Occam's razor on the mechanism of resistive-wall-mode-induced ß limits in diverted tokamaks.

External kink modes, believed to be the drive of the ß-limiting resistive wall mode, are strongly stabilized by the presence of a separatrix. We thus propose a novel mechanism explaining the appearance of long-wavelength global instabilities in free boundary high-ß diverted tokamaks, retrieving the experimental observables within a physical framework dramatically simpler than most of the models employed for the description of such phenomena. It is shown that the magnetohydrodynamic stability is worsened by the synergy of ß and plasma resistivity, with wall effects significantly screened in an ideal, i.e., with vanishing resistivity, plasma with separatrix. Stability can be improved by toroidal flows, depending on the proximity to the resistive marginal boundary. The analysis is performed in tokamak toroidal geometry, and includes averaged curvature and essential separatrix effects.

Identification of an Optimized Heating and Fast Ion Generation Scheme for the Wendelstein 7-X Stellarator.

A Doppler shifted resonance minority species ion cyclotron range of frequency (ICRF) scheme for heating neutral beam ions has been identified and optimized for the Wendelstein 7-X stellarator. Compared with more conventional methods, the synergetic scheme increases the normalized core collisional power transfer to the background plasma, and induces larger concentrations of energetic ions. Simulations in the intricate 3D magnetic stellarator geometry reveal an energetic distribution function that is only weakly anisotropic, and is thus relevant to fast ion and alpha particle driven Alfvén eigenmode experimental preparation. Quasilinear theory and simulations of the Joint European Torus indicate that the excellent confinement properties are due to increased velocity diffusion from ICRF interaction along the magnetic field lines. Agreement is found between SCENIC simulations and Joint European Torus experimental measurements for the total neutron rate and the energy distribution of the fast ions.

Excitation Mechanism of Low-n Edge Harmonic Oscillations in Edge Localized Mode-Free, High Performance, Tokamak Plasmas.

The excitation mechanism for low-n edge harmonic oscillations in quiescent H-mode regimes is identified analytically. We show that the combined effect of diamagnetic and poloidal magnetohydrodynamic flows, with the constraint of a Doppler-like effect of the ion flow, leads to the stabilization of short wavelength modes, allowing low-n perturbation to grow. The analysis, performed in tokamak toroidal geometry, includes the effects of large edge pressure gradients, associated with the local flattening of the safety factor and diamagnetic flows, sheared parallel and E×B rotation, and a vacuum region between plasma and the ideal metallic wall. The separatrix also is modeled analytically.

Control of magnetohydrodynamic stability by phase space engineering of energetic ions in tokamak plasmas.

Virtually collisionless magnetic mirror-trapped energetic ion populations often partially stabilize internally driven magnetohydrodynamic disturbances in the magnetosphere and in toroidal laboratory plasma devices such as the tokamak. This results in less frequent but dangerously enlarged plasma reorganization. Unique to the toroidal magnetic configuration are confined 'circulating' energetic particles that are not mirror trapped. Here we show that a newly discovered effect from hybrid kinetic-magnetohydrodynamic theory has been exploited in sophisticated phase space engineering techniques for controlling stability in the tokamak. These theoretical predictions have been confirmed, and the technique successfully applied in the Joint European Torus. Manipulation of auxiliary ion heating systems can create an asymmetry in the distribution of energetic circulating ions in the velocity orientated along magnetic field lines. We show the first experiments in which large sawtooth collapses have been controlled by this technique, and neoclassical tearing modes avoided, in high-performance reactor-relevant plasmas.

Sawtooth pacing by real-time auxiliary power control in a tokamak plasma.

In the standard scenario of tokamak plasma operation, sawtooth crashes are the main perturbations that can trigger performance-degrading, and potentially disruption-generating, neoclassical tearing modes. This Letter demonstrates sawtooth pacing by real-time control of the auxiliary power. It is shown that the sawtooth crash takes place in a reproducible manner shortly after the removal of that power, and this can be used to precisely prescribe, i.e., pace, the individual sawteeth. In combination with preemptive stabilization of the neoclassical tearing modes, sawtooth pacing provides a new sawtooth control paradigm for improved performance in burning plasmas.

Tokamak magnetohydrodynamic equilibrium states with axisymmetric boundary and a 3D helical core.

Magnetohydrodynamic (MHD) equilibrium states with imposed axisymmetric boundary are computed in which a spontaneous bifurcation develops to produce an internal three-dimensional (3D) configuration with a helical structure in addition to the standard axisymmetric system. Equilibrium states with similar MHD energy levels are shown to develop very different geometric structures. The helical equilibrium states resemble saturated internal kink mode structures.

Magnetic reconnection triggering magnetohydrodynamic instabilities during a sawtooth crash in a Tokamak plasma.

Thomson scattering measurements with subcentimeter spatial resolution have been made during a sawtooth crash in a Mega Ampere Spherical Tokamak fusion plasma. The unparalleled resolution of the temperature profile has shed new light on the mechanisms that underlie the sawtooth. As magnetic reconnection occurs, the temperature gradient at the island boundary increases. The increased local temperature gradient is sufficient to make the helical core unstable to ideal magnetohydrodynamic instabilities, thought to be responsible for the rapidity of the collapse.

Sawtooth-control mechanism using toroidally propagating ion-cyclotron-resonance waves in tokamaks.

The sawtooth control mechanism in plasmas employing off-axis toroidally propagating ion cyclotron resonance waves in tokamaks is reinvestigated. The radial drift excursion of energetic passing ions distributed asymmetrically in the velocity parallel to the magnetic field determines stability when the rational q=1 surface resides within a narrow region centered about the shifted fundamental cyclotron resonance.

Differential renal gene expression in prehypertensive and hypertensive spontaneously hypertensive rats.

Development of hypertension stems from both environmental and genetic factors wherein the kidney plays a central role. Spontaneously hypertensive rats (SHR) and the nonhypertensive Wistar-Kyoto (WKY) controls are widely used as a model for studying hypertension. The present study examined the renal gene expression profiles between SHR and WKY at a prehypertensive stage (3 wk of age) and hypertensive stage (9 wk of age). Additionally, age-related changes in gene expression patterns were examined from 3 to 9 wk in both WKY and SHR. Five to six individual kidney samples of the same experimental group were pooled together, and quadruplicate hybridizations were performed using the National Institute of Environmental Health Sciences Rat version 2.0 Chip, which contains approximately 6,700 genes. Twenty two genes were found to be differentially expressed between SHR and WKY at 3 wk of age, and 104 genes were differentially expressed at 9 wk of age. Soluble epoxide hydrolase (Ephx2) was found to be significantly upregulated in SHR at both time points and was the predominant outlier. Conversely, elastase 1 (Ela1) was found to be the predominant gene downregulated in SHR at both time points. Analysis of profiles at 3 vs. 9 wk of age identified 508 differentially expressed genes in WKY rats. In contrast, only 211 genes were found to be differentially expressed during this time period in SHR. The altered gene expression patterns observed in the age-related analysis suggested significant differences in the vascular extracellular matrix system between SHR and WKY kidney. Together, our data highlight the complexity of hypertension and the numerous genes involved in and affected by this condition.

Fractional non-Brownian motion and trapping-time distributions of grains in rice piles.

Non-Gaussian height fluctuations occurring on the fueling time scale of a slowly driven rice pile match those observed in some turbulent/critical phenomena, forming an anticorrelated random fractal process with Hurst exponent H=0.2. Inspired by this observation, the concept of fractional Brownian motion (FBM) is extended to treat stochastic processes with skewed increments. Simulations of this process for antipersistent motion have first return time distribution deviating from the t(-2+H) law for FBM. The first return time distribution of this fractional non-Brownian motion describes and quantitatively determines the trapping-time distribution of grains in rice piles upon incorporating a continuous representation of the additional height fluctuations that occur on the time scale between fueling events.

Effect of aspiration of milk on mechanisms of neural control in the airways of developing rabbits.

We studied the effects of recurrent aspiration of milk on neural control of airways in young developing rabbits. Beginning at 1 week of age, rabbits received 0.5 ml/kg of whole milk or sterile physiologic saline intranasally while under light methoxyflourane anesthesia 5 days a week for a period of 3 weeks. At 4 and 8 weeks of age, in vitro studies of contractile and relaxant responses of tracheal smooth muscle (TSM) segments were evaluated. To assess the neurally mediated contractile responses, frequency response curves to electrical field stimulation (EFS) were performed with results expressed in terms of frequency of EFS causing 50% of the maximal contractile response (ES50) values. In addition, the contractile responsiveness of TSM to methacholine (MCh) as reflected by the concentration causing 50% of the maximal contractile response (EC50) values was also determined to evaluate the underlying cholinergic reactivity of this segment of airway. To assess nonadrenergic noncholinergic inhibitory (NANCi) responses, experiments were performed on TSM contracted with neurokinin A in the presence of atropine, propranolol, and indomethacin. EFS was delivered to the contracted tissue at stimulation frequencies ranging from 5 to 30 Hz with results expressed as mean percent relaxation. Recurrent aspiration of milk but not saline increased EFS-induced contractile responses, as shown by significantly lower ES50 values compared with the control group: P = 0.02 and P = 0.001 at 4 and 8 weeks of age, respectively. TSM responsiveness to MCh was no different between the two groups, suggesting that alterations in prejunctional mechanisms of neural control were most likely responsible for the increased contractile response to EFS. The NANCi responses were significantly decreased by milk aspiration at both 4 and 8 weeks of age, with the abnormalities less pronounced at the later time point. These findings demonstrate that repeated aspiration of milk leads to abnormal mechanisms of neural control within airways of developing rabbits. While aspiration of milk altered both contractile and relaxant responses to EFS, the former abnormalities became more pronounced with time while the latter appeared to be resolving. These observations suggest that injury to an airway early in development does not necessarily resolve with time but may persist, with functional abnormalities becoming more pronounced even after the airway insult has ceased.

Human respiratory syncytial virus affects nonadrenergic noncholinergic inhibition in cotton rat airways.

A dysfunction of the nonadrenergic noncholinergic inhibitory (NANCi) system has been invoked as a possible mechanism underlying or contributing to altered airway function. In the present study we assessed whether human respiratory syncytial virus (HRSV) infection affects the airways' neurally mediated contractile and relaxant (NANCi) responses in vitro. NANCi responses were studied on tracheal smooth muscle (TSM) segments obtained from young adult cotton rats, a well-established model for HRSV infection. To assess NANCi responses, TSM segments were removed and placed in tissue baths containing modified Krebs-Henseleit, atropine (1 x 10(-6) M) and propranolol (5 x 10(-6) M). After contraction with neurokinin A (1 x 10(-5) M), electrical field stimulation (EFS) was applied at stimulation frequencies ranging from 5 to 30 Hz. The NANCi responses were measured and expressed as the mean (+/- SE) percent relaxation. To evaluate neurally mediated contractile responses, full frequency response curves (0.5-30 Hz) to EFS were also performed. We found significantly decreased NANCi responses in TSM segments obtained from infected cotton rats (n = 12) compared with control animals (n = 9) (P < 0.002). Furthermore, the contractile responses to EFS were increased in infected animals compared with the control group (P = 0.0001). These findings demonstrate that HRSV infection leads to an enhanced contractile response to EFS and a significant decrease in NANCi response in cotton rat airways in vitro. This disruption of the neural control of airways may lead to the development of altered airway function.

Modulation of acetylcholine release in rabbit airways in vitro.

We investigated the effects of substance P (SP) and vasoactive intestinal peptide (VIP) on acetylcholine (ACh) released from nerve endings by electrical field stimulation (EFS) in rabbit airways in vitro. ACh release was directly measured using high-performance liquid chromatography with electrochemical detection. Airway smooth muscle (ASM) segments, dissected from the midtrachea down to the left mainstem bronchus, were obtained from New Zealand White rabbits and mounted in organ baths containing modified Krebs-Henseleit solution, physostigmine, and choline. EFS at 20 Hz was delivered for 15 min to define baseline ACh release (pmol per gram of tissue per minute). There were no significant regional differences in ACh release during these baseline studies. A second stimulation was then performed in the absence (control) and presence of one or more of the following substances: SP (10(-7) M), a nonpeptide antagonist of the NK1 receptor (10(-7) M CP-96,345; Pfizer), and VIP (10(-7) M). Results for ACh release are expressed as a percentage of the first stimulation (means +/- SE). SP significantly increased ACh release in all ASM segments. This effect was abolished by CP-96,345. VIP alone did not affect ACh release. However, it significantly decreased SP-induced ACh release in all ASM segments. We conclude that SP significantly increases ACh release, thus facilitating cholinergic neurotransmission; its effect is abolished by CP-96,345. VIP decreases SP-induced ACh release, indicating a modulatory effect on cholinergic neurotransmission.

SP-induced contraction of airway smooth muscle in normal and allergen-sensitized rabbits: mechanism of action.

We studied the mechanisms involved in the airway smooth muscle (ASM) contraction to substance P (SP) in normal (control) and allergen-sensitized (immune) rabbits as well as immune rabbits exposed to allergen via the airways (immune challenged). Cumulative concentration-response curves to SP (1 x 10(-9) to 1 x 10(-4) M) were performed in ASM segments in the absence and presence of atropine (10(-5) M) in vitro. The maximal contractile response (g tension/g tissue) at 10(-4) M SP and ASM contractions at various concentrations of SP were expressed as means +/- SE. We found no difference in the contractile response to SP between control and immune animals. ASM segments obtained from immune-challenged rabbits were more responsive to SP. Atropine shifted to the right the concentration-response curves and decreased the maximal ASM contraction at 10(-4) M SP in all three groups; this effect, however, was greater in immune-challenged tissues. These findings demonstrate an increased contractile response to SP in immune-challenged animals mediated by a more pronounced facilitation of cholinergic neurotransmission. We conclude that the final ASM response to SP is the result of a complex interaction between direct effects on ASM and indirect effects through modulation of cholinergic neurotransmission.

Maturation of nonadrenergic noncholinergic inhibitory system in normal and allergen-sensitized rabbits.

We investigated the functional existence of the nonadrenergic noncholinergic inhibitory (NANCi) system in developing rabbit airways in vitro. Furthermore, we evaluated the effect of parenteral exposure to a specific allergen (ragweed) on the maturation of this neural pathway. NANCi responses were studied on tracheal smooth muscle (TSM) segments obtained from normal and ragweed-sensitized New Zealand White rabbits at 1, 2, 4, and 12 wk of age. The TSM segments were removed and placed in tissue baths containing modified Krebs-Henseleit solution, atropine (1 x 10(-5) M), and propranolol (5 x 10(-6) M). After contraction with neurokinin A (1 x 10(-5) M), electrical field stimulation was applied at stimulation frequencies ranging from 5 to 30 Hz to determine the frequency that produced maximal relaxation. The NANCi response to EFS was measured and expressed as the mean (+/- SE) percent relaxation at 20 Hz, because this stimulation frequency gave the maximal NANCi response at each age studied. TSM segments obtained from control rabbits at 1 wk of age did not demonstrate a NANCi response at the frequencies of stimulation used. By contrast, a reproducible NANC relaxation was demonstrated in TSM from 2-, 4-, and 12-wk-old rabbits. The magnitude of this response was 27 +/- 4.7 (n = 10), 29 +/- 4.8 (n = 9), and 37 +/- 4% (n = 18), respectively. The same experiments performed on TSM segments obtained from ragweed-sensitized animals gave significantly decreased values of NANCi response. In 2-, 4-, and 12-wk-old rabbits, the NANCi responses were 11.5 +/- 3.4 (n = 9), 11 +/- 2 (n = 13), and 16 +/- 4.2% (n = 14).(ABSTRACT TRUNCATED AT 250 WORDS)

Decrease in the airways' nonadrenergic noncholinergic inhibitory system in allergen sensitized rabbits.

A decrease in the airways' nonadrenergic noncholinergic inhibitory (NANC-i) system is one of the mechanisms that may contribute to allergen-induced changes in neural control within airways. We measured the airways' neurally mediated contractile and relaxant (NANC-i) responses in tracheal segments and left mainstem bronchus (LMB) from normal (control), immune (ragweed sensitized), and immune challenged rabbits. Immune rabbits were sensitized to mixed ragweed extract through parenteral injections from birth, while the immune challenged group had an additional airway exposure to aerosolized ragweed 48 hours prior to the in vitro studies. Neurally mediated contractile responses to electrical field stimulation (EFS) were increased in the immune challenged group, with the increase most significant in tracheal smooth muscle at a stimulation frequency of 20 Hz. To assess NANC-i responses, airway smooth muscle (ASM) segments from these groups were placed in tissue baths containing atropine (10(-6) M) and propranolol (5 x 10(-6) M). After contraction of the tissue with neurokinin A (NKA, 10(-5) M), the NANC-i response to EFS at 20 Hz was measured and reported as the mean (+/- SEM) percent relaxation. No significant differences were seen in the contractile responses of ASM segments to NKA among the three groups. The tracheal segments showed a significantly different NANC-i relaxation response among all groups: in the control group, 29.1 +/- 3.7; in the immune group 15.8 +/- 2.3%; and in the immune challenged group, 2.1 +/- 4.2%.(ABSTRACT TRUNCATED AT 250 WORDS)

The Drosophila suppressor of sable gene encodes a polypeptide with regions similar to those of RNA-binding proteins.

The nucleotide sequence of the Drosophila melanogaster suppressor of sable [su(s)] gene has been determined. Comparison of genomic and cDNA sequences indicates that an approximately 7,860-nucleotide primary transcript is processed into an approximately 5-kb message, expressed during all stages of the life cycle, that contains an open reading frame capable of encoding a 1,322-amino-acid protein of approximately 150 kDa. The putative protein contains an RNA recognition motif-like region and a highly charged arginine-, lysine-, serine-, aspartic or glutamic acid-rich region that is similar to a region contained in several RNA-processing proteins. In vitro translation of in vitro-transcribed RNA from a complete cDNA yields a product whose size agrees with the size predicted by the open reading frame. Antisera against su(s) fusion proteins recognize the in vitro-translated protein and detect a protein of identical size in the nuclear fractions from tissue culture cells and embryos. The protein is also present in smaller amounts in cytoplasmic fractions of embryos. That the su(s) protein has regions similar in structure to RNA-processing protein is consistent with its known role in affecting the transcript levels of those alleles that it suppresses.

The effect of intravascular complement activation and brief episodes of hypoxia on protein in bronchoalveolar lavage fluid in C5 sufficient and deficient mice.

Our earlier investigations indicated that systemic complement activation with iv cobra venom factor (CVF) or infused zymosan-activated rabbit plasma or rabbit C5a does not significantly increase bronchoalveolar lavage albumin in rabbits (Am Rev Respir Dis 1982; 125:335-340); but that complement activation due to CVF combined with a brief episode of hypoxia increases lavage albumin and is associated with the presence of neutrophils for its expression (J Clin Invest 1985; 75:902-910). In order to determine if intravenous CVF and hypoxia cause similar alterations in mice, and to investigate the time course of the response as well as the importance of C5 fragments to the process, we challenged the B10.D2/nSn strain of C5 sufficient mice (C5+) and the congenic B10.D2/oSn strain of C5 deficient mice (C5-) with intravenous CVF, 15 min of 12% oxygen, or CVF followed by hypoxia. Neither C5+ nor C5- mice had significant increases in lavage protein after either CVF or hypoxia. However, the combined insults significantly increased lavage protein in C5+ but not C5- mice; polyacrylamide gel electrophoresis showed increased amounts of proteins of low and high molecular weights in lavage fluid from the C5+ strain. While the time course of abnormalities in mice was different from that in rabbits, both meclofenamate pretreatment and neutrophil depletion attenuated the increases in lavage protein after the combined insults in both animal species. Infusion of prostaglandin E2 (PGE2) with CVF in the C5+ mice also led to significant increases in lavage protein. We conclude that in mice, intravenous complement activation, as an isolated event, does not cause a significant increase in lavage protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of the evolving histopathology of early and late cutaneous and asthmatic responses in rabbits after a single antigen challenge.

Histopathologic changes during the immediate cutaneous response (ICR) and late cutaneous response (LCR) to antigen challenge in allergic humans include dermal edema in the ICR (15 to 30 minutes) followed by increasing cellular infiltration in the LCR (6 hours and more). No description of the evolving histopathologic changes that occur during an immediate asthmatic response (IAR) followed by a late asthmatic response (LAR) exists in either clinical studies or animal models. We examined cutaneous and pulmonary histopathology at 1/2, 6, 24, and 48 hours as well as 7 days after simultaneous intradermal and aerosol antigen challenge of rabbits immunize with Alternaria tenuis extract. Nonimmunized rabbits challenged with Alternaria tenuis extract and immunized rabbits challenged with normal saline served as controls. Immediate wheal and flare responses followed by a LCR were seen in immunized but not control animals. Pulmonary function tests documented immediate and LAR in immunized but not control animals. Thirty minutes after antigen challenge of sensitized animals (ICR and IAR), both dermal sites and large airway submucosal sites had interstitial edema and vessel dilatation while small airways were essentially normal. At 6 hours after challenge, the dermal and large airway submucosal sites of immune animals (LCR and LAR) demonstrated a moderate mixed leukocyte infiltrate as well as residual edema. Additionally, bronchioles and pulmonary vessel adventitia from these responding animals had an intense and widespread leukocyte infiltration. At 24 and 48 hours, immune challenged animals but not controls had a marked mixed cellular infiltrate near skin vessels and near the bronchioles and pulmonary vessels with little or no residual interstitial edema. At 7 days, three of four animals showed resolution of the inflammation while the fourth showed minimal residual changes. Morphometric analysis of airway inflammation substantiated these qualitative observations and demonstrated that the granulocytes around airways of immune rabbits were a mixture of neutrophils and eosinophils at 6 hours, but were predominantly eosinophils at 48 hours. Immunofluorescent studies of skin and lung tissue did not demonstrate any granular or linear deposition of immunoglobulin or complement at the sites of inflammation, however, fibrin deposition was noted in the skin and lungs of immune rabbits. These observations show that immunized rabbits challenged with antigen develop cutaneous and pulmonary inflammation.(ABSTRACT TRUNCATED AT 400 WORDS)