Structural plasticity of the cardiac nuclear pore complex in response to regulators of nuclear import

Abstract-Communication between the cytoplasm and nucleoplasm of cardiac cells occurs by molecular transport through nuclear pores. In lower eukaryotes, nuclear transport requires the maintenance of cellular energetics and ion homeostasis. Although heart muscle is particularly sensitive to metabolic stress, the regulation of nuclear transport through nuclear pores in cardiomyocytes has not yet been characterized. With the use of laser confocal and atomic force microscopy, we observed nuclear transport in cardiomyocytes and the structure of individual nuclear pores under different cellular conditions. In response to the depletion of Ca 2ϩ stores or ATP/GTP pools, the cardiac nuclear pore complex adopted 2 distinct conformations that led to different patterns of nuclear import regulation. Depletion of Ca 2ϩ indiscriminately prevented the nuclear import of macromolecules through closure of the nuclear pore opening. Depletion of ATP/GTP only blocked facilitated transport through a simultaneous closure of the pore and relaxation of the entire complex, which allowed other molecules to pass into the nucleus through peripheral routes. The current study of the structural plasticity of the cardiac nuclear pore complex, which was observed in response to changes in cellular conditions, identifies a gating mechanism for molecular translocation across the nuclear envelope of cardiac cells. The cardiac nuclear pore complex serves as a conduit that differentially regulates nuclear transport of macromolecules and provides a mechanism for the control of nucleocytoplasmic communication in cardiac cells, in particular under stress conditions associated with disturbances in cellular bioenergetics and Ca 2ϩ homeostasis. (Circ Res. 1999;84:1292-1301.

Progress from ASDEX Upgrade experiments in preparing the physics basis of ITER operation and DEMO scenario development

An overview of recent results obtained at the tokamak ASDEX Upgrade (AUG) is given. A work flow for predictive profile modelling of AUG discharges was established which is able to reproduce experimental H-mode plasma profiles based on engineering parameters only. In the plasma center, theoretical predictions on plasma current redistribution by a dynamo effect were confirmed experimentally. For core transport, the stabilizing effect of fast ion distributions on turbulent transport is shown to be important to explain the core isotope effect and improves the description of hollow low-Z impurity profiles. The L-H power threshold of hydrogen plasmas is not affected by small helium admixtures and it increases continuously from the deuterium to the hydrogen level when the hydrogen concentration is raised from 0 to 100%. One focus of recent campaigns was the search for a fusion relevant integrated plasma scenario without large edge localised modes (ELMs). Results from six different ELM-free confinement regimes are compared with respect to reactor relevance: ELM suppression by magnetic perturbation coils could be attributed to toroidally asymmetric turbulent fluctuations in the vicinity of the separatrix. Stable improved confinement mode plasma phases with a detached inner divertor were obtained using a feedback control of the plasma β. The enhanced D α H-mode regime was extended to higher heating power by feedback controlled radiative cooling with argon. The quasi-coherent exhaust regime was developed into an integrated scenario at high heating power and energy confinement, with a detached divertor and without large ELMs. Small ELMs close to the separatrix lead to peeling-ballooning stability and quasi continuous power exhaust. Helium beam density fluctuation measurements confirm that transport close to the separatrix is important to achieve the different ELM-free regimes. Based on separatrix plasma parameters and interchange-drift-Alfvén turbulence, an analytic model was derived that reproduces the experimentally found important operational boundaries of the density limit and between L- and H-mode confinement. Feedback control for the X-point radiator (XPR) position was established as an important element for divertor detachment control. Stable and detached ELM-free phases with H-mode confinement quality were obtained when the XPR was moved 10 cm above the X-point. Investigations of the plasma in the future flexible snow-flake divertor of AUG by means of first SOLPS-ITER simulations with drifts activated predict beneficial detachment properties and the activation of an additional strike point by the drifts

Overview of physics studies on ASDEX Upgrade

The ASDEX Upgrade (AUG) programme, jointly run with the EUROfusion MST1 task force, continues to significantly enhance the physics base of ITER and DEMO. Here, the full tungsten wall is a key asset for extrapolating to future devices. The high overall heating power, flexible heating mix and comprehensive diagnostic set allows studies ranging from mimicking the scrape-off-layer and divertor conditions of ITER and DEMO at high density to fully non-inductive operation (q 95 = 5.5, ) at low density. Higher installed electron cyclotron resonance heating power 6 MW, new diagnostics and improved analysis techniques have further enhanced the capabilities of AUG. Stable high-density H-modes with MW m-1 with fully detached strike-points have been demonstrated. The ballooning instability close to the separatrix has been identified as a potential cause leading to the H-mode density limit and is also found to play an important role for the access to small edge-localized modes (ELMs). Density limit disruptions have been successfully avoided using a path-oriented approach to disruption handling and progress has been made in understanding the dissipation and avoidance of runaway electron beams. ELM suppression with resonant magnetic perturbations is now routinely achieved reaching transiently . This gives new insight into the field penetration physics, in particular with respect to plasma flows. Modelling agrees well with plasma response measurements and a helically localised ballooning structure observed prior to the ELM is evidence for the changed edge stability due to the magnetic perturbations. The impact of 3D perturbations on heat load patterns and fast-ion losses have been further elaborated. Progress has also been made in understanding the ELM cycle itself. Here, new fast measurements of and E r allow for inter ELM transport analysis confirming that E r is dominated by the diamagnetic term even for fast timescales. New analysis techniques allow detailed comparison of the ELM crash and are in good agreement with nonlinear MHD modelling. The observation of accelerated ions during the ELM crash can be seen as evidence for the reconnection during the ELM. As type-I ELMs (even mitigated) are likely not a viable operational regime in DEMO studies of 'natural' no ELM regimes have been extended. Stable I-modes up to have been characterised using -feedback. Core physics has been advanced by more detailed characterisation of the turbulence with new measurements such as the eddy tilt angle - measured for the first time - or the cross-phase angle of and fluctuations. These new data put strong constraints on gyro-kinetic turbulence modelling. In addition, carefully executed studies in different main species (H, D and He) and with different heating mixes highlight the importance of the collisional energy exchange for interpreting energy confinement. A new regime with a hollow profile now gives access to regimes mimicking aspects of burning plasma conditions and lead to nonlinear interactions of energetic particle modes despite the sub-Alfvénic beam energy. This will help to validate the fast-ion codes for predicting ITER and DEMO

An overview of recent physics results from NSTX

The National Spherical Torus Experiment (NSTX) is currently being upgraded to operate at twice the toroidal field and plasma current (up to 1 T and 2 MA), with a second, more tangentially aimed neutral beam (NB) for current and rotation control, allowing for pulse lengths up to 5 s. Recent NSTX physics analyses have addressed topics that will allow NSTX-Upgrade to achieve the research goals critical to a Fusion Nuclear Science Facility. These include producing stable, 100% non-inductive operation in high-performance plasmas, assessing plasma-material interface (PMI) solutions to handle the high heat loads expected in the next-step devices and exploring the unique spherical torus (ST) parameter regimes to advance predictive capability. Non-inductive operation and current profile control in NSTX-U will be facilitated by co-axial helicity injection (CHI) as well as radio frequency (RF) and NB heating. CHI studies using NIMROD indicate that the reconnection process is consistent with the 2D Sweet-Parker theory. Full-wave AORSA simulations show that RF power losses in the scrape-off layer (SOL) increase significantly for both NSTX and NSTX-U when the launched waves propagate in the SOL. Toroidal Alfven eigenmode avalanches and higher frequency Alfven eigenmodes can affect NB-driven current through energy loss and redistribution of fast ions. The inclusion of rotation and kinetic resonances, which depend on collisionality, is necessary for predicting experimental stability thresholds of fast growing ideal wall and resistive wall modes. Neutral beams and neoclassical toroidal viscosity generated from applied 3D fields can be used as actuators to produce rotation profiles optimized for global stability. DEGAS-2 has been used to study the dependence of gas penetration on SOL temperatures and densities for the MGI system being implemented on the Upgrade for disruption mitigation. PMI studies have focused on the effect of ELMs and 3D fields on plasma detachment and heat flux handling. Simulations indicate that snowflake and impurity seeded radiative divertors are candidates for heat flux mitigation in NSTX-U. Studies of lithium evaporation on graphite surfaces indicate that lithium increases oxygen surface concentrations on graphite, and deuterium-oxygen affinity, which increases deuterium pumping and reduces recycling. In situ and test-stand experiments of lithiated graphite and molybdenum indicate temperature-enhanced sputtering, although that test-stand studies also show the potential for heat flux reduction through lithium vapour shielding. Non-linear gyro kinetic simulations have indicated that ion transport can be enhanced by a shear-flow instability, and that non-local effects are necessary to explain the observed rapid changes in plasma turbulence. Predictive simulations have shown agreement between a microtearing-based reduced transport model and the measured electron temperatures in a microtearing unstable regime. Two Alfven eigenmode-driven fast ion transport models have been developed and successfully benchmarked against NSTX data. Upgrade construction is moving on schedule with initial physics research operation of NSTX-U planned for mid-2015

Overview of physics results from NSTX

In the last two experimental campaigns, the low aspect ratio NSTX has explored physics issues critical to both toroidal confinement physics and ITER. Experiments have made extensive use of lithium coatings for wall conditioning, correction of non-axisymmetric field errors and control of n = 1 resistive wall modes (RWMs) to produce high-performance neutral-beam heated discharges extending to 1.7 s in duration with non-inductive current fractions up to 0.7. The RWM control coils have been used to trigger repetitive ELMs with high reliability, and they have also contributed to an improved understanding of both neoclassical tearing mode and RWM stabilization physics, including the interplay between rotation and kinetic effects on stability. High harmonic fast wave (HHFW) heating has produced plasmas with central electron temperatures exceeding 6 keV. The HHFW heating was used to show that there was a 20-40% higher power threshold for the L-H transition for helium than for deuterium plasmas. A new diagnostic showed a depletion of the fast-ion density profile over a broad spatial region as a result of toroidicity-induced Alfvén eigenmodes (TAEs) and energetic-particle modes (EPMs) bursts. In addition, it was observed that other modes (e.g. global Alfvén eigenmodes) can trigger TAE and EPM bursts, suggesting that fast ions are redistributed by high-frequency AEs. The momentum pinch velocity determined by a perturbative technique decreased as the collisionality was reduced, although the pinch to diffusion ratio, Vpinch/χ, remained approximately constant. The mechanisms of deuterium retention by graphite and lithium-coated graphite plasma-facing components have been investigated. To reduce divertor heat flux, a novel divertor configuration, the 'snowflake' divertor, was tested in NSTX and many beneficial aspects were found. A reduction in the required central solenoid flux has been realized in NSTX when discharges initiated by coaxial helicity injection were ramped in current using induction. The resulting plasmas have characteristics needed to meet the objectives of the non-inductive start-up and ramp-up program of NSTX. © 2011 IAEA, Vienna

Overview of physics results from the conclusive operation of the National Spherical Torus Experiment

Research on the National Spherical Torus Experiment, NSTX, targets physics understanding needed for extrapolation to a steady-state ST Fusion Nuclear Science Facility, pilot plant, or DEMO. The unique ST operational space is leveraged to test physics theories for next-step tokamak operation, including ITER. Present research also examines implications for the coming device upgrade, NSTX-U. An energy confinement time, tau(E), scaling unified for varied wall conditions exhibits a strong improvement of B-T tau(E) with decreased electron collisionality, accentuated by lithium (Li) wall conditioning. This result is consistent with nonlinear microtearing simulations that match the experimental electron diffusivity quantitatively and predict reduced electron heat transport at lower collisionality. Beam-emission spectroscopy measurements in the steep gradient region of the pedestal indicate the poloidal correlation length of turbulence of about ten ion gyroradii increases at higher electron density gradient and lower T-i gradient, consistent with turbulence caused by trapped electron instabilities. Density fluctuations in the pedestal top region indicate ion-scale microturbulence compatible with ion temperature gradient and/or kinetic ballooning mode instabilities. Plasma characteristics change nearly continuously with increasing Li evaporation and edge localized modes (ELMs) stabilize due to edge density gradient alteration. Global mode stability studies show stabilizing resonant kinetic effects are enhanced at lower collisionality, but in stark contrast have almost no dependence on collisionality when the plasma is off-resonance. Combined resistive wall mode radial and poloidal field sensor feedback was used to control n = 1 perturbations and improve stability. The disruption probability due to unstable resistive wall modes (RWMs) was surprisingly reduced at very high beta(N)/l(i) > 10 consistent with low frequency magnetohydrodynamic spectroscopy measurements of mode stability. Greater instability seen at intermediate beta(N) is consistent with decreased kinetic RWM stabilization. A model-based RWM state-space controller produced long-pulse discharges exceeding beta(N) = 6.4 and beta(N)/l(i) = 13. Precursor analysis shows 96.3% of disruptions can be predicted with 10 ms warning and a false positive rate of only 2.8%. Disruption halo currents rotate toroidally and can have significant toroidal asymmetry. Global kinks cause measured fast ion redistribution, with full-orbit calculations showing redistribution from the core outward and towards V-parallel to/V = 1 where destabilizing compressional Alfven eigenmode resonances are expected. Applied 3D fields altered global Alfven eigenmode characteristics. High-harmonic fast-wave (HHFW) power couples to field lines across the entire width of the scrape-off layer, showing the importance of the inclusion of this phenomenon in designing future RF systems. The snowflake divertor configuration enhanced by radiative detachment showed large reductions in both steady-state and ELM heat fluxes (ELMing peak values down from 19 MW m(-2) to less than 1.5 MW m(-2)). Toroidal asymmetry of heat deposition was observed during ELMs or by 3D fields. The heating power required for accessing H-mode decreased by 30% as the triangularity was decreased by moving the X-point to larger radius, consistent with calculations of the dependence of E x B shear in the edge region on ion heat flux and X-point radius. Co-axial helicity injection reduced the inductive start-up flux, with plasmas ramped to 1 MA requiring 35% less inductive flux. Non-inductive current fraction (NICF) up to 65% is reached experimentally with neutral beam injection at plasma current I-p = 0.7 MA and between 70-100% with HHFW application at I-p = 0.3 MA. NSTX-U scenario development calculations project 100% NICF for a large range of 0.6 < I-p(MA) < 1.35close117

Progress from ASDEX Upgrade experiments in preparing the physics basis of ITER operation and DEMO scenario development

International audienceAbstract An overview of recent results obtained at the tokamak ASDEX Upgrade (AUG) is given. A work flow for predictive profile modelling of AUG discharges was established which is able to reproduce experimental H-mode plasma profiles based on engineering parameters only. In the plasma center, theoretical predictions on plasma current redistribution by a dynamo effect were confirmed experimentally. For core transport, the stabilizing effect of fast ion distributions on turbulent transport is shown to be important to explain the core isotope effect and improves the description of hollow low- Z impurity profiles. The L–H power threshold of hydrogen plasmas is not affected by small helium admixtures and it increases continuously from the deuterium to the hydrogen level when the hydrogen concentration is raised from 0 to 100%. One focus of recent campaigns was the search for a fusion relevant integrated plasma scenario without large edge localised modes (ELMs). Results from six different ELM-free confinement regimes are compared with respect to reactor relevance: ELM suppression by magnetic perturbation coils could be attributed to toroidally asymmetric turbulent fluctuations in the vicinity of the separatrix. Stable improved confinement mode plasma phases with a detached inner divertor were obtained using a feedback control of the plasma β . The enhanced D α H-mode regime was extended to higher heating power by feedback controlled radiative cooling with argon. The quasi-coherent exhaust regime was developed into an integrated scenario at high heating power and energy confinement, with a detached divertor and without large ELMs. Small ELMs close to the separatrix lead to peeling-ballooning stability and quasi continuous power exhaust. Helium beam density fluctuation measurements confirm that transport close to the separatrix is important to achieve the different ELM-free regimes. Based on separatrix plasma parameters and interchange-drift-Alfvén turbulence, an analytic model was derived that reproduces the experimentally found important operational boundaries of the density limit and between L- and H-mode confinement. Feedback control for the X-point radiator (XPR) position was established as an important element for divertor detachment control. Stable and detached ELM-free phases with H-mode confinement quality were obtained when the XPR was moved 10 cm above the X-point. Investigations of the plasma in the future flexible snow-flake divertor of AUG by means of first SOLPS-ITER simulations with drifts activated predict beneficial detachment properties and the activation of an additional strike point by the drifts