We derive a new nonlinear criterion for the occurrence of fast relaxation (crash) events at the edge of high-confinement-mode plasmas. These fast relaxation events called ELMs (edge-localized modes) ...evolve from ideal magnetohydrodynamics (MHD) instabilities, but the crash is not due only to linear physics. We show that for an ELM crash to occur, the coherence time of the relative phase between potential and pressure perturbations must be long enough to allow growth to large amplitude. This phase coherence time is determined by both linear and nonlinear dynamics. An ELM crash requires that the instability growth rate exceed a critical value, i.e., gamma > gamma sub(c) where gamma sub(c)is set by 1/tau sub(c)and tau sub(c)is the phase coherence time. For 0 < gamma < gamma sub(c) MHD turbulence develops and drives enhanced turbulent transport. The results indicate that the shape of the growth rate spectrum gamma (n) is important to whether the result is a crash or turbulence. We demonstrate that ELMs can be mitigated by reducing the phase coherence time without changing linear instability. These findings also offer an explanation of the occurrence of ELM-free H-mode regimes.
Basal extracellular glutamate sampled in vivo is present in micromolar concentrations in the extracellular space outside the synaptic cleft, and neither the origin nor the function of this glutamate ...is known. This report reveals that blockade of glutamate release from the cystine-glutamate antiporter produced a significant decrease (60%) in extrasynaptic glutamate levels in the rat striatum, whereas blockade of voltage-dependent Na+ and Ca2+ channels produced relatively minimal changes (0-30%). This indicates that the primary origin of in vivo extrasynaptic glutamate in the striatum arises from nonvesicular glutamate release by the cystine-glutamate antiporter. By measuring 35Scystine uptake, it was shown that similar to vesicular release, the activity of the cystine-glutamate antiporter is negatively regulated by group II metabotropic glutamate receptors (mGluR2/3) via a cAMP-dependent protein kinase mechanism. Extracellular glutamate derived from the antiporter was shown to regulate extracellular levels of glutamate and dopamine. Infusion of the mGluR2/3 antagonist (RS)-1-amino-5-phosphonoindan-1-carboxylic acid (APICA) increased extracellular glutamate levels, and previous blockade of the antiporter prevented the APICA-induced rise in extracellular glutamate. This suggests that glutamate released from the antiporter is a source of endogenous tone on mGluR2/3. Blockade of the antiporter also produced an increase in extracellular dopamine that was reversed by infusing the mGluR2/3 agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxlylate, indicating that antiporter-derived glutamate can modulate dopamine transmission via mGluR2/3 heteroreceptors. These results suggest that nonvesicular release from the cystine-glutamate antiporter is the primary source of in vivo extracellular glutamate and that this glutamate can modulate both glutamate and dopamine transmission.
We study the dependence of the galaxy contents within halos on the halo formation time using two galaxy formation models, one being a semianalytic model utilizing the halo assembly history from a ...high-resolution N-body simulation and the other being a smoothed particle hydrodynamics simulation including radiative cooling, star formation, and energy feedback from galactic winds. We confirm the finding by Gao et al. that at fixed mass, the clustering of halos depends on the halo formation time, especially for low-mass halos. This age dependence of halo clustering makes it desirable to study the correlation between the occupation of galaxies within halos and the halo age. We find that, in halos of fixed mass, the number of satellite galaxies has a strong dependence on halo age, with fewer satellites in older halos. The youngest one-third of the halos can have an order of magnitude more satellites than the oldest one-third. For central galaxies, in halos that form earlier, they tend to have more stars and thus appear to be more luminous, and the dependence of their luminosity on halo age is not as strong as that of stellar mass. The results can be understood through the star formation history in halos and the merging of satellites onto central galaxies. The age dependence of the galaxy contents within halos would constitute an important ingredient in a more accurate halo-based model of galaxy clustering.
BackgroundFacial infiltrating lipomatosis (FIL) is a congenital disorder that causes overgrowth of one side of the face. The purpose of this study was to determine whether PIK3CA mutations are ...present in tissues outside of the subcutaneous adipose.MethodsFIL tissues from three patients were dissected to enrich for cells from skin, subcutaneous tissue, orbicularis oris muscle, buccal fat, zygomatic bone, and mucosal neuroma. Endothelial cells within the affected tissue also were enriched using CD31 microbeads. Laser capture microdissection on formalin-fixed paraffin-embedded histologic sections was performed to collect specific cell types. DNA was extracted from each tissue and cell type, and measured for the abundance of mutant PIK3CA alleles using droplet digital PCR.ResultsWe detected mutant PIK3CA alleles in every tissue and cell type tested from each overgrown face; frequencies ranged from 1.5 to 53%. There were fewer mutant endothelial cells compared with nonendothelial cells, and the stromal cell compartment had the highest frequency of mutant cells in each tissue.ConclusionsPIK3CA mutations are not restricted to a single tissue or cell type in FIL. Overgrowth in this condition is likely due to the mutation arising in a cell that contributes to several different facial structures during embryogenesis.
Severe combined immunodeficiencies (SCID) are a group of rare inherited disorders with profound defects in T cell and B cell immunity. From 2005 to 2010, our unit performed testing for
IL2RG
,
JAK3
,
...IL7R
,
RAG1
,
RAG2
,
DCLRE1C
,
LIG4
,
AK2
, and
ZAP70
mutations in 42 Chinese and Southeast Asian infants with SCID adopting a candidate gene approach, based on patient’s gender, immune phenotype, and inheritance pattern. Mutations were identified in 26 patients, including
IL2RG
(
n
= 19),
IL7R
(
n
= 2),
JAK3
(
n
= 2),
RAG1
(
n
= 1),
RAG2
(
n
= 1), and
DCLRE1C
(
n
= 1). Among 12 patients who underwent hematopoietic stem cell transplantation, eight patients survived. Complications and morbidities during transplant period were significant, especially disseminated bacillus Calmette–Guérin disease which was often difficult to control. This is the first cohort study on SCID in the Chinese and Southeast Asian population, based on a multi-centered collaborative research network. The foremost issue is service provision for early detection, diagnosis, management, and definitive treatment for patients with SCID. National management guidelines for SCID should be established, and research into an efficient platform for genetic diagnosis is needed.
Repeated cocaine causes enduring changes in dopamine and glutamate transmission in the nucleus accumbens, and dopamine and glutamate terminals synapse on GABAergic accumbens neurons. The present ...study demonstrates that there are changes in GABA transmission in the accumbens at 3 weeks after discontinuing daily cocaine injections. No-net flux microdialysis revealed a significant increase in the basal levels of extracellular GABA in the accumbens of cocaine-treated rats. The elevated extracellular GABA was normalized by blocking voltage-dependent Na+ channels and provided increased tone on GABA(B) presynaptic autoreceptors and heteroreceptors because blocking GABA(B) receptors produced a greater elevation in extracellular GABA, dopamine, and glutamate in cocaine-treated compared with control subjects. For many G-protein-coupled receptors, increased agonist can cause receptor desensitization. Consistent with GABA(B) receptor desensitization, baclofen-stimulated GTPgammaS binding was reduced, and the reduction in G-protein coupling was accompanied by reduced Ser phosphorylation of the GABA(B2) receptor subunit. No effect by repeated cocaine was found in the levels of total GABA(B1) or GABA(B2) protein. Together, these data demonstrate that withdrawal from repeated cocaine treatment produces an increase in the basal levels of extracellular GABA in the accumbens that depends on neuronal activity. The increase may be mediated in part by functional desensitization of GABA(B) receptors, likely the result of diminished Ser phosphorylation of the GABA(B2) receptor.
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