Suppression of Alfvén Modes on the National Spherical Torus Experiment Upgrade with Outboard Beam Injection.

In this Letter we present data from experiments on the National Spherical Torus Experiment Upgrade, where it is shown for the first time that small amounts of high pitch-angle beam ions can strongly suppress the counterpropagating global Alfvén eigenmodes (GAE). GAE have been implicated in the redistribution of fast ions and modification of the electron power balance in previous experiments on NSTX. The ability to predict the stability of Alfvén modes, and developing methods to control them, is important for fusion reactors like the International Tokamak Experimental Reactor, which are heated by a large population of nonthermal, super-Alfvénic ions consisting of fusion generated α's and beam ions injected for current profile control. We present a qualitative interpretation of these observations using an analytic model of the Doppler-shifted ion-cyclotron resonance drive responsible for GAE instability which has an important dependence on k_{⊥}ρ_{L}. A quantitative analysis of this data with the hym stability code predicts both the frequencies and instability of the GAE prior to, and suppression of the GAE after the injection of high pitch-angle beam ions.

The goal of making friends for youth with disabilities: creating a goal menu.

BACKGROUND: Clinicians working with youth with disabilities have acknowledged making friends as a commonly identified client goal. Clinicians find this goal difficult to address, as there are no measures that provide a breakdown of making friends into functional steps. In addition, research on friendship has traditionally focused on characteristics and quality of friendships rather than the friend-making process as a whole. A goal menu, comprised of a variety of steps that address the goal of making friends, would provide guidance to clinicians challenged with this goal in practice. PURPOSE: To develop an understanding of the friend-making process as a first step towards the development of a goal menu for the goal of making friends. METHODS: A literature review, youth focus group and expert clinician semi-structured interviews and consultation were used to generate a comprehensive data set. Established qualitative methods were used to sort and group the data into categories. A thematic analysis of the categories was performed. RESULTS: Analysis revealed four themes integral to the friend-making process: person factors influencing friend-making, making friend-making a priority, opportunity for friend-making and motivation to make friends. An additional theme identified as occasionally involved in the process was a little bit of luck in making friends. CONCLUSIONS: The themes generated by this research indicate that actionable target areas exist for the somewhat abstract notion of friend-making and the authors recommend that clinicians explore beyond person factors when addressing the goal of making friends. As a next step, the identified themes will provide the foundation for a goal menu, ultimately enabling clinicians to address the goal of making friends in a more efficient and effective manner.

High-harmonic fast-wave power flow along magnetic field lines in the scrape-off layer of NSTX.

A significant fraction of high-harmonic fast-wave (HHFW) power applied to NSTX can be lost to the scrape-off layer (SOL) and deposited in bright and hot spirals on the divertor rather than in the core plasma. We show that the HHFW power flows to these spirals along magnetic field lines passing through the SOL in front of the antenna, implying that the HHFW power couples across the entire width of the SOL rather than mostly at the antenna face. This result will help guide future efforts to understand and minimize these edge losses in order to maximize fast-wave heating and current drive.

AC compensation of 3D magnetic diagnostic signals in DIII-D and National Spherical Torus Experiment-Upgrade (NSTX-U) for real-time application.

A time domain algorithm has been developed to remove the vacuum pickup generated by both coil current (DC) and induced vessel current (AC) in real time from three dimensional (3D) magnetic diagnostic signals in the National Spherical Torus Experiment-Upgrade (NSTX-U) and DIII-D tokamaks. The possibility of detecting 3D plasma perturbations in real time is essential in modern and future tokamaks to avoid and control MHD instabilities. The presence of vacuum field pickup, due to toroidally asymmetric (3D) coils or to misalignment between sensors and axisymmetric (2D) coils, pollutes the measured plasma 3D field, making the detection of the magnetic field produced by the plasma challenging. Although the DC coupling between coils and sensors can be easily calculated and removed, the AC part is more difficult. An algorithm based on a layered low-pass filter approach for the AC compensation and its application for DIII-D and NSTX-U data is presented, showing that this method reduces the vacuum pickup to the noise level. Comparison of plasma response measurements with and without vacuum compensation shows that accurate mode locking detection and plasma response identification require precise AC and DC compensations.

Effect of collisionality on kinetic stability of the resistive wall mode.

The impact of collisionless, energy-independent, and energy-dependent collisionality models on the kinetic stability of the resistive wall mode is examined for high pressure plasmas in the National Spherical Torus Experiment. Future devices will have decreased collisionality, which previous stability models predict to be universally destabilizing. In contrast, in kinetic theory reduced ion-ion collisions are shown to lead to a significant stability increase when the plasma rotation frequency is in a stabilizing resonance with the ion precession drift frequency. When the plasma is in a reduced stability state with rotation in between resonances, collisionality will have little effect on stability.

Resistive wall mode instability at intermediate plasma rotation.

Experimental observation of resistive wall mode (RWM) instability in the National Spherical Torus Experiment (NSTX) at plasma rotation levels intermediate to the ion precession drift and ion bounce frequencies suggests that low critical rotation threshold models are insufficient. Kinetic modifications to the ideal stability criterion yield a more complex relationship between plasma rotation and RWM stability. Good agreement is found between an experimental RWM instability at intermediate plasma rotation and the RWM marginal point calculated with kinetic effects included, by the MISK code. By self-similarly scaling the experimental plasma rotation profile and the collisionality in the calculation, resonances of the mode with the precession drift and bounce frequencies are explored. Experimentally, RWMs go unstable when the plasma rotation is between the stabilizing precession drift and bounce resonances.

Demonstration of Tokamak ohmic flux saving by transient coaxial helicity injection in the national spherical torus experiment.

Transient coaxial helicity injection (CHI) started discharges in the National Spherical Torus Experiment (NSTX) have attained peak currents up to 300 kA and when coupled to induction, it has produced up to 200 kA additional current over inductive-only operation. CHI in NSTX has shown to be energetically quite efficient, producing a plasma current of about 10 A/J of capacitor bank energy. In addition, for the first time, the CHI-produced toroidal current that couples to induction continues to increase with the energy supplied by the CHI power supply at otherwise similar values of the injector flux, indicating the potential for substantial current generation capability by CHI in NSTX and in future toroidal devices.

Triggered confinement enhancement and pedestal expansion in high-confinement-mode discharges in the national spherical torus experiment.

We report observation of a new high performance regime in discharges in the National Spherical Torus Experiment, where the H mode edge "pedestal" temperature doubles and the energy confinement increases by 50%. The spontaneous transition is triggered by a large edge-localized mode, either natural or externally triggered by 3D fields. The transport barrier grows inward from the edge, with a doubling of both the pedestal pressure width and the spatial extent of steep radial electric field shear. The dynamics suggest that 3D fields could be applied to reduce edge transport in fusion devices.

On demand triggering of edge localized instabilities using external nonaxisymmetric magnetic perturbations in toroidal plasmas.

The application of nonaxisymmetric magnetic fields is shown to destabilize edge-localized modes (ELMs) during otherwise ELM-free periods of discharges in the National Spherical Torus Experiment (NSTX). Profile analysis shows the applied fields increased the temperature and pressure gradients, decreasing edge stability. This robust effect was exploited for a new form of ELM control: the triggering of ELMs at will in high performance H mode plasmas enabled by lithium conditioning, yielding high time-averaged energy confinement with reduced core impurity density and radiated power.

Interaction between behavioral inhibition and neural alcohol cue-reactivity in ADHD and alcohol use disorder.

RATIONALE: Compared to the general population, adult Attention-Deficit / Hyperactivity Disorder (ADHD) is more prevalent in patients with Alcohol Use Disorder (AUD). Impaired behavioral inhibition is a common characteristic in both ADHD and AUD. Relapse risk is increased in patients with AUD and comorbid, untreated ADHD and in AUD patients with increased neural cue-reactivity. OBJECTIVES: In this study, we examined the interaction between neural correlates of behavioral inhibition and alcohol cue-reactivity with a hybrid imaging task. METHODS: Out of 69 adult study participants, we included n = 49 in our final analyses: Individuals had a diagnosis of either AUD (n = 13), ADHD (n = 14) or both (n = 5), or were healthy controls (HC; n = 17). The functional magnetic resonance imaging paradigm aimed to examine the combined effects of both an interference-inhibition task ("Simon-task") and an alcohol cue-reactivity task. Instead of segregating by diagnostic group, we pursued a dimensional approach in which we compared measures of AUD and ADHD severity, as well as the interaction of both, using multiple regression analyses. RESULTS: The four groups did not differ on the behavioral level on either the inhibition task or the alcohol cue-reactivity task. However, brain activation in frontal control and reward-related regions during completion of the combined tasks were related to ADHD and AUD severity (symptom load). During presentation of both alcohol cues and the inhibition task, participants with higher AUD and ADHD symptom load exhibited greater BOLD (blood oxygen level dependent) responses in subcortical reward-related regions. CONCLUSIONS: Our findings support the hypothesis that ADHD additionally diminishes inhibition ability in individuals with AUD. This may increase relapse risk when confronted with alcohol cues. Further, it is crucial for patients with comorbid AUD and ADHD to take into account not only reduced cognitive control over behavioral inhibition but also simultaneously heightened alcohol cue-reactivity.

Prevention of vertical transmission of Neospora caninum in C57BL/6 mice vaccinated with Brucella abortus strain RB51 expressing N. caninum protective antigens.

Bovine abortions caused by the apicomplexan parasite Neospora caninum have been responsible for severe economic losses to the cattle industry. Infected cows either experience abortion or transmit the parasite transplacentally at a rate of up to 95%. Neospora caninum vaccines that can prevent vertical transmission and ensure disruption in the life cycle of the parasite greatly aid in the management of neosporosis in the cattle industry. Brucella abortus strain RB51, a commercially available vaccine for bovine brucellosis, can also be used as a vector to express plasmid-encoded proteins from other pathogens. Neospora caninum protective antigens MIC1, MIC3, GRA2, GRA6 and SRS2 were expressed in strain RB51. Female C57BL/6 mice were vaccinated with a recombinant strain RB51 expressing N. caninum antigen or irradiated tachyzoites, boosted 4 weeks later and then bred. Antigen-specific IgG, IFN-gamma and IL-10 were detected in vaccinated pregnant mice. Vaccinated mice were challenged with 5 x 10(6)N. caninum tachyzoites between days 11-13 of pregnancy. Brain tissue was collected from pups 3 weeks after birth and examined for the presence of N. caninum by real-time PCR. The RB51-MIC3, RB51-GRA6, irradiated tachyzoite vaccine, pooled strain RB51-Neospora vaccine, RB51-MIC1 and RB51-SRS2 vaccines elicited approximately 6-38% protection against vertical transmission. However, the differences in parasite burden in brain tissue of pups from the control and vaccinated groups were highly significant for all groups. Thus, B. abortus strain RB51 expressing the specific N. caninum antigens induced substantial protection against vertical transmission of N. caninum in mice.

Simultaneous feedback control of plasma rotation and stored energy on NSTX-U using neoclassical toroidal viscosity and neutral beam injection.

A model-based feedback system is presented enabling the simultaneous control of the stored energy through ßn and the toroidal rotation profile of the plasma in National Spherical Torus eXperiment Upgrade device. Actuation is obtained using the momentum from six injected neutral beams and the neoclassical toroidal viscosity generated by applying three-dimensional magnetic fields. Based on a model of the momentum diffusion and torque balance, a feedback controller is designed and tested in closed-loop simulations using TRANSP, a time dependent transport analysis code, in predictive mode. Promising results for the ongoing experimental implementation of controllers are obtained.

Compared with cyclosporine, ISATX247 significantly prolongs renal-allograft survival in a nonhuman primate model.

BACKGROUND: ISATX247 is a novel calcineurin inhibitor that has shown more potency than cyclosporine in vitro. This is the first study to compare the survival times of renal allografts in nonhuman primates treated with either ISATX247 or cyclosporine. METHODS: Adult, male cynomolgus monkeys were divided into blood-group compatible and mixed-lymphocyte, stimulation-mismatched, donor-recipient pairs. Heterotopic renal transplantation and bilateral native nephrectomies were performed. The monkeys were placed into either an ISATX247 or cyclosporine treatment group. Both groups were dosed twice daily to maintain a 12-hour drug-trough level of 150 ng/mL. Whole-blood concentrations of ISATX247 and cyclosporine, complete blood counts, and serum chemistry profiles were performed three times a week. Euthanasia was performed if the serum creatinine concentration became 7 or more mg/dL or a serious complication developed. RESULTS: The group receiving ISATX247 (n=8) survived significantly (P=0.0036) longer than the group receiving cyclosporine (n=7). The mean trough blood concentration of ISATX247 was 120 +/- 32 ng/mL and cyclosporine was 189 +/- 130 ng/mL. The average area under the curve 0-12 for ISATX247 was 6045 +/- 1679 ng/mL/hr and for cyclosporine was 4919 +/- 823 ng/mL/hr. The average calcineurin inhibition at trough blood concentrations was 80 +/- 11% for ISATX247 and 48 +/- 12% for cyclosporine. CONCLUSIONS: Allografts in monkeys treated with ISATX247 survived significantly longer than those treated with cyclosporine. On the basis of survival times and degree of calcineurin inhibition, ISATX247 is a more potent immunosuppressive agent than cyclosporine in this nonhuman primate model of renal-allograft transplantation.

CD4+ T cells and monocytes elicited by immunization of rhesus monkeys with antigen-pulsed dendritic cells control SIV replication.

Most HIV infections occur by transmission across mucosal surfaces, where dendritic cells (DCs) are the first cells to encounter the virus. Dendritic cells are specialized antigen-presenting cells critical for eliciting T cell-mediated immune responses. Delayed-type hypersensitivity (DTH) is a cellular immune response in some viral infections and it is mediated by CD4+ and/or CD8+ T cells. We hypothesized that a DTH response to HIV induced by antigen-pulsed DCs would protect against a mucosal exposure to the virus. In a small pilot experiment, six rhesus monkeys were immunized with autologous, antigen-pulsed DCs by the intradermal route and five of the monkeys were boosted with a second dose of DCs at 3 months. Antibody responses to SIV were detected in two of six vaccinated monkeys, lymphocyte-proliferative responses were detected in five of the six monkeys and cytotoxic T lymphocyte (CTL) responses were detected in four of the six monkeys. Using a novel in vitro assay of SIV replication in DCs cocultured with autologous CD4+ T cells and monocytes, suppression of viral replication was detected from five of the six monkeys at multiple time points before and after SIV challenge. Macaques were orally challenged with SIVmac239 at 1-3 months after the booster inoculation. Peak viral loads were similar to those of four naive animals but, compared with naive monkeys, declined at 6 months to levels 1 log(10) or more lower in monkeys that had been vaccinated and that had > or = 50% suppression of SIV replication in DCs. Optimizing this immunization strategy may result in a strong antiviral DTH response that could better control a mucosal lentiviral infection.

Motor activity changes following cerebral ischemia in gerbils are correlated with the degree of neuronal degeneration in hippocampus.

Cerebral ischemia was induced in Mongolian gerbils by bilateral occlusion of the carotid arteries. Subsequent histological assessment revealed neuronal degeneration in the CA1 area of the hippocampus. A functional behavioral change was reflected in an elevation of motor activity compared with sham-operated animals. The degree of hippocampal damage was positively correlated with the increase in motor activity. It is concluded that alterations in both measures result from the interruption of blood flow to the brain but may be brought about by different mechanisms.

Effects of 5-HT1A agonists and 5-HT2 antagonists on haloperidol-induced dyskinesias in squirrel monkeys: no evidence for reciprocal 5-HT-dopamine interaction.

Dyskinetic movements and dystonic postures may be induced by neuroleptics in monkeys that have undergone previous neuroleptic treatment, and these motor abnormalities constitute a primate model of drug-induced extrapyramidal symptomatology. In view of previous suggestions that brain serotonergic systems may tonically inhibit dopamine neurons, the effects of several new and selective 5-HT2 receptor antagonists and 5-HT1A receptor agonists were investigated in this model. Setoperone, a dopamine D2 receptor antagonist with extremely potent 5-HT2 antagonism, caused dyskinetic movements. Although ritanserin is a potent 5-HT2 antagonist with very weak dopamine antagonist properties, this drug did not antagonize dyskinesias but induced them when administered at a high dose (30 mg/kg). Buspirone induced dyskinesias and blocked apomorphine-induced climbing, supporting prior reports that it has dopamine antagonist effects. Gepirone, a 5-HT1A agonist with less marked dopamine antagonist properties, induced dyskinesias in only one of six monkeys at 30 mg/kg and did not block haloperidol-induced dyskinesias. 8-OH-DPAT partly attenuated haloperidol-induced dyskinesias, an effect possibly attributable to its weak dopamine agonist properties. Tonic inhibition of brain extrapyramidal dopamine systems by serotonin systems does not appear to characterize neuroleptic-related dyskinesias in squirrel monkeys.

Effects of dopamine agonists, catecholamine depletors, and cholinergic and GABAergic drugs on acute dyskinesias in squirrel monkeys.

It has been suggested that the neuroleptic-induced acute dyskinetic syndrome in monkeys may be a useful model of extrapyramidal dysfunction. Various drugs that have well-characterized effects on clinical extrapyramidal syndromes and on catecholaminergic, cholinergic, or GABAergic neurotransmission were assessed in dyskinesia-susceptible squirrel monkeys. Catecholamine depletors (alpha-methyl-p-tyrosine, tetrabenazine) induced the syndrome, as do dopamine (DA) receptor antagonists, and d-amphetamine reversed the effects of tetrabenazine. The haloperidol-induced syndrome was reversed by the indirectly acting DA agonists amantadine and L-dopa. Neither of the DA autoreceptor agonist TL-99 or 3-PPP elicited this syndrome, suggesting that these agents lack extrapyramidal involvement. Anticholinergics reversed haloperidol-induced dyskinesias and the cholinomimetic arecoline was capable of inducing dyskinesias. When coadministered repeatedly with haloperidol, benztropine suppressed the emergence of susceptibility to neuroleptic-induced dyskinesias. These results confirm that the acute dyskinetic syndrome in the monkey is characterized by DA deficiency and acetylcholine excess. Diazepam and baclofen, which have been reported to have some clinical benefit in tardive dyskinesia, suppressed haloperidol-induced acute dyskinesias without causing gross motor depression. Pharmacological manipulation of GABAergic pathways from striatum may constitute a fruitful approach to the treatment of dyskinetic motor disorders.

Progressive changes in the acute dyskinetic syndrome as a function of repeated elicitation in squirrel monkeys.

Various neuroleptic-induced motor disorders that appear in primates previously treated with neuroleptics are collectively designated the acute dyskinetic syndrome. The relative incidence of these motor disorders was examined as the syndrome was repeatedly elicited by haloperidol and other dopamine antagonists in individual monkeys. After several weekly or biweekly treatments with haloperidol (1.25 mg/kg orally), catalepsy began to appear, which was then accompanied by athetoid movements (writhing and limb extensions) as intermittent neuroleptic treatment continued. Other dyskinetic movements ('duck walk', oral dyskinesias, pushing of the head into a cage corner, and perseverative circling) that were suggestive of hyperkinesia subsequently began to be elicited by haloperidol and other neuroleptics after additional treatments with these drugs had intervened. As intermittent treatments continued, tolerance to the athetoid movements gradually developed and, eventually, only circling and pushing could be consistently elicited by haloperidol. In monkeys that had reached this phase, the athetoid movements were not again induced by higher doses of haloperidol (up to 5 mg/kg), chlorpromazine (3 mg/kg), or metoclopramide (3 mg/kg). In these tolerant monkeys, haloperidol impaired Sidman avoidance performance less and benztropine more than in drug-naive monkeys. Neither pharmacokinetic changes nor behavioral tolerance could readily account for these results. It is hypothesized that they reflect progressive functional alterations in dopaminergic or cholinergic neurotransmission.

Acute dyskinesias in monkeys elicited by halopemide, mezilamine and the "antidyskinetic" drugs, oxiperomide and tiapride.

Oxiperomide and tiapride are dopamine receptor antagonists claimed to have "antidyskinetic" properties in animal models and the clinic. Halopemide and mezilamine are other dopamine antagonists predicted to lack extrapyramidal side effects in man on the basis of animal studies. Acute dyskinesias, a neuroleptic-induced acute extrapyramidal syndrome, were elicited in squirrel monkeys by oxiperomide (1 mg/kg), tiapride (30 mg/kg), and halopemide (10 mg/kg). The dyskinesias were virtually indistinguishable from those caused by a standard behaviorally equivalent dose of haloperidol (1.25 mg/kg PO) in the same individual monkeys. Mezilamine (0.3 mg/kg) also induced dyskinesias, which appeared to be less pronounced than those following haloperidol. The antidyskinetic properties of oxiperomide and tiapride evidently do not confer protection against dyskinetic movements induced by dopamine antagonism.

Comparative effects of beta 2-adrenoceptor agonists on intracranial self-stimulation, Sidman avoidance, and motor activity in rats.

The effects of beta-adrenoceptor agonists were compared in various operant behavioral tasks, particularly intracranial self-stimulation (ICSS). Clenbuterol, salbutamol, and terbutaline all reduced responding by rats that lever-pressed for low stimulation intensities. The effects of clenbuterol in this test were completely reversed by propranolol, and those of salbutamol were partly reversed. Intermediate doses of clenbuterol and salbutamol slowed the initiation of rewarding brain stimulation in a shuttlebox but had little or no effect on the termination latencies. However, higher doses of both drugs lengthened the termination latencies. Motor activity was reduced at doses that attenuated ICSS responding. Complete tolerance occurred within 4 days to the effects of clenbuterol and salbutamol on lever-pressing ICSS and to the effects of clenbuterol on motor activity. The apparent performance deficits induced by these drugs were overcome by more intense motivation. For example, even at high doses, clenbuterol reduced ICSS lever-pressing only partially when animals bar-pressed for high rather than low stimulation intensities. Furthermore, all three drugs failed to alter Sidman avoidance responding at doses up to 100 times those that attenuated ICSS responding. It is concluded that although beta-adrenoceptor agonists cause apparent sedation in rats, this sedation is limited and shows rapid tolerance.