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Sample records for atf-1 torsatron

  1. Compact Torsatron configurations

    International Nuclear Information System (INIS)

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

  2. Divertor for a torsatron

    International Nuclear Information System (INIS)

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

  3. Compact torsatron reactors

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2003-09-01

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

  5. Wisconsin Torsatron/Stellarator Program, FY 1987

    International Nuclear Information System (INIS)

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

  6. Wisconsin torsatron/stellarator program, FY 1989

    International Nuclear Information System (INIS)

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

  7. Design of the Compact Auburn Torsatron

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  9. [Wisconsin Torsatron/Stellarator Program: FY 1988

    International Nuclear Information System (INIS)

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

  10. 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.

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  13. 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.

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

    International Nuclear Information System (INIS)

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

  15. MHD stability of torsatrons using the average method

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-09-01

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

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2008-04-01

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    CERN Document Server

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

    2014-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-12-15

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

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2016-07-01

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

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

    Science.gov (United States)

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

    1997-02-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-02-01

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  13. Torsatron equilibrium and stability studies

    International Nuclear Information System (INIS)

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

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    杨颖; 杨传燕; 刘箭

    2010-01-01

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

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

    International Nuclear Information System (INIS)

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

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

    OpenAIRE

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  20. Construction and initial operation of the Advanced Toroidal Facility

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Brooke M Baker

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

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

    Directory of Open Access Journals (Sweden)

    Jyun-Liang Lin

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

  3. Magnetic field of a combined plasma trap

    Science.gov (United States)

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

    2012-06-01

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

  4. Modular stellarator reactor: a fusion power plant

    International Nuclear Information System (INIS)

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

  5. Modular stellarator reactor: a fusion power plant

    Energy Technology Data Exchange (ETDEWEB)

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

    1983-07-01

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

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

    Lifescience Database Archive (English)

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

  7. Different approaches to the thermonuclear fusion problem

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  9. Fermentation of Apple Juice with a Selected Yeast Strain Isolated from the Fermented Foods of Himalayan Regions and Its Organoleptic Properties.

    Science.gov (United States)

    Kanwar, S S; Keshani

    2016-01-01

    Twenty-three Saccharomyces cerevisiae strains isolated from different fermented foods of Western Himalayas have been studied for strain level and functional diversity in our department. Among these 23 strains, 10 S. cerevisiae strains on the basis of variation in their brewing traits were selected to study their organoleptic effect at gene level by targeting ATF1 gene, which is responsible for ester synthesis during fermentation. Significant variation was observed in ATF1 gene sequences, suggesting differences in aroma and flavor of their brewing products. Apple is a predominant fruit in Himachal Pradesh and apple cider is one of the most popular drinks all around the world hence, it was chosen for sensory evaluation of six selected yeast strains. Organoleptic studies and sensory analysis suggested Sc21 and Sc01 as best indigenous strains for soft and hard cider, respectively, indicating their potential in enriching the local products with enhanced quality. PMID:27446050

  10. Chronic lymphocytic leukemia and B and T cells differ in their response to cyclic nucleotide phosphodiesterase inhibitors.

    Science.gov (United States)

    Meyers, John A; Su, Derrick W; Lerner, Adam

    2009-05-01

    Phosphodiesterase (PDE)4 inhibitors, which activate cAMP signaling by reducing cAMP catabolism, are known to induce apoptosis in B lineage chronic lymphocytic leukemia (CLL) cells but not normal human T cells. The explanation for such differential sensitivity remains unknown. In this study, we report studies contrasting the response to PDE4 inhibitor treatment in CLL cells and normal human T and B cells. Affymetrix gene chip analysis in the three cell populations following treatment with the PDE4 inhibitor rolipram identified a set of up-regulated transcripts with unusually high fold changes in the CLL samples, several of which are likely part of compensatory negative feedback loops. The high fold changes were due to low basal transcript levels in CLL cells, suggesting that cAMP-mediated signaling may be unusually tightly regulated in this cell type. Rolipram treatment augmented cAMP levels and induced ATF-1/CREB serine 63/133 phosphorylation in both B lineage cell types but not T cells. As treatment with the broad-spectrum PDE inhibitor 3-isobutyl-1-methylxanthine induced T cell CREB phosphorylation, we tested a series of family-specific PDE inhibitors for their ability to mimic 3-isobutyl-1-methylxanthine-induced ATF-1/CREB phosphorylation. Whereas PDE3 inhibitors alone had no effect, the combination of PDE3 and PDE4 inhibitors induced ATF-1/CREB serine 63/133 phosphorylation in T cells. Consistent with this observation, PDE3B transcript and protein levels were low in CLL cells but easily detectable in T cells. Combined PDE3/4 inhibition did not induce T cell apoptosis, suggesting that cAMP-mediated signal transduction that leads to robust ATF-1/CREB serine 63/133 phosphorylation is not sufficient to induce apoptosis in this lymphoid lineage.

  11. The Mitochondrial Unfolded Protein Response Protects against Anoxia in Caenorhabditis elegans

    Science.gov (United States)

    Peña, Salvador; Sherman, Teresa; Brookes, Paul S.; Nehrke, Keith

    2016-01-01

    The mitochondrial unfolded protein response (UPRmt) is a surveillance pathway that defends proteostasis in the “powerhouse” of the cell. Activation of the UPRmt protects against stresses imposed by reactive oxygen species, respiratory chain deficits, and pathologic bacteria. Consistent with the UPRmt’s role in adaption, we found that either its pharmacological or genetic activation by ethidium bromide (EtBr) or RNAi of the mitochondrial AAA-protease spg-7 was sufficient to reduce death in an anoxia-based Caenorhabditis elegans model of ischemia-reperfusion injury. The UPRmt-specific transcription factor atfs-1 was necessary for protection and atfs-1 gain-of-function (gf) mutants were endogenously protected from both death and dysfunction. Neurons exhibited less axonal degeneration following non-lethal anoxia-reperfusion (A-R) when the UPRmt was pre-activated, and consistent with the concept of mitochondrial stress leading to cell non-autonomous (ie. “remote”) effects, we found that restricted activation of the UPRmt in neurons decreased A-R death. However, expression of the atfs-1(gf) mutant in neurons, which resulted in a robust activation of a neuronal UPRmt, did not upregulate the UPRmt in distal tissues, nor did it protect the worms from A-R toxicity. These findings suggest that remote signaling requires additional component(s) acting downstream of de facto mitochondrial stress. PMID:27459203

  12. A Mutation in Caenorhabditis elegans NDUF-7 Activates the Mitochondrial Stress Response and Prolongs Lifespan via ROS and CED-4.

    Science.gov (United States)

    Rauthan, Manish; Ranji, Parmida; Abukar, Ragda; Pilon, Marc

    2015-06-01

    The mevalonate pathway is responsible for the synthesis of cholesterol, coenzyme Q, and prenyl groups essential for small GTPase modification and function, and for the production of dolichols important for protein glycosylation. Statins, i.e., cholesterol-lowering drugs that inhibit the rate-limiting enzyme in the mevalonate pathway, HMG-CoA reductase, are lethal to Caenorhabditis elegans even though this animal lacks the branch of the mevalonate pathway that leads to cholesterol synthesis. To better understand the effects of statins that are not related to cholesterol, we have adopted the strategy of isolating statin-resistant C. elegans mutants. Previously, we showed that such mutants often have gain-of-function mutations in ATFS-1, a protein that activates the mitochondrial unfolded protein response. Here, we describe the isolation of a statin-resistant mutant allele of the NDUF-7 protein, which is a component of complex I in the mitochondrial electron transport chain. The novel nduf-7(et19) mutant also exhibits constitutive and ATFS-1-dependent activation of the mitochondrial unfolded protein response (UPR(mt)) and prolonged life span, both of which are mediated through production of ROS. Additionally, lifespan extension, but not activation, of the mitochondrial unfolded protein response was dependent on the pro-apoptotic gene ced-4. We conclude that the nduf-7(et19) mutant allele causes an increase in reactive oxygen species that activate ATFS-1, hence UPR(mt)-mediated statin resistance, and extends life span via CED-4.

  13. Advanced fusion concepts: project summaries

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  16. Pulsed supersonic helium beams for plasma edge diagnosis

    Science.gov (United States)

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

    1997-03-01

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

  17. Pulsed supersonic helium beams for plasma edge diagnosis

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-03-01

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

  18. Profiling of histone H3 lysine 9 trimethylation levels predicts transcription factor activity and survival in acute myeloid leukemia

    DEFF Research Database (Denmark)

    Müller-Tidow, Carsten; Klein, Hans-Ulrich; Hascher, Antje;

    2010-01-01

    . The altered genomic regions showed an overrepresentation of cis-binding sites for ets and c-AMP response elements (CREs) for transcription factors of the CREB/CREM/ATF1 family. The decrease in H3K9me3 levels at CREs was associated with increased CRE-driven promoter activity in AML blasts in vivo. AML......Acute Myeloid Leukemia (AML) is commonly associated with alterations in transcription factors due to altered expression or gene mutations. These changes might induce leukemia- specific patterns of histone modifications. We used ChIP-Chip to analyze histone H3 Lysine 9 trimethylation (H3K9me3...

  19. Fusion theory and computations

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

    1982-02-01

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

  2. Alternative approaches to plasma confinement

    Science.gov (United States)

    Roth, J. R.

    1978-01-01

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

  3. DLK-1, SEK-3 and PMK-3 Are Required for the Life Extension Induced by Mitochondrial Bioenergetic Disruption in C. elegans

    Science.gov (United States)

    Lane, Rebecca K.; Borror, Megan B.; Bokov, Alex F.; Link, Christopher D.; Rea, Shane L.

    2016-01-01

    Mitochondrial dysfunction underlies numerous age-related pathologies. In an effort to uncover how the detrimental effects of mitochondrial dysfunction might be alleviated, we examined how the nematode C. elegans not only adapts to disruption of the mitochondrial electron transport chain, but in many instances responds with extended lifespan. Studies have shown various retrograde responses are activated in these animals, including the well-studied ATFS-1-dependent mitochondrial unfolded protein response (UPRmt). Such processes fall under the greater rubric of cellular surveillance mechanisms. Here we identify a novel p38 signaling cascade that is required to extend life when the mitochondrial electron transport chain is disrupted in worms, and which is blocked by disruption of the Mitochondrial-associated Degradation (MAD) pathway. This novel cascade is defined by DLK-1 (MAP3K), SEK-3 (MAP2K), PMK-3 (MAPK) and the reporter gene Ptbb-6::GFP. Inhibition of known mitochondrial retrograde responses does not alter induction of Ptbb-6::GFP, instead induction of this reporter often occurs in counterpoint to activation of SKN-1, which we show is under the control of ATFS-1. In those mitochondrial bioenergetic mutants which activate Ptbb-6::GFP, we find that dlk-1, sek-3 and pmk-3 are all required for their life extension. PMID:27420916

  4. Reactive oxygen species (ROS) production triggered by prostaglandin D2 (PGD2) regulates lactate dehydrogenase (LDH) expression/activity in TM4 Sertoli cells.

    Science.gov (United States)

    Rossi, Soledad P; Windschüttl, Stefanie; Matzkin, María E; Rey-Ares, Verónica; Terradas, Claudio; Ponzio, Roberto; Puigdomenech, Elisa; Levalle, Oscar; Calandra, Ricardo S; Mayerhofer, Artur; Frungieri, Mónica B

    2016-10-15

    Reactive oxygen species (ROS) regulate testicular function in health and disease. We previously described a prostaglandin D2 (PGD2) system in Sertoli cells. Now, we found that PGD2 increases ROS and hydrogen peroxide (H2O2) generation in murine TM4 Sertoli cells, and also induces antioxidant enzymes expression suggesting that defense systems are triggered as an adaptive stress mechanism that guarantees cell survival. ROS and specially H2O2 may act as second messengers regulating signal transduction pathways and gene expression. We describe a stimulatory effect of PGD2 on lactate dehydrogenase (LDH) expression via DP1/DP2 receptors, which is prevented by the antioxidant N-acetyl-L-cysteine and the PI3K/Akt pathway inhibitor LY 294002. PGD2 also enhances Akt and CREB/ATF-1 phosphorylation. Our results provide evidence for a role of PGD2 in the regulation of the oxidant/antioxidant status in Sertoli cells and, more importantly, in the modulation of LDH expression which takes place through ROS generation and the Akt-CREB/ATF-1 pathway. PMID:27329155

  5. Superficial paramucosal clear cell sarcoma of the soft parts resembling melanoma in a 13-year-old boy.

    Science.gov (United States)

    Sidiropoulos, Michael; Busam, Klaus; Guitart, Joan; Laskin, William B; Wagner, Annette M; Gerami, Pedram

    2013-02-01

    Clear cell sarcoma (CCS) of tendons and aponeuroses, also known as melanoma of soft parts, represents an aggressive rare malignancy that is characterized by a nested or fascicular pattern of spindled cells and a pathognomonic reciprocal translocation, t(12;22)(q13;q12), that results in the fusion of EWSR1 and ATF1 genes. Numerous recent studies have recognized the importance of a cutaneous CCS variant that can mimic a broad spectrum of entities, including spindle cell melanoma, spindle cell squamous carcinoma, cutaneous leiomyosarcoma and atypical fibroxanthoma. We report a case of a 13-year-old boy with cutaneous CCS who presented with a few months history of an asymptomatic papule on the lower lip that was suggestive of a mucocele. Biopsy of the lesion showed a wedge shaped neoplasm arranged in nests and fascicles of epithelioid- to oval-shaped cells with pale cytoplasm, open chromatin and prominent nucleolus. The superficial component was closely opposed to the basal epithelium resembling the junctional nests of a melanocytic neoplasm. The process extended into and involved the striated muscle of the lip. The cells expressed S-100, CD99 and synaptophysin by immunohistochemistry, and there was focal HMB-45 and microphthalmia transcription factor (MiTF) positivity as well. Fluorescence in situ hybridization confirmed the presence of the t(12;22) (ESWR1-ATF1) translocation. PMID:23228147

  6. Signaling pathways in PACAP regulation of VIP gene expression in human neuroblastoma cells

    DEFF Research Database (Denmark)

    Falktoft, Birgitte; Georg, Birgitte; Fahrenkrug, Jan

    2009-01-01

    of PAC1 and VPAC2 receptors, respectively, abolished and did not affect the PACAP-induced VIP mRNA expression, respectively. A pivotal role of PKA was implicated in addition to partial involvement of PKC and ERK1/2 in PACAP-induced VIP gene expression as H-89, Bisindolylmaleimide I (BIS), Gö6976 and U......0126 attenuated the VIP mRNA expression by 93%, 58%, 58% and 40%, respectively. PACAP modulated the phosphorylation of ERK1/2 (pERK1/2) and CREB/ATF-1 (pCREB/ATF-1) concomitant with a translocation of PKA to the nucleus. Inhibition of conventional PKC isoforms and MEK1/2 completely abolished pERK1/2...... completely suppressed the PACAP induced FOS mRNA expression. Immunoblotting confirmed expression of FOS protein upon addition of PACAP, which was diminished by impairment of PKC, ERK1/2 and PKA activities. The resemblance of the signaling pathways involving concomitant activities of PKC, ERK1/2 and PKA...

  7. Signaling pathways in PACAP regulation of VIP gene expression in human neuroblastoma cells

    DEFF Research Database (Denmark)

    Falktoft, B.; Georg, B.; Fahrenkrug, J.

    2009-01-01

    of PAC1 and VPAC2 receptors, respectively, abolished and did not affect the PACAP-induced VIP mRNA expression, respectively. A pivotal role of PKA was implicated in addition to partial involvement of PKC and ERK1/2 in PACAP-induced VIP gene expression as H-89, Bisindolylmaleimide I (BIS), Go6976 and U......0126 attenuated the VIP mRNA expression by 93%. 58%, 58% and 40%, respectively. PACAP modulated the phosphorylation of ERK1/2 (pERK1/2) and CREB/ATF-1 (pCREB/ATF-1) concomitant with a translocation of PKA to the nucleus. Inhibition of conventional PKC isoforms and MEK1/2 completely abolished pERK1/2...... completely suppressed the PACAP induced FOS mRNA expression. Immunoblotting confirmed expression of FOS protein upon addition of PACAP, which was diminished by impairment of PKC, ERK1/2 and PKA activities. The resemblance of the signaling pathways involving concomitant activities of PKC, ERK1/2 and PKA...

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

    Science.gov (United States)

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

    2016-05-01

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

  9. Status Report on the Fabrication of Fuel Cladding Chemical Interaction Test Articles for ATR Irradiations

    Energy Technology Data Exchange (ETDEWEB)

    Field, Kevin G. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Howard, Richard H. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-09-28

    FeCrAl alloys are a promising new class of alloys for light water reactor (LWR) applications due to their superior oxidation and corrosion resistance in high temperature environments. The current R&D efforts have focused on the alloy composition and processing routes to generate nuclear grade FeCrAl alloys with optimized properties for enhanced accident tolerance while maintaining properties needed for normal operation conditions. Therefore, the composition and processing routes must be optimized to maintain the high temperature steam oxidation (typically achieved by increasing the Cr and Al content) while still exhibiting properties conducive to normal operation in a LWR (such as radiation tolerance where reducing Cr content is favorable). Within this balancing act is the addition of understanding the influence on composition and processing routes on the FeCrAl alloys for fuel-cladding chemical interactions (FCCI). Currently, limited knowledge exists on FCCI for the FeCrAl-UO2 clad-fuel system. To overcome the knowledge gaps on the FCCI for the FeCrAl-UO2 clad-fuel system a series of fueled irradiation tests have been developed for irradiation in the Advanced Test Reactor (ATR) housed at the Idaho National Laboratory (INL). The first series of tests has already been reported. These tests used miniaturized 17x17 PWR fuel geometry rodlets of second-generation FeCrAl alloys fueled with industrial Westinghouse UO2 fuel. These rodlets were encapsulated within a stainless steel housing.To provide high fidelity experiments and more robust testing, a new series of rodlets have been developed deemed the Accident Tolerant Fuel Experiment #1 Oak Ridge National Laboratory FCCI test (ATF-1 ORNL FCCI). The main driving factor, which is discussed in detail, was to provide a radiation environment where prototypical fuel-clad interface temperatures are met while still maintaining constant contact between industrial fuel and the candidate cladding alloys

  10. Effects of wort gravity and nitrogen level on fermentation performance of brewer's yeast and the formation of flavor volatiles.

    Science.gov (United States)

    Lei, Hongjie; Zhao, Haifeng; Yu, Zhimin; Zhao, Mouming

    2012-03-01

    Normal gravity wort and high gravity wort with different nitrogen levels were used to examine their effects on the fermentation performance of brewer's yeast and the formation of flavor volatiles. Results showed that both the wort gravity and nitrogen level had significant impacts on the growth rate, viability, flocculation, and gene expression of brewer's yeast and the levels of flavor volatiles. The sugar (glucose, maltose, and maltotriose) consumption rates and net cell growth decreased when high gravity worts were used, while these increased with increasing nitrogen level. Moreover, high gravity resulted in lower expression levels of ATF1, BAP2, BAT1, HSP12, and TDH, whereas the higher nitrogen level caused higher expression levels for these genes. Furthermore, the lower nitrogen level resulted in increases in the levels of higher alcohols and esters at high wort gravity. All these results demonstrated that yeast physiology and flavor balance during beer brewing were significantly affected by the wort gravity and nitrogen level.

  11. Delphinidin Inhibits Tumor Growth by Acting on VEGF Signalling in Endothelial Cells.

    Directory of Open Access Journals (Sweden)

    Thérèse Keravis

    Full Text Available The vasculoprotective properties of delphinidin are driven mainly by its action on endothelial cells. Moreover, delphinidin displays anti-angiogenic properties in both in vitro and in vivo angiogenesis models and thereby might prevent the development of tumors associated with excessive vascularization. This study was aimed to test the effect of delphinidin on melanoma-induced tumor growth with emphasis on its molecular mechanism on endothelial cells. Delphinidin treatment significantly decreased in vivo tumor growth induced by B16-F10 melanoma cell xenograft in mice. In vitro, delphinidin was not able to inhibit VEGFR2-mediated B16-F10 melanoma cell proliferation but it specifically reduced basal and VEGFR2-mediated endothelial cell proliferation. The anti-proliferative effect of delphinidin was reversed either by the MEK1/2 MAP kinase inhibitor, U-0126, or the PI3K inhibitor, LY-294002. VEGF-induced proliferation was reduced either by U-0126 or LY-294002. Under these conditions, delphinidin failed to decrease further endothelial cell proliferation. Delphinidin prevented VEGF-induced phosphorylation of ERK1/2 and p38 MAPK and decreased the expression of the transcription factors, CREB and ATF1. Finally, delphinidin was more potent in inhibiting in vitro cyclic nucleotide phosphodiesterases (PDEs, PDE1 and PDE2, compared to PDE3-PDE5. Altogether delphinidin reduced tumor growth of melanoma cell in vivo by acting specifically on endothelial cell proliferation. The mechanism implies an association between inhibition of VEGF-induced proliferation via VEGFR2 signalling, MAPK, PI3K and at transcription level on CREB/ATF1 factors, and the inhibition of PDE2. In conjunction with our previous studies, we demonstrate that delphinidin is a promising compound to prevent pathologies associated with generation of vascular network in tumorigenesis.

  12. Physics models in the toroidal transport code PROCTR

    Energy Technology Data Exchange (ETDEWEB)

    Howe, H.C.

    1990-08-01

    The physics models that are contained in the toroidal transport code PROCTR are described in detail. Time- and space-dependent models are included for the plasma hydrogenic-ion, helium, and impurity densities, the electron and ion temperatures, the toroidal rotation velocity, and the toroidal current profile. Time- and depth-dependent models for the trapped and mobile hydrogenic particle concentrations in the wall and a time-dependent point model for the number of particles in the limiter are also included. Time-dependent models for neutral particle transport, neutral beam deposition and thermalization, fusion heating, impurity radiation, pellet injection, and the radial electric potential are included and recalculated periodically as the time-dependent models evolve. The plasma solution is obtained either in simple flux coordinates, where the radial shift of each elliptical, toroidal flux surface is included to maintain an approximate pressure equilibrium, or in general three-dimensional torsatron coordinates represented by series of helical harmonics. The detailed coupling of the plasma, scrape-off layer, limiter, and wall models through the neutral transport model makes PROCTR especially suited for modeling of recycling and particle control in toroidal plasmas. The model may also be used in a steady-state profile analysis mode for studying energy and particle balances starting with measured plasma profiles.

  13. Multi-Channel Detector Arrays for Heavy Ion Beam Probes

    Science.gov (United States)

    Aceto, Steven; Beckstead, Jeffrey; Castracane, James; Iguchi, H.; Fujisawa, A.; Demers, Diane; Schatz, John

    1997-11-01

    InterScience, Inc. has developed a multiple slit detector array for use with heavy ion beam probes. The first array was a twenty element array installed on the TEXT tokamak. An initial set of data was obtained with this array prior to the shutdown on the TEXT tokamak in December of 1995. More recently, a smaller detector array has been developed for use in the CHS torsatron in Nagoya. This array is smaller than the TEXT array, with ten elements, but contains two prototype sets of detector plates to determine the beam position. The operating conditions in CHS are expected to be much harsher than in TEXT, with ECH and NBI plasmas. Trajectory simulations allowed for the design of a tilted detector array in the CHS vacuum vessel. First tests of the CHS array will begin in the late summer of 1997. Other candidate machines for detector arrays are the MST reversed field pinch, in which a beam probe is expected to be installed in late 1997 or early 1998 and the Large Helical Device (LHD) which is expected to be operational in 1998. Design issues, trajectory simulations and array test results will be presented. Supported in part by the U.S. Department of Energy under Grant #DE-FG02-94ER81788

  14. Research on stellarator-mirror fission-fusion hybrid

    Science.gov (United States)

    Moiseenko, V. E.; Kotenko, V. G.; Chernitskiy, S. V.; Nemov, V. V.; Ågren, O.; Noack, K.; Kalyuzhnyi, V. N.; Hagnestål, A.; Källne, J.; Voitsenya, V. S.; Garkusha, I. E.

    2014-09-01

    The development of a stellarator-mirror fission-fusion hybrid concept is reviewed. The hybrid comprises of a fusion neutron source and a powerful sub-critical fast fission reactor core. The aim is the transmutation of spent nuclear fuel and safe fission energy production. In its fusion part, neutrons are generated in deuterium-tritium (D-T) plasma, confined magnetically in a stellarator-type system with an embedded magnetic mirror. Based on kinetic calculations, the energy balance for such a system is analyzed. Neutron calculations have been performed with the MCNPX code, and the principal design of the reactor part is developed. Neutron outflux at different outer parts of the reactor is calculated. Numerical simulations have been performed on the structure of a magnetic field in a model of the stellarator-mirror device, and that is achieved by switching off one or two coils of toroidal field in the Uragan-2M torsatron. The calculations predict the existence of closed magnetic surfaces under certain conditions. The confinement of fast particles in such a magnetic trap is analyzed.

  15. Curvature dependance of blob dynamics in TJ-K

    Energy Technology Data Exchange (ETDEWEB)

    Garland, Stephen; Ramisch, Mirko [Institut fuer Grenzflaechenverfahrenstechnik und Plasmatechnologie, Universitaet Stuttgart (Germany); Fuchert, Golo [Institut Jean Lamour, Universite de Lorraine (France)

    2014-07-01

    Turbulent transport in the scrape-off layer (SOL) is an important area of investigation in magnetic confinement fusion research. Relatively dense and hot, field-aligned, filament-like structures (blobs) have been observed to propagate radially through the SOL in many fusion devices, and contribute significantly to SOL transport. The torsatron TJ-K operates with a low-temperature plasma, allowing Langmuir probe measurements in the entire plasma volume. Despite the low temperature, investigations are relevant to fusion research due to dimensionless plasma parameters similar to those in the edge region of fusion plasmas. Analytical blob models link blob velocity in the SOL to blob polarisation, which can be driven by magnetic field line curvature. In TJ-K, average blob dynamics can be studied in detail using a 2D movable probe and a conditional averaging technique. In addition, a fast camera can be used to supplement probe data, and provide information on individual blob trajectories. With these tools, the connection between magnetic field line curvature and the poloidal component of blob velocity has been studied. Taking into account background E x B flows, initial investigations suggest a correlation between the poloidal component of blob velocity and averaged geodesic magnetic field line curvature.

  16. Curvature dependence of blob dynamics in TJ-K

    Energy Technology Data Exchange (ETDEWEB)

    Garland, Stephen; Ramisch, Mirko; Hirth, Thomas [Institut fuer Grenzflaechenverfahrenstechnik und Plasmatechnologie, Universitaet Stuttgart (Germany)

    2015-05-01

    Turbulent transport in the scrape-off layer (SOL) is an important area of investigation in magnetic confinement fusion research. Relatively dense and hot, field-aligned, filament-like structures (blobs) have been observed to propagate radially through the SOL in many fusion devices, and contribute significantly to SOL transport. The torsatron TJ-K is well suited to turbulence studies since it operates with a low-temperature plasma, allowing Langmuir probe measurements in the entire plasma volume. Despite the low temperature, investigations are relevant to fusion research due to dimensionless plasma parameters similar to those in the edge region of fusion plasmas. Blob dynamics have been studied in the SOL of TJ-K using a 2D movable probe and the conditional averaging technique. In addition, emissive probes have been used to determine equilibrium electric fields, allowing the calculation of background E x B flows. Experimentally deduced centre of mass radial and poloidal blob velocity components have been compared to an analytical blob model, which has been simplified to express blob velocity in terms of the magnetic field curvature vector. Experimental radial blob velocity components compare well to the model, confirming the normal curvature drive of blob polarisation. On the other hand, poloidal velocity components are comparable to the model only when background E x B flow is also taken into account.

  17. ATF [Advanced Toroidal Facility]-2 studies

    International Nuclear Information System (INIS)

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

  18. Stellarator News, Issue 38, March 1995

    CERN Document Server

    Rome, J A

    1995-01-01

    Stellarator News, an international journal of the stellarator community, is Published by Fusion Energy Division, Oak Ridge National Laboratory, James A. Rome, Editor In the March 1995 issue . . . **** Exerpts from the U.S. Congress Office of Technology Assment report on TPX and Alternate Concepts. **** Edge transport and turbulence studies on U-3M The turbulent-driven particle flow is shown to be comparable with the equilibrium flow at the boundary of the configuration under Alfven-heating conditions in the U-3M torsatron. **** Topological aspects of island divertor studies on W7-AS The structure of the edge plasma in W7-AS, observed with probes, television camera, and H-alpha light agrees at low beta with vacuum field calculations: the low-valued resonances at iotabar=5/m are resolved for m = 8 to 11; external perturbations are not significant at the edge, even for iotabar = 5/10. **** 140-GHz second harmonic O-mode electron cyclotron heating at W7-AS First experimental results are presented of 140-GHz secon...

  19. Physics models in the toroidal transport code PROCTR

    International Nuclear Information System (INIS)

    The physics models that are contained in the toroidal transport code PROCTR are described in detail. Time- and space-dependent models are included for the plasma hydrogenic-ion, helium, and impurity densities, the electron and ion temperatures, the toroidal rotation velocity, and the toroidal current profile. Time- and depth-dependent models for the trapped and mobile hydrogenic particle concentrations in the wall and a time-dependent point model for the number of particles in the limiter are also included. Time-dependent models for neutral particle transport, neutral beam deposition and thermalization, fusion heating, impurity radiation, pellet injection, and the radial electric potential are included and recalculated periodically as the time-dependent models evolve. The plasma solution is obtained either in simple flux coordinates, where the radial shift of each elliptical, toroidal flux surface is included to maintain an approximate pressure equilibrium, or in general three-dimensional torsatron coordinates represented by series of helical harmonics. The detailed coupling of the plasma, scrape-off layer, limiter, and wall models through the neutral transport model makes PROCTR especially suited for modeling of recycling and particle control in toroidal plasmas. The model may also be used in a steady-state profile analysis mode for studying energy and particle balances starting with measured plasma profiles

  20. Parametric systems analysis of the Modular Stellarator Reactor (MSR)

    International Nuclear Information System (INIS)

    The close coupling in the stellarator/torsatron/heliotron (S/T/H) between coil design (peak field, current density, forces), magnetics topology (transform, shear, well depth), and plasma performance (equilibrium, stability, transport, beta) complicates the reactor assessment more so than for most magnetic confinement systems. In order to provide an additional degree of resolution of this problem for the Modular Stellarator Reactor (MSR), a parametric systems model has been developed and applied. This model reduces key issues associted ith plasma performance, first-wall/blanket/shield (FW/B/S), and coil design to a simple relationship between beta, system geometry, and a number of indicators of overall plant performance. The results of this analysis can then be used to guide more detailed, multidimensional plasma, magnetics, and coil design efforts towards technically and economically viable operating regimes. In general, it is shown that beta values > 0.08 may be needed if the MSR approach is to be substantially competitive with other approaches to magnetic fusion in terms of system power density, mass utilization, and cost for total power output around 4.0 GWt; lower powers will require even higher betas

  1. Role of the fission yeast cell integrity MAPK pathway in response to glucose limitation

    Directory of Open Access Journals (Sweden)

    Madrid Marisa

    2013-02-01

    Full Text Available Abstract Background Glucose is a signaling molecule which regulates multiple events in eukaryotic organisms and the most preferred carbon source in the fission yeast Schizosaccharomyces pombe. The ability of this yeast to grow in the absence of glucose becomes strongly limited due to lack of enzymes of the glyoxylate cycle that support diauxic growth. The stress-activated protein kinase (SAPK pathway and its effectors, Sty1 MAPK and transcription factor Atf1, play a critical role in the adaptation of fission yeast to grow on alternative non-fermentable carbon sources by inducing the expression of fbp1+ gene, coding for the gluconeogenic enzyme fructose-1,6-bisphosphatase. The cell integrity Pmk1 pathway is another MAPK cascade that regulates various processes in fission yeast, including cell wall construction, cytokinesis, and ionic homeostasis. Pmk1 pathway also becomes strongly activated in response to glucose deprivation but its role during glucose exhaustion and ensuing adaptation to respiratory metabolism is currently unknown. Results We found that Pmk1 activation in the absence of glucose takes place only after complete depletion of this carbon source and that such activation is not related to an endogenous oxidative stress. Notably, Pmk1 MAPK activation relies on de novo protein synthesis, is independent on known upstream activators of the pathway like Rho2 GTPase, and involves PKC ortholog Pck2. Also, the Glucose/cAMP pathway is required operative for full activation of the Pmk1 signaling cascade. Mutants lacking Pmk1 displayed a partial growth defect in respiratory media which was not observed in the presence of glucose. This phenotype was accompanied by a decreased and delayed expression of transcription factor Atf1 and target genes fbp1+ and pyp2+. Intriguingly, the kinetics of Sty1 activation in Pmk1-less cells was clearly altered during growth adaptation to non-fermentable carbon sources. Conclusions Unknown upstream elements

  2. Gene expression analysis in human breast cancer associated blood vessels.

    Directory of Open Access Journals (Sweden)

    Dylan T Jones

    Full Text Available Angiogenesis is essential for solid tumour growth, whilst the molecular profiles of tumour blood vessels have been reported to be different between cancer types. Although presently available anti-angiogenic strategies are providing some promise for the treatment of some cancers it is perhaps not surprisingly that, none of the anti-angiogenic agents available work on all tumours. Thus, the discovery of novel anti-angiogenic targets, relevant to individual cancer types, is required. Using Affymetrix microarray analysis of laser-captured, CD31-positive blood vessels we have identified 63 genes that are upregulated significantly (5-72 fold in angiogenic blood vessels associated with human invasive ductal carcinoma (IDC of the breast as compared with blood vessels in normal human breast. We tested the angiogenic capacity of a subset of these genes. Genes were selected based on either their known cellular functions, their enriched expression in endothelial cells and/or their sensitivity to anti-VEGF treatment; all features implicating their involvement in angiogenesis. For example, RRM2, a ribonucleotide reductase involved in DNA synthesis, was upregulated 32-fold in IDC-associated blood vessels; ATF1, a nuclear activating transcription factor involved in cellular growth and survival was upregulated 23-fold in IDC-associated blood vessels and HEX-B, a hexosaminidase involved in the breakdown of GM2 gangliosides, was upregulated 8-fold in IDC-associated blood vessels. Furthermore, in silico analysis confirmed that AFT1 and HEX-B also were enriched in endothelial cells when compared with non-endothelial cells. None of these genes have been reported previously to be involved in neovascularisation. However, our data establish that siRNA depletion of Rrm2, Atf1 or Hex-B had significant anti-angiogenic effects in VEGF-stimulated ex vivo mouse aortic ring assays. Overall, our results provide proof-of-principle that our approach can identify a cohort of

  3. UvHOG1 is important for hyphal growth and stress responses in the rice false smut fungus Ustilaginoidea virens.

    Science.gov (United States)

    Zheng, Dawei; Wang, Yi; Han, Yu; Xu, Jin-Rong; Wang, Chenfang

    2016-01-01

    Rice false smut caused by Ustilaginoidea virens is one of the most important diseases of rice worldwide. Although its genome has been sequenced, to date there is no report on targeted gene deletion in U. virens and no molecular studies on genetic mechanisms regulating the infection processes of this destructive pathogen. In this study, we attempted to generate knockout mutants of the ortholog of yeast HOG1 MAP kinase gene in U. virens. One Uvhog1 deletion mutant was identified after screening over 600 hygromycin-resistant transformants generated by Agrobacterium tumefaciens mediated transformation. The Uvhog1 mutant was reduced in growth rate and conidiation but had increased sensitivities to SDS, Congo red, and hyperosmotic stress. Deletion of UvHOG1 resulted in reduced expression of the stress response-related genes UvATF1 and UvSKN7. In the Uvhog1 mutant, NaCl treatment failed to stimulate the accumulation of sorbitol and glycerol. In addition, the Uvhog1 mutant had reduced toxicity on shoot growth in rice seed germination assays. Overall, as the first report of targeted gene deletion mutant in U. virens, our results showed that UvHOG1 likely has conserved roles in regulating stress responses, hyphal growth, and possibly secondary metabolism. PMID:27095476

  4. Genome-wide Screening of Regulators of Catalase Expression: ROLE OF A TRANSCRIPTION COMPLEX AND HISTONE AND tRNA MODIFICATION COMPLEXES ON ADAPTATION TO STRESS.

    Science.gov (United States)

    García, Patricia; Encinar Del Dedo, Javier; Ayté, José; Hidalgo, Elena

    2016-01-01

    In response to environmental cues, the mitogen-activated protein kinase Sty1-driven signaling cascade activates hundreds of genes to induce a robust anti-stress cellular response in fission yeast. Thus, upon stress imposition Sty1 transiently accumulates in the nucleus where it up-regulates transcription through the Atf1 transcription factor. Several regulators of transcription and translation have been identified as important to mount an integral response to oxidative stress, such as the Spt-Ada-Gcn5-acetyl transferase or Elongator complexes, respectively. With the aim of identifying new regulators of this massive gene expression program, we have used a GFP-based protein reporter and screened a fission yeast deletion collection using flow cytometry. We find that the levels of catalase fused to GFP, both before and after a threat of peroxides, are altered in hundreds of strains lacking components of chromatin modifiers, transcription complexes, and modulators of translation. Thus, the transcription elongation complex Paf1, the histone methylase Set1-COMPASS, and the translation-related Trm112 dimers are all involved in full expression of Ctt1-GFP and in wild-type tolerance to peroxides.

  5. A Breast Tissue Protein Expression Profile Contributing to Early Parity-Induced Protection Against Breast Cancer

    Directory of Open Access Journals (Sweden)

    Christina Marie Gutierrez

    2015-11-01

    Full Text Available Background/Aims: Early parity reduces breast cancer risk, whereas, late parity and nulliparity increase breast cancer risk. Despite substantial efforts to understand the protective effects of early parity, the precise molecular circuitry responsible for these changes is not yet fully defined. Methods: Here, we have conducted the first study assessing protein expression profiles in normal breast tissue of healthy early parous, late parous, and nulliparous women. Breast tissue biopsies were obtained from 132 healthy parous and nulliparous volunteers. These samples were subjected to global protein expression profiling and immunohistochemistry. GeneSpring and MetaCore bioinformatics analysis software were used to identify protein expression profiles associated with early parity (low risk versus late/nulliparity (high risk. Results: Early parity reduces expression of key proteins involved in mitogenic signaling pathways in breast tissue through down regulation of EGFR1/3, ESR1, AKT1, ATF, Fos, and SRC. Early parity is also characterized by greater genomic stability and reduced tissue inflammation based on differential expression of aurora kinases, p53, RAD52, BRCA1, MAPKAPK-2, ATF-1, ICAM1, and NF-kappaB compared to late and nulli parity. Conclusions: Early parity reduces basal cell proliferation in breast tissue, which translates to enhanced genomic stability, reduced cellular stress/inflammation, and thus reduced breast cancer risk.

  6. Schizosaccharomyces pombe Homologs of Human DJ-1 Are Stationary Phase-Associated Proteins That Are Involved in Autophagy and Oxidative Stress Resistance.

    Directory of Open Access Journals (Sweden)

    Yang Su

    Full Text Available The Parkinson's disease protein DJ-1 is involved in various cellular functions including detoxification of dicarbonyl compounds, autophagy and oxidative stress response. DJ-1 homologs are widely found in both prokaryotes and eukaryotes, constituting a superfamily of proteins that appear to be involved in stress response. Schizosaccharomyces pombe contains six DJ-1 homologs, designated Hsp3101-Hsp3105 and Sdj1 (previously named SpDJ-1. Here we show that deletion of any one of these six genes somehow affects autophagy during prolonged stationary phase. Furthermore, deletions of each of these DJ-1 homologs result in reduced stationary phase survival. Deletion of sdj1 also increases the sensitivity of stationary-phase cells to oxidative stress induced by hydrogen peroxide (H2O2 whereas overexpression of sdj1 has the opposite effect. Consistent with their role in stationary phase, expression of hsp3101, hsp3102, hsp3105 and sdj1, and to a lesser extent hsp3103 and hsp3104, is increased in stationary phase. The induction of hsp3101, hsp3102, hsp3105 and sdj1 involves the Sty1-regulated transcription factor Atf1 but not the transcription factor Pap1. Our results firmly establish that S. pombe homologs of DJ-1 are stationary-phase associated proteins and are likely involved in autophagy and antioxidant defense in stationary phase of S. pombe cells.

  7. Genome-wide Screening of Regulators of Catalase Expression: ROLE OF A TRANSCRIPTION COMPLEX AND HISTONE AND tRNA MODIFICATION COMPLEXES ON ADAPTATION TO STRESS.

    Science.gov (United States)

    García, Patricia; Encinar Del Dedo, Javier; Ayté, José; Hidalgo, Elena

    2016-01-01

    In response to environmental cues, the mitogen-activated protein kinase Sty1-driven signaling cascade activates hundreds of genes to induce a robust anti-stress cellular response in fission yeast. Thus, upon stress imposition Sty1 transiently accumulates in the nucleus where it up-regulates transcription through the Atf1 transcription factor. Several regulators of transcription and translation have been identified as important to mount an integral response to oxidative stress, such as the Spt-Ada-Gcn5-acetyl transferase or Elongator complexes, respectively. With the aim of identifying new regulators of this massive gene expression program, we have used a GFP-based protein reporter and screened a fission yeast deletion collection using flow cytometry. We find that the levels of catalase fused to GFP, both before and after a threat of peroxides, are altered in hundreds of strains lacking components of chromatin modifiers, transcription complexes, and modulators of translation. Thus, the transcription elongation complex Paf1, the histone methylase Set1-COMPASS, and the translation-related Trm112 dimers are all involved in full expression of Ctt1-GFP and in wild-type tolerance to peroxides. PMID:26567340

  8. Regulation of the antioxidant system in cells of the fission yeast Schizosaccharomyces pombe after combined treatment with patulin and citrinin.

    Science.gov (United States)

    Papp, Gábor; Máté, Gábor; Mike, Nóra; Gazdag, Zoltán; Pesti, Miklós

    2016-03-01

    The effects of combined treatment with patulin (PAT) and citrinin (CTN) on Schizosaccharomyces pombe cells were investigated in acute toxicity tests. In comparison with the controls the exposure of fission yeast cells (10(7) cells ml(-1)) to PAT + CTN (250 μM each) for 1 h at a survival rate of 66.6% significantly elevated the concentration of total reactive oxygen species (ROS) via increased levels of peroxides without affecting the concentrations of superoxides or the hydroxyl radical. This treatment induced a 3.08-fold increase in the specific concentration of glutathione and elevated specific activities of catalase and glutathione S-transferase, while at the same time the activity of glutathione reductase decreased. The pattern of the ROS was the same as that induced by CTN (Máté et al., 2014), while the presence of PAT in the PAT + CTN combination treatment modified the activities of the antioxidant system (Papp et al., 2012) in comparison with the individual PAT or CTN treatment, suggesting toxin-specific regulation of glutathione and the enzymes of the antioxidant system and the possibility that the transcription factor (pap1 and atf1) -regulated processes might be influenced directly by ROS. PMID:26752674

  9. Installation of a Thomson scattering diagnostic on the Compact Toroidal Hybrid Experiment

    Science.gov (United States)

    Traverso, P. J.; Maurer, D. A.; Ennis, D. A.; Hartwell, G. J.; Cianciosa, M. R.

    2015-11-01

    A Thomson scattering system is being commissioned for the non-axisymmetric plasmas of the Compact Toroidal Hybrid (CTH), a five-field period current-carrying torsatron. The initial system takes a single point measurement on the magnetic axis and will be used to assess options for an expansion to a multi-point system to enable better 3D equilibrium reconstructions using the V3FIT code. A single point measurement will reduce the uncertainty in the reconstructed peak pressure by an order of magnitude for both current-carrying plasmas and future gyrotron-heated stellarator plasmas. The beam, generated by a frequency doubled Continuum 2 J, Nd:YaG laser, is passed vertically through an entrance Brewster window and a two-aperture optical baffle system to minimize stray light. The beam line is designed to propagate ~ 8 m to the mid-plane of the CTH device with the beam diameter < 3 mm inside the plasma volume. An Andor iStar DH740-18U-C3 image intensified CCD camera is used in conjunction with a Holospec f/1.8 spectrograph to collect the red-shifted scattered light from 532-580 nm. A single point system will initially measure plasmas with core electron temperatures of 100 to 200 eV and densities of 5 ×1018 to 5 ×1019 m-3. This work is supported by U.S. Department of Energy Grant No. DE-FG02-00ER54610.

  10. Calculation of continuum damping of Alfvén eigenmodes in tokamak and stellarator equilibria

    Energy Technology Data Exchange (ETDEWEB)

    Bowden, G. W.; Hole, M. J. [Plasma Theory and Modelling, Research School of Physics and Engineering, Australian National University, Acton 2601, Australian Capital Territory (Australia); Könies, A. [Max-Planck-Institut für Plasmaphysik, EURATOM-Association, D-17491 Greifswald (Germany)

    2015-09-15

    In an ideal magnetohydrodynamic (MHD) plasma, shear Alfvén eigenmodes may experience dissipationless damping due to resonant interaction with the shear Alfvén continuum. This continuum damping can make a significant contribution to the overall growth/decay rate of shear Alfvén eigenmodes, with consequent implications for fast ion transport. One method for calculating continuum damping is to solve the MHD eigenvalue problem over a suitable contour in the complex plane, thereby satisfying the causality condition. Such an approach can be implemented in three-dimensional ideal MHD codes which use the Galerkin method. Analytic functions can be fitted to numerical data for equilibrium quantities in order to determine the value of these quantities along the complex contour. This approach requires less resolution than the established technique of calculating damping as resistivity vanishes and is thus more computationally efficient. The complex contour method has been applied to the three-dimensional finite element ideal MHD Code for Kinetic Alfvén waves. In this paper, we discuss the application of the complex contour technique to calculate the continuum damping of global modes in tokamak as well as torsatron, W7-X and H-1NF stellarator cases. To the authors' knowledge, these stellarator calculations represent the first calculation of continuum damping for eigenmodes in fully three-dimensional equilibria. The continuum damping of global modes in W7-X and H-1NF stellarator configurations investigated is found to depend sensitively on coupling to numerous poloidal and toroidal harmonics.

  11. Calculation of continuum damping of Alfvén eigenmodes in tokamak and stellarator equilibria

    International Nuclear Information System (INIS)

    In an ideal magnetohydrodynamic (MHD) plasma, shear Alfvén eigenmodes may experience dissipationless damping due to resonant interaction with the shear Alfvén continuum. This continuum damping can make a significant contribution to the overall growth/decay rate of shear Alfvén eigenmodes, with consequent implications for fast ion transport. One method for calculating continuum damping is to solve the MHD eigenvalue problem over a suitable contour in the complex plane, thereby satisfying the causality condition. Such an approach can be implemented in three-dimensional ideal MHD codes which use the Galerkin method. Analytic functions can be fitted to numerical data for equilibrium quantities in order to determine the value of these quantities along the complex contour. This approach requires less resolution than the established technique of calculating damping as resistivity vanishes and is thus more computationally efficient. The complex contour method has been applied to the three-dimensional finite element ideal MHD Code for Kinetic Alfvén waves. In this paper, we discuss the application of the complex contour technique to calculate the continuum damping of global modes in tokamak as well as torsatron, W7-X and H-1NF stellarator cases. To the authors' knowledge, these stellarator calculations represent the first calculation of continuum damping for eigenmodes in fully three-dimensional equilibria. The continuum damping of global modes in W7-X and H-1NF stellarator configurations investigated is found to depend sensitively on coupling to numerous poloidal and toroidal harmonics

  12. Calculation of continuum damping of Alfvén eigenmodes in tokamak and stellarator equilibria

    Science.gov (United States)

    Bowden, G. W.; Hole, M. J.; Könies, A.

    2015-09-01

    In an ideal magnetohydrodynamic (MHD) plasma, shear Alfvén eigenmodes may experience dissipationless damping due to resonant interaction with the shear Alfvén continuum. This continuum damping can make a significant contribution to the overall growth/decay rate of shear Alfvén eigenmodes, with consequent implications for fast ion transport. One method for calculating continuum damping is to solve the MHD eigenvalue problem over a suitable contour in the complex plane, thereby satisfying the causality condition. Such an approach can be implemented in three-dimensional ideal MHD codes which use the Galerkin method. Analytic functions can be fitted to numerical data for equilibrium quantities in order to determine the value of these quantities along the complex contour. This approach requires less resolution than the established technique of calculating damping as resistivity vanishes and is thus more computationally efficient. The complex contour method has been applied to the three-dimensional finite element ideal MHD Code for Kinetic Alfvén waves. In this paper, we discuss the application of the complex contour technique to calculate the continuum damping of global modes in tokamak as well as torsatron, W7-X and H-1NF stellarator cases. To the authors' knowledge, these stellarator calculations represent the first calculation of continuum damping for eigenmodes in fully three-dimensional equilibria. The continuum damping of global modes in W7-X and H-1NF stellarator configurations investigated is found to depend sensitively on coupling to numerous poloidal and toroidal harmonics.

  13. 重金属Cr(Ⅵ)与血清蛋白质组的结合反应性能研究%Performance of Binding Interaction between Cr(Ⅵ) and Serum Proteome

    Institute of Scientific and Technical Information of China (English)

    郭明; 黄凤琴; 刘咪咪; 李铭慧

    2013-01-01

    The binding reaction between heavy metal ions Cr(Ⅵ) and serum proteome was investigated using affinity capillary electrophoresis (ACE) method. Based on the site binding model, a model about the interaction between Cr(Ⅵ) as the ligand and FBS as the receptor, was established. The binding performance of heavy metal ions Cr(Ⅵ) and the serum proteome was studied under proteomic conditions, and the results showed that, Cr(Ⅵ)-protein complexes formed between Cr(Ⅵ) and the high abundance component albumin in FBS, such as albumin (bovine serum albumin, BSA), transferrin protein (Bovine apo transferrin, bATF), immunogolobulin (Bovine IgG, IgG) and so on, and the binding reactions of Cr(Ⅵ) -FBS are fast equilibrium reactions. The apparent binding constant was determined through non-linear fitting binding reaction and based on changes of the effective mobility, and KCr(Ⅵ)-bATF=1.27×104 L·mol-1, KCr(Ⅵ)-IgG=4.91×104 L·mol-1, KCr(Ⅵ)-bsa=8.98×104 L·mol-1. Dosage-dependent effect exists among the concentration of Cr(Ⅵ) and the strength of the binding reactions. This work has referential meaning for understanding deeply the binding reaction echanism of chromium(Ⅵ) with serum proteome.%利用亲和毛细管电泳(Affinity capillary electrophoresis,ACE)方法,基于位点结合模型,构建配体(Cr(Ⅵ))-血清蛋白质组受体(Fetal bovine serum,FBS)结合反应方程,研究重金属离子Cr(Ⅵ)和血清蛋白质组的结合反应性能.结果表明,组学条件下,Cr(Ⅵ)与FBS中高丰度组分白蛋白(Bovine serum albumin,BSA)、转铁蛋白(Bovine apo transferrin,bATF)、免疫球蛋白(Bovine IgG,IgG)之间形成Cr(Ⅵ)-蛋白质络合物;结合反应均为快平衡反应;依据有效淌度的变化,通过结合方程测得结合反应的表观结合常数KC(Ⅵ)ATF=1.27× 104L·mol-1 、KCr(Ⅵ)-IgG=4.91×104L·mol-1、KC(Ⅵ)-BSA=8.98× 104L·mol-1;同时根据实验数据非线性模拟结果表明,C(Ⅵ)与FBS中高丰度组分发生相互

  14. High risk of adrenal toxicity of N1-desoxy quinoxaline 1,4-dioxide derivatives and the protection of oligomeric proanthocyanidins (OPC) in the inhibition of the expression of aldosterone synthetase in H295R cells.

    Science.gov (United States)

    Wang, Xu; Yang, Chunhui; Ihsan, Awais; Luo, Xun; Guo, Pu; Cheng, Guyue; Dai, Menghong; Chen, Dongmei; Liu, Zhenli; Yuan, Zonghui

    2016-02-01

    Quinoxaline 1,4-dioxide derivatives (QdNOs) with a wide range of biological activities are used in animal husbandry worldwide. It was found that QdNOs significantly inhibited the gene expression of CYP11B1 and CYP11B2, the key aldosterone synthases, and thus reduced aldosterone levels. However, whether the metabolites of QdNOs have potential adrenal toxicity and the role of oxidative stress in the adrenal toxicity of QdNOs remains unclear. The relatively new QdNOs, cyadox (CYA), mequindox (MEQ), quinocetone (QCT) and their metabolites, were selected for elucidation of their toxic mechanisms in H295R cells. Interestingly, the results showed that the main toxic metabolites of QCT, MEQ, and CYA were their N1-desoxy metabolites, which were more harmful than other metabolites and evoked dose and time-dependent cell damage on adrenal cells and inhibited aldosterone production. Gene and protein expression of CYP11B1 and CYP11B2 and mRNA expression of transcription factors, such as NURR1, NGFIB, CREB, SF-1, and ATF-1, were down regulated by N1-desoxy QdNOs. The natural inhibitors of oxidant stress, oligomeric proanthocyanidins (OPC), could upregulate the expression of diverse transcription factors, including CYP11B1 and CYP11B2, and elevated aldosterone levels to reduce adrenal toxicity. This study demonstrated for the first time that N1-desoxy QdNOs have the potential to be the major toxic metabolites in adrenal toxicity, which may shed new light on the adrenal toxicity of these fascinating compounds and help to provide a basic foundation for the formulation of safety controls for animal products and the design of new QdNOs with less harmful effects.

  15. High risk of adrenal toxicity of N1-desoxy quinoxaline 1,4-dioxide derivatives and the protection of oligomeric proanthocyanidins (OPC) in the inhibition of the expression of aldosterone synthetase in H295R cells.

    Science.gov (United States)

    Wang, Xu; Yang, Chunhui; Ihsan, Awais; Luo, Xun; Guo, Pu; Cheng, Guyue; Dai, Menghong; Chen, Dongmei; Liu, Zhenli; Yuan, Zonghui

    2016-02-01

    Quinoxaline 1,4-dioxide derivatives (QdNOs) with a wide range of biological activities are used in animal husbandry worldwide. It was found that QdNOs significantly inhibited the gene expression of CYP11B1 and CYP11B2, the key aldosterone synthases, and thus reduced aldosterone levels. However, whether the metabolites of QdNOs have potential adrenal toxicity and the role of oxidative stress in the adrenal toxicity of QdNOs remains unclear. The relatively new QdNOs, cyadox (CYA), mequindox (MEQ), quinocetone (QCT) and their metabolites, were selected for elucidation of their toxic mechanisms in H295R cells. Interestingly, the results showed that the main toxic metabolites of QCT, MEQ, and CYA were their N1-desoxy metabolites, which were more harmful than other metabolites and evoked dose and time-dependent cell damage on adrenal cells and inhibited aldosterone production. Gene and protein expression of CYP11B1 and CYP11B2 and mRNA expression of transcription factors, such as NURR1, NGFIB, CREB, SF-1, and ATF-1, were down regulated by N1-desoxy QdNOs. The natural inhibitors of oxidant stress, oligomeric proanthocyanidins (OPC), could upregulate the expression of diverse transcription factors, including CYP11B1 and CYP11B2, and elevated aldosterone levels to reduce adrenal toxicity. This study demonstrated for the first time that N1-desoxy QdNOs have the potential to be the major toxic metabolites in adrenal toxicity, which may shed new light on the adrenal toxicity of these fascinating compounds and help to provide a basic foundation for the formulation of safety controls for animal products and the design of new QdNOs with less harmful effects. PMID:26802905

  16. Hippocampal and behavioral dysfunctions in a mouse model of environmental stress: normalization by agomelatine.

    Science.gov (United States)

    Boulle, F; Massart, R; Stragier, E; Païzanis, E; Zaidan, L; Marday, S; Gabriel, C; Mocaer, E; Mongeau, R; Lanfumey, L

    2014-01-01

    Stress-induced alterations in neuronal plasticity and in hippocampal functions have been suggested to be involved in the development of mood disorders. In this context, we investigated in the hippocampus the activation of intracellular signaling cascades, the expression of epigenetic markers and plasticity-related genes in a mouse model of stress-induced hyperactivity and of mixed affective disorders. We also determined whether the antidepressant drug agomelatine, a MT1/MT2 melatonergic receptor agonist/5-HT2C receptor antagonist, could prevent some neurobiological and behavioral alterations produced by stress. C57BL/6J mice, exposed for 3 weeks to daily unpredictable socio-environmental stressors of mild intensity, were treated during the whole procedure with agomelatine (50 mg kg(-1) per day, intraperitoneal). Stressed mice displayed robust increases in emotional arousal, vigilance and motor activity, together with a reward deficit and a reduction in anxiety-like behavior. Neurobiological investigations showed an increased phosphorylation of intracellular signaling proteins, including Atf1, Creb and p38, in the hippocampus of stressed mice. Decreased hippocampal level of the repressive epigenetic marks HDAC2 and H3K9me2, as well as increased level of the permissive mark H3K9/14ac suggested that chronic mild stress was associated with increased gene transcription, and clear-cut evidence was further indicated by changes in neuroplasticity-related genes, including Arc, Bcl2, Bdnf, Gdnf, Igf1 and Neurod1. Together with other findings, the present data suggest that chronic ultra-mild stress can model the hyperactivity or psychomotor agitation, as well as the mixed affective behaviors often observed during the manic state of bipolar disorder patients. Interestingly, agomelatine could normalize both the behavioral and the molecular alterations induced by stress, providing further insights into the mechanism of action of this new generation antidepressant drug. PMID

  17. Rapamycin induces mitogen-activated protein (MAP) kinase phosphatase-1 (MKP-1) expression through activation of protein kinase B and mitogen-activated protein kinase kinase pathways.

    Science.gov (United States)

    Rastogi, Ruchi; Jiang, Zhongliang; Ahmad, Nisar; Rosati, Rita; Liu, Yusen; Beuret, Laurent; Monks, Robert; Charron, Jean; Birnbaum, Morris J; Samavati, Lobelia

    2013-11-22

    Mitogen-activated protein kinase phosphatase-1 (MKP-1), also known as dual specificity phosphatase-1 (DUSP-1), plays a crucial role in the deactivation of MAPKs. Several drugs with immune-suppressive properties modulate MKP-1 expression as part of their mechanism of action. We investigated the effect of mTOR inhibition through rapamycin and a dual mTOR inhibitor (AZD2014) on MKP-1 expression. Low dose rapamycin led to a rapid activation of both AKT and ERK pathways with a subsequent increase in MKP-1 expression. Rapamycin treatment led to phosphorylation of CREB, transcription factor 1 (ATF1), and ATF2, three transcription factors that bind to the cyclic AMP-responsive elements on the Mkp-1 promoter. Inhibition of either the MEK/ERK or the AKT pathway attenuated rapamycin-mediated MKP-1 induction. AZD2014 did not activate AKT but activated the ERK pathway, leading to a moderate MKP-1 induction. Using bone marrow-derived macrophages (BMDMs) derived from wild-type (WT) mice or mice deficient in AKT1 and AKT2 isoforms or BMDM from targeted deficiency in MEK1 and MEK2, we show that rapamycin treatment led to an increased MKP1 expression in BMDM from WT but failed to do so in BMDMs lacking the AKT1 isoform or MEK1 and MEK2. Importantly, rapamycin pretreatment inhibited LPS-mediated p38 activation and decreased nitric oxide and IL-6 production. Our work provides a conceptual framework for the observed immune modulatory effect of mTOR inhibition.

  18. Inhibition of leukocyte function and interleukin-2 gene expression by 2-methylarachidonyl-(2'-fluoroethyl)amide, a stable congener of the endogenous cannabinoid receptor ligand anandamide

    International Nuclear Information System (INIS)

    Arachidonylethanolamide (anandamide, AEA) has been identified as an endogenous ligand for cannabinoid receptors CB1 and CB2. Characterization of the direct cannabimimetic actions of anandamide has been hampered by its short duration of action and rapid degradation in in vivo and in vitro systems to arachidonic acid, a precursor in the biosynthesis of a broad range of biologically active molecules. In the present studies, we utilized 2-methylarachidonyl-(2'-fluoroethyl)amide (F-Me-AEA), an analog of anandamide resistant to enzymatic degradation, to determine whether F-Me-AEA modulated T cell function similar to that of plant-derived cannabinoids. Indeed, F-Me-AEA at low micromolar concentrations exhibited a marked inhibition of phorbol ester plus calcium ionophore (PMA/Io)-induced IL-2 protein secretion and steady state mRNA expression. Likewise, a modest suppression of the mixed lymphocyte response was observed in the presence of F-Me-AEA indicating an alteration in T cell responsiveness to allogeneic MHC class II antigens. F-Me-AEA was also found to modestly inhibit forskolin-stimulated adenylate cyclase activity in thymocytes and splenocytes, a hallmark of cannabinoid receptor agonists. Further characterization of the influence of F-Me-AEA on the cAMP signaling cascade revealed an inhibition of CREB-1/ATF-1 phosphorylation and subsequently, an inhibition of CRE DNA binding activity. Characterization of nuclear binding proteins further revealed that NF-AT and, to a lesser extent, NF-κB DNA binding activities were also suppressed. These studies demonstrate that F-Me-AEA modulates T cell function in a similar manner to plant-derived and endogenous cannabinoids and therefore can be utilized as an amidase- and hydrolysis-resistant endogenous cannabinoid

  19. Genomics of glycopeptidolipid biosynthesis in Mycobacterium abscessus and M. chelonae

    Directory of Open Access Journals (Sweden)

    Etienne Gilles

    2007-05-01

    Full Text Available Abstract Background The outermost layer of the bacterial surface is of crucial importance because it is in constant interaction with the host. Glycopeptidolipids (GPLs are major surface glycolipids present on various mycobacterial species. In the fast-grower model organism Mycobacterium smegmatis, GPL biosynthesis involves approximately 30 genes all mapping to a single region of 65 kb. Results We have recently sequenced the complete genomes of two fast-growers causing human infections, Mycobacterium abscessus (CIP 104536T and M. chelonae (CIP 104535T. We show here that these two species contain genes corresponding to all those of the M. smegmatis "GPL locus", with extensive conservation of the predicted protein sequences consistent with the production of GPL molecules indistinguishable by biochemical analysis. However, the GPL locus appears to be split into several parts in M. chelonae and M. abscessus. One large cluster (19 genes comprises all genes involved in the synthesis of the tripeptide-aminoalcohol moiety, the glycosylation of the lipopeptide and methylation/acetylation modifications. We provide evidence that a duplicated acetyltransferase (atf1 and atf2 in M. abscessus and M. chelonae has evolved through specialization, being able to transfer one acetyl at once in a sequential manner. There is a second smaller and distant (M. chelonae, 900 kb; M. abscessus, 3 Mb cluster of six genes involved in the synthesis of the fatty acyl moiety and its attachment to the tripeptide-aminoalcohol moiety. The other genes are scattered throughout the genome, including two genes encoding putative regulatory proteins. Conclusion Although these three species produce identical GPL molecules, the organization of GPL genes differ between them, thus constituting species-specific signatures. An hypothesis is that the compact organization of the GPL locus in M. smegmatis represents the ancestral form and that evolution has scattered various pieces throughout the

  20. A marker-derived gene network reveals the regulatory role of PPARGC1A, HNF4G, and FOXP3 in intramuscular fat deposition of beef cattle.

    Science.gov (United States)

    Ramayo-Caldas, Y; Fortes, M R S; Hudson, N J; Porto-Neto, L R; Bolormaa, S; Barendse, W; Kelly, M; Moore, S S; Goddard, M E; Lehnert, S A; Reverter, A

    2014-07-01

    High intramuscular fat (IMF) awards price premiums to beef producers and is associated with meat quality and flavor. Studying gene interactions and pathways that affect IMF might unveil causative physiological mechanisms and inform genomic selection, leading to increased accuracy of predictions of breeding value. To study gene interactions and pathways, a gene network was derived from genetic markers associated with direct measures of IMF, other fat phenotypes, feedlot performance, and a number of meat quality traits relating to body conformation, development, and metabolism that might be plausibly expected to interact with IMF biology. Marker associations were inferred from genomewide association studies (GWAS) based on high density genotypes and 29 traits measured on 10,181 beef cattle animals from 3 breed types. For the network inference, SNP pairs were assessed according to the strength of the correlation between their additive association effects across the 29 traits. The co-association inferred network was formed by 2,434 genes connected by 28,283 edges. Topological network parameters suggested a highly cohesive network, in which the genes are strongly functionally interconnected. Pathway and network analyses pointed towards a trio of transcription factors (TF) as key regulators of carcass IMF: PPARGC1A, HNF4G, and FOXP3. Importantly, none of these genes would have been deemed as significantly associated with IMF from the GWAS. Instead, a total of 313 network genes show significant co-association with the 3 TF. These genes belong to a wide variety of biological functions, canonical pathways, and genetic networks linked to IMF-related phenotypes. In summary, our GWAS and network predictions are supported by the current literature and suggest a cooperative role for the 3 TF and other interacting genes including CAPN6, STC2, MAP2K4, EYA1, COPS5, XKR4, NR2E1, TOX, ATF1, ASPH, TGS1, and TTPA as modulators of carcass and meat quality traits in beef cattle.

  1. Final report on accident tolerant fuel performance analysis of APMT-Steel Clad/UO₂ fuel and APMT-Steel Clad/UN-U₃Si₅ fuel concepts

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-09-12

    In FY2014 our group completed and documented analysis of new Accident Tolerant Fuel (ATF) concepts using BISON. We have modeled the viability of moving from Zircaloy to stainless steel cladding in traditional light water reactors (LWRs). We have explored the reactivity penalty of this change using the MCNP-based burnup code Monteburns, while attempting to minimize this penalty by increasing the fuel pellet radius and decreasing the cladding thickness. Fuel performance simulations using BISON have also been performed to quantify changes to structural integrity resulting from thinner stainless steel claddings. We account for thermal and irradiation creep, fission gas swelling, thermal swelling and fuel relocation in the models for both Zircaloy and stainless steel claddings. Additional models that account for the lower oxidation stainless steel APMT are also invoked where available. Irradiation data for HT9 is used as a fallback in the absence of appropriate models. In this study the isotopic vectors within each natural element are varied to assess potential reactivity gains if advanced enrichment capabilities were levied towards cladding technologies. Recommendations on cladding thicknesses for a robust cladding as well as the constitutive components of a less penalizing composition are provided. In the first section (section 1-3), we present results accepted for publication in the 2014 TOPFUEL conference regarding the APMT/UO₂ ATF concept (J. Galloway & C. Unal, Accident Tolerant and Neutronically Favorable LWR Cladding, Proceedings of WRFPM 2014, Sendai, Japan, Paper No.1000050). Next we discuss our preliminary findings from the thermo-mechanical analysis of UN-U₃Si₅ fuel with APMT clad. In this analysis we used models developed from limited data that need to be updated when the irradiation data from ATF-1 test is available. Initial results indicate a swelling rate less than 1.5% is needed to prevent excessive clad stress.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-06-10

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

  3. Structural basis for the oligomerization-state switch from a dimer to a trimer of an engineered cortexillin-1 coiled-coil variant.

    Directory of Open Access Journals (Sweden)

    Saša Bjelić

    Full Text Available Coiled coils are well suited to drive subunit oligomerization and are widely used in applications ranging from basic research to medicine. The optimization of these applications requires a detailed understanding of the molecular determinants that control of coiled-coil formation. Although many of these determinants have been identified and characterized in great detail, a puzzling observation is that their presence does not necessarily correlate with the oligomerization state of a given coiled-coil structure. Thus, other determinants must play a key role. To address this issue, we recently investigated the unrelated coiled-coil domains from GCN4, ATF1 and cortexillin-1 as model systems. We found that well-known trimer-specific oligomerization-state determinants, such as the distribution of isoleucine residues at heptad-repeat core positions or the trimerization motif Arg-h-x-x-h-Glu (where h = hydrophobic amino acid; x = any amino acid, switch the peptide's topology from a dimer to a trimer only when inserted into the trigger sequence, a site indispensable for coiled-coil formation. Because high-resolution structural information could not be obtained for the full-length, three-stranded cortexillin-1 coiled coil, we here report the detailed biophysical and structural characterization of a shorter variant spanning the trigger sequence using circular dichroism, anatytical ultracentrifugation and x-ray crystallography. We show that the peptide forms a stable α-helical trimer in solution. We further determined the crystal structure of an optimised variant at a resolution of 1.65 Å, revealing that the peptide folds into a parallel, three-stranded coiled coil. The two complemented R-IxxIE trimerization motifs and the additional hydrophobic core isoleucine residue adopt the conformations seen in other extensively characterized parallel, three-stranded coiled coils. These findings not only confirm the structural basis for the switch in

  4. Transcription factor proteomics: identification by a novel gel mobility shift-three-dimensional electrophoresis method coupled with southwestern blot and high-performance liquid chromatography-electrospray-mass spectrometry analysis.

    Science.gov (United States)

    Jiang, Daifeng; Jia, Yinshan; Jarrett, Harry W

    2011-09-28

    Transcription factor (TF) purification and identification is an important step in elucidating gene regulatory mechanisms. In this study, we present two new electrophoretic mobility shift assay (EMSA)-based multi-dimensional electrophoresis approaches to isolate and characterize TFs, using detection with either southwestern or western blotting and HPLC-nanoESI-MS/MS analysis for identification. These new techniques involve several major steps. First, EMSA is performed with agents that diminish non-specific DNA-binding and the DNA-protein complex is separated by native PAGE gel. The gel is then electrotransferred to PVDF membrane and visualized by autoradiography. Next, the DNA-protein complex, which has been transferred onto the blot, is extracted using a detergent-containing elution buffer. Following detergent removal, concentrated extract is separated by SDS-PAGE (EMSA-2DE), followed by in-gel trypsin digestion and HPLC-nanoESI-MS/MS analysis, or the concentrated extract is separated by two-dimensional gel electrophoresis (EMSA-3DE), followed by southwestern or western blot analysis to localize DNA binding proteins on blot which are further identified by on-blot trypsin digestion and HPLC-nanoESI-MS/MS analysis. Finally, the identified DNA binding proteins are further validated by EMSA-immunoblotting or EMSA antibody supershift assay. This approach is used to purify and identify GFP-C/EBP fusion protein from bacterial crude extract, as well as purifying AP1 and CEBP DNA binding proteins from a human embryonic kidney cell line (HEK293) nuclear extract. AP1 components, c-Jun, Jun-D, c-Fos, CREB, ATF1 and ATF2 were successfully identified from 1.5 mg of nuclear extract (equivalent to 3×10(7) HEK293 cells) with AP1 binding activity of 750 fmol. In conclusion, this new strategy of combining EMSA with additional dimensions of electrophoresis and using southwestern blotting for detection proves to be a valuable approach in the identification of transcriptional complexes

  5. Recurrent Coding Sequence Variation Explains Only A Small Fraction of the Genetic Architecture of Colorectal Cancer

    Science.gov (United States)

    Timofeeva, Maria N.; Kinnersley, Ben; Farrington, Susan M.; Whiffin, Nicola; Palles, Claire; Svinti, Victoria; Lloyd, Amy; Gorman, Maggie; Ooi, Li-Yin; Hosking, Fay; Barclay, Ella; Zgaga, Lina; Dobbins, Sara; Martin, Lynn; Theodoratou, Evropi; Broderick, Peter; Tenesa, Albert; Smillie, Claire; Grimes, Graeme; Hayward, Caroline; Campbell, Archie; Porteous, David; Deary, Ian J.; Harris, Sarah E.; Northwood, Emma L.; Barrett, Jennifer H.; Smith, Gillian; Wolf, Roland; Forman, David; Morreau, Hans; Ruano, Dina; Tops, Carli; Wijnen, Juul; Schrumpf, Melanie; Boot, Arnoud; Vasen, Hans F A; Hes, Frederik J.; van Wezel, Tom; Franke, Andre; Lieb, Wolgang; Schafmayer, Clemens; Hampe, Jochen; Buch, Stephan; Propping, Peter; Hemminki, Kari; Försti, Asta; Westers, Helga; Hofstra, Robert; Pinheiro, Manuela; Pinto, Carla; Teixeira, Manuel; Ruiz-Ponte, Clara; Fernández-Rozadilla, Ceres; Carracedo, Angel; Castells, Antoni; Castellví-Bel, Sergi; Campbell, Harry; Bishop, D. Timothy; Tomlinson, Ian P M; Dunlop, Malcolm G.; Houlston, Richard S.

    2015-01-01

    Whilst common genetic variation in many non-coding genomic regulatory regions are known to impart risk of colorectal cancer (CRC), much of the heritability of CRC remains unexplained. To examine the role of recurrent coding sequence variation in CRC aetiology, we genotyped 12,638 CRCs cases and 29,045 controls from six European populations. Single-variant analysis identified a coding variant (rs3184504) in SH2B3 (12q24) associated with CRC risk (OR = 1.08, P = 3.9 × 10−7), and novel damaging coding variants in 3 genes previously tagged by GWAS efforts; rs16888728 (8q24) in UTP23 (OR = 1.15, P = 1.4 × 10−7); rs6580742 and rs12303082 (12q13) in FAM186A (OR = 1.11, P = 1.2 × 10−7 and OR = 1.09, P = 7.4 × 10−8); rs1129406 (12q13) in ATF1 (OR = 1.11, P = 8.3 × 10−9), all reaching exome-wide significance levels. Gene based tests identified associations between CRC and PCDHGA genes (P < 2.90 × 10−6). We found an excess of rare, damaging variants in base-excision (P = 2.4 × 10−4) and DNA mismatch repair genes (P = 6.1 × 10−4) consistent with a recessive mode of inheritance. This study comprehensively explores the contribution of coding sequence variation to CRC risk, identifying associations with coding variation in 4 genes and PCDHG gene cluster and several candidate recessive alleles. However, these findings suggest that recurrent, low-frequency coding variants account for a minority of the unexplained heritability of CRC. PMID:26553438

  6. A closer look at evolution: Variants (SNPs) of genes involved in skin pigmentation, including EXOC2, TYR, TYRP1, and DCT, are associated with 25(OH)D serum concentration.

    Science.gov (United States)

    Saternus, Roman; Pilz, Stefan; Gräber, Stefan; Kleber, Marcus; März, Winfried; Vogt, Thomas; Reichrath, Jörg

    2015-01-01

    Vitamin D deficiency is common in the Caucasian population and is associated with increased incidence and unfavorable outcome of many diseases, including various types of cancer, infectious, cardiovascular, and autoimmune diseases. Individual factors that predispose for a person's vitamin D status, such as skin type, have been identified, but limited data exist on genetic determinants of serum 25-hydroxyvitamin D (25[OH]D) concentration. We have tested the hypothesis that variants of genes (single nucleotide polymorphisms [SNPs]) involved in skin pigmentation are predictive of serum 25(OH)D levels. Serum 25(OH)D and SNPs (n = 960) related to genes with relevance for skin pigmentation (tyrosinase [TYR], TYR-related protein 1 [TYRP1], dopachrome tautomerase [DCT], oculocutaneous albinism II [OCA2], two pore segment channel 2 [TPCN2], solute carrier family 24 A4 [SLC24A4], solute carrier family 45 A2 [SLC45A2], agouti signalling peptide [ASIP], cyclic AMP-dependent transcription factor [ATF1], microphthalmia-associated transcription factor [MITF], proopiomelanocortin [POMC], cAMP-dependent protein kinase catalytic subunit beta [PRKACB], cAMP-dependent protein kinase catalytic subunit gamma [PRKACG], cAMP-dependent protein kinase type I-alpha regulatory subunit [PRKAR1A], cAMP-dependent protein kinase type II-alpha regulatory subunit [PRKAR2A], cAMP-dependent protein kinase type II-beta regulatory subunit [PRKAR2B], tubulin beta-3 chain/melanocortin receptor 1 [TUBB3/MC1R], Cadherin-1 [CDH1], catenin beta 1 [CTNNB1], Endothelin 1 [EDN1], endothelin 3 [EDN3], endothelin receptor type B [EDNRB], fibroblast growth factor 2 [FGF2], KIT, KIT ligand [KITLG], nerve growth factor [NGF], interferon regulatory factor 4 [IRF4], exocyst complex component 2 [EXOC2], and tumor protein 53 [TP53]) were analyzed in a cohort of participants of the Ludwigshafen Risk and Cardiovascular Health Study (n = 2970). A total of 46 SNPs were associated (P <.05) with lower or higher serum 25(OH