Fast Ion Effects During Test Blanket Module Simulation Experiments in DIII-D

Fast beam-ion losses were studied in DIII-D in the presence of a scaled mockup of two Test Blanket Modules (TBM) for ITER. Heating of the protective tiles on the front of the TBM surface was found when neutral beams were injected and the TBM fields were engaged. The fast-ion core confinement was not significantly affected. Different orbit-following codes predict the formation of a hot spot on the TBM surface arising from beam-ions deposited near the edge of the plasma. The codes are in good agreement with each other on the total power deposited at the hot spot predicting an increase in power with decreasing separation between the plasma edge and the TBM surface. A thermal analysis of the heat flow through the tiles shows that the simulated power can account for the measured tile temperature rise. The thermal analysis, however, is very sensitive to the details of the localization of the hot spot which is predicted to be different among the various codes

Ciliary Beating Recovery in Deficient Human Airway Epithelial Cells after Lentivirus Ex Vivo Gene Therapy

Primary Ciliary Dyskinesia is a heterogeneous genetic disease that is characterized by cilia dysfunction of the epithelial cells lining the respiratory tracts, resulting in recurrent respiratory tract infections. Despite lifelong physiological therapy and antibiotics, the lungs of affected patients are progressively destroyed, leading to respiratory insufficiency. Recessive mutations in Dynein Axonemal Intermediate chain type 1 (DNAI1) gene have been described in 10% of cases of Primary Ciliary Dyskinesia. Our goal was to restore normal ciliary beating in DNAI1–deficient human airway epithelial cells. A lentiviral vector based on Simian Immunodeficiency Virus pseudotyped with Vesicular Stomatitis Virus Glycoprotein was used to transduce cultured human airway epithelial cells with a cDNA of DNAI1 driven by the Elongation Factor 1 promoter. Transcription and translation of the transduced gene were tested by RT–PCR and western blot, respectively. Human airway epithelial cells that were DNAI1–deficient due to compound heterozygous mutations, and consequently had immotile cilia and no outer dynein arm, were transduced by the lentivirus. Cilia beating was recorded and electron microscopy of the cilia was performed. Transcription and translation of the transduced DNAI1 gene were detected in human cells treated with the lentivirus. In addition, immotile cilia recovered a normal beat and outer dynein arms reappeared. We demonstrated that it is possible to obtain a normalization of ciliary beat frequency of deficient human airway epithelial cells by using a lentivirus to transduce cells with the therapeutic gene. This preliminary step constitutes a conceptual proof that is indispensable in the perspective of Primary Ciliary Dyskinesia's in vivo gene therapy. This is the first time that recovery of cilia beating is demonstrated in this disease

Ligand selectivity by seeking hydrophobicity in thyroid hormone receptor

Selective therapeutics for nuclear receptors would revolutionize treatment for endocrine disease. Specific control of nuclear receptor activity is challenging because the internal cavities that bind hormones can be virtually identical. Only one highly selective hormone analog is known for the thyroid receptor, GC-24, an agonist for human thyroid hormone receptor beta. The compound differs from natural hormone in benzyl, substituting for an iodine atom in the 3' position. The benzyl is too large to fit into the enclosed pocket of the receptor. The crystal structure of human thyroid hormone receptor beta at 2.8-A resolution with GC-24 bound explains its agonist activity and unique isoform specificity. The benzyl of GC-24 is accommodated through shifts of 3-4 A in two helices. These helices are required for binding hormone and positioning the critical helix 12 at the C terminus. Despite these changes, the complex associates with coactivator as tightly as human thyroid hormone receptor bound to thyroid hormone and is fully active. Our data suggest that increased specificity of ligand recognition derives from creating a new hydrophobic cluster with ligand and protein components

Advances in understanding the generation and evolution of the toroidal rotation profile on DIII-D

Recent experiments using DIII-D's capability to vary the injected torque at constant power have focused on developing the physics basis for understanding rotation through the detailed study of momentum sources, sinks and transport. Non-resonant magnetic braking has generally been considered a sink of momentum; however, recent results from DIII-D suggest that it may also act as a source. The torque applied by the field depends on the rotation relative to a non-zero 'offset' rotation. Therefore, at low initial rotation, the application of non-resonant magnetic fields can actually result in a spin-up of the plasma. Direct evidence of the effect of reverse shear Alfvén eigenmodes on plasma rotation has been observed, which has been explained through a redistribution of the fast ions and subsequent modification to the neutral beam torque profile. An effective momentum source has been identified by varying the input torque from neutral beam injection at fixed βN, until the plasma rotation across the entire profile is essentially zero. This torque profile is largest near the edge, but is still non-negligible in the core, qualitatively consistent with models for a so-called 'residual stress'. Perturbative studies of the rotation using combinations of co- and counter-neutral beams have uncovered the existence of a momentum pinch in DIII-D H-mode plasmas, which is quantitatively similar to theoretical predictions resulting from consideration of low-k turbulence. © 2009 IAEA, Vienna

Simulation of localized fast-ion heat loads in test blanket module simulation experiments on DIII-D

Infrared imaging of hot spots induced by localized magnetic perturbations using the test blanket module (TBM) mock-up on DIII-D is in good agreement with beam-ion loss simulations. The hot spots were seen on the carbon protective tiles surrounding the TBM as they reached temperatures over 1000 °C. The localization of the hot spots on the protective tiles is in fair agreement with fast-ion loss simulations using a range of codes: ASCOT, SPIRAL and OFMCs while the codes predicted peak heat loads that are within 30% of the measured ones. The orbit calculations take into account the birth profile of the beam ions as well as the scattering and slowing down of the ions as they interact with the localized TBM field. The close agreement between orbit calculations and measurements validate the analysis of beam-ion loss calculations for ITER where ferritic material inside the tritium breeding TBMs is expected to produce localized hot spots on the first wall. © 2013 IAEA, Vienna

Simulation of localized fast-ion heat loads in test blanket module simulation experiments on DIII-D

Infrared imaging of hot spots induced by localized magnetic perturbations using the test blanket module (TBM) mock-up on DIII-D is in good agreement with beam-ion loss simulations. The hot spots were seen on the carbon protective tiles surrounding the TBM as they reached temperatures over 1000 °C. The localization of the hot spots on the protective tiles is in fair agreement with fast-ion loss simulations using a range of codes: ASCOT, SPIRAL and OFMCs while the codes predicted peak heat loads that are within 30% of the measured ones. The orbit calculations take into account the birth profile of the beam ions as well as the scattering and slowing down of the ions as they interact with the localized TBM field. The close agreement between orbit calculations and measurements validate the analysis of beam-ion loss calculations for ITER where ferritic material inside the tritium breeding TBMs is expected to produce localized hot spots on the first wall. © 2013 IAEA, Vienna

Fast-ion effects during test blanket module simulation experiments in DIII-D

Fast beam-ion losses were studied in DIII-D in the presence of a scaled mock-up of two test blanket modules (TBM) for ITER. Heating of the protective tiles on the front of the TBM surface was found when neutral beams were injected and the TBM fields were engaged. The fast-ion core confinement was not significantly affected. Different orbit-following codes predict the formation of a hot spot on the TBM surface arising from beam ions deposited near the edge of the plasma. The codes are in good agreement with each other on the total power deposited at the hot spot, predicting an increase in power with decreasing separation between the plasma edge and the TBM surface. A thermal analysis of the heat flow through the tiles shows that the simulated power can account for the measured tile temperature rise. The thermal analysis, however, is very sensitive to the details of the localization of the hot spot, which is predicted to be different among the various codes. © 2011 IAEA, Vienna

Off-axis fishbone-like instability and excitation of resistive wall modes in JT-60U and DIII-D

An energetic-particle (EP)-driven off-axis-fishbone-like mode (OFM) often triggers a resistive wall mode (RWM) in JT-60U and DIII-D devices, preventing long-duration high-βN discharges. In these experiments, the EPs are energetic ions (70-85 keV) injected by neutral beams to produce high-pressure plasmas. EP-driven bursting events reduce the EP density and the plasma rotation simultaneously. These changes are significant in high-βN low-rotation plasmas, where the RWM stability is predicted to be strongly influenced by the EP precession drift resonance and by the plasma rotation near the q = 2 surface (kinetic effects). Analysis of these effects on stability with a self-consistent perturbation to the mode structure using the MARS-K code showed that the impact of EP losses and rotation drop is sufficient to destabilize the RWM in low-rotation plasmas, when the plasma rotation normalized by Alfvén frequency is only a few tenths of a percent near the q = 2 surface. The OFM characteristics are very similar in JT-60U and DIII-D, including nonlinear mode evolution. The modes grow initially like a classical fishbone, and then the mode structure becomes strongly distorted. The dynamic response of the OFM to an applied n = 1 external field indicates that the mode retains its external kink character. These comparative studies suggest that an energetic particle-driven off-axis-fishbone-like mode is a new EP-driven branch of the external kink mode in wall-stabilized plasmas, analogous to the relationship of the classical fishbone branch to the internal kink mode. © 2011 American Institute of Physics

Off-axis fishbone-like instability and excitation of resistive wall modes in JT-60U and DIII-D

An energetic-particle (EP)-driven off-axis-fishbone-like mode (OFM) often triggers a resistive wall mode (RWM) in JT-60U and DIII-D devices, preventing long-duration high-βN discharges. In these experiments, the EPs are energetic ions (70-85 keV) injected by neutral beams to produce high-pressure plasmas. EP-driven bursting events reduce the EP density and the plasma rotation simultaneously. These changes are significant in high-βN low-rotation plasmas, where the RWM stability is predicted to be strongly influenced by the EP precession drift resonance and by the plasma rotation near the q = 2 surface (kinetic effects). Analysis of these effects on stability with a self-consistent perturbation to the mode structure using the MARS-K code showed that the impact of EP losses and rotation drop is sufficient to destabilize the RWM in low-rotation plasmas, when the plasma rotation normalized by Alfvén frequency is only a few tenths of a percent near the q = 2 surface. The OFM characteristics are very similar in JT-60U and DIII-D, including nonlinear mode evolution. The modes grow initially like a classical fishbone, and then the mode structure becomes strongly distorted. The dynamic response of the OFM to an applied n = 1 external field indicates that the mode retains its external kink character. These comparative studies suggest that an energetic particle-driven off-axis-fishbone-like mode is a new EP-driven branch of the external kink mode in wall-stabilized plasmas, analogous to the relationship of the classical fishbone branch to the internal kink mode. © 2011 American Institute of Physics