Current Research into Applications of Tomography for Fusion Diagnostics

Retrieving spatial distribution of plasma emissivity from line integrated measurements on tokamaks presents a challenging task due to ill-posedness of the tomography problem and limited number of the lines of sight. Modern methods of plasma tomography therefore implement a-priori information as well as constraints, in particular some form of penalisation of complexity. In this contribution, the current tomography methods under development (Tikhonov regularisation, Bayesian methods and neural networks) are briefly explained taking into account their potential for integration into the fusion reactor diagnostics. In particular, current development of the Minimum Fisher Regularisation method is exemplified with respect to real-time reconstruction capability, combination with spectral unfolding and other prospective tasks.EURATOM 63305

Seizure control in patients with epilepsy: the physician vs. medication factors

<p>Abstract</p> <p>Background</p> <p>Little is known about the relationship between types of healthcare providers and outcomes in patients with epilepsy. This study compares the relative effects of provider type (epileptologist vs. other neurologist) and pharmacologic treatment (newer vs. older antiepileptic drugs) on seizure control in patients with epilepsy.</p> <p>Methods</p> <p>We conducted a retrospective study of patients with medication-resistant epilepsy. Consecutive charts of 200 patients were abstracted using a standard case report form. For each patient, data included seizure frequency and medication use prior to, and while being treated by an epileptologist. Changes in seizure frequency were modeled using a generalized linear model.</p> <p>Results</p> <p>After transferring care from a general neurologist to specialized epilepsy center, patients experienced fewer seizures (p < 0.001) and were more frequently seizure-free (p < 0.001). The improved seizure control was not related to treatment with newer vs. older antiepileptic drugs (p = 0.305).</p> <p>Conclusion</p> <p>Our findings suggest an association between subspecialty epilepsy care and improved seizure control in patients with medication-resistant epilepsy. Further research should prospectively determine whether patients with medication-resistant epilepsy would benefit from being routinely referred to an epilepsy specialist.</p

A novel path to runaway electron mitigation via deuterium injection and current-driven MHD instability

Relativistic electron (RE) beams at high current density (low safety factor, q ( a )) yet very low free-electron density accessed with D-2 secondary injection in the DIII-D and JET tokamak are found to exhibit large-scale MHD instabilities that benignly terminate the RE beam. In JET, this technique has enabled termination of MA-level RE currents without measurable first-wall heating. This scenario thus offers an unexpected alternate pathway to achieve RE mitigation without collisional dissipation. Benign termination is explained by two synergistic effects. First, during the MHD-driven RE loss events both experiment and MHD orbit-loss modeling supports a significant increase in the wetted area of the RE loss. Second, as previously identified at JET and DIII-D, the fast kink loss timescale precludes RE beam regeneration and the resulting dangerous conversion of magnetic to RE kinetic energy. During the termination, the RE kinetic energy is lost to the wall, but the current fully transfers to the cold bulk thus enabling benign Ohmic dissipation of the magnetic energy on longer timescales via a conventional current quench. Hydrogenic (D-2) secondary injection is found to be the only injected species that enables access to the benign termination. D-2 injection: (1) facilitates access to low q ( a ) in existing devices (via reduced collisionality & resistivity), (2) minimizes the RE avalanche by 'purging' the high-Z atoms from the RE beam, (3) drives recombination of the background plasma, reducing the density and Alfven time, thus accelerating the MHD growth. This phenomenon is found to be accessible when crossing the low q ( a ) stability boundary with rising current, falling toroidal field, or contracting minor radius-the latter being the expected scenario for vertically unstable RE beams in ITER. While unexpected, this path scales favorably to fusion-grade tokamaks and offers a novel RE mitigation scenario in principle accessible with the day-one disruption mitigation system of ITER

Trafficking Defect and Proteasomal Degradation Contribute to the Phenotype of a Novel KCNH2 Long QT Syndrome Mutation

The Kv11.1 (hERG) K+ channel plays a fundamental role in cardiac repolarization. Missense mutations in KCNH2, the gene encoding Kv11.1, cause long QT syndrome (LQTS) and frequently cause channel trafficking-deficiencies. This study characterized the properties of a novel KCNH2 mutation discovered in a LQT2 patient resuscitated from a ventricular fibrillation arrest. Proband genotyping was performed by SSCP and DNA sequencing. The electrophysiological and biochemical properties of the mutant channel were investigated after expression in HEK293 cells. The proband manifested a QTc of 554 ms prior to electrolyte normalization. Mutation analysis revealed an autosomal dominant frameshift mutation at proline 1086 (P1086fs+32X; 3256InsG). Co-immunoprecipitation demonstrated that wild-type Kv11.1 and mutant channels coassemble. Western blot showed that the mutation did not produce mature complex-glycosylated Kv11.1 channels and coexpression resulted in reduced channel maturation. Electrophysiological recordings revealed mutant channel peak currents to be similar to untransfected cells. Co-expression of channels in a 1∶1 ratio demonstrated dominant negative suppression of peak Kv11.1 currents. Immunocytochemistry confirmed that mutant channels were not present at the plasma membrane. Mutant channel trafficking rescue was attempted by incubation at reduced temperature or with the pharmacological agents E-4031. These treatments did not significantly increase peak mutant currents or induce the formation of mature complex-glycosylated channels. The proteasomal inhibitor lactacystin increased the protein levels of the mutant channels demonstrating proteasomal degradation, but failed to induce mutant Kv11.1 protein trafficking. Our study demonstrates a novel dominant-negative Kv11.1 mutation, which results in degraded non-functional channels leading to a LQT2 phenotype

Delayed Rectifier and A-Type Potassium Channels Associated with Kv 2.1 and Kv 4.3 Expression in Embryonic Rat Neural Progenitor Cells

BACKGROUND: Because of the importance of voltage-activated K(+) channels during embryonic development and in cell proliferation, we present here the first description of these channels in E15 rat embryonic neural progenitor cells derived from the subventricular zone (SVZ). Activation, inactivation, and single-channel conductance properties of recorded progenitor cells were compared with those obtained by others when these Kv gene products were expressed in oocytes. METHODOLOGY/PRINCIPAL FINDINGS: Neural progenitor cells derived from the subventricular zone of E15 embryonic rats were cultured under conditions that did not promote differentiation. Immunocytochemical and Western blot assays for nestin expression indicated that almost all of the cells available for recording expressed this intermediate filament protein, which is generally accepted as a marker for uncommitted embryonic neural progenitor cells. However, a very small numbers of the cells expressed GFAP, a marker for astrocytes, O4, a marker for immature oligodendrocytes, and betaIII-tubulin, a marker for neurons. Using immunocytochemistry and Western blots, we detected consistently the expression of Kv2.1, and 4.3. In whole-cell mode, we recorded two outward currents, a delayed rectifier and an A-type current. CONCLUSIONS/SIGNIFICANCE: We conclude that Kv2.1, and 4.3 are expressed in E15 SVZ neural progenitor cells, and we propose that they may be associated with the delayed-rectifier and the A-type currents, respectively, that we recorded. These results demonstrate the early expression of delayed rectifier and A-type K(+) currents and channels in embryonic neural progenitor cells prior to the differentiation of these cells

Trafficking Defect and Proteasomal Degradation Contribute to the Phenotype of a Novel KCNH2 Long QT Syndrome Mutation

The Kv11.1 (hERG) K+ channel plays a fundamental role in cardiac repolarization. Missense mutations in KCNH2, the gene encoding Kv11.1, cause long QT syndrome (LQTS) and frequently cause channel trafficking-deficiencies. This study characterized the properties of a novel KCNH2 mutation discovered in a LQT2 patient resuscitated from a ventricular fibrillation arrest. Proband genotyping was performed by SSCP and DNA sequencing. The electrophysiological and biochemical properties of the mutant channel were investigated after expression in HEK293 cells. The proband manifested a QTc of 554 ms prior to electrolyte normalization. Mutation analysis revealed an autosomal dominant frameshift mutation at proline 1086 (P1086fs+32X; 3256InsG). Co-immunoprecipitation demonstrated that wild-type Kv11.1 and mutant channels coassemble. Western blot showed that the mutation did not produce mature complex-glycosylated Kv11.1 channels and coexpression resulted in reduced channel maturation. Electrophysiological recordings revealed mutant channel peak currents to be similar to untransfected cells. Co-expression of channels in a 1∶1 ratio demonstrated dominant negative suppression of peak Kv11.1 currents. Immunocytochemistry confirmed that mutant channels were not present at the plasma membrane. Mutant channel trafficking rescue was attempted by incubation at reduced temperature or with the pharmacological agents E-4031. These treatments did not significantly increase peak mutant currents or induce the formation of mature complex-glycosylated channels. The proteasomal inhibitor lactacystin increased the protein levels of the mutant channels demonstrating proteasomal degradation, but failed to induce mutant Kv11.1 protein trafficking. Our study demonstrates a novel dominant-negative Kv11.1 mutation, which results in degraded non-functional channels leading to a LQT2 phenotype

Overview of the TCV tokamak experimental programme

The tokamak a configuration variable (TCV) continues to leverage its unique shaping capabilities, flexible heating systems and modern control system to address critical issues in preparation for ITER and a fusion power plant. For the 2019-20 campaign its configurational flexibility has been enhanced with the installation of removable divertor gas baffles, its diagnostic capabilities with an extensive set of upgrades and its heating systems with new dual frequency gyrotrons. The gas baffles reduce coupling between the divertor and the main chamber and allow for detailed investigations on the role of fuelling in general and, together with upgraded boundary diagnostics, test divertor and edge models in particular. The increased heating capabilities broaden the operational regime to include T (e)/T (i) similar to 1 and have stimulated refocussing studies from L-mode to H-mode across a range of research topics. ITER baseline parameters were reached in type-I ELMy H-modes and alternative regimes with \u27small\u27 (or no) ELMs explored. Most prominently, negative triangularity was investigated in detail and confirmed as an attractive scenario with H-mode level core confinement but an L-mode edge. Emphasis was also placed on control, where an increased number of observers, actuators and control solutions became available and are now integrated into a generic control framework as will be needed in future devices. The quantity and quality of results of the 2019-20 TCV campaign are a testament to its successful integration within the European research effort alongside a vibrant domestic programme and international collaborations