Demonstration of reduced neoclassical energy transport in Wendelstein 7-X.

Research on magnetic confinement of high-temperature plasmas has the ultimate goal of harnessing nuclear fusion for the production of electricity. Although the tokamak1 is the leading toroidal magnetic-confinement concept, it is not without shortcomings and the fusion community has therefore also pursued alternative concepts such as the stellarator. Unlike axisymmetric tokamaks, stellarators possess a three-dimensional (3D) magnetic field geometry. The availability of this additional dimension opens up an extensive configuration space for computational optimization of both the field geometry itself and the current-carrying coils that produce it. Such an optimization was undertaken in designing Wendelstein 7-X (W7-X)2, a large helical-axis advanced stellarator (HELIAS), which began operation in 2015 at Greifswald, Germany. A major drawback of 3D magnetic field geometry, however, is that it introduces a strong temperature dependence into the stellarator's non-turbulent 'neoclassical' energy transport. Indeed, such energy losses will become prohibitive in high-temperature reactor plasmas unless a strong reduction of the geometrical factor associated with this transport can be achieved; such a reduction was therefore a principal goal of the design of W7-X. In spite of the modest heating power currently available, W7-X has already been able to achieve high-temperature plasma conditions during its 2017 and 2018 experimental campaigns, producing record values of the fusion triple product for such stellarator plasmas3,4. The triple product of plasma density, ion temperature and energy confinement time is used in fusion research as a figure of merit, as it must attain a certain threshold value before net-energy-producing operation of a reactor becomes possible1,5. Here we demonstrate that such record values provide evidence for reduced neoclassical energy transport in W7-X, as the plasma profiles that produced these results could not have been obtained in stellarators lacking a comparably high level of neoclassical optimization.

First Observation of a Stable Highly Dissipative Divertor Plasma Regime on the Wendelstein 7-X Stellarator.

For the first time, the optimized stellarator Wendelstein 7-X has operated with an island divertor. An operation regime in hydrogen was found in which the total plasma radiation approached the absorbed heating power without noticeable loss of stored energy. The divertor thermography recorded simultaneously a strong reduction of the heat load on all divertor targets, indicating almost complete power detachment. This operation regime was stably sustained over several energy confinement times until the preprogrammed end of the discharge. The plasma radiation is mainly due to oxygen and is located at the plasma edge. This plasma scenario is reproducible and robust at various heating powers, plasma densities, and gas fueling locations. These experimental results show that the island divertor concept actually works and displays good power dissipation potential, producing a promising exhaust concept for the stellarator reactor line.

Inference of temperature and density profiles via forward modeling of an x-ray imaging crystal spectrometer within the Minerva Bayesian analysis framework.

At the Wendelstein 7-X stellarator, the X-ray imaging crystal spectrometer provides line integrated measurements of ion and electron temperatures, plasma flows, as well as impurity densities from a spectroscopic analysis of tracer impurity radiation. In order to infer the actual profiles from line integrated data, a forward modeling approach has been developed within the Minerva Bayesian analysis framework. In this framework, the inversion is realized on the basis of a complete forward model of the diagnostic, including error propagation and utilizing Gaussian processes for generation and inference of arbitrary shaped plasma parameter profiles. For modeling of line integrated data as measured by the detector, the installation geometry of the spectrometer, imaging properties of the crystal, and Gaussian detection noise are considered. The inversion of line integrated data is achieved using the maximum posterior method for plasma parameter profile inference and a Markov chain Monte Carlo sampling of the posterior distribution for calculating uncertainties of the inference process. The inversion method shows a correct and reliable inference of temperature and impurity density profiles from synthesized data within the estimated uncertainties along the whole plasma radius. The application to measured data yields a good match of derived electron temperature profiles to data of the Thomson scattering diagnostic for central electron temperatures between 2 and 5 keV using argon impurities.

Phased array Doppler reflectometry at Wendelstein 7-X.

A passive phased array Doppler reflectometry system has recently been installed in the Wendelstein-7X stellarator. In contrast to conventional Doppler reflectometry systems, the microwave beam can be steered on short time scales in the measurement plane perpendicular to the magnetic field in the range of ±25° without mechanical steering components. This paper characterizes the design and properties of the phased array antenna system and presents the first measurement results from the latest OP1.2a campaign.

Activation by beta-carbolines of G-proteins in HL-60 membranes and the bovine retinal G-protein transducin in a receptor-independent manner.

Naturally occurring beta-carbolines are lipophilic compounds which show psychotropic and physiological effects in mammals. They bind to distinct high-affinity binding sites in various mammalian tissues. However, the mechanism by which the beta-carbolines affect transmembrane signal transduction processes is still unknown. Since beta-carbolines are cationic-amphiphilic substances and since such substances are known to activate heterotrimeric regulatory guanine nucleotide binding proteins (G-proteins) in a receptor-independent manner, we put forward the hypothesis that beta-carbolines act directly on G-proteins. Therefore, we investigated the ability of beta-carbolines to stimulate high-affinity GTP hydrolysis in membranes of dibutyryl-cAMP differentiated HL-60 cells and of the purified bovine G-protein, transducin (TD). The beta-carbolines norharman and harman, stimulated the GTPase in HL-60 membranes with an EC50 of 410 microM and 450 microM, respectively, and a maximum effect at 1 mM each. Norharman and harman stimulated the GTPase of TD with an EC50 of 60 microM and 300 microM, and a maximum at 1 mM for both compounds. The stimulatory effect of norharman in HL-60 membranes was pertussis toxin-sensitive. Structure/activity characteristics of the beta-carbolines showed a specificity of norharman to stimulate the GTPase of TD, because norharman activated GTP hydrolysis in HL-60 membranes approximately 7 times less potently than that of TD. Norharman was a five-fold more potent activator of TD than tetrahydronorharman. Hydroxylation of the beta-carboline molecule in position 6 led to a loss of GTPase-activating properties. Our data suggest that naturally occurring beta-carbolines are a novel class of receptor-independent G-protein activating substances. This mechanism could contribute to their diverse biological effects.

Activation of pertussis toxin-sensitive G-proteins in membranes of SH-SY5Y human neuroblastoma cells and bovine transducin by ethanol.

Effects of ethanol on signal transduction in neuronal membranes are supposed to occur by the interaction with heterotrimeric guanine nucleotide-binding proteins (G-proteins). Several substances affect signal transduction by activation of G-proteins directly independent of receptors. We show that similar to those substances, ethanol stimulates high-affinity guanosine triphosphate (GTP)-hydrolysis in SH-SY5Y membranes at concentrations of 50 mM and higher in a pertussis toxin-sensitive manner. Compared with ethanol at a concentration of 170 mM, other alcohols were without or with respect to methanol with a slight effect on high-affinity GTP-hydrolysis in SH-SY5Y membranes. Ethanol also stimulates the GTPase of the purified G-protein transducin. The findings suggest that ethanol affects signal transduction in neuronal membranes by direct activation of pertussis toxin-sensitive G-proteins.

Engineering aspects in fermentation of meat products.

This paper focuses on the engineering aspects of the drying and ripening process of dry sausages. It describes the physical and chemical phenomena during the ripening time. The influence of the intrinsic and extrinsic control quantities of the dry sausage ripening on the mass transfer parameter in the sausages is determined. Measuring techniques and experiments for the examination of these parameters are introduced and the influence of the parameters on the drying explained. Mathematical tools for numerical simulations and their application to the above mentioned problems are described. For the problem of inhomogeneous drying of dry sausages in industrial ripening chambers, solutions will be suggested.

Harman (1-methyl-beta-carboline) in blood plasma and erythrocytes of nonalcoholics following ethanol loading.

Eleven subjects having no history of substance abuse or dependence who agreed to abstain from alcohol for one week prior to the investigation were selected to participate in the present study. On two occasions, separated by four to six weeks, blood was drawn over an 8-hour period (0, 0.5, 1, 2, 4 and 8 hours). On the first occasion, subjects were given an oral dose of ethanol (1 g/kg) after the first blood sample was drawn (ethanol-loading condition). On the second occasion no ethanol was administered (control condition). On both occasions no detectable harman was found in the plasma of subjects. In the control condition harman was detected in the erythrocytes of 7 subjects which remained relatively stable over time. In the ethanol-loading condition, however, a time-dependent increase of harman in the erythrocytes was observed. The concentration of ethanol, acetaldehyde, and erythrocyte-harman showed a parallel trend over time. These findings demonstrate an increased level of harman following ethanol loading in humans.

Formation of a new biogenic aldehyde adduct by incubation of tryptamine with rat brain tissue.

Tryptamine was degraded by incubation with rat brain homogenate to an unknown product. The reaction was stimulated by the nonionic detergents Triton X-100 and Lubrol PX and less by the zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]1-propanesulfonate (CHAPS). The same results were obtained with pig brain and bovine brain. The monoamine oxidase inhibitor pargyline inhibited the reaction strongly, indicating the participation of the enzyme on the reaction. Addition of 17,000 g supernatant from rat brain homogenate increased the formation effectively whereas phospholipids or chloroform/methanol (7:3) extract from the 17,000 g supernatant showed only little or no effect. Chromatographic and electrophoretic properties as well as the chemical reaction of the product with specific reagents suggest that the compound consists of an indole part and an amino acid part. The product could be identified by fast atom bombardment mass spectrometry and by comparison with the synthetic substance (4R)-2-(3-indolylmethyl)-1,3-thiazolidine-4-carboxylic acid. It is formed by the enzymatic oxidation of tryptamine producing indole-3-acetaldehyde which spontaneously cyclizes with free L-cysteine from the tissue. The results suggest that the reaction of biogenic aldehydes with brain macromolecules may proceed via an analogous reaction.

Biotransformation of 1-methyl-1,2,3,4-tetrahydro-beta-carboline-1-carboxylic acid to harmalan, tetrahydroharman and harman in rats.

1-Methyl-1,2,3,4-tetrahydro-beta-carboline-1-carboxylic acid (1-carboxytetrahydroharman, 1-CTHH) has been detected in the brain of rats following intracerebroventricular injection of tryptamine and pyruvic acid. We now report the metabolism of this compound. Following intraperitoneal injection of 1-CTHH into rats, harmalan was found to be the major metabolite besides tetrahydroharman (THH) and harman. A high concentration of THH was measured in the lung while most of harman was found in the urine. Harmalan and THH could be detected in the brain in low concentrations. The products were separated following extraction from tissues by high-performance liquid chromatography (HPLC) on a reversed phase C18-DB column. The identity of the metabolites was confirmed by mass spectrometry (MS) analysis. The results demonstrate the role of 1-CTHH as a precursor of the biologically active compounds harmalan, THH and harman.

Increased excretion of harman by alcoholics depends on events of their life history and the state of the liver.

Based on the hypothesis of a relationship between the concentration of trace amines like tetrahydroisoquinolines (TIQ's) and beta-carbolines (BC's) in the brain and an increased voluntary ingestion of ethanol, the concentrations of ethanol, acetaldehyde and harman (a beta-carboline) were examined in a group of 20 alcoholics. The patients excreted a higher amount of harman into the urine than non-alcoholics on the day of admission (harman-1) as well as at the end of the detoxication period, 14 days later (harman-14). Certain factors were related to the increased excretion of harman by alcoholics: The younger the patient when he/she consumed ethanol for the first time, the higher the concentration of acetaldehyde in the blood and the amount of harman (harman-14) excreted in the urine. Furthermore, the younger the patient when he/she was intoxicated with ethanol for the first time the higher the amount of harman (harman-14) in the urine. Patients with first grade relatives who were alcoholics excreted more harman (harman-14) than those without such relatives. The following variables were not related to harman-14: The average amount of ethanol consumed daily during the 6 months prior to admission, the presence of signs of intoxication and symptoms of withdrawal at admission to hospital, and the consumption of other psychotropic substances. A negative correlation was found between the state of the liver, as assessed by liver histology and gamma-glutamate transferase (gamma-GT) levels, and the concentration of harman in the urine. Thus, some events in the patient's history as well as the state of the liver are important for the increased excretion of harman into urine of alcoholics.

Ethanol induces an increase of harman in the brain and urine of rats.

Harman occurs in rat brain, with the highest concentration in the cerebellum and the lowest in the striatum. 2 g/kg ethanol were ineffective with respect to the concentration of harman in the brain whereas 5 g/kg ethanol caused a time-dependent increase in the cerebral cortex as well as the cerebellum. A toxic dose (8 g/kg) of ethanol elicited no change of harman in the brain 3 h following the application. The rise in the harman concentration in the brain did not correlate with the increase of acetaldehyde in the blood after treatment with ethanol suggesting that several mechanisms are involved in the changes of the levels of harman. In subchronic experiments rats were treated with ethanol over a period of 5 or 6 days. Harman increased in the brain whereby the effect seemed to be more pronounced in the cerebellum than in the cerebral cortex. The concentration tended to increase over time and reached control levels again during withdrawal. The time course of the excretion of harman into the urine was similar to that of the brain in that it increased continuously during the period of ethanol treatment and reached control levels again during withdrawal.

Pharmacokinetics of human interferon-beta in monkeys.

Human fibroblast-derived interferon (HuIFN-beta) was administered to cynomolgus monkeys i.m. (2 x 10(5) iu/kg), i.v. (2 x 10(5) iu/kg) or intrathecally (3 x 10(5) iu/monkey) or given by a 3 hr i.v. infusion (2 x 10(5) iu/kg). One hr after intrathecal administration, interferon titers in the CSF were 1000-2000 iu/ml, and declined to less than 10 iu/ml during the first 24 hr. At the same time only minute amounts of HuIFN-beta were found in the sera of these animals. After i.m. administration, 5 iu/ml were found on average in the serum during the first 8 hr, with no interferon titer ever exceeding 10 iu/ml. No antiviral activity was found 24 hr after HuIFN-beta injection. HuIFN-beta injected i.v. resulted in serum interferon titers of approx. 300 iu/ml 30 min after administration, which then decreased to about 5 iu/ml during the first 8 hr 24 hr after injection no antiviral activity was detectable. Daily HuIFN-beta i.v. administrations over a period of four days did not affect the interferon clearance from the circulation. During HuIFN-beta infusion, constant HuIFN-beta titers of about 80 iu/ml were observed which then decreased during the following 5 hr to 2 iu/ml. The choice between a single i.v. injection, resulting in high serum titers for a few minutes, and a 3 hr infusion, resulting in an about fourfold lower but constant interferon level for over two hr, will depend on the mechanism of interferon action in vivo and on the question as to whether side effects can be diminished by infusion.

Sensitivity of various human lymphoblastoid cells to the antiviral and anticellular activity of human leukocyte interferon.

Of eight lymphoblastoid cell lines studied five were insensitive to both the anticellular and antiviral activities of human leukocyte interferon, and two were sensitive to both activities. One line could not be fully evaluated since it was not possible to study its sensitivity to the antiviral activity.

A rapid microassay for detecting antibodies against poliovirus based on [14C]thymidine uptake of treated cell cultures.

DNA synthesis of mammalian cells propagated in microplates can easily be measured if cell cultures incubated with [14C]thymidine are harvested on the glass fibre filters by a semiautomatic harvesting technique. Soon after infection with poliovirus, [14C]thymidine uptake of U cells (established, human amniotic cell line) is inhibited. This inhibition can be prevented by previous virus neutralization with antibody. Based on this effect a rapid, precise assay method was set up to determine neutralizing antibody titres against poliovirus. There was a good correlation between titres obtained by this assay and those obtained by 50% end point titrations in cytopathogenic effect inhibition assays.

Growth inhibition of human lymphoblastoid Daudi cells in vitro by interferon preparations.

Human interferon (HIF) preparations inhibited the propagation of Daudi cells in stationary suspension cultures, while a control preparation showed no such effect. The growth inhibition (= anticellular) activity of differently pretreated HIF preparations was determined by the reduction of 14C-labelled thymidine (14C-TDR) uptake in a microassay system. These studies demonstrated that the degree of anticellular activity is directly proportional to the antiviral activity of different HIF preparations. These preparations were obtained from peripheral leukocytes (lHIF) or diploid fibroblasts (fHIF). Together with gel chromatography results, and the sensitivity of the anticellular activity to tryptic digestion and heat inactivation, these results suggest that the anticellularly active substance is a protein which is very similar to, or identical with, interferon.