax and Trade Bureau proposes to amend the wine labeling regulations to...
Acidosis Activates Endoplasmic Reticulum Stress Pathways through GPR4 in Human Vascular Endothelial Cells.

Science.gov (United States)

Dong, Lixue; Krewson, Elizabeth A; Yang, Li V

2017-01-27

Acidosis commonly exists in the tissue microenvironment of various pathophysiological conditions such as tumors, inflammation, ischemia, metabolic disease, and respiratory disease. For instance, the tumor microenvironment is characterized by acidosis and hypoxia due to tumor heterogeneity, aerobic glycolysis (the "Warburg effect"), and the defective vasculature that cannot efficiently deliver oxygen and nutrients or remove metabolic acid byproduct. How the acidic microenvironment affects the function of blood vessels, however, is not well defined. GPR4 (G protein-coupled receptor 4) is a member of the proton-sensing G protein-coupled receptors and it has high expression in endothelial cells (ECs). We have previously reported that acidosis induces a broad inflammatory response in ECs. Acidosis also increases the expression of several endoplasmic reticulum (ER) stress response genes such as CHOP (C/EBP homologous protein) and ATF3 (activating transcription factor 3). In the current study, we have examined acidosis/GPR4- induced ER stress pathways in human umbilical vein endothelial cells (HUVEC) and other types of ECs. All three arms of the ER stress/unfolded protein response (UPR) pathways were activated by acidosis in ECs as an increased expression of phosphorylated eIF2α (eukaryotic initiation factor 2α), phosphorylated IRE1α (inositol-requiring enzyme 1α), and cleaved ATF6 upon acidic pH treatment was observed. The expression of other downstream mediators of the UPR, such as ATF4, ATF3, and spliced XBP-1 (X box-binding protein 1), was also induced by acidosis. Through genetic and pharmacological approaches to modulate the expression level or activity of GPR4 in HUVEC, we found that GPR4 plays an important role in mediating the ER stress response induced by acidosis. As ER stress/UPR can cause inflammation and cell apoptosis, acidosis/GPR4-induced ER stress pathways in ECs may regulate vascular growth and inflammatory response in the acidic microenvironment.
Development Status of Accident Tolerant Fuels for Light Water Reactors in Korea

Energy Technology Data Exchange (ETDEWEB)

Yang, Jae Ho; Kim, Hyun Gil; In, Wang Kee; Kim, Weon Ju; Koo, Yang Hyum [KAERI, Daejeon (Korea, Republic of); Lee, Seung Jae [KEPCONF, Daejeon (Korea, Republic of)

2016-05-15

Research on accident tolerant fuels (ATFs) is aimed at developing innovative fuels, which can mitigate or prevent the consequences of accidents. In Korea, innovative concepts are being developed to improve fuel safety and reliability of LWRs during accident events and normal operations. ATF technologies will be developed and commercialized through a sequence of long-lead and extensive activities. The interim milestone for new fuel program is that we would be ready for an irradiation test in commercial reactor by 2021. This presentation deals with the status of ATF development in KOREA and plan to implement new fuel technology successfully in commercial nuclear power plants.
78 FR 2441 - Agency Information Collection Activities: Proposed Collection; Comments Requested; Report of Lost...

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2013-01-11

... Stolen ATF F 5400.30, Intrastate Purchase of Explosives Coupon ACTION: 30-Day notice. The Department of... and assumptions used; --Enhance the quality, utility, and clarity of the information to be collected... collection. (2) Title of the Form/Collection: Report of Stolen or Lost ATF F 5400.30, Intrastate Purchase of...
Unique properties of multiple tandem copies of the M26 recombination hotspot in mitosis and meiosis in Schizosaccharomyces pombe.

Science.gov (United States)

Steiner, Walter W; Recor, Chelsea L; Zakrzewski, Bethany M

2016-11-15

The M26 hotspot of the fission yeast Schizosaccharomyces pombe is one of the best-characterized eukaryotic hotspots of recombination. The hotspot requires a seven bp sequence, ATGACGT, that serves as a binding site for the Atf1-Pcr1 transcription factor, which is also required for activity. The M26 hotspot is active in meiosis but not mitosis and is active in some but not all chromosomal contexts and not on a plasmid. A longer palindromic version of M26, ATGACGTCAT, shows significantly greater activity than the seven bp sequence. Here, we tested whether the properties of the seven bp sequence were also true of the longer sequence by placing one, two, or three copies of the sequence into the ade6 gene, where M26 was originally discovered. These constructs were tested for activity when located on a plasmid or on a chromosome in mitosis and meiosis. We found that two copies of the 10bp M26 motif on a chromosome were significantly more active for meiotic recombination than one, but no further increase was observed with three copies. However, three copies of M26 on a chromosome created an Atf1-dependent mitotic recombination hotspot. When located on a plasmid, M26 also appears to behave as a mitotic recombination hotspot; however, this behavior most likely results from Atf1-dependent inter-allelic complementation between the plasmid and chromosomal ade6 alleles. Copyright © 2016 Elsevier B.V. All rights reserved.
Proteolysis of MDA5 and IPS-1 is not required for inhibition of the type I IFN response by poliovirus.

Science.gov (United States)

Kotla, Swathi; Gustin, Kurt E

2015-10-06

The type I interferon (IFN) response is a critical component of the innate immune response to infection by RNA viruses and is initiated via recognition of viral nucleic acids by RIG-like receptors (RLR). Engagement of these receptors in the cytoplasm initiates a signal transduction pathway leading to activation of the transcription factors NF-κB, ATF-2 and IRF-3 that coordinately upregulate transcription of type I IFN genes, such as that encoding IFN-β. In this study the impact of poliovirus infection on the type I interferon response has been examined. The type I IFN response was assessed by measuring IFN-β mRNA levels using qRT-PCR and normalizing to levels of β-actin mRNA. The status of host factors involved in activation of the type I IFN response was examined by immunoblot, immunofluorescence microcopy and qRT-PCR. The results show that poliovirus infection results in induction of very low levels of IFN-β mRNA despite clear activation of NF-κB and ATF-2. In contrast, analysis of IRF-3 revealed no transcriptional induction of an IRF-3-responsive promoter or homodimerization of IRF-3 indicating it is not activated in poliovirus-infected cells. Exposure of poliovirus-infected cells to poly(I:C) results in lower levels of IFN-β mRNA synthesis and IRF-3 activation compared to mock-infected cells. Analysis of MDA-5 and IPS-1 revealed that these components of the RLR pathway were largely intact at times when the type I IFN response was suppressed. Collectively, these results demonstrate that poliovirus infection actively suppresses the host type I interferon response by blocking activation of IRF-3 and suggests that this is not mediated by cleavage of MDA-5 or IPS-1.

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)

2016-09-01

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 (TF1) includes definition of evaluation metrics for ATF, technology readiness level definition, definition of illustrative scenarios for ATF evaluation, and identification of fuel performance and system codes applicable to ATF evaluation. The Cladding and Core Materials (TF2) and Fuel Concepts (TF3) 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 (Idaho National Laboratory [INL], U.S.), the Cladding Task Force is chaired by Marie Moatti (Electricite de France [EdF], France), and the Fuels Task Force is chaired by a Masaki Kurata (Japan Atomic Energy Agency [JAEA], Japan). The original Expert Group mandate was established for June 2014 to June 2016. In April 2016 the Expert Group voted to extend the mandate one additional year to June 2017 in order to complete the task force deliverables; this request was subsequently approved by the Nuclear Science Committee. This
Status Report on Activities of the Systems Assessment Task Force, OECD-NEA Expert Group on Accident Tolerant Fuels for LWRs

International Nuclear Information System (INIS)

Bragg-Sitton, Shannon Michelle

2016-01-01

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 (TF1) includes definition of evaluation metrics for ATF, technology readiness level definition, definition of illustrative scenarios for ATF evaluation, and identification of fuel performance and system codes applicable to ATF evaluation. The Cladding and Core Materials (TF2) and Fuel Concepts (TF3) 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 (Idaho National Laboratory [INL], U.S.), the Cladding Task Force is chaired by Marie Moatti (Electricite de France [EdF], France), and the Fuels Task Force is chaired by a Masaki Kurata (Japan Atomic Energy Agency [JAEA], Japan). The original Expert Group mandate was established for June 2014 to June 2016. In April 2016 the Expert Group voted to extend the mandate one additional year to June 2017 in order to complete the task force deliverables; this request was subsequently approved by the Nuclear Science Committee. This
Anti-inflammatory and anti-cancer activity of mulberry (Morus alba L.) root bark

Science.gov (United States)

2014-01-01

Background Root bark of mulberry (Morus alba L.) has been used in herbal medicine as anti-phlogistic, liver protective, kidney protective, hypotensive, diuretic, anti-cough and analgesic agent. However, the anti-cancer activity and the potential anti-cancer mechanisms of mulberry root bark have not been elucidated. We performed in vitro study to investigate whether mulberry root bark extract (MRBE) shows anti-inflammatory and anti-cancer activity. Methods In anti-inflammatory activity, NO was measured using the griess method. iNOS and proteins regulating NF-κB and ERK1/2 signaling were analyzed by Western blot. In anti-cancer activity, cell growth was measured by MTT assay. Cleaved PARP, ATF3 and cyclin D1 were analyzed by Western blot. Results In anti-inflammatory effect, MRBE blocked NO production via suppressing iNOS over-expression in LPS-stimulated RAW264.7 cells. In addition, MRBE inhibited NF-κB activation through p65 nuclear translocation via blocking IκB-α degradation and ERK1/2 activation via its hyper-phosphorylation. In anti-cancer activity, MRBE deos-dependently induced cell growth arrest and apoptosis in human colorectal cancer cells, SW480. MRBE treatment to SW480 cells activated ATF3 expression and down-regulated cyclin D1 level. We also observed that MRBE-induced ATF3 expression was dependent on ROS and GSK3β. Moreover, MRBE-induced cyclin D1 down-regulation was mediated from cyclin D1 proteasomal degradation, which was dependent on ROS. Conclusions These findings suggest that mulberry root bark exerts anti-inflammatory and anti-cancer activity. PMID:24962785
Cavity beam position monitor system for the Accelerator Test Facility 2

Science.gov (United States)

Kim, Y. I.; Ainsworth, R.; Aryshev, A.; Boogert, S. T.; Boorman, G.; Frisch, J.; Heo, A.; Honda, Y.; Hwang, W. H.; Huang, J. Y.; Kim, E.-S.; Kim, S. H.; Lyapin, A.; Naito, T.; May, J.; McCormick, D.; Mellor, R. E.; Molloy, S.; Nelson, J.; Park, S. J.; Park, Y. J.; Ross, M.; Shin, S.; Swinson, C.; Smith, T.; Terunuma, N.; Tauchi, T.; Urakawa, J.; White, G. R.

2012-04-01

The Accelerator Test Facility 2 (ATF2) is a scaled demonstrator system for final focus beam lines of linear high energy colliders. This paper describes the high resolution cavity beam position monitor (BPM) system, which is a part of the ATF2 diagnostics. Two types of cavity BPMs are used, C-band operating at 6.423 GHz, and S-band at 2.888 GHz with an increased beam aperture. The cavities, electronics, and digital processing are described. The resolution of the C-band system with attenuators was determined to be approximately 250 nm and 1μm for the S-band system. Without attenuation the best recorded C-band cavity resolution was 27 nm.
The unfolded protein response in melanocytes: activation in response to chemical stressors of the endoplasmic reticulum and tyrosinase misfolding.

Science.gov (United States)

Manga, Prashiela; Bis, Sabina; Knoll, Kristen; Perez, Beremis; Orlow, Seth J

2010-10-01

Accumulation of proteins in the endoplasmic reticulum (ER) triggers the unfolded protein response (UPR), comprising three signaling pathways initiated by Ire1, Perk and Atf6 respectively. Unfolded protein response activation was compared in chemically stressed murine wildtype melanocytes and mutant melanocytes that retain tyrosinase in the ER. Thapsigargin, an ER stressor, activated all pathways in wildtype melanocytes, triggering Caspase 12-mediated apoptosis at toxic doses. Albino melanocytes expressing mutant tyrosinase showed evidence of ER stress with increased Ire1 expression, but the downstream effector, Xbp1, was not activated even following thapsigargin treatment. Attenuation of Ire1 signaling was recapitulated in wildtype melanocytes treated with thapsigargin for 8 days, with diminished Xbp1 activation observed after 4 days. Atf6 was also activated in albino melanocytes, with no response to thapsigargin, while the Perk pathway was not activated and thapsigargin treatment elicited robust expression of the downstream effector CCAAT-enhancer-binding protein homologous protein. Thus, melanocytes adapt to ER stress by attenuating two UPR pathways.
Dynamics of r.f. production of Stellarator plasmas in the ion cyclotron range of frequency

International Nuclear Information System (INIS)

Moiseenko, V.E.; Lysoivan, A.I.; Kasilov, S.V.; Plyusnin, V.V.

1995-01-01

The present study investigated numerically the process of r.f. production of plasma in the URAGAN-3M torsatron in the frequency range below the ion cyclotron frequency (ω ci ). The dynamics of r.f. plasma build-up at the stages of neutral gas burnout and plasma heating were studied using a zero-dimensional transport code, in which the plasma confinement law was determined by large helical device scaling. Two models for input r.f. power were used. In the first case, the r.f. power absorbed by the electrons was computed by a one-dimensional r.f. code solving Maxwell's boundary problem equations. The mechanisms of electron heating through direct excitation of the slow wave (SW) by antennae as well as the conversion of fast wave (FW) into SW in the vicinity of Alfven resonance (scenario of Alfven heating) were taken into account in the computations. In the second case, an 'ideal' model of r.f. power deposition onto the electrons as a linear function of plasma density was employed. A noticeable difference in plasma production dynamics computed for these two cases was found. Better agreement with experimental data obtained from the URAGAN-3M torsatron was found for the first case resulting from combination of the one-dimensional r.f. and zero-dimensional transport codes. ((orig.))
Activating transcription factor 3 promotes loss of the acinar cell phenotype in response to cerulein-induced pancreatitis in mice.

Science.gov (United States)

Fazio, Elena N; Young, Claire C; Toma, Jelena; Levy, Michael; Berger, Kurt R; Johnson, Charis L; Mehmood, Rashid; Swan, Patrick; Chu, Alphonse; Cregan, Sean P; Dilworth, F Jeffrey; Howlett, Christopher J; Pin, Christopher L

2017-09-01

Pancreatitis is a debilitating disease of the exocrine pancreas that, under chronic conditions, is a major susceptibility factor for pancreatic ductal adenocarcinoma (PDAC). Although down-regulation of genes that promote the mature acinar cell fate is required to reduce injury associated with pancreatitis, the factors that promote this repression are unknown. Activating transcription factor 3 (ATF3) is a key mediator of the unfolded protein response, a pathway rapidly activated during pancreatic insult. Using chromatin immunoprecipitation followed by next-generation sequencing, we show that ATF3 is bound to the transcriptional regulatory regions of >30% of differentially expressed genes during the initiation of pancreatitis. Of importance, ATF3-dependent regulation of these genes was observed only upon induction of pancreatitis, with pathways involved in inflammation, acinar cell differentiation, and cell junctions being specifically targeted. Characterizing expression of transcription factors that affect acinar cell differentiation suggested that acinar cells lacking ATF3 maintain a mature cell phenotype during pancreatitis, a finding supported by maintenance of junctional proteins and polarity markers. As a result, Atf3 -/- pancreatic tissue displayed increased tissue damage and inflammatory cell infiltration at early time points during injury but, at later time points, showed reduced acinar-to-duct cell metaplasia. Thus our results reveal a critical role for ATF3 as a key regulator of the acinar cell transcriptional response during injury and may provide a link between chronic pancreatitis and PDAC. © 2017 Fazio et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
Pramana – Journal of Physics | Indian Academy of Sciences

Indian Academy of Sciences (India)

... (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.
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.
The BNL Accelerator Test Facility and experimental program

International Nuclear Information System (INIS)

Ben-Zvi, I.; State Univ. of New York, Stony Brook, NY

1992-01-01

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 MeV by two traveling wave accelerator sections. The lasers include a 10 mJ, 10 ps ND:YAG laser and a 500 mJ, 10 to 100 ps C0 2 laser. A number of users from National Laboratories, universities and industry take part in experiments at the ATF. The experimental program includes various laser acceleration schemes, Free-Electron Laser experiments and a program on the development of high-brightness electron beams. The ATF'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
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....
Beam based alignment at the KEK accelerator test facility

International Nuclear Information System (INIS)

Ross, M.; Nelson, J.; Woodley, M.; Wolski, A.

2002-01-01

The KEK Accelerator Test Facility (ATF) damping ring is a prototype low emittance source for the NLC/JLC linear collider. To achieve the goal normalized vertical emittance gey = 20 nm-rad, magnet placement accuracy better than 30 mm must be achieved. Accurate beam-based alignment (BBA) is required. The ATF arc optics uses a FOBO cell with two horizontally focusing quadrupoles, two sextupoles and a horizontally defocusing gradient dipole, all of which must be aligned with BBA. BBA at ATF uses the quadrupole and sextupole trim windings to find the trajectory through the center of each magnet. The results can be interpreted to assess the accuracy of the mechanical alignment and the beam position monitor offsets
Improving Accident Tolerance of Nuclear Fuel with Coated Mo-alloy Cladding

Directory of Open Access Journals (Sweden)

Bo Cheng

2016-02-01

Full Text Available In severe loss of coolant accidents (LOCA, similar to those experienced at Fukushima Daiichi and Three Mile Island Unit 1, the zirconium alloy fuel cladding materials are rapidly heated due to nuclear decay heating and rapid exothermic oxidation of zirconium with steam. This heating causes the cladding to rapidly react with steam, lose strength, burst or collapse, and generate large quantities of hydrogen gas. Although maintaining core cooling remains the highest priority in accident management, an accident tolerant fuel (ATF design may extend coping and recovery time for operators to restore emergency power, and cooling, and achieve safe shutdown. An ATF is required to possess high resistance to steam oxidation to reduce hydrogen generation and sufficient mechanical strength to maintain fuel rod integrity and core coolability. The initiative undertaken by Electric Power Research Institute (EPRI is to demonstrate the feasibility of developing an ATF cladding with capability to maintain its integrity in 1,200–1,500°C steam for at least 24 hours. This ATF cladding utilizes thin-walled Mo-alloys coated with oxidation-resistant surface layers. The basic design consists of a thin-walled Mo alloy structural tube with a metallurgically bonded, oxidation-resistant outer layer. Two options are being investigated: a commercially available iron, chromium, and aluminum alloy with excellent high temperature oxidation resistance, and a Zr alloy with demonstrated corrosion resistance. As these composite claddings will incorporate either no Zr, or thin Zr outer layers, hydrogen generation under severe LOCA conditions will be greatly reduced. Key technical challenges and uncertainties specific to Mo alloy fuel cladding include: economic core design, industrial scale fabricability, radiation embrittlement, and corrosion and oxidation resistance during normal operation, transients, and severe accidents. Progress in each aspect has been made and key results are
Hypothesis for the mechanics and seismic behaviour of low-angle normal faults: the example of the Altotiberina fault Northern Apennines

Directory of Open Access Journals (Sweden)

C. Collettini

2002-06-01

Full Text Available Widespread mapping of low-angle normal faults in areas of former continental extension continues to prompt debate as to whether such structures may be seismically active at very low dips (? <30 °in the upper continental crust.The Northern Apennines provide an example where an active low-angle normal fault (Altotiberina fault, ATFcan be studied.A set of commercial seismic reflection profiles plus deep boreholes have been used to constrain the geometry of the fault at depth.These data have been integrated with a microseismic survey showing that part of the microseismicity (M <3.0is consistent with the geometry of the ATF as imaged by depth converted seismic reflection profiles.Frictional fault mechanics under Byerlee ?s friction coefficient and vertical ? 1 (constrained from the inversion of the focal mechanismsdefines the peculiar condition for reactivation of the ATF:small values of differential stress,? 1 ?? 3 <28 MPa,relatively high value of tensile strength of the fault surrounding rocks (T ~10 MPaand tensile fluid overpressure P f >? 3 (i.e.? v >0.93.The short-lived attainment of P f >? 3 along small fault portions,in an area characterised by large amounts of CO2,account for the microseismic activity located along the ATF,which occurs on rupture surfaces in the range of 10 ??10 ? 3 km 2..
Upregulation of the coagulation factor VII gene during glucose deprivation is mediated by activating transcription factor 4.

Science.gov (United States)

Cronin, Katherine R; Mangan, Thomas P; Carew, Josephine A

2012-01-01

Constitutive production of blood coagulation proteins by hepatocytes is necessary for hemostasis. Stressful conditions trigger adaptive cellular responses and delay processing of most proteins, potentially affecting plasma levels of proteins secreted exclusively by hepatocytes. We examined the effect of glucose deprivation on expression of coagulation proteins by the human hepatoma cell line, HepG2. Expression of coagulation factor VII, which is required for initiation of blood coagulation, was elevated by glucose deprivation, while expression of other coagulation proteins decreased. Realtime PCR and ELISA demonstrated that the relative percentage expression +/- SD of steady-state F7 mRNA and secreted factor VII antigen were significantly increased (from 100+/-15% to 188+/-27% and 100+/-8.8% to 176.3+/-17.3% respectively, pfactor ATF4 and of additional stress-responsive genes. Small interfering RNAs directed against ATF4 potently reduced basal F7 expression, and prevented F7 upregulation by glucose deprivation. The response of the endogenous F7 gene was replicated in reporter gene assays, which further indicated that ATF4 effects were mediated via interaction with an amino acid response element in the F7 promoter. Our data indicated that glucose deprivation enhanced F7 expression in a mechanism reliant on prior ATF4 upregulation primarily due to increased transcription from the ATF4 gene. Of five coagulation protein genes examined, only F7 was upregulated, suggesting that its functions may be important in a systemic response to glucose deprivation stress.
A Taiwanese Propolis Derivative Induces Apoptosis through Inducing Endoplasmic Reticular Stress and Activating Transcription Factor-3 in Human Hepatoma Cells

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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.
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)

Arana, Maite Rocío; Tocchetti, Guillermo Nicolás; Domizi, Pablo; Arias, Agostina; Rigalli, Juan Pablo; Ruiz, María Laura

2015-01-01

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
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
Cavity beam position monitor system for the Accelerator Test Facility 2

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Y. I. Kim

2012-04-01

Full Text Available The Accelerator Test Facility 2 (ATF2 is a scaled demonstrator system for final focus beam lines of linear high energy colliders. This paper describes the high resolution cavity beam position monitor (BPM system, which is a part of the ATF2 diagnostics. Two types of cavity BPMs are used, C-band operating at 6.423 GHz, and S-band at 2.888 GHz with an increased beam aperture. The cavities, electronics, and digital processing are described. The resolution of the C-band system with attenuators was determined to be approximately 250 nm and 1 μm for the S-band system. Without attenuation the best recorded C-band cavity resolution was 27 nm.
MHD kink-driven instabilities in net-current-free stellarators

International Nuclear Information System (INIS)

Rewoldt, G.; Johnson, J.L.

1984-02-01

The Pfirsch-Schlueter current, which is induced in a toroidal device to keep the plasma current diverence-free, is shown to drive a free-boundary instability in a model of a net-current-free ATF-1 stellarator if = 2.6%

Report from the ATLAS Architecture TaskForce

CERN Document Server

Haywood, S

1999-01-01

In this report, the activities and conclusions of the ATLAS Architecture TaskForce (ATF) are summarised. A key part of the ATF's work has been the first attempt at a design of the global architecture for the ATLAS Offline Software. This is contained in this document and an auxillary report and should lead to a realisation of the ATLAS Framework.
RFX Transcription Factor DAF-19 Regulates 5-HT and Innate Immune Responses to Pathogenic Bacteria in Caenorhabditis elegans

Science.gov (United States)

Choi, Sunju; Xu, Lu; Sze, Ji Ying

2013-01-01

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/Ca2+/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. PMID:23505381
On a possibility of operating the ''Vint-20'' one-cut torsatron as a β approximately 1 stellarator

International Nuclear Information System (INIS)

Vojtsenya, V.S.

1975-01-01

Magnetic configuration of one-way thorsatron VINT-20 is investigated as regards of satisfying the conditions required for the equilibrium of plasma featuring high β (herein β = (nk(Tsub(i) + Tsub(e))/(Bsub(0)sup(2)/18π)). It is revealed that in certain modes which are elaborated at great lateral fields (Bsub(2)/Bsub(0) = -7.5 %), the shape of magnetic surfaces satisfies the requirements to the equilibrium configuration. Values β as estimated from the parameters of the magnetic surface in these favourable modes reach 0.8
Development and Testing of Atomic Beam-Based Plasma Edge Diagnostics in the CIEMAT Fusion Devices

International Nuclear Information System (INIS)

Tafalla, D.; Tabares, F.L.; Ortiz, P.; Herrero, V.J.; Tanarro, I.

1998-01-01

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
Cyclic adenosine 3',5'-monophosphate (cAMP) enhances cAMP-responsive element binding (CREB) protein phosphorylation and phospho-CREB interaction with the mouse steroidogenic acute regulatory protein gene promoter.

Science.gov (United States)

Clem, Brian F; Hudson, Elizabeth A; Clark, Barbara J

2005-03-01

Steroidogenic acute regulatory protein (StAR) transcription is regulated through cAMP-protein kinase A-dependent mechanisms that involve multiple transcription factors including the cAMP-responsive element binding protein (CREB) family members. Classically, binding of phosphorylated CREB to cis-acting cAMP-responsive elements (5'-TGACGTCA-3') within target gene promoters leads to recruitment of the coactivator CREB binding protein (CBP). Herein we examined the extent of CREB family member phosphorylation on protein-DNA interactions and CBP recruitment with the StAR promoter. Immunoblot analysis revealed that CREB, cAMP-responsive element modulator (CREM), and activating transcription factor (ATF)-1 are expressed in MA-10 mouse Leydig tumor cells, yet only CREB and ATF-1 are phosphorylated. (Bu)2cAMP treatment of MA-10 cells increased CREB phosphorylation approximately 2.3-fold within 30 min but did not change total nuclear CREB expression levels. Using DNA-affinity chromatography, we now show that CREB and ATF-1, but not CREM, interact with the StAR promoter, and this interaction is dependent on the activator protein-1 (AP-1) cis-acting element within the cAMP-responsive region. In addition, (Bu)2cAMP-treatment increased phosphorylated CREB (P-CREB) association with the StAR promoter but did not influence total CREB interaction. In vivo chromatin immunoprecipitation assays demonstrated CREB binding to the StAR proximal promoter is independent of (Bu)2cAMP-treatment, confirming our in vitro analysis. However, (Bu)2cAMP-treatment increased P-CREB and CBP interaction with the StAR promoter, demonstrating for the first time the physical role of P-CREB:DNA interactions in CBP recruitment to the StAR proximal promoter.
Fast Extraction Kicker for the Accelerator Test Facility

International Nuclear Information System (INIS)

De Santis, Stefano; Urakawa, Junji; Naito, Takashi

2007-01-01

We present the results of a study for the design of a fast extraction kicker to be installed in the Accelerator Test Facility ring at KEK. This activity is carried on in the framework of the ATF2 project, which will be built on the KEK Tsukuba campus as an extension of the existing ATF, taking advantage of the worlds smallest normalized emittance achieved there. ATF2's primary goal is to operate as a test facility and establish the hardware and beam handling technologies envisaged for the International Linear Collider. In particular, the fast extraction kicker object of the present paper is an important component of the ILC damping rings, since its rise and fall time define the minimum distance between bunches and ultimately the damping rings length itself. Building on the initial results presented at EPAC '06, we report on the present status of the kicker design and define the minimum characteristics for pulsers and other subsystems. In addition to the original scheme with multiple stripline modules producing a total deflection of 5 mrad, we also investigated a scheme with a single kicker module for a reduced deflection of 1 mrad placed inside a closed orbit bump, which takes the electron closer to the extraction septum
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.
APOE genotype-function relationship: evidence of -491 A/T promoter polymorphism modifying transcription control but not type 2 diabetes risk.

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Hua Geng

Full Text Available BACKGROUND: The apolipoprotein E gene (APOE coding polymorphism modifies the risks of Alzheimer's disease, type 2 diabetes, and coronary heart disease. Aside from the coding variants, single nucleotide polymorphism (SNP of the APOE promoter has also been shown to modify the risk of Alzheimer's disease. METHODOLOGY/PRINCIPAL FINDINGS: In this study we investigate the genotype-function relationship of APOE promoter polymorphism at molecular level and at physiological level: i.e., in transcription control of the gene and in the risk of type 2 diabetes. In molecular studies, the effect of the APOE -491A/T (rs449647 polymorphism on gene transcription was accessed by dual-luciferase reporter gene assays. The -491 A to T substitution decreased the activity (p<0.05 of the cloned APOE promoter (-1017 to +406. Using the -501 to -481 nucleotide sequence of the APOE promoter as a 'bait' to screen the human brain cDNA library by yeast one-hybrid system yielded ATF4, an endoplasmic reticulum stress response gene, as one of the interacting factors. Electrophoretic-mobility-shift assays (EMSA and chromatin immuno-precipitation (ChIP analyses further substantiated the physical interaction between ATF4 and the APOE promoter. Over-expression of ATF4 stimulated APOE expression whereas siRNA against ATF4 suppressed the expression of the gene. However, interaction between APOE promoter and ATF4 was not -491A/T-specific. At physiological level, the genotype-function relationship of APOE promoter polymorphism was studied in type 2 diabetes. In 630 cases and 595 controls, three APOE promoter SNPs -491A/T, -219G/T (rs405509, and +113G/C (rs440446 were genotyped and tested for association with type 2 diabetes in Hong Kong Chinese. No SNP or haplotype association with type 2 diabetes was detected. CONCLUSIONS/SIGNIFICANCE: At molecular level, polymorphism -491A/T and ATF4 elicit independent control of APOE gene expression. At physiological level, no genotype
Prevention of Paclitaxel-induced allodynia by Minocycline: Effect on loss of peripheral nerve fibers and infiltration of macrophages in rats

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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
Identification of Noncanonical Wnt Receptors Required for Wnt-3a-Induced Early Differentiation of Human Neural Stem Cells.

Science.gov (United States)

Bengoa-Vergniory, Nora; Gorroño-Etxebarria, Irantzu; López-Sánchez, Inmaculada; Marra, Michele; Di Chiaro, Pierluigi; Kypta, Robert

2017-10-01

Wnt proteins preferentially activate either β-catenin-dependent or β-catenin-independent signals, but the activity of a particular Wnt also depends on cellular context and receptor availability. We previously reported that Wnt-3a induces neural differentiation of human embryonic stem cell-derived neural stem cells (NSCs) in a β-catenin-independent manner by activating a signal involving JNK and the AP-1 family member ATF-2. Here, we report the results of a gene silencing approach to identify the Wnt receptors that mediate this response to Wnt-3a. Silencing of ROR2 increased neuronal differentiation, as measured by expression of the genes DCX, NEUROD1, and NGN1, suggesting ROR2 signals normally prevent differentiation. Silencing of the other Wnt receptors singly did not affect Wnt-3a-induced neuronal differentiation. However, pairwise silencing of ROR1 and FZD4 or FZD5 and of LRP6 and FZD4 or FZD5 inhibited neuronal differentiation, as detected by reductions in the expression of neuronal genes and immunocytochemical detection of DCX, NEUROD1 and DCX. Ectopic expression of these receptors in HEK 293 cells increased ATF2-dependent transcription. In addition, ROR1 coimmunoprecipitated with FZD4 and LRP6 in transfected HEK 293 cells and colocalized with FZD4 and with LRP6 at the cell surface of transfected L cells. Wnt-3a did not appear to affect these interactions but did alter the interactions between LRP6 and FZD4/5. Together, these observations highlight roles for ROR1, LRP6, FZD4, and FZD5 in neural stem cell differentiation and provide support for a model in which dynamic interactions among these receptors mediate Wnt-3a activation of ATF2 signaling.
78 FR 6765 - Amendment to the International Traffic in Arms Regulations: Revision of U.S. Munitions List...

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2013-01-31

... articles on the USML that are controlled by the Bureau of Alcohol, Tobacco, Firearms and Explosives (ATF... category); (22) Radomes, sensor windows, and antenna windows ``specially designed'' for articles enumerated...)(1) of this category and for any radomes, sensor windows, or antenna windows manufactured as...
ELANE mutant-specific activation of different UPR pathways in congenital neutropenia.

Science.gov (United States)

Nustede, Rainer; Klimiankou, Maksim; Klimenkova, Olga; Kuznetsova, Inna; Zeidler, Cornelia; Welte, Karl; Skokowa, Julia

2016-01-01

A number of studies have demonstrated induction of the unfolded protein response (UPR) in patients with severe congenital neutropenia (CN) harbouring mutations of ELANE, encoding neutrophil elastase. Why UPR is not activated in patients with cyclic neutropenia (CyN) carrying the same ELANE mutations is unclear. We evaluated the effects of ELANE mutants on UPR induction in myeloid cells from CN and CyN patients, and analysed whether additional CN-specific defects contribute to the differences in UPR induction between CN and CyN patients harbouring identical ELANE mutations. We investigated CN-specific p.C71R and p.V174_C181del (NP_001963.1) and CN/CyN-shared p.S126L (NP_001963.1) ELANE mutants. We found that transduction of haematopoietic cells with p.C71R, but not with p.V174_C181del or p.S126L ELANE mutants induced expression of ATF6, and the ATF6 target genes PPP1R15A, DDIT3 and HSPA5. Recently, we found that levels of secretory leucocyte protease inhibitor (SLPI), a natural ELANE inhibitor, are diminished in myeloid cells from CN patients, but not CyN patients. Combined knockdown of SLPI by shRNA and transduction of ELANE p.S126L in myeloid cells led to elevated levels of ATF6, PPP1R15A and HSPA5 RNA, suggesting that normal levels of SLPI in CyN patients might protect them from the UPR induced by mutant ELANE. In summary, different ELANE mutants have different effects on UPR activation, and SLPI regulates the extent of ELANE-triggered UPR. © 2015 John Wiley & Sons Ltd.
Establishment of a novel clear cell sarcoma cell line (Hewga-CCS), and investigation of the antitumor effects of pazopanib on Hewga-CCS.

Science.gov (United States)

Outani, Hidetatsu; Tanaka, Takaaki; Wakamatsu, Toru; Imura, Yoshinori; Hamada, Kenichiro; Araki, Nobuhito; Itoh, Kazuyuki; Yoshikawa, Hideki; Naka, Norifumi

2014-06-19

Clear cell sarcoma (CCS) is a therapeutically unresolved, aggressive, soft tissue sarcoma (STS) that predominantly affects young adults. This sarcoma is defined by t(12;22)(q13;q12) translocation, which leads to the fusion of Ewing sarcoma gene (EWS) to activating transcription factor 1 (ATF1) gene, producing a chimeric EWS-ATF1 fusion gene. We established a novel CCS cell line called Hewga-CCS and developed an orthotopic tumor xenograft model to enable comprehensive bench-side investigation for intensive basic and preclinical research in CCS with a paucity of experimental cell lines. Hewga-CCS was derived from skin metastatic lesions of a CCS developed in a 34-year-old female. The karyotype and chimeric transcript were analyzed. Xenografts were established and characterized by morphology and immunohistochemical reactivity. Subsequently, the antitumor effects of pazopanib, a recently approved, novel, multitargeted, tyrosine kinase inhibitor (TKI) used for the treatment of advanced soft tissue sarcoma, on Hewga-CCS were assessed in vitro and in vivo. Hewga-CCS harbored the type 2 EWS-ATF1 transcript. Xenografts morphologically mimicked the primary tumor and expressed S-100 protein and antigens associated with melanin synthesis (Melan-A, HMB45). Pazopanib suppressed the growth of Hewga-CCS both in vivo and in vitro. A phospho-receptor tyrosine kinase array revealed phosphorylation of c-MET, but not of VEGFR, in Hewga-CCS. Subsequent experiments showed that pazopanib exerted antitumor effects through the inhibition of HGF/c-MET signaling. CCS is a rare, devastating disease, and our established CCS cell line and xenograft model may be a useful tool for further in-depth investigation and understanding of the drug-sensitivity mechanism.
Glutathione Peroxidase-1 Suppresses the Unfolded Protein Response upon Cigarette Smoke Exposure

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Patrick Geraghty

2016-01-01

Full Text Available Oxidative stress provokes endoplasmic reticulum (ER stress-induced unfolded protein response (UPR in the lungs of chronic obstructive pulmonary (COPD subjects. The antioxidant, glutathione peroxidase-1 (GPx-1, counters oxidative stress induced by cigarette smoke exposure. Here, we investigate whether GPx-1 expression deters the UPR following exposure to cigarette smoke. Expression of ER stress markers was investigated in fully differentiated normal human bronchial epithelial (NHBE cells isolated from nonsmoking, smoking, and COPD donors and redifferentiated at the air liquid interface. NHBE cells from COPD donors expressed heightened ATF4, XBP1, GRP78, GRP94, EDEM1, and CHOP compared to cells from nonsmoking donors. These changes coincided with reduced GPx-1 expression. Reintroduction of GPx-1 into NHBE cells isolated from COPD donors reduced the UPR. To determine whether the loss of GPx-1 expression has a direct impact on these ER stress markers during smoke exposure, Gpx-1−/− mice were exposed to cigarette smoke for 1 year. Loss of Gpx-1 expression enhanced cigarette smoke-induced ER stress and apoptosis. Equally, induction of ER stress with tunicamycin enhanced antioxidant expression in mouse precision-cut lung slices. Smoke inhalation also exacerbated the UPR response during respiratory syncytial virus infection. Therefore, ER stress may be an antioxidant-related pathophysiological event in COPD.
Paleoseismology of the Xorxol Segment of the Central Altyn Tagh Fault, Xinjiang, China

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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.
Drug-Induced HSP90 Inhibition Alleviates Pain in Monoarthritic Rats and Alters the Expression of New Putative Pain Players at the DRG.

Science.gov (United States)

Nascimento, Diana Sofia Marques; Potes, Catarina Soares; Soares, Miguel Luz; Ferreira, António Carlos; Malcangio, Marzia; Castro-Lopes, José Manuel; Neto, Fani Lourença Moreira

2018-05-01

Purinergic receptors (P2XRs) have been widely associated with pain states mostly due to their involvement in neuron-glia communication. Interestingly, we have previously shown that satellite glial cells (SGC), surrounding dorsal root ganglia (DRG) neurons, become activated and proliferate during monoarthritis (MA) in the rat. Here, we demonstrate that P2X7R expression increases in ipsilateral DRG after 1 week of disease, while P2X3R immunoreactivity decreases. We have also reported a significant induction of the activating transcriptional factor 3 (ATF3) in MA. In this study, we show that ATF3 knocked down in DRG cell cultures does not affect the expression of P2X7R, P2X3R, or glial fibrillary acidic protein (GFAP). We suggest that P2X7R negatively regulates P2X3R, which, however, is unlikely mediated by ATF3. Interestingly, we found that ATF3 knockdown in vitro induced significant decreases in the heat shock protein 90 (HSP90) expression. Thus, we evaluated in vivo the involvement of HSP90 in MA and demonstrated that the HSP90 messenger RNA levels increase in ipsilateral DRG of inflamed animals. We also show that HSP90 is mostly found in a cleaved form in this condition. Moreover, administration of a HSP90 inhibitor, 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), attenuated MA-induced mechanical allodynia in the first hours. The drug also reversed the HSP90 upregulation and cleavage. 17-DMAG seemed to attenuate glial activation and neuronal sensitization (as inferred by downregulation of GFAP and P2X3R in ipsilateral DRG) which might correlate with the observed pain alleviation. Our data indicate a role of HSP90 in MA pathophysiology, but further investigation is necessary to clarify the underlying mechanisms.
The Drosophila MAPK p38c regulates oxidative stress and lipid homeostasis in the intestine.

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Sveta Chakrabarti

2014-09-01

Full Text Available The p38 mitogen-activated protein (MAP kinase signaling cassette has been implicated in stress and immunity in evolutionarily diverse species. In response to a wide variety of physical, chemical and biological stresses p38 kinases phosphorylate various substrates, transcription factors of the ATF family and other protein kinases, regulating cellular adaptation to stress. The Drosophila genome encodes three p38 kinases named p38a, p38b and p38c. In this study, we have analyzed the role of p38c in the Drosophila intestine. The p38c gene is expressed in the midgut and upregulated upon intestinal infection. We showed that p38c mutant flies are more resistant to infection with the lethal pathogen Pseudomonas entomophila but are more susceptible to the non-pathogenic bacterium Erwinia carotovora 15. This phenotype was linked to a lower production of Reactive Oxygen Species (ROS in the gut of p38c mutants, whereby the transcription of the ROS-producing enzyme Duox is reduced in p38c mutant flies. Our genetic analysis shows that p38c functions in a pathway with Mekk1 and Mkk3 to induce the phosphorylation of Atf-2, a transcription factor that controls Duox expression. Interestingly, p38c deficient flies accumulate lipids in the intestine while expressing higher levels of antimicrobial peptide and metabolic genes. The role of p38c in lipid metabolism is mediated by the Atf3 transcription factor. This observation suggests that p38c and Atf3 function in a common pathway in the intestine to regulate lipid metabolism and immune homeostasis. Collectively, our study demonstrates that p38c plays a central role in the intestine of Drosophila. It also reveals that many roles initially attributed to p38a are in fact mediated by p38c.
The Drosophila MAPK p38c regulates oxidative stress and lipid homeostasis in the intestine.

Science.gov (United States)

Chakrabarti, Sveta; Poidevin, Mickaël; Lemaitre, Bruno

2014-09-01

The p38 mitogen-activated protein (MAP) kinase signaling cassette has been implicated in stress and immunity in evolutionarily diverse species. In response to a wide variety of physical, chemical and biological stresses p38 kinases phosphorylate various substrates, transcription factors of the ATF family and other protein kinases, regulating cellular adaptation to stress. The Drosophila genome encodes three p38 kinases named p38a, p38b and p38c. In this study, we have analyzed the role of p38c in the Drosophila intestine. The p38c gene is expressed in the midgut and upregulated upon intestinal infection. We showed that p38c mutant flies are more resistant to infection with the lethal pathogen Pseudomonas entomophila but are more susceptible to the non-pathogenic bacterium Erwinia carotovora 15. This phenotype was linked to a lower production of Reactive Oxygen Species (ROS) in the gut of p38c mutants, whereby the transcription of the ROS-producing enzyme Duox is reduced in p38c mutant flies. Our genetic analysis shows that p38c functions in a pathway with Mekk1 and Mkk3 to induce the phosphorylation of Atf-2, a transcription factor that controls Duox expression. Interestingly, p38c deficient flies accumulate lipids in the intestine while expressing higher levels of antimicrobial peptide and metabolic genes. The role of p38c in lipid metabolism is mediated by the Atf3 transcription factor. This observation suggests that p38c and Atf3 function in a common pathway in the intestine to regulate lipid metabolism and immune homeostasis. Collectively, our study demonstrates that p38c plays a central role in the intestine of Drosophila. It also reveals that many roles initially attributed to p38a are in fact mediated by p38c.
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.
Neoclassical transport and radial electric fields in TJ-K

International Nuclear Information System (INIS)

Rahbarnia, K.; Greiner, F.; Ramisch, M.; Stroth, U.; Greiner, F.

2003-01-01

The neoclassical transport is investigated in the torsatron TJ-K, which is operated with a low-temperature plasma. In the low-collisionality regime neoclassical losses are not intrinsically ambipolar, leading to the formation of a radial electric field which acts on both neoclassical and turbulent transport. This electric field is measured with a combination of Langmuir and emissive probes. The data are compared with the ambipolar electric field calculated with an analytic model. The experimental fields are positive and larger than the calculated ones. Direct losses of the fast electrons might explain this discrepancy. (orig.)

The effect of magnetic field configuration on particle pinch velocity in compact helical system (CHS)

International Nuclear Information System (INIS)

Iguchi, H.; Ida, K.; Yamada, H.

1994-01-01

Radial particle transport has been experimentally studied in the low-aspect-ratio heliotron/torsatron device CHS. A non-diffusive outward particle flow (inverse pinch) is observed in the magnetic configuration with the magnetic axis shifted outward, while an inward pinch, like in tokamaks, is observed with the magnetic axis shifted inward. This change in the direction of anomalous particle flow is not due to the reversal of temperature gradient nor the radial electric field. The observation suggests that the particle pinch velocity is sensitive to the magnetic field structure. (author)
Upregulation of the coagulation factor VII gene during glucose deprivation is mediated by activating transcription factor 4.

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Katherine R Cronin

Full Text Available BACKGROUND: Constitutive production of blood coagulation proteins by hepatocytes is necessary for hemostasis. Stressful conditions trigger adaptive cellular responses and delay processing of most proteins, potentially affecting plasma levels of proteins secreted exclusively by hepatocytes. We examined the effect of glucose deprivation on expression of coagulation proteins by the human hepatoma cell line, HepG2. METHODOLOGY/PRINCIPAL FINDINGS: Expression of coagulation factor VII, which is required for initiation of blood coagulation, was elevated by glucose deprivation, while expression of other coagulation proteins decreased. Realtime PCR and ELISA demonstrated that the relative percentage expression +/- SD of steady-state F7 mRNA and secreted factor VII antigen were significantly increased (from 100+/-15% to 188+/-27% and 100+/-8.8% to 176.3+/-17.3% respectively, p<0.001 at 24 hr of treatment. The integrated stress response was induced, as indicated by upregulation of transcription factor ATF4 and of additional stress-responsive genes. Small interfering RNAs directed against ATF4 potently reduced basal F7 expression, and prevented F7 upregulation by glucose deprivation. The response of the endogenous F7 gene was replicated in reporter gene assays, which further indicated that ATF4 effects were mediated via interaction with an amino acid response element in the F7 promoter. CONCLUSIONS/SIGNIFICANCE: Our data indicated that glucose deprivation enhanced F7 expression in a mechanism reliant on prior ATF4 upregulation primarily due to increased transcription from the ATF4 gene. Of five coagulation protein genes examined, only F7 was upregulated, suggesting that its functions may be important in a systemic response to glucose deprivation stress.
48 CFR 908.7107 - Alcohol.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Alcohol. 908.7107 Section... REQUIRED SOURCES OF SUPPLIES AND SERVICES Acquisition of Special Items 908.7107 Alcohol. (a) This section covers (1) Bureau of Alcohol, Tobacco and Firearms, (ATF), Treasury Department, alcohol regulations...
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...
APETALA 2-domain-containing transcription factors: focusing on abscisic acid and gibberellins antagonism.

Science.gov (United States)

Shu, Kai; Zhou, Wenguan; Yang, Wenyu

2018-02-01

The phytohormones abscisic acid (ABA) and gibberellin (GA) antagonistically mediate diverse plant developmental processes including seed dormancy and germination, root development, and flowering time control, and thus the optimal balance between ABA and GA is essential for plant growth and development. Although more than a half and one century have passed since the initial discoveries of ABA and GA, respectively, the precise mechanisms underlying ABA-GA antagonism still need further investigation. Emerging evidence indicates that two APETALA 2 (AP2)-domain-containing transcription factors (ATFs), ABI4 in Arabidopsis and OsAP2-39 in rice, play key roles in ABA and GA antagonism. These two transcription factors precisely regulate the transcription pattern of ABA and GA biosynthesis or inactivation genes, mediating ABA and GA levels. In this Viewpoint article, we try to shed light on the effects of ATFs on ABA-GA antagonism, and summarize the overlapping but distinct biological functions of these ATFs in the antagonism between ABA and GA. Finally, we strongly propose that further research is needed into the detailed roles of additional numerous ATFs in ABA and GA crosstalk, which will improve our understanding of the antagonism between these two phytohormones. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.
Achiral Mannich-Base Curcumin Analogs Induce Unfolded Protein Response and Mitochondrial Membrane Depolarization in PANC-1 Cells

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Gábor J. Szebeni

2017-10-01

Full Text Available Achiral Mannich-type curcumin analogs have been synthetized and assayed for their cytotoxic activity. The anti-proliferative and cytotoxic activity of curcuminoids has been tested on human non-small-cell lung carcinoma (A549, hepatocellular carcinoma (HepG2 and pancreatic cancer cell line (PANC-1. Based on the highest anti-proliferative activity nine drug candidates were further tested and proved to cause phosphatidylserine exposure as an early sign of apoptosis. Curcumin analogs with the highest apoptotic activity were selected for mechanistic studies in the most sensitive PANC-1 cells. Cytotoxic activity was accompanied by cytostatic effect since curcumin and analogs treatment led to G0/G1 cell cycle arrest. Moreover, cytotoxic effect could be also detected via the accumulation of curcuminoids in the endoplasmic reticulum (ER and the up-regulation of ER stress-related unfolded protein response (UPR genes: HSPA5, ATF4, XBP1, and DDIT3. The activated UPR induced mitochondrial membrane depolarization, caspase-3 activation and subsequent DNA breakdown in PANC-1 cells. Achiral curcumin analogs, C509, C521 and C524 possessed superior, 40-times more potent cytotoxic activity compared to natural dihydroxy-dimetoxycurcumin in PANC-1 cells.
Accessibility of receptor-bound urokinase to type-1 plasminogen activator inhibitor

Energy Technology Data Exchange (ETDEWEB)

Cubellis, M.V.; Andreasen, P.; Ragno, P.; Mayer, M.; Dano, K.; Blasi, F. (Univ. of Copenhagen (Denmark))

1989-07-01

Urokinase plasminogen activator (uPA) interacts with a surface receptor and with specific inhibitors, such as plasminogen activator inhibitor type 1 (PAI-1). These interactions are mediated by two functionally independent domains of the molecule: the catalytic domain (at the carboxyl terminus) and the growth factor domain (at the amino terminus). The authors have now investigated whether PAI-1 can bind and inhibit receptor-bound uPA. Binding of {sup 125}I-labeled ATF (amino-terminal fragment of uPA) to human U937 monocyte-like cells can be competed for by uPA-PAI-1 complexes, but not by PAI-1 alone. Preformed {sup 125}I-labeled uPA-PAI-1 complexes can bind to uPA receptor with the same binding specificity as uPA. PAI-1 also binds to, and inhibits the activity of, receptor-bound uPA in U937 cells, as shown in U937 cells by a caseinolytic plaque assay. Plasminogen activator activity of these cells is dependent on exogenous uPA, is competed for by receptor-binding diisopropyl fluorophosphate-treated uPA, and is inhibited by the addition of PAI-1. In conclusion, in U937 cells the binding to the receptor does not shield uPA from the action of PAI-1. The possibility that in adherent cells a different localization of PAI-1 and uPA leads to protection of uPA from PAI-1 is to be considered.
Regulation of Cancer Cell Responsiveness to Ionizing Radiation Treatment by Cyclic AMP Response Element Binding Nuclear Transcription Factor

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Francesca D’Auria

2017-05-01

Full Text Available Cyclic AMP response element binding (CREB protein is a member of the CREB/activating transcription factor (ATF family of transcription factors that play an important role in the cell response to different environmental stimuli leading to proliferation, differentiation, apoptosis, and survival. A number of studies highlight the involvement of CREB in the resistance to ionizing radiation (IR therapy, demonstrating a relationship between IR-induced CREB family members’ activation and cell survival. Consistent with these observations, we have recently demonstrated that CREB and ATF-1 are expressed in leukemia cell lines and that low-dose radiation treatment can trigger CREB activation, leading to survival of erythro-leukemia cells (K562. On the other hand, a number of evidences highlight a proapoptotic role of CREB following IR treatment of cancer cells. Since the development of multiple mechanisms of resistance is one key problem of most malignancies, including those of hematological origin, it is highly desirable to identify biological markers of responsiveness/unresponsiveness useful to follow-up the individual response and to adjust anticancer treatments. Taking into account all these considerations, this mini-review will be focused on the involvement of CREB/ATF family members in response to IR therapy, to deepen our knowledge of this topic, and to pave the way to translation into a therapeutic context.
Measurements of emittance growth through the achromatic bend at the BNL Accelerator Test Facility

International Nuclear Information System (INIS)

Wang, X.J.; Kehne, D.

1997-07-01

Measurements of emittance growth in a high peak current beam as it passes through an achromatic double bend are summarized. Experiments were performed using the ATF at Brookhaven National Laboratory by X.J. Wang and D. Kehne as a collaboration resulting from the proposal attached at the end of the document. The ATF consists off an RF gun (1 MeV), two sections of linac (40-75 MeV), a diagnostic section immediately following the linac, a 20 degree bend magnet, a variable aperture slit at a high dispersion point, 5 quadrupoles, then another 20 degree bend followed by another diagnostic section. The TRANSPORT deck describing the region from the end of the linac to the end of the diagnostic line following the achromatic bends is attached to the end of this document. Printouts of the control screens are also attached
Achiral Mannich-Base Curcumin Analogs Induce Unfolded Protein Response and Mitochondrial Membrane Depolarization in PANC-1 Cells.

Science.gov (United States)

Szebeni, Gábor J; Balázs, Árpád; Madarász, Ildikó; Pócz, Gábor; Ayaydin, Ferhan; Kanizsai, Iván; Fajka-Boja, Roberta; Alföldi, Róbert; Hackler, László; Puskás, László G

2017-10-07

Achiral Mannich-type curcumin analogs have been synthetized and assayed for their cytotoxic activity. The anti-proliferative and cytotoxic activity of curcuminoids has been tested on human non-small-cell lung carcinoma (A549), hepatocellular carcinoma (HepG2) and pancreatic cancer cell line (PANC-1). Based on the highest anti-proliferative activity nine drug candidates were further tested and proved to cause phosphatidylserine exposure as an early sign of apoptosis. Curcumin analogs with the highest apoptotic activity were selected for mechanistic studies in the most sensitive PANC-1 cells. Cytotoxic activity was accompanied by cytostatic effect since curcumin and analogs treatment led to G₀/G₁ cell cycle arrest. Moreover, cytotoxic effect could be also detected via the accumulation of curcuminoids in the endoplasmic reticulum (ER) and the up-regulation of ER stress-related unfolded protein response (UPR) genes: HSPA5 , ATF4, XBP1 , and DDIT3 . The activated UPR induced mitochondrial membrane depolarization, caspase-3 activation and subsequent DNA breakdown in PANC-1 cells. Achiral curcumin analogs, C509, C521 and C524 possessed superior, 40-times more potent cytotoxic activity compared to natural dihydroxy-dimetoxycurcumin in PANC-1 cells.
Involvement of HTLV-I Tax and CREB in aneuploidy: a bioinformatics approach

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Pumfery Anne

2006-07-01

Full Text Available Abstract Background Adult T-cell leukemia (ATL is a complex and multifaceted disease associated with human T-cell leukemia virus type 1 (HTLV-I infection. Tax, the viral oncoprotein, is considered a major contributor to cell cycle deregulation in HTLV-I transformed cells by either directly disrupting cellular factors (protein-protein interactions or altering their transcription profile. Tax transactivates these cellular promoters by interacting with transcription factors such as CREB/ATF, NF-κB, and SRF. Therefore by examining which factors upregulate a particular set of promoters we may begin to understand how Tax orchestrates leukemia development. Results We observed that CTLL cells stably expressing wild-type Tax (CTLL/WT exhibited aneuploidy as compared to a Tax clone deficient for CREB transactivation (CTLL/703. To better understand the contribution of Tax transactivation through the CREB/ATF pathway to the aneuploid phenotype, we performed microarray analysis comparing CTLL/WT to CTLL/703 cells. Promoter analysis of altered genes revealed that a subset of these genes contain CREB/ATF consensus sequences. While these genes had diverse functions, smaller subsets of genes were found to be involved in G2/M phase regulation, in particular kinetochore assembly. Furthermore, we confirmed the presence of CREB, Tax and RNA Polymerase II at the p97Vcp and Sgt1 promoters in vivo through chromatin immunoprecipitation in CTLL/WT cells. Conclusion These results indicate that the development of aneuploidy in Tax-expressing cells may occur in response to an alteration in the transcription profile, in addition to direct protein interactions.
Present Status And First Results of the Final Focus Beam Line at the KEK Accelerator Test Facility

International Nuclear Information System (INIS)

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.
Proceedings of US-Japan heliotron-stellarator workshop: Volume 2

International Nuclear Information System (INIS)

1987-01-01

This paper is the second of four volumes on the US-Japan Heliotron-Stellarator workshop. It contains talks on the following: Ripple Transport at Arbitrary Collision Frequency, Transport Scaling in the Collisionless-Detrapping Regime, Transport Analysis for Heliotron E, Transport Analysis for ATF, Simulation Analysis of Heating and Transport, Analysis of W VII-A Data, Numerical Study of Fast Ion Confinement, Benchmarks of NBI Codes for Stellarators, ECH Commissioning and Plans for ATF, and ECH and ICH Startup Analysis
Psychological Stress, Cocaine and Natural Reward Each Induce Endoplasmic Reticulum Stress Genes in Rat Brain

OpenAIRE

Pavlovsky, Ashly A.; Boehning, Darren; Li, Dingge; Zhang, Yafang; Fan, Xiuzhen; Green, Thomas A.

2013-01-01

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 it is unknown the full extent of ER stress responses to psychological stress or cocaine, and which of the three ER stress pathways is activated. The current study examines transcriptional responses of key ER stress target genes subsequent to psychologi...
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; 10.1103/PhysRevSTAB.13.042801

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.
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. Keywords: Macrophage, ATF7, Innate immune memory, Microarray
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.
A Comparative Physics Study of Commercial PWR Cores using Metallic Micro-cell UO{sub 2}-Cr (or Mo) Pellets with Cr-based Cladding Coating

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)

2016-05-15

In this work, a comparative neutronic analysis of the cores using ATFs which include metallic micro-cell UO{sub 2}-Cr, UO{sub 2}-Mo pellets and Cr-based alloy coating on cladding was performed to show the effects of the ATF fuels on the core performance. In this study, the cores having different ATFs use the same initial uranium enrichments. The ATF concepts studied in this work are the metallic microcell UO{sub 2} pellets containing Cr or Mo with cladding outer coating composed of Cr-based alloy which have been suggested as the ATF concepts in KAERI (Korea Atomic Energy Research Institute). The metallic micro-cell pellets and Cr-based alloy coating can enhance thermal conductivity of fuel and reduce the production of hydrogen from the reaction of cladding with coolant, respectively. The objective of this work is to compare neutronic characteristics of commercial PWR equilibrium cores utilizing the different variations of metallic micro-cell UO{sub 2} pellets with cladding coating composed of Cr-based alloy. The results showed that the cores using UO{sub 2}-Cr and UO{sub 2}-Mo pellets with Cr-based alloy coating on cladding have reduced cycle lengths by 60 and 106 EFPDs, respectively, in comparison with the reference UO{sub 2} fueled core due to the reduced heavy metal inventories and large thermal absorption cross section but they do not have any significant differences in the core performances parameters. However, it is notable that the core fueled the micro-cell UO{sub 2}-Mo pellet and Cr-based alloy coating has considerably more negative MTC and slightly more negative FTC than the other cases. These characteristics of the core using micro-cell UO{sub 2}-Mo pellet and Cr-based alloy coating is due to the hard neutron spectrum and large capture resonance cross section of Mo isotopes.
Inverse Cerenkov experiment

International Nuclear Information System (INIS)

Kimura, W.D.

1993-01-01

The final report describes work performed to investigate inverse Cherenkov acceleration (ICA) as a promising method for laser particle acceleration. In particular, an improved configuration of ICA is being tested in a experiment presently underway on the Accelerator Test Facility (ATF). In the experiment, the high peak power (∼ 10 GW) linearly polarized ATF CO 2 laser beam is converted to a radially polarized beam. This is beam is focused with an axicon at the Cherenkov angle onto the ATF 50-MeV e-beam inside a hydrogen gas cell, where the gas acts as the phase matching medium of the interaction. An energy gain of ∼12 MeV is predicted assuming a delivered laser peak power of 5 GW. The experiment is divided into two phases. The Phase I experiments, which were completed in the spring of 1992, were conducted before the ATF e-beam was available and involved several successful tests of the optical systems. Phase II experiments are with the e-beam and laser beam, and are still in progress. The ATF demonstrated delivery of the e-beam to the experiment in Dec. 1992. A preliminary ''debugging'' run with the e-beam and laser beam occurred in May 1993. This revealed the need for some experimental modifications, which have been implemented. The second run is tentatively scheduled for October or November 1993. In parallel to the experimental efforts has been ongoing theoretical work to support the experiment and investigate improvement and/or offshoots. One exciting offshoot has been theoretical work showing that free-space laser acceleration of electrons is possible using a radially-polarized, axicon-focused laser beam, but without any phase-matching gas. The Monte Carlo code used to model the ICA process has been upgraded and expanded to handle different types of laser beam input profiles
Preclinical evaluation of a urokinase plasminogen activator receptor-targeted nanoprobe in rhesus monkeys

Directory of Open Access Journals (Sweden)

Chen Y

2015-10-01

Full Text Available Yushu Chen,1 Li Gong,2 Ning Gao,3 Jichun Liao,1 Jiayu Sun,1 Yuqing Wang,1 Lei Wang,1 Pengjin Zhu,1 Qing Fan,1 Yongqiang Andrew Wang,4 Wen Zeng,2 Hui Mao,3 Lily Yang,5 Fabao Gao11Molecular Imaging Center, Department of Radiology, West China Hospital, Sichuan University, Chengdu, 2Sichuan Primed Bio-Tech Group Co, Ltd, Chengdu, People’s Republic of China; 3Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, 4Ocean NanoTech, LLC, San Diego, CA, 5Department of Surgery, Emory University School of Medicine, Atlanta, GA, USAPurpose: To translate a recombinant peptide containing the amino-terminal fragment (ATF of urokinase plasminogen activator receptor-targeted magnetic iron oxide (IO nanoparticles (uPAR-targeted human ATF-IONPs into clinical applications, we conducted a pilot study to evaluate the toxicity and pharmacokinetics of this nanoparticle in normal rhesus monkeys.Methods: We assessed the changes in the following: magnetic resonance imaging (MRI signals from pretreatment stage to 14 days posttreatment, serum iron concentrations from 5 minutes posttreatment to 12 weeks posttreatment, routine blood examination and serum chemistry analysis results from pretreatment stage to 12 weeks after administration, and results of staining of the liver with Perls’ Prussian Blue and hematoxylin–eosin at 24 hours and 3 months posttreatment in two rhesus monkeys following an intravenous administration of the targeted nanoparticles either with a polyethylene glycol (ATF-PEG-IONP or without a PEG (ATF-IONP coating.Results: The levels of alkaline phosphatase, alanine transaminase, and direct bilirubin in the two monkeys increased immediately after the administration of the IONPs but returned to normal within 20 days and stayed within the normal reference range 3 months after the injection. The creatinine levels of the two monkeys stayed within the normal range during the study. In addition, red blood cells

Proceedings of the Second OECD/NEA Organisation Meeting on Increased Accident Tolerance of Fuels for LWRs

International Nuclear Information System (INIS)

Massara, Simone; ); Bragg-Sitton, Shannon; Braase, Lori; Merrill, Brad; Teague, Melissa; Stanek, Chris R.; Montgomery, Robert H.; Ott, Larry J.; Robb, Kevin; Snead, Lance; Farmer, Mitch; Billone, Michael C.; Todosow, Michael; Brown, Nicholas; Brachet, J.C.; Le Flem, M.; Sauder, C.; Idarraga-Trujillo, I.; Michaux, A.; Lorrette, C.; Le Saux, M.; Blanpain, P.; Park, Jeong-Yong; Yang, Jae-Ho; Kim, Weon-Ju; Koo, Yang-Hyun; Liu, T.; Hallstadius, Lars; Lahoda, Ed; Waeckel, N.; Bonnet, J.M.; Vitanza, Carlo; Ohta, Hirokazu; Ogata, Takanari; Nakamura, Kinya; Dyck, Gary; Inozemtsev, Victor; )

2013-01-01

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/UO 2 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 2. Meeting on Increased Accident Tolerance of Fuels for LWRs. Content: 1 - Overview of the exchanges after the December-2012 Workshop through the discussion forum established at the OECD-NEA (S. Massara, NEA); 2 - Metrics Development for Enhanced Accident Tolerant LWR Fuels (S. Bragg-Sitton, INL); 3 - Candidate ATF Clad Technologies and Key Feasibility Issues (L. Snead, ORNL); 4 - CEA studies on nuclear fuel claddings for LWRs enhanced accident tolerant fuel. Some recent results, pending issues and prospects (J.C. Brachet, CEA); 5 - Current status on the accident tolerant fuel development in the Republic of Korea (J.Y. Park, J.H. Chang, KAERI); 6 - The current status of fuel R and D in the P.R. of China (T. Liu, CGN). Session 2: Key elements for a work programme on ATF: 7 - Beneficial characteristics of ATF (metrics) (L. Hallstadius, Westinghouse); 8 - Reactor types of interest (applicability) (L. Ott, ORNL); 9 - Impact on normal operations
ATLAS 60’ Fording Study

Science.gov (United States)

1992-03-03

8217orma parta~ do la pieze utilizable inmediatarnente quo se encuentra en ef cubretabloro. arriba . Los distribuidores Caterpillar necesitaii estos n...ER91 1 CBEA.-ET T RE 14 985721 2 P.CLIP l~mm EAR3T190H ALAS ATF 1 SENDER UEEA LG-6PNM 34 842 I WSE2 G372 TURSEASPLU-S IN 35 EARTH7 WAHE
Assessment of Neutronic Characteristics of Accident-Tolerant Fuel and Claddings for CANDU Reactors

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Simon Younan

2018-01-01

Full Text Available The objective of this study was to evaluate accident-tolerant fuel (ATF concepts being considered for CANDU reactors. Several concepts, including uranium dioxide/silicon carbide (UO2-SiC composite fuel, dense fuels, microencapsulated fuels, and ATF cladding, were modelled in Serpent 2 to obtain reactor physics parameters, including important feedback parameters such as coolant void reactivity and fuel temperature coefficient. In addition, fuel heat transfer was modelled, and a simple accident model was tested on several ATF cases to compare with UO2. Overall, several concepts would require enrichment of uranium to avoid significant burnup penalties, particularly uranium-molybdenum (U-Mo and fully ceramic microencapsulated (FCM fuels. In addition, none of the fuel types have a significant advantage over UO2 in terms of overall accident response or coping time, though U-9Mo fuel melts significantly sooner due to its low melting point. Instead, the different ATF concepts appear to have more modest advantages, such as reduced fission product release upon cladding failure, or reduced hydrogen generation, though a proper risk assessment would be required to determine the magnitude of these advantages to weigh against economic disadvantages. The use of uranium nitride (UN enriched in N15 would increase exit burnup for natural uranium, providing a possible economic advantage depending on fuel manufacturing costs.
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.
Present status and first results of the final focus beam line at the KEK Accelerator Test Facility

Directory of Open Access Journals (Sweden)

2010-04-01

Full Text Available 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.
Design of the ILC Prototype FONT4 Digital Intra-Train Beam-Based Feedback System

International Nuclear Information System (INIS)

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

2007-01-01

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

Science.gov (United States)

2010-01-20

..., Firearms, and Explosives, U.S. Department of Justice, 99 New York Avenue, NE., Washington, DC 20226... separate magazines for each explosive product. ATF estimates the average cost for a new type 4 magazine (4... Reading Room, Room 1E-063, 99 New York Avenue, NE., Washington, DC 20226; telephone: (202) 648-7080...
49 CFR 40.251 - What are the first steps in an alcohol confirmation test?

Science.gov (United States)

2010-10-01

... or STT conducted the screening test. (c) Complete Step 1 of the ATF. (d) Direct the employee to... ensure that the waiting period lasts at least 15 minutes, starting with the completion of the screening..., but not more than 30 minutes after the completion of the screening test. (i) If the confirmation test...
Bootstrap currents in stellarators and tokamaks

International Nuclear Information System (INIS)

Okamoto, Masao; Nakajima, Noriyoshi.

1990-09-01

The remarkable feature of the bootstrap current in stellarators is it's strong dependence on the magnetic field configuration. Neoclassical bootstrap currents in a large helical device of torsatron/heliotron type (L = 2, M = 10, R = 4 m, B = 4 T) is evaluated in the banana (1/ν) and the plateau regime. Various vacuum magnetic field configurations are studied with a view to minimizing the bootstrap current. It is found that in the banana regime, shifting of the magnetic axis and shaping of magnetic surfaces have a remarkable influence on the bootstrap current; a small outward shift of the magnetic axis and vertically elongated magnetic surfaces are favourable for a reduction of the bootstrap current. It is noted, however, that the ripple diffusion in the 1/ν regime has opposite tendency to the bootstrap current; it increases with the outward shift and increases as the plasma cross section is vertically elongated. The comparison will be made between bootstrap currents in stellarators and tokamaks. (author)
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. Copyright © 2012 Elsevier Ltd. All rights reserved.
Development of a high-resolution cavity-beam position monitor

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Yoichi Inoue

2008-06-01

Full Text Available We have developed a high-resolution cavity-beam position monitor (BPM to be used at the focal point of the ATF2, which is a test beam line that is now being built to demonstrate stable orbit control at ∼nanometer resolution. The design of the cavity structure was optimized for the Accelerator Test Facility (ATF beam in various ways. For example, the cavity has a rectangular shape in order to isolate two dipole modes in orthogonal directions, and a relatively thin gap that is less sensitive to trajectory inclination. A two stage homodyne mixer with highly sensitive electronics and phase-sensitive detection was also developed. Two BPM blocks, each containing two cavity BPMs, were installed in the existing ATF beam line using a rigid support frame. After testing the basic characteristics, we measured the resolution using three BPMs. The system demonstrated 8.7 nm position resolution over a dynamic range of 5 μm.
Development of a high-resolution cavity-beam position monitor

Science.gov (United States)

Inoue, Yoichi; Hayano, Hitoshi; Honda, Yosuke; Takatomi, Toshikazu; Tauchi, Toshiaki; Urakawa, Junji; Komamiya, Sachio; Nakamura, Tomoya; Sanuki, Tomoyuki; Kim, Eun-San; Shin, Seung-Hwan; Vogel, Vladimir

2008-06-01

We have developed a high-resolution cavity-beam position monitor (BPM) to be used at the focal point of the ATF2, which is a test beam line that is now being built to demonstrate stable orbit control at ˜nanometer resolution. The design of the cavity structure was optimized for the Accelerator Test Facility (ATF) beam in various ways. For example, the cavity has a rectangular shape in order to isolate two dipole modes in orthogonal directions, and a relatively thin gap that is less sensitive to trajectory inclination. A two stage homodyne mixer with highly sensitive electronics and phase-sensitive detection was also developed. Two BPM blocks, each containing two cavity BPMs, were installed in the existing ATF beam line using a rigid support frame. After testing the basic characteristics, we measured the resolution using three BPMs. The system demonstrated 8.7 nm position resolution over a dynamic range of 5μm.
National synchrotron light source. Activity report, October 1, 1994--September 30, 1995

Energy Technology Data Exchange (ETDEWEB)

Rothman, E.Z.; Hastings, J. [eds.

1996-05-01

This report discusses research conducted at the National Synchrotron Light Source in the following areas: atomic and molecular science; energy dispersive diffraction; lithography, microscopy, and tomography; nuclear physics; scattering and crystallography studies of biological materials; time resolved spectroscopy; UV photoemission and surface science; x-ray absorption spectroscopy; x-ray scattering and crystallography; x-ray topography; the 1995 NSLS annual users` meeting; 17th international free electron laser conference; micro bunches workshop; VUV machine; VUV storage ring parameters; beamline technical improvements; x-ray beamlines; x-ray storage ring parameters; the NSLS source development laboratory; the accelerator test facility (ATF); NSLS facility improvements; NSLS advisory committees; NSLS staff; VUV beamline guide; and x-ray beamline guide.
National synchrotron light source. Activity report, October 1, 1994--September 30, 1995

International Nuclear Information System (INIS)

Rothman, E.Z.; Hastings, J.

1996-05-01

This report discusses research conducted at the National Synchrotron Light Source in the following areas: atomic and molecular science; energy dispersive diffraction; lithography, microscopy, and tomography; nuclear physics; scattering and crystallography studies of biological materials; time resolved spectroscopy; UV photoemission and surface science; x-ray absorption spectroscopy; x-ray scattering and crystallography; x-ray topography; the 1995 NSLS annual users' meeting; 17th international free electron laser conference; micro bunches workshop; VUV machine; VUV storage ring parameters; beamline technical improvements; x-ray beamlines; x-ray storage ring parameters; the NSLS source development laboratory; the accelerator test facility (ATF); NSLS facility improvements; NSLS advisory committees; NSLS staff; VUV beamline guide; and x-ray beamline guide
Exogenous FABP4 induces endoplasmic reticulum stress in HepG2 liver cells.

Science.gov (United States)

Bosquet, Alba; Guaita-Esteruelas, Sandra; Saavedra, Paula; Rodríguez-Calvo, Ricardo; Heras, Mercedes; Girona, Josefa; Masana, Lluís

2016-06-01

Fatty acid binding protein 4 (FABP4) is an intracellular fatty acid (FA) carrier protein that is, in part, secreted into circulation. Circulating FABP4 levels are increased in obesity, diabetes and other insulin resistance (IR) diseases. FAs contribute to IR by promoting endoplasmic reticulum stress (ER stress) and altering the insulin signaling pathway. The effect of FABP4 on ER stress in the liver is not known. The aim of this study was to investigate whether exogenous FABP4 (eFABP4) is involved in the lipid-induced ER stress in the liver. HepG2 cells were cultured with eFABP4 (40 ng/ml) with or without linoleic acid (LA, 200 μM) for 18 h. The expression of ER stress-related markers was determined by Western blotting (ATF6, EIF2α, IRE1 and ubiquitin) and real-time PCR (ATF6, CHOP, EIF2α and IRE1). Apoptosis was studied by flow cytometry using Annexin V-FITC and propidium iodide staining. eFABP4 increased the ER stress markers ATF6 and IRE1 in HepG2 cells. This effect led to insulin resistance mediated by changes in AKT and JNK phosphorylation. Furthermore, eFABP4 significantly induced both apoptosis, as assessed by flow cytometry, and CHOP expression, without affecting necrosis and ubiquitination. The presence of LA increased the ER stress response induced by eFABP4. eFABP4, per se, induces ER stress and potentiates the effect of LA in HepG2 cells, suggesting that FABP4 could be a link between obesity-associated metabolic abnormalities and hepatic IR mechanisms. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
The effect of chronic ozone exposure on the activation of endoplasmic reticulum stress and apoptosis in rat hippocampus

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Erika Rodríguez-Martínez

2016-10-01

Full Text Available The chronic exposure to low doses of ozone, like in environmental pollution, leads to a state of oxidative stress, which has been proposed to contribute to neurodegenerative disorders, including Alzheimer's disease. It induces an increase of calcium in the endoplasmic reticulum (ER, which produces ER stress. On the other hand, different studies show that, in diseases such as Alzheimer’s, there exist disturbances in protein folding where ER plays an important role. The objective of this study was to evaluate the state of chronic oxidative stress on ER stress and its relationship with apoptotic death in the hippocampus of rats exposed to low doses of ozone. We used 108 male Wistar rats randomly divided into five groups. The groups received one of the following treatments: 1 Control (air, 2 Ozone (O3 7 days, 3 O3 15 days, 4 O3 30 days, 5 O3 60 days, and 6 O3 90 days. Two hours after each treatment, the animals were sacrificed and the hippocampus was extracted. Afterwards, the tissue was processed for western blot and immunohistochemistry using the following antibodies: ATF6, GRP8 and caspase 12. It was also performed TUNEL assay and electronic microscopy. Our results show an increase in ATF6, GRP78 and caspase 12 as well as ER ultrastructural alterations and an increase of TUNEL positive cells after 60 and 90 days of exposure to ozone. With the obtained results, we can conclude that oxidative stress induced by chronic exposure to low doses of ozone leads to ER stress. ER stress activates ATF6 inducing the increase of GRP78 in the cytoplasm, which leads to the increase in the nuclear translocation of ATF6. Finally, the translocation creates a vicious cycle that, together with the activation of the cascade for apoptotic cell death, contributes to the maintenance of ER stress. These events potentially contribute in the neurodegeneration processes in diseases like Alzheimer’s Disease.
Design, fabrication and testing of a thermal diode

Science.gov (United States)

Swerdling, B.; Kosson, R.

1972-01-01

Heat pipe diode types are discussed. The design, fabrication and test of a flight qualified diode for the Advanced Thermal Control Flight Experiment (ATFE) are described. The review covers the use of non-condensable gas, freezing, liquid trap, and liquid blockage techniques. Test data and parametric performance are presented for the liquid trap and liquid blockage techniques. The liquid blockage technique was selected for the ATFE diode on the basis of small reservoir size, low reverse mode heat transfer, and apparent rapid shut-off.
Infrared and far-infrared laser development for plasma diagnostics at Oak Ridge National Laboratory

International Nuclear Information System (INIS)

Casson, W.H.; Bennett, C.A.; Fletcher, L.K.; Hunter, H.T.; Hutchinson, D.P.; Lee, J.; Ma, C.DH.; Richards, R.K.; Vander Sluis, K.L.

1987-01-01

Three IR and FIR based diagnostics will be developed ann installed on the Advanced Toroidal Facility (ATF) at ORNL. An interferometer operating at 119 mu m will measure plasma density along 14 vertical chords across the plasma cross-section. A small-angle Thomson scattering experiment using a 10.6-mu m pulsed laser will determine the feasibility of measuring alpha particle distribution in a burning plasma. Plans are being developed for installing an FIR-based scattering experiment on ATF to measure density fluctuations. 4 refs., 4 figs
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.
27 CFR 26.199f - Consignee premises.

Science.gov (United States)

2010-04-01

..., DEPARTMENT OF THE TREASURY LIQUORS LIQUORS AND ARTICLES FROM PUERTO RICO AND THE VIRGIN ISLANDS Shipment of... spirits were lost by theft or unusual event, the proprietor shall determine the quantity of spirits lost... Management and Budget under control numbers 1512-0200 and 1512-0250) [T.D. ATF-198, 50 FR 8552, Mar. 1, 1985...

GPBAR1/TGR5 mediates bile acid-induced cytokine expression in murine Kupffer cells.

Directory of Open Access Journals (Sweden)

Guiyu Lou

Full Text Available GPBAR1/TGR5 is a novel plasma membrane-bound G protein-coupled bile acid (BA receptor. BAs are known to induce the expression of inflammatory cytokines in the liver with unknown mechanism. Here we show that without other external stimuli, TGR5 activation alone induced the expression of interleukin 1β (IL-1β and tumor necrosis factor-α (TNF-α in murine macrophage cell line RAW264.7 or murine Kupffer cells. The TGR5-mediated increase of pro-inflammatory cytokine expression was suppressed by JNK inhibition. Moreover, the induced pro-inflammatory cytokine expression in mouse liver by 1% cholic acid (CA diet was blunted in JNK-/- mice. TGR5 activation by its ligands enhanced the phosphorylation levels, DNA-binding and trans-activities of c-Jun and ATF2 transcription factors. Finally, the induced pro-inflammatory cytokine expression in Kupffer cells by TGR5 activation correlated with the suppression of Cholesterol 7α-hydroxylase (Cyp7a1 expression in murine hepatocytes. These results suggest that TGR5 mediates the BA-induced pro-inflammatory cytokine production in murine Kupffer cells through JNK-dependent pathway. This novel role of TGR5 may correlate to the suppression of Cyp7a1 expression in hepatocytes and contribute to the delicate BA feedback regulation.
Bilateral Neuropathy of Primary Sensory Neurons by the Chronic Compression of Multiple Unilateral DRGs

Directory of Open Access Journals (Sweden)

Ya-Bin Xie

2016-01-01

Full Text Available To mimic multilevel nerve root compression and intervertebral foramina stenosis in human, we established a new animal model of the chronic compression of unilateral multiple lumbar DRGs (mCCD in the rat. A higher occurrence of signs of spontaneous pain behaviors, such as wet-dog shaking and spontaneous hind paw shrinking behaviors, was firstly observed from day 1 onward. In the meantime, the unilateral mCCD rat exhibited significant bilateral hind paw mechanical and cold allodynia and hyperalgesia, as well as a thermal preference to 30°C plate between 30 and 35°C. The expression of activating transcription factor 3 (ATF3 was significantly increased in the ipsilateral and contralateral all-sized DRG neurons after the mCCD. And the expression of CGRP was significantly increased in the ipsilateral and contralateral large- and medium-sized DRG neurons. ATF3 and CGRP expressions correlated to evoked pain hypersensitivities such as mechanical and cold allodynia on postoperative day 1. The results suggested that bilateral neuropathy of primary sensory neurons might contribute to bilateral hypersensitivity in the mCCD rat.
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.
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.
Influence of carbon and nitrogen source on production of volatile fragrance and flavour metabolites by the yeast Kluyveromyces marxianus.

Science.gov (United States)

Gethins, Loughlin; Guneser, Onur; Demirkol, Aslı; Rea, Mary C; Stanton, Catherine; Ross, R Paul; Yuceer, Yonca; Morrissey, John P

2015-01-01

The yeast Kluyveromyces marxianus produces a range of volatile molecules with applications as fragrances or flavours. The purpose of this study was to establish how nutritional conditions influence the production of these metabolites. Four strains were grown on synthetic media, using a variety of carbon and nitrogen sources and volatile metabolites analysed using gas chromatography-mass spectrometry (GC-MS). The nitrogen source had pronounced effects on metabolite production: levels of the fusel alcohols 2-phenylethanol and isoamyl alcohol were highest when yeast extract was the nitrogen source, and ammonium had a strong repressing effect on production of 2-phenylethyl acetate. In contrast, the nitrogen source did not affect production of isoamyl acetate or ethyl acetate, indicating that more than one alcohol acetyl transferase activity is present in K. marxianus. Production of all acetate esters was low when cells were growing on lactose (as opposed to glucose or fructose), with a lower intracellular pool of acetyl CoA being one explanation for this observation. Bioinformatic and phylogenetic analysis of the known yeast alcohol acetyl transferases ATF1 and ATF2 suggests that the ancestral protein Atf2p may not be involved in synthesis of volatile acetate esters in K. marxianus, and raises interesting questions as to what other genes encode this activity in non-Saccharomyces yeasts. Identification of all the genes involved in ester synthesis will be important for development of the K. marxianus platform for flavour and fragrance production. Copyright © 2014 John Wiley & Sons, Ltd.
Obesity has an interactive effect with genetic variation in the activating transcription factor 6 gene on the risk of pre-diabetes in individuals of Chinese Han descent.

Science.gov (United States)

Gu, Nan; Ma, Xiaowei; Zhang, Junqing; Dong, Aimei; Jin, Mengmeng; Feng, Nan; Zhang, Hong; Guo, Xiaohui

2014-01-01

Endoplasmic reticulum (ER) stress is one of the contributing factors to the development of β-cell failure in type 2 diabetes. ER stress response through ATF6 has been shown to play an important role in insulin resistance and pancreatic β-cell function. We investigated whether genetic polymorphisms in ATF6 were associated with the risk of pre-diabetes in a Chinese Han population, and whether they had a synergistic effect with obesity. Our samples included 828 individuals who were diagnosed as pre-diabetic, and 620 controls. The minor allele A at rs2340721 was associated with increased risk for pre-diabetes(p = 0.013), and this association was still significant after adjusting for gender, age, body mass index (BMI), and waist-hip ratio(p' = 0.011). BMI, treated as a continuous variable, and rs2340721 had an interactive effect on pre-diabetic risk(p for interaction = 0.003, β = 0.106). Carriers of GG at rs7522210 were also at a higher risk compared to non-carriers (OR = 1.390, 95%CI:1.206-1.818, p = 0.013, adjusted OR' = 1.516, 95%CI:1.101-2.006, p' = 0.006). GG homozygotes had increased fasting blood glucose (FBG) levels(GG vs CX: 5.6 ± 0.52 vs 5.5 ± 0.57 mmol/L, p = 0.016), lower insulin levels (0,30,120 minutes after glucose load) (p < 0.05), and reduced areas under the insulin curve than non-carriers(GG vs CX:67.3(44.2-102.3) vs 73.1(49.4-111.4), p = 0.014). rs10918270 was associated with FBG, and rs4657103 with 2 hour glucose levels after a 75 g glucose load. We also identified a haplotype of TTAG composed of rs4657103, rs2134697, rs2340721, and rs12079579, which was associated with pre-diabetes. The genetic variation in ATF6 is associated with pre-diabetes and has interactive effects with BMI on pre-diabetes in the Chinese Han population.
Obesity has an interactive effect with genetic variation in the activating transcription factor 6 gene on the risk of pre-diabetes in individuals of Chinese Han descent.

Directory of Open Access Journals (Sweden)

Nan Gu

Full Text Available Endoplasmic reticulum (ER stress is one of the contributing factors to the development of β-cell failure in type 2 diabetes. ER stress response through ATF6 has been shown to play an important role in insulin resistance and pancreatic β-cell function. We investigated whether genetic polymorphisms in ATF6 were associated with the risk of pre-diabetes in a Chinese Han population, and whether they had a synergistic effect with obesity. Our samples included 828 individuals who were diagnosed as pre-diabetic, and 620 controls. The minor allele A at rs2340721 was associated with increased risk for pre-diabetes(p = 0.013, and this association was still significant after adjusting for gender, age, body mass index (BMI, and waist-hip ratio(p' = 0.011. BMI, treated as a continuous variable, and rs2340721 had an interactive effect on pre-diabetic risk(p for interaction = 0.003, β = 0.106. Carriers of GG at rs7522210 were also at a higher risk compared to non-carriers (OR = 1.390, 95%CI:1.206-1.818, p = 0.013, adjusted OR' = 1.516, 95%CI:1.101-2.006, p' = 0.006. GG homozygotes had increased fasting blood glucose (FBG levels(GG vs CX: 5.6 ± 0.52 vs 5.5 ± 0.57 mmol/L, p = 0.016, lower insulin levels (0,30,120 minutes after glucose load (p < 0.05, and reduced areas under the insulin curve than non-carriers(GG vs CX:67.3(44.2-102.3 vs 73.1(49.4-111.4, p = 0.014. rs10918270 was associated with FBG, and rs4657103 with 2 hour glucose levels after a 75 g glucose load. We also identified a haplotype of TTAG composed of rs4657103, rs2134697, rs2340721, and rs12079579, which was associated with pre-diabetes. The genetic variation in ATF6 is associated with pre-diabetes and has interactive effects with BMI on pre-diabetes in the Chinese Han population.
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

2016-05-24

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.
Endoplasmic reticulum stress and IRE-1 signaling cause apoptosis in colon cancer cells in response to andrographolide treatment.

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Banerjee, Aditi; Ahmed, Hafiz; Yang, Peixin; Czinn, Steven J; Blanchard, Thomas G

2016-07-05

The plant metabolite andrographolide induces cell cycle arrest and apoptosis in cancer cells. The mechanism(s) by which andrographolide induces apoptosis however, have not been elucidated. The present study was performed to determine the molecular events that promote apoptosis in andrographolide treated cells using T84, HCT116 and COLO 205 colon cancer cell lines. Andrographolide was determined to limit colony formation and Ki67 expression, alter nuclear morphology, increase cytoplasmic histone-associated-DNA-fragments, and increase cleaved caspase-3 levels. Andrographolide also induced significantly higher expression of endoplasmic reticulum (ER) stress proteins GRP-78 and IRE-1 by 48 h but not PERK or ATF6. Apoptosis signaling molecules BAX, spliced XBP-1 and CHOP were also significantly increased. Moreover, chemical inhibition of ER stress or IRE-1 depletion with siRNA in andrographolide treated cells significantly limited expression of IRE-1 and CHOP as determined by immunofluorescence staining, real time PCR, or immunobloting. This was accompanied by a decreased BAX/Bcl-2 ratio. Andrographolide significantly promotes cancer cell death compared to normal cells. These data demonstrate that andrographolide associated ER stress contributes to apoptosis through the activation of a pro-apoptotic GRP-78/IRE-1/XBP-1/CHOP signaling pathway.
Modeling of compact loop antennas

International Nuclear Information System (INIS)

Baity, F.W.

1987-01-01

A general compact loop antenna model which treats all elements of the antenna as lossy transmission lines has been developed. In addition to capacitively-tuned resonant double loop (RDL) antennas the model treats stub-tuned resonant double loop antennas. Calculations using the model have been compared with measurements on full-scale mockups of resonant double loop antennas for ATF and TFTR in order to refine the transmission line parameters. Results from the model are presented for RDL antenna designs for ATF, TFTR, Tore Supra, and for the Compact Ignition Tokamak
Evidence of galectin-1 involvement in glioma chemoresistance

International Nuclear Information System (INIS)

Le Mercier, Marie; Lefranc, Florence; Mijatovic, Tatjana; Debeir, Olivier; Haibe-Kains, Benjamin; Bontempi, Gianluca; Decaestecker, Christine; Kiss, Robert; Mathieu, Veronique

2008-01-01

Glioblastomas (GBMs) are resistant to apoptosis but less so to autophagy; a fact that may at least partly explain the therapeutic benefits of the pro-autophagic drug temozolomide in the treatment of GBM patients. Galectin-1 (Gal1) whose expression is stimulated by hypoxia is a potent modulator of GBM cell migration and a pro-angiogenic molecule. Hypoxia is also known to confer cancer cells with resistance to chemotherapy and radiotherapy and to modulate the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress. The present study investigates whether decreasing Gal1 expression (by means of a siRNA approach) in human Hs683 GBM cells increases their sensitivity to pro-autophagic or pro-apoptotic drugs. The data reveal that temozolomide, the standard treatment for glioma patients, increases Gal1 expression in Hs683 cells both in vitro and in vivo. However, reducing Gal1 expression in these cells by siRNA increases the anti-tumor effects of various chemotherapeutic agents, in particular temozolomide both in vitro and in vivo. This decrease in Gal1 expression in Hs683 cells does not induce apoptotic or autophagic features, but is found to modulate p53 transcriptional activity and decrease p53-targeted gene expression including DDIT3/GADD153/CHOP, DUSP5 ATF3 and GADD45A. The decrease in Gal1 expression also impairs the expression levels of seven other genes implicated in chemoresistance: ORP150, HERP, GRP78/Bip, TRA1, BNIP3L, GADD45B and CYR61, some of which are located in the ER and whose expression is also known to be modified by hypoxia. This novel facet of Gal1 involvement in glioblastoma biology may be amenable to therapeutic manipulation
Oxidative and endoplasmic reticulum stress is impaired in leukocytes from metabolically unhealthy vs healthy obese individuals.

Science.gov (United States)

Bañuls, C; Rovira-Llopis, S; Lopez-Domenech, S; Diaz-Morales, N; Blas-Garcia, A; Veses, S; Morillas, C; Victor, V M; Rocha, M; Hernandez-Mijares, A

2017-10-01

Oxidative stress and inflammation are related to obesity, but the influence of metabolic disturbances on these parameters and their relationship with endoplasmic reticulum (ER) stress is unknown. Therefore, this study was performed to evaluate whether metabolic profile influences ER and oxidative stress in an obese population with/without comorbidities. A total of 113 obese patients were enrolled in the study; 29 were metabolically healthy (MHO), 53 were metabolically abnormal (MAO) and 31 had type 2 diabetes (MADO). We assessed metabolic parameters, proinflammatory cytokines (TNFα and IL-6), mitochondrial and total reactive oxygen species (ROS) production, glutathione levels, antioxidant enzymes activity, total antioxidant status, mitochondrial membrane potential and ER stress marker expression levels (glucose-regulated protein (GRP78), spliced X-box binding protein 1 (XBP1), P-subunit 1 alpha (P-eIF2α) and activating transcription factor 6 (ATF6). The MAO and MADO groups showed higher blood pressure, atherogenic dyslipidemia, insulin resistance and inflammatory profile than that of MHO subjects. Total and mitochondrial ROS production was enhanced in MAO and MADO patients, and mitochondrial membrane potential and catalase activity differed significantly between the MADO and MHO groups. In addition, decreases in glutathione levels and superoxide dismutase activity were observed in the MADO vs MAO and MHO groups. GRP78 and CHOP protein and gene expression were higher in the MAO and MADO groups with respect to MHO subjects, and sXBP1 gene expression was associated with the presence of diabetes. Furthermore, MAO patients exhibited higher levels of ATF6 than their MHO counterparts. Waist circumference was positively correlated with ATF6 and GRP78, and A1c was positively correlated with P-Eif2α. Interestingly, CHOP was positively correlated with TNFα and total ROS production and GRP78 was negatively correlated with glutathione levels. Our findings support the
Fed-batch and perfusion culture processes: economic, environmental, and operational feasibility under uncertainty.

Science.gov (United States)

Pollock, James; Ho, Sa V; Farid, Suzanne S

2013-01-01

This article evaluates the current and future potential of batch and continuous cell culture technologies via a case study based on the commercial manufacture of monoclonal antibodies. The case study compares fed-batch culture to two perfusion technologies: spin-filter perfusion and an emerging perfusion technology utilizing alternating tangential flow (ATF) perfusion. The operational, economic, and environmental feasibility of whole bioprocesses based on these systems was evaluated using a prototype dynamic decision-support tool built at UCL encompassing process economics, discrete-event simulation and uncertainty analysis, and combined with a multi-attribute decision-making technique so as to enable a holistic assessment. The strategies were compared across a range of scales and titres so as to visualize how their ranking changes in different industry scenarios. The deterministic analysis indicated that the ATF perfusion strategy has the potential to offer cost of goods savings of 20% when compared to conventional fed-batch manufacturing processes when a fivefold increase in maximum viable cell densities was assumed. Savings were also seen when the ATF cell density dropped to a threefold increase over the fed-batch strategy for most combinations of titres and production scales. In contrast, the fed-batch strategy performed better in terms of environmental sustainability with a lower water and consumable usage profile. The impact of uncertainty and failure rates on the feasibility of the strategies was explored using Monte Carlo simulation. The risk analysis results demonstrated the enhanced robustness of the fed-batch process but also highlighted that the ATF process was still the most cost-effective option even under uncertainty. The multi-attribute decision-making analysis provided insight into the limited use of spin-filter perfusion strategies in industry. The resulting sensitivity spider plots enabled identification of the critical ratio of weightings of
Effects of Reynold's number on flight performance of turbofan engine

Energy Technology Data Exchange (ETDEWEB)

Kozu, Masao; Yajima, Satoshi [Defense Agency Tokyo (Japan); Ishikawajima-Harima Heavy Industries Co. Ltd., Tokyo (Japan))

1988-12-10

Concerning the performance of the F3-30 turbofan engine which is carried on the intermediate trainer XT-4 of the Air Self Defense Force, tests simulating its flight conditions were conducted at the Altitude Test Facility (ATF) of the Arnold Engineering Development Center (AEDC), U.S. Air Force in order to adjust the effect of Reynold's number corresponding to the flight condition. This report summarizes the results of the above tests. As the results of the tests, it was revealed that in order to calculate with precision the flight performance of the F3-30 turbofan engine, it was required to adjust Reynold's number against the following figures, namely the fan air flow, compressor air flow, compressor adiabatic efficiency, low pressure turbine gas flow and low pressure turbine adiabatic efficiency. The engine performance calculated by using the above adjustments agreed well with the measured values of the ATF tests. 7 refs., 17 figs., 1 tab.
The BNL Accelerator Test Facility and experimental program

International Nuclear Information System (INIS)

Ben-Zvi, I.; State Univ. of New York, Stony Brook, NY

1991-01-01

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 CO 2 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
Characterization of a human cell line stably over-expressing the candidate oncogene, dual specificity phosphatase 12.

Directory of Open Access Journals (Sweden)

Erica L Cain

2011-04-01

Full Text Available Analysis of chromosomal rearrangements within primary tumors has been influential in the identification of novel oncogenes. Identification of the "driver" gene(s within cancer-derived amplicons is, however, hampered by the fact that most amplicons contain many gene products. Amplification of 1q21-1q23 is strongly associated with liposarcomas and microarray-based comparative genomic hybridization narrowed down the likely candidate oncogenes to two: the activating transcription factor 6 (atf6 and the dual specificity phosphatase 12 (dusp12. While atf6 is an established transcriptional regulator of the unfolded protein response, the potential role of dusp12 in cancer remains uncharacterized.To evaluate the oncogenic potential of dusp12, we established stable cell lines that ectopically over-express dusp12 in isolation and determined whether this cell line acquired properties frequently associated with transformed cells. Here, we demonstrate that cells over-expressing dusp12 display increased cell motility and resistance to apoptosis. Additionally, over-expression of dusp12 promoted increased expression of the c-met proto-oncogene and the collagen and laminin receptor intergrin alpha 1 (itga1 which is implicated in metastasis.Collectively, these results suggest that dusp12 is oncologically relevant and exposes a potential association between dusp12 and established oncogenes that could be therapeutically targeted.
Improving performance with accident tolerant-fuels

International Nuclear Information System (INIS)

Gomes, Daniel S.; Muniz, Rafael O.R.; Giovedi, Claudia; Universidade de São Paulo

2017-01-01

After the Fukushima reactor accident, efforts to improve risk management in nuclear operations have included the intensification of research on accident-tolerant fuels (ATFs). In this investigation, the physical properties of recently developed ATFs were compared with those of the current standard fuel, UO 2 - Zr. The goals for innovative fuel design include a rigorous characterization of the thermal, mechanical, and chemical considerations. The intentions are to lengthen the burnup cycle, raise the power density, and improve safety. Fuels must have a high uranium density - above that supported by UO 2 - and possess a coating that exhibits better oxidation resistance than Zircaloys. ATFs such as U 3 Si 2 , UN, and UC contain a higher uranium density and thermal conductivity than UO 2 , providing significant benefits. The ideal combination of fuel and cladding must increase performance in a loss-of-coolant accident. However, U 3 Si 2 , UN, and UC have a disadvantage; their respective swelling rates are higher than that of UO 2 . These ATFs also have thermal conductivities approximately four times higher than that of UO 2 . A study was conducted investigating the hydrogen generated by the oxidation of zirconium alloys in contact with steam using cladding options such as Fe-Cr-Al and silicon carbide. It was confirmed that ferritic alloys offer a better response under severe conditions, because of their mechanical properties as creep rate. The findings of this study indicate that advanced fuels should replace UO 2 - Zr as the fuel system of choice. (author)
Improving performance with accident tolerant-fuels

Energy Technology Data Exchange (ETDEWEB)

Gomes, Daniel S.; Muniz, Rafael O.R.; Giovedi, Claudia, E-mail: dsgomes@ipen.br, E-mail: rafael.orm@gmail.com, E-mail: claudia.giovedi@ctmsp.mar.mil.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Universidade de São Paulo (USP), SP (Brazil). Departamento de Engenharia Naval e Oceânica

2017-07-01

After the Fukushima reactor accident, efforts to improve risk management in nuclear operations have included the intensification of research on accident-tolerant fuels (ATFs). In this investigation, the physical properties of recently developed ATFs were compared with those of the current standard fuel, UO{sub 2} - Zr. The goals for innovative fuel design include a rigorous characterization of the thermal, mechanical, and chemical considerations. The intentions are to lengthen the burnup cycle, raise the power density, and improve safety. Fuels must have a high uranium density - above that supported by UO{sub 2} - and possess a coating that exhibits better oxidation resistance than Zircaloys. ATFs such as U{sub 3}Si{sub 2}, UN, and UC contain a higher uranium density and thermal conductivity than UO{sub 2}, providing significant benefits. The ideal combination of fuel and cladding must increase performance in a loss-of-coolant accident. However, U{sub 3}Si{sub 2}, UN, and UC have a disadvantage; their respective swelling rates are higher than that of UO{sub 2}. These ATFs also have thermal conductivities approximately four times higher than that of UO{sub 2}. A study was conducted investigating the hydrogen generated by the oxidation of zirconium alloys in contact with steam using cladding options such as Fe-Cr-Al and silicon carbide. It was confirmed that ferritic alloys offer a better response under severe conditions, because of their mechanical properties as creep rate. The findings of this study indicate that advanced fuels should replace UO{sub 2} - Zr as the fuel system of choice. (author)
Progesterone production is affected by unfolded protein response (UPR) signaling during the luteal phase in mice.

Science.gov (United States)

Park, Hyo-Jin; Park, Sun-Ji; Koo, Deog-Bon; Lee, Sang-Rae; Kong, Il-Keun; Ryoo, Jae-Woong; Park, Young-Il; Chang, Kyu-Tae; Lee, Dong-Seok

2014-09-15

We examined whether the three unfolded protein response (UPR) signaling pathways, which are activated in response to endoplasmic reticulum (ER)-stress, are involved in progesterone production in the luteal cells of the corpus luteum (CL) during the mouse estrous cycle. The luteal phase of C57BL/6 female mice (8 weeks old) was divided into two stages: the functional stage (16, 24, and 48 h) and the regression stage (72 and 96 h). Western blotting and reverse transcription (RT)-PCR were performed to analyze UPR protein/gene expression levels in each stage. We investigated whether ER stress affects the progesterone production by using Tm (0.5 μg/g BW) or TUDCA (0.5 μg/g BW) through intra-peritoneal injection. Our results indicate that expressions of Grp78/Bip, p-eIF2α/ATF4, p50ATF6, and p-IRE1/sXBP1 induced by UPR activation were predominantly maintained in functional and early regression stages of the CL. Furthermore, the expression of p-JNK, CHOP, and cleaved caspase3 as ER-stress mediated apoptotic factors increased during the regression stage. Cleaved caspase3 levels increased in the late-regression stage after p-JNK and CHOP expression in the early-regression stage. Additionally, although progesterone secretion and levels of steroidogenic enzymes decreased following intra-peritoneal injection of Tunicamycin, an ER stress inducer, the expression of Grp78/Bip, p50ATF6, and CHOP dramatically increased. These results suggest that the UPR signaling pathways activated in response to ER stress may play important roles in the regulation of the CL function. Furthermore, our findings enhance the understanding of the basic mechanisms affecting the CL life span. Copyright © 2014 Elsevier Inc. All rights reserved.
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.

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