RESUMEN
Nuclear fusion is one of the most attractive alternatives to carbon-dependent energy sources1. Harnessing energy from nuclear fusion in a large reactor scale, however, still presents many scientific challenges despite the many years of research and steady advances in magnetic confinement approaches. State-of-the-art magnetic fusion devices cannot yet achieve a sustainable fusion performance, which requires a high temperature above 100 million kelvin and sufficient control of instabilities to ensure steady-state operation on the order of tens of seconds2,3. Here we report experiments at the Korea Superconducting Tokamak Advanced Research4 device producing a plasma fusion regime that satisfies most of the above requirements: thanks to abundant fast ions stabilizing the core plasma turbulence, we generate plasmas at a temperature of 100 million kelvin lasting up to 20 seconds without plasma edge instabilities or impurity accumulation. A low plasma density combined with a moderate input power for operation is key to establishing this regime by preserving a high fraction of fast ions. This regime is rarely subject to disruption and can be sustained reliably even without a sophisticated control, and thus represents a promising path towards commercial fusion reactors.
RESUMEN
Predictive 3D optimization reveals a novel approach to modify a nonaxisymmetric magnetic perturbation to be entirely harmless for tokamaks, by essentially restoring quasisymmetry in perturbed particle orbits as much as possible. Such a quasisymmetric magnetic perturbation (QSMP) has been designed and successfully tested in the KSTAR and DIII-D tokamaks, demonstrating no performance degradation despite the large overall amplitudes of nonaxisymmetric fields and strong response otherwise expected in the tested plasmas. The results indicate that a quasisymmetric optimization is a robust path of error field correction across the resonant and nonresonant field spectrum in a tokamak, leveraging the prevailing concept of quasisymmetry for general 3D plasma confinement systems such as stellarators. The optimization becomes, in fact, a simple eigenvalue problem to the so-called torque response matrices if a perturbed equilibrium is calculated consistent with nonaxisymmetric neoclassical transport.
RESUMEN
A small nonaxisymmetric (3D) magnetic field can induce nonambipolar transport of the particle species confined in a tokamak and thus a significant change of plasma rotation. This process can be in a favor of instability control in the region where the tokamak plasma is sufficiently collisional and resistive, as observed in the applications of n=1 resonant magnetic perturbations to the KSTAR tokamak. The plasma rotation can be globally accelerated due to radially drifting electrons and constrained to the electron root, if the radial transport is enhanced by an amplified 3D response. This mechanism is verified by a kinetically self-consistent magnetohydrodynamic modeling for both response and transport, which offers the quantitative explanations on the internal n=1 structure detected by electron-cyclotron-emission imaging and the cocurrent plasma spinning observed in the experiments.
RESUMEN
The propagation dynamics of resonant magnetic perturbation fields in KSTAR H-mode plasmas with injection of small edge perturbations produced by a supersonic molecular beam injection is reported for the first time. The results show that the perturbation field first excites a plasma response on the q=3 magnetic surface and then propagates inward to the q=2 surface with a radially averaged propagation velocity of resonant magnetic perturbations field equal to 32.5 m/ s. As a result, the perturbation field brakes the toroidal rotation on the q=3 surface first causing a momentum transport perturbation that propagates both inward and outward. A higher density fluctuation level is observed. The propagation velocity of the resonant magnetic perturbations field is larger than the radial propagation velocity of the perturbation in the toroidal rotation.
RESUMEN
The path of tokamak fusion and International thermonuclear experimental reactor (ITER) is maintaining high-performance plasma to produce sufficient fusion power. This effort is hindered by the transient energy burst arising from the instabilities at the boundary of plasmas. Conventional 3D magnetic perturbations used to suppress these instabilities often degrade fusion performance and increase the risk of other instabilities. This study presents an innovative 3D field optimization approach that leverages machine learning and real-time adaptability to overcome these challenges. Implemented in the DIII-D and KSTAR tokamaks, this method has consistently achieved reactor-relevant core confinement and the highest fusion performance without triggering damaging bursts. This is enabled by advances in the physics understanding of self-organized transport in the plasma edge and machine learning techniques to optimize the 3D field spectrum. The success of automated, real-time adaptive control of such complex systems paves the way for maximizing fusion efficiency in ITER and beyond while minimizing damage to device components.
RESUMEN
One of the important rotational resonances in nonaxisymmetric neoclassical transport has been experimentally validated in the KSTAR tokamak by applying highly nonresonant n=1 magnetic perturbations to rapidly rotating plasmas. These so-called bounce-harmonic resonances are expected to occur in the presence of magnetic braking perturbations when the toroidal rotation is fast enough to resonate with periodic parallel motions of trapped particles. The predicted and observed resonant peak along with the toroidal rotation implies that the toroidal rotation in tokamaks can be controlled naturally in favorable conditions to stability, using nonaxisymmetric magnetic perturbations.
RESUMEN
Edge localized modes (ELMs) in high-confinement mode plasmas were completely suppressed in KSTAR by applying n=1 nonaxisymmetric magnetic perturbations. Initially, the ELMs were intensified with a reduction of frequency, but completely suppressed later. The electron density had an initial 10% decrease followed by a gradual increase as ELMs were suppressed. Interesting phenomena such as a saturated evolution of edge T(e) and broadband changes of magnetic fluctuations were observed, suggesting the change of edge transport by the applied magnetic perturbations.
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It is observed that the magnitude of the toroidal rotation speed is reduced by the central electron cyclotron resonance heating (ECRH) regardless of the direction of the toroidal rotation. The magnetohydrodynamics activities generally appear with the rotation change due to ECRH. It is shown that the internal kink mode is induced by the central ECRH and breaks the toroidal symmetry. When the magnetohydrodynamics activities are present, the toroidal plasma viscosity is not negligible. The observed effects of ECRH on the toroidal plasma rotation are explained by the neoclassical toroidal viscosity in this Letter. It is found that the neoclassical toroidal viscosity torque caused by the internal kink mode damps the toroidal rotation.
RESUMEN
A fast-ion Dα (FIDA) diagnostics system was installed for core and edge measurements on KSTAR. This system has two tangential FIDA arrays that cover both blue- and redshifted Dα lines (cold: 656.09 nm) in active views along the neutral beam 1 A centerline. The spectral band is 647-662.5 nm, and it covers the Doppler shift of the emission from the maximum energy of the neutral beam (100 keV). A curved filter strip with a motorized stage adequately prevents saturation of the electron multiplying charge-coupled device signal by the cold Dα line from the plasma edge. From comparisons of the measured spectra and FIDASIM modeling code, the FIDA spectra are well matched quantitatively. Moreover, the first measurements show that the FIDA radiance agrees with the neutron rate in the time trace during external heating and perturbation. In addition, responses are observed in the core FIDA radiance during the edge-localized mode cycle.
Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Células Epiteliales/efectos de los fármacos , Inflamación/tratamiento farmacológico , Infecciones por Picornaviridae/complicaciones , Extractos Vegetales/farmacología , Rhinovirus/efectos de los fármacos , Scutellaria baicalensis , Bronquios , Células Epiteliales/metabolismo , Células Epiteliales/virología , Humanos , Inflamación/virología , Interleucina-1/biosíntesis , Interleucina-6/biosíntesis , ARN Mensajero/análisis , Rhinovirus/genéticaRESUMEN
Solitary perturbations (SPs) localized both poloidally and radially are detected within ~100 µs before the partial collapse of the high pressure gradient boundary region (called pedestal) of magnetized toroidal plasma in the KSTAR tokamak device. The SP develops with a low toroidal mode number (typically unity) in the pedestal ingrained with quasi-stable edge-localized mode (QSM) which commonly appears during the inter-collapse period. The SPs have smaller mode pitch and different (often opposite) rotation velocity compared to the QSMs. Similar solitary perturbations are also frequently observed before the onset of complete pedestal collapse, suggesting a strong connection between the SP generation and the pedestal collapse.
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BACKGROUND AND PURPOSE: Experiments were designed to determine the mechanism of the relaxation induced by tamoxifen in porcine coronary arteries at the tissue, cellular and molecular levels. EXPERIMENTAL APPROACH: Porcine left circumflex coronary arteries were isolated and isometric tension was measured. [Ca2+]i in native endothelial cells of intact arteries was determined by a calcium fluorescence imaging technique and eNOS ser1177 phosphorylation was assayed by Western blotting. KEY RESULTS: Tamoxifen induced an endothelium-dependent relaxation that was antagonized by ICI 182,780 and abolished by NG-nitro-L-arginine methyl ester (L-NAME) or 1H-[1,2,4]oxadizolo[4,3-a]quinoxalin-1-one (ODQ). L-Arginine reversed the effect of L-NAME while indomethacin was without effect. Tamoxifen-induced relaxation was attenuated by charybdotoxin (CTX) plus apamin, ouabain or by incubation in a K+ -free solution. Moreover, tamoxifen triggered extracellular Ca2+ -dependent increases in endothelial [Ca2+]i and this effect was abolished by ICI 182,780. Endothelium-independent relaxation to sodium nitroprusside was also inhibited by ouabain or in a K+ -free solution. Furthermore, tamoxifen increased endothelial nitric oxide synthase (eNOS) phosphorylation at Ser-1177 and ICI 182,780 prevented this effect. CONCLUSIONS AND IMPLICATIONS: The present results suggest that tamoxifen mainly induces endothelium-dependent relaxation and that endothelial nitric oxide (NO) is the primary mediator of this effect. NO-dependent responses may result from elevated [Ca2+]i in endothelial cells; an effect abolished by ICI 182,780. NO activates Na+/K+ -ATPase in vascular smooth muscle, leading to relaxation. These results suggest that tamoxifen is able to modulate eNOS phosphorylation directly.
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Vasos Coronarios/efectos de los fármacos , Óxido Nítrico/fisiología , Ouabaína/farmacología , Tamoxifeno/farmacología , Animales , Calcio/metabolismo , Vasos Coronarios/enzimología , Vasos Coronarios/fisiología , Cicloheximida/farmacología , Dactinomicina/farmacología , Estradiol/farmacología , Depuradores de Radicales Libres/farmacología , Óxido Nítrico Sintasa de Tipo III/metabolismo , Nitroprusiato/farmacología , Fosforilación , Bloqueadores de los Canales de Potasio/farmacología , PorcinosRESUMEN
BACKGROUND AND PURPOSE: Absorptive epithelia express apical receptors that allow nucleotides to inhibit Na(+) transport but ATP unexpectedly stimulated this process in an absorptive cell line derived from human bronchiolar epithelium (H441 cells) whilst UTP consistently caused inhibition. We have therefore examined the pharmacological basis of this anomalous effect of ATP. EXPERIMENTAL APPROACH: H441 cells were grown on membranes and the short circuit current (I(SC)) measured in Ussing chambers. In some experiments, [Ca(2+)](i) was measured fluorimetrically using Fura -2. mRNAs for adenosine receptors were determined by the polymerase chain reaction (PCR). KEY RESULTS: Cross desensitization experiments showed that the inhibitory response to UTP was abolished by prior exposure to ATP whilst the stimulatory response to ATP persisted in UTP-pre-stimulated cells. Apical adenosine evoked an increase in I(SC) and this response resembled the stimulatory component of the response to ATP, and could be mimicked by adenosine receptor agonists. Pre-stimulation with adenosine abolished the stimulatory component of the response to ATP. mRNA encoding A(1), A(2A) and A(2B) receptor subtypes, but not the A(3) subtype, was detected in H441 cells and adenosine receptor antagonists could abolish the ATP-evoked stimulation of Na(+) absorption. CONCLUSIONS AND IMPLICATIONS: The ATP-induced stimulation of Na(+) absorption seems to be mediated via A(2A/B) receptors activated by adenosine produced from the extracellular hydrolysis of ATP. The present data thus provide the first description of adenosine-evoked Na(+) transport in airway epithelial cells and reveal a previously undocumented aspect of the control of this physiologically important ion transport process.
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Adenosina/farmacología , Mucosa Respiratoria/metabolismo , Sodio/metabolismo , Adenosina Trifosfato/análogos & derivados , Adenosina Trifosfato/farmacología , Transporte Biológico Activo/efectos de los fármacos , Calcio/metabolismo , Línea Celular , Interpretación Estadística de Datos , Colorantes Fluorescentes , Fura-2 , Humanos , Antagonistas de Receptores Purinérgicos P1 , ARN/biosíntesis , ARN/genética , Receptores Purinérgicos P2/efectos de los fármacos , Receptores Purinérgicos P2Y2 , Mucosa Respiratoria/citología , Mucosa Respiratoria/efectos de los fármacos , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
More than 21% of the Chinese herbs tested contained substances in their aqueous extracts inhibitory to conidial germination of the powdery mildew fungus Oidium murrayae. Extracts from Chinese rhubarb and Japanese knotweed were very effective in controlling powdery mildew on cucumber, pumpkin, and eggplant. The inhibitory substance in Chinese rhubarb was soluble in polar solvents and less soluble in nonpolar solvents. The inhibitor in the aqueous extract was not dialyzable in the membrane tubing with molecular weight cut-off of 14,000, but was exchangeable by anion but not cation exchange resins, indicating that the inhibitor has a molecular weight larger than 14,000 and negative charge on its molecule.
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This paper reports long-term evaluation of a micropackage technology for an implantable MEMS pressure sensor. The all-polymer micropackage survived 160 days when subjected to accelerated lifetime testing at 85 °C in a 1% wt. saline solution. The package shows minimum effect on sensors' sensitivity and nonlinearity, which deviated by less than 5% and 0.3%, respectively. A 6-month in vivo evaluation of 16 MEMS-based pressure sensors demonstrated that the proposed micropackage has good biocompatibility and can protect the MEMS pressure sensor. To the best of our knowledge, these results establish new lifetime records for devices packaged using an all-polymer micropackaging approach.
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1. The short circuit current (ISC) technique was used to quantify electrolyte transport by equine cultured sweat gland epithelia. Adenosine 5'-triphosphate (ATP) and certain related compounds, caused transient increases in ISC when added to the apical solution. The order of potency was uridine triphosphate (UTP) > ATP > ADP > > AMP = adenosine. 2. The responses to apical nucleotides were due to chloride and bicarbonate secretion and were reduced in pertussis toxin-treated cells. P2-receptors sensitive to uridine 5'-triphosphate (UTP), that interact with inhibitory G proteins, therefore appear to be present in the apical membrane. 3. Responses to ATP and UTP were reduced in cells loaded with BAPTA, a calcium chelator. BAPTA attenuated the response to ATP more than the response to UTP suggesting that these nucleotides may not act via a common pathway. 4. Cross-desensitization experiments indicated that two populations of UTP-sensitive receptor were present. One was sensitive to UTP and ATP, whereas the second was sensitive only to UTP. Uridine diphosphate appeared to activate the ATP-insensitive receptor population selectively. 5. These data suggest that apical pyrimidinoceptors may be expressed by these cells. The physiological role of these receptors is unknown but they may allow the autocrine regulation of epithelial function.
Asunto(s)
Bicarbonatos/metabolismo , Cloruros/metabolismo , Receptores Purinérgicos/metabolismo , Glándulas Sudoríparas/metabolismo , Adenosina/farmacología , Adenosina Difosfato/farmacología , Adenosina Monofosfato/farmacología , Adenosina Trifosfato/farmacología , Animales , Unión Competitiva , Células Cultivadas , Quelantes/farmacología , Ácido Egtácico/análogos & derivados , Ácido Egtácico/farmacología , Epitelio/metabolismo , Caballos , Toxina del Pertussis , Receptores Purinérgicos/efectos de los fármacos , Glándulas Sudoríparas/citología , Uridina Trifosfato/farmacología , Vasodilatadores/farmacología , Factores de Virulencia de Bordetella/toxicidadRESUMEN
Apical ATP, ATP, UTP and UDP evoked transient increases in short circuit current (I(SC), a direct measure of transepithelial ion transport) in confluent Caco-2 cells grown on permeable supports. These responses were mediated by a population of at least three pharmacologically distinct receptors. Experiments using cells grown on glass coverslips showed that ATP and UTP consistently increased intracellular free calcium ([Ca(2+)](i)) whilst sensitivity to UDP was variable. Cross desensitization experiments suggested that the responses to UTP and ATP were mediated by a common receptor population. Messenger RNA transcripts corresponding to the P2Y(2), P2Y(4) and P2Y(6) receptors genes were detected in cells grown on Transwell membranes by the reverse transcriptase - polymerase chain reaction. Identical results were obtained for cells grown on glass. Experiments in which I(SC) and [Ca(2+)](i) were monitored simultaneously in cells on Transwell membranes, confirmed that apical ATP and UTP increased both parameters and showed that the UDP-evoked increase in I(SC) was accompanied by a [Ca(2+)](i)-signal. Ionomycin consistently increased [Ca(2+)](i) in such polarized cells but caused no discernible change in I(SC). However, subsequent application of apical ATP or UTP evoked a small rise in I(SC) but no rise in [Ca(2+)](i). UDP evoked no such response. As well as evoking increases in [Ca(2+)](i), the ATP/UTP-sensitive receptors present in Caco-2 cells thus allow direct control over ion channels in the apical membrane. The UDP-sensitive receptors, however, appear to simply evoke a rise in [Ca(2+)](i).
Asunto(s)
Membrana Celular/fisiología , Células Epiteliales/fisiología , Receptores Purinérgicos P2/fisiología , Adenosina Trifosfato/farmacología , Células CACO-2 , Calcio/metabolismo , Membrana Celular/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Transporte Iónico/efectos de los fármacos , Potenciales de la Membrana/efectos de los fármacos , ARN Mensajero/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores Purinérgicos P2/efectos de los fármacos , Receptores Purinérgicos P2/genética , Receptores Purinérgicos P2Y2 , Transcripción Genética , Uridina Trifosfato/farmacologíaRESUMEN
1. Experiments with a spontaneously transformed equine epithelial cell line showed that certain nucleotides increased intracellular free calcium ([Ca2+]i) in cells plated on glass coverslips. The rank order of potency was ATP UTP > 5-Br-UTP, whilst UDP and ADP were ineffective. The response thus appears to be mediated by P2Y2 receptors. 2. Nucleotides also increased short circuit current (Isc) in cells grown into epithelial monolayers and the rank order of potency was UDP> UTP > 5-Br-UTP > ATP > ADP. The increase in [Ca2+]i and the rise in ISC thus have different pharmacological properties. Cross-desensitization experiments indicated that, as well as P2Y2 receptors, the monolayer cultures express at least one additional receptor population that allowed nucleotides to increase ISC. 3. The UDP-evoked increase in ISC was essentially abolished in BAPTA-loaded epithelia suggesting that this response is dependent upon increased [Ca2+]i. Moreover, experiments in which ISC and [Ca2+]i were measured simultaneously showed that the UDP- and ADP-evoked increases in ISC were accompanied by increases in [Ca2+]i. 4. When grown under conditions which favour the development of a polarized phenotype, these epithelial cells thus appear to express [Ca2+]i-mobilizing receptors sensitive to UDP and ADP that are not present in non-polarized cells on coverslips.
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Calcio/fisiología , Células Epiteliales/efectos de los fármacos , Nucleótidos/farmacología , Receptores Purinérgicos P2/metabolismo , Transducción de Señal/fisiología , Adenosina Difosfato/metabolismo , Adenosina Difosfato/farmacología , Adenosina Trifosfato/metabolismo , Adenosina Trifosfato/farmacología , Animales , Aniones/metabolismo , Calcio/metabolismo , Polaridad Celular , Células Cultivadas , Células Epiteliales/metabolismo , Células Epiteliales/fisiología , Caballos , Receptores Purinérgicos P2Y2 , Glándulas Sudoríparas/citología , Uridina Difosfato/metabolismo , Uridina Difosfato/farmacología , Uridina Trifosfato/análogos & derivados , Uridina Trifosfato/metabolismo , Uridina Trifosfato/farmacologíaRESUMEN
Trichosanthin (TCS) is a plant protein which has a wide spectrum of pharmacological activities. It was demonstrated recently that this compound suppressed the replication of human immunodeficiency virus (HIV-1) in vitro. The mechanism of action is believed to be inhibition of protein synthesis. Trichosanthin is a low molecular weight protein which is expected to be easily filtered and eliminated through the kidney. To minimize renal loss, the molecular size of trichosanthin can be increased by coupling to dextran. The larger complex will not undergo glomerular filtration and therefore renal loss can be prevented. This study investigates the kidney's role in trichosanthin elimination and the beneficial effect afforded by coupling to dextran in prolonging plasma half-life. For this purpose, a radioimmunoassay has been developed to determine the concentration of TCS in plasma and urine. The sensitivity of this assay is in the nanogram range. Trichosanthin was coupled to dextran T40 by a dialdehyde method and successful coupling was confirmed by gel filtration chromatography. The complex retained specific binding to trichosanthin antibodies with decreased affinity which can be partially reversed after incubation with dextranase; an enzyme that digested dextran. The pharmacokinetics of intravenously administered trichosanthin (0.75 mg/kg) was compared between two groups of rats with normal and impaired renal function (bilateral renal arterial ligation). Rats with ligation showed a decrease in plasma clearance from 4780 +/- 570 to 220 +/- 20 microL/min and an increase in the mean residence time from 9 +/- 1 to 145 +/- 16 min. Despite the several-fold difference in these parameters, recovery of trichosanthin from normal rat urine was only 0.38 +/- 0.05%. This value can be increased by using higher injection doses. The data indicate that the kidney is an important organ for the elimination of trichosanthin. When the dextran-trichosanthin complex was injected into normal rats trichosanthin activity was not detected in the urine. All the pharmacokinetic parameters suggest that the dextran-trichosanthin complex stayed longer in the body and maintained a much higher plasma concentration than trichosanthin.