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Reactors are key components in large-scale commercial projects where reactions convert feed to product. Fischer–Tropsch synthesis converts small molecules (CO and H2) into a wide range of hydrocarbons over a solid catalyst with some degree of tunable selectivity. The reaction products include petrol, diesel and wax. A reactor is not only a vessel that contains the catalyst, but it also determines the interactions between the catalyst, the reaction kinetics and the process streams. The primary goal when designing and operating a reactor is to create a suitable environment for the catalyst in order to sustain the desired reaction(s). Therefore, a good reactor design always considers the thermodynamics, kinetics, mass transfer and heat transfer related to the reaction, as well as the catalyst, the flow and mixing required in the reactor and the reactor type. Furthermore, the design must consider the possible risks during start-up, normal operation and catalyst regeneration, from both the engineering perspective, as well as with regard to the science behind the engineering. In this chapter, reactors that have been used in commercial FT projects are introduced, and their characteristics are discussed. The special requirements for reactors used in biomass-to-liquid plants are described, and current developments and potential future applications are introduced and discussed.

Ser54 of G(s)α binds guanine nucleotide and Mg(2+) as part of a conserved sequence motif in GTP binding proteins. Mutating the homologous residue in small and heterotrimeric G proteins generates dominant-negative proteins, but by protein-specific mechanisms. For α(i/o), this results from persistent binding of α to βγ, whereas for small GTP binding proteins and α(s) this results from persistent binding to guanine nucleotide exchange factor or receptor. This work examined the role of βγ interactions in mediating the properties of the Ser54-like mutants of Gα subunits. Unexpectedly, WT–α(s) or N54-α(s) coexpressed with α(1B)-adrenergic receptor in human embryonic kidney 293 cells decreased receptor stimulation of IP3 production by a cAMP-independent mechanism, but WT-α(s) was more effective than the mutant. One explanation for this result would be that α(s), like Ser47 α(i/o), blocks receptor activation by sequestering βγ; implying that N54-α(S) has reduced affinity for βγ since it was less effective at blocking IP3 production. This possibility was more directly supported by the observation that WT-α(s) was more effective than the mutant in inhibiting βγ activation of phospholipase Cβ2. Further, in vitro synthesized N54-α(s) bound biotinylated-βγ with lower apparent affinity than did WT-α(s). The Cys54 mutation also decreased βγ binding but less effectively than N54-α(s). Substitution of the conserved Ser in α(o) with Cys or Asn increased βγ binding, with the Cys mutant being more effective. This suggests that Ser54 of α(s) is involved in coupling changes in nucleotide binding with altered subunit interactions, and has important implications for how receptors activate G proteins.

Background CT perfusion (CTP) and diffusion or perfusion MRI might assist patient selection for endovascular thrombectomy. We aimed to establish whether imaging assessments of irreversibly injured ischaemic core and potentially salvageable penumbra volumes were associated with functional outcome and whether they interacted with the treatment effect of endovascular thrombectomy on functional outcome.Methods In this systematic review and meta-analysis, the HERMES collaboration pooled patient-level data from all randomised controlled trials that compared endovascular thrombectomy (predominantly using stent retrievers) with standard medical therapy in patients with anterior circulation ischaemic stroke, published in PubMed from Jan 1,2010, to May 31, 2017. The primary endpoint was functional outcome, assessed by the modified Rankin Scale (mRS) at 90 days after stroke. Ischaemic core was estimated, before treatment with either endovascular thrombectomy or standard medical therapy, by CTP as relative cerebral blood flow less than 30% of normal brain blood flow or by MRI as an apparent diffusion coefficient less than 620 mu m(2)/s. Critically hypoperfused tissue was estimated as the volume of tissue with a CTP time to maximum longer than 6 s. Mismatch volume (ie, the estimated penumbral volume) was calculated as critically hypoperfused tissue volume minus ischaemic core volume. The association of ischaemic core and penumbral volumes with 90-day mRS score was analysed with multivariable logistic regression (functional independence, defined as mRS score 0-2) and ordinal logistic regression (functional improvement by at least one mRS category) in all patients and in a subset of those with more than 50% endovascular reperfusion, adjusted for baseline prognostic variables. The meta-analysis was prospectively designed by the HERMES executive committee, but not registered.Findings We identified seven studies with 1764 patients, all of which were included in the meta-analysis. CTP was available and assessable for 591 (34%) patients and diffusion MRI for 309 (18%) patients. Functional independence was worse in patients who had CTP versus those who had diffusion MRI, after adjustment for ischaemic core volume (odds ratio [OR] 0.47 [95% CI 0.30-0.72], p=0.0007), so the imaging modalities were not pooled. Increasing ischaemic core volume was associated with reduced likelihood of functional independence (CTP OR 0.77 [0.69-0.86] per 10 mL, p(interaction)=0.29; diffusion MRI OR 0.87 [0.81-0.94] per 10 mL, p(interaction)=0.94). Mismatch volume, examined only in the CTP group because of the small numbers of patients who had perfusion MRI, was not associated with either functional independence or functional improvement. In patients with CTP with more than 50% endovascular reperfusion (n=186), age, ischaemic core volume, and imaging-to-reperfusion time were independently associated with functional improvement. Risk of bias between studies was generally low.Interpretation Estimated ischaemic core volume was independently associated with functional independence and functional improvement but did not modify the treatment benefit of endovascular thrombectomy over standard medical therapy for improved functional outcome. Combining ischaemic core volume with age and expected imagingto-reperfusion time will improve assessment of prognosis and might inform endovascular thrombectomy treatment decisions. Copyright (C) 2018 Elsevier Ltd. All rights reserved.

BACKGROUND: General anaesthesia (GA) during endovascular thrombectomy has been associated with worse patient outcomes in observational studies compared with patients treated without GA. We assessed functional outcome in ischaemic stroke patients with large vessel anterior circulation occlusion undergoing endovascular thrombectomy under GA, versus thrombectomy not under GA (with or without sedation) versus standard care (ie, no thrombectomy), stratified by the use of GA versus standard care.METHODS: For this meta-analysis, patient-level data were pooled from all patients included in randomised trials in PuMed published between Jan 1, 2010, and May 31, 2017, that compared endovascular thrombectomy predominantly done with stent retrievers with standard care in anterior circulation ischaemic stroke patients (HERMES Collaboration). The primary outcome was functional outcome assessed by ordinal analysis of the modified Rankin scale (mRS) at 90 days in the GA and non-GA subgroups of patients treated with endovascular therapy versus those patients treated with standard care, adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modelling with a random effect for trials incorporated in all models. Bias was assessed using the Cochrane method. The meta-analysis was prospectively designed, but not registered.FINDINGS: Seven trials were identified by our search; of 1764 patients included in these trials, 871 were allocated to endovascular thrombectomy and 893 were assigned standard care. After exclusion of 74 patients (72 did not undergo the procedure and two had missing data on anaesthetic strategy), 236 (30%) of 797 patients who had endovascular procedures were treated under GA. At baseline, patients receiving GA were younger and had a shorter delay between stroke onset and randomisation but they had similar pre-treatment clinical severity compared with patients who did not have GA. Endovascular thrombectomy improved functional outcome at 3 months both in patients who had GA (adjusted common odds ratio (cOR) 1·52, 95% CI 1·09-2·11, p=0·014) and in those who did not have GA (adjusted cOR 2·33, 95% CI 1·75-3·10, pINTERPRETATION: Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons.FUNDING: Medtronic.

The pyrolysis characteristics and coke microstructure of a large variety of electrode binders have been examined. Examination techniques included (1) thermogravimetric analysis with simultaneous differential thermal analysis, (2) optical and scanning electron microscopy, (3) proton nuclear magnetic resonance analysis, and (4) bondcoke strength measurements. Coaltar pitches exhibited more uniformity in pyrolytic behavior than the petroleum pitches studied. Petroleum binder quality varied widely from unacceptable to essentially equal that for coaltar pitch. While early stages of pyrolysis are basically endothermic for all binders, the later stages involve several exotherms related to the carbon polymerization process. In particular, exotherms at about 430°C and 470°C were repeatedly observed, both singly and together, which appeared to be related to binder aromaticity and degree of condensation.

The characteristics of a variety of fluid and delayed cokes have been examined both in the laboratory and as fillers in statistically-significant numbers of full-size reduction cell anodes. Sulfur content varied from one to five percent and sulfur emission and anode performance indicated unique coke properties independent of sulfur level. Performance of high-sulfur filler anodes ranged from excellent to poor and is much more dependent on the amount of oxidant-accessible surface than on sulfur level. The significance of coke blend compatibility was investigated to improve anode performance with available fillers as coke quality changes.

Die vorliegende Studie untersucht kurz- und mittelfristige ortheseninduzierte Veranderungen von Gangparametern und schmerzbedingten Einschrankungen der Alltagsaktivitaten bei Patientinnen mit Osteoporose. Im Rahmen eines Zwei-Stichproben-Messwiederholungsdesigns erfolgten im Abstand von 3 und 6 Monaten in 2 randomisiert zugewiesenen Gruppen (Versuchs- [n=35] vs. Wartekontrollgruppe [n=34]) wiederholt ganganalytische Messungen (ohne Orthese) sturzassoziierter Gangparameter (Gehgeschwindigkeit, Schrittlange, Schrittbreite, Doppelstutzphase [% des Gangzyklus]) und standardisierte Befragungen hinsichtlich schmerzinduzierter Aktivitatseinschrankungen im Alltag (numerische Ratingskala 1–10; 1 beste, 10 schlechteste Situation). Die Probandinnen der Versuchsgruppe wurden angehalten, eine Osteoporoseorthese (Thamert Osteo-Med) uber den Untersuchungszeitraum zu tragen, die Wartekontrollgruppe erhielt keine Orthese. Nach 6 Monaten weist die ANCOVA (Kovariate: Frakturstatus) fur die Versuchs- im Vergleich zur Kontrollgruppe signifikante Reduktionen der Doppelstutzphase auf. Fur die ubrigen Gangparameter ergeben sich nichtsignifikante Effekte. Im Hinblick auf schmerzbedingte Alltagseinschrankungen zeigen sich innerhalb der Verumgruppe in Abhangigkeit vom Ausgangsniveau signifikante Unterschiede der Veranderung uber 6 Monate. Stratifiziert in Terzile (≤2,5; 2,6–5,0; > 5) weisen Patienten mit initial groster Einschrankung (>5) eine signifikant hohere Reduktion der Alltagslimitationen im Studienverlauf im Vergleich zu Patientinnen im untersten Terzil (≤2,5) auf (−2,7±2,7 vs. 1,5±2,1; p

We characterized the variable processing of the G protein gamma subunit isoforms associated with bovine brain G proteins, a primary mediator of cellular communication. Ggamma subunits were isolated from purified brain G proteins and characterized by Edman sequencing, by MALDI MS, by chemical and/or enzymatic fragmentation assayed by MALDI MS, and by MS/MS fragmentation and sequencing. Multiple forms of six different Ggamma isoforms were detected. Significant variation in processing was found at both the amino termini and particularly the carboxyl termini of the proteins. All Ggamma isoforms contain a carboxyl-terminal CAAX motif for prenylation, carboxyl-terminal proteolysis, and carboxymethylation. Characterization of these proteins indicates significant variability in the normal processing of all of these steps in the prenylation reaction, including a new variation of prenyl processing resulting from cysteinylation of the carboxyl terminus. These results have multiple implications for intracellular signaling mechanisms by G proteins, for the role of prenyl processing variation in cell signaling, and for the site of action and consequences of drugs that target the prenylation modification.

Analysis of the genomic sequences, cDNAs and expressed sequence tags (ESTs) in human and mouse for the 12 genes of the gamma subunits of the heterotrimeric G proteins has allowed us to identify the common versus unique elements of the organization and expression of the members of this important gene family. All of the G protein gamma subunit genes are organized around two coding exons, each containing about 100 nucleotides coding for 30-40 amino acids. These two exons each correspond to a functional domain of the protein, which interestingly appears to impose constraints on both the structure of the protein and the structure of the gene. There is large variation in the intron size between these two coding exons, the number and size of 5' and 3' UTRs, and the overall size of the genes. There is general but not absolute conservation in the size and structure of these genes between humans and mice. Alternative splicing and potential differential promoter usage were detected for several Ggamma subunits, indicating possible differential regulation in expression. Only for Ggamma10, however, did we find an alternative coding transcript. This alternative transcript appears to code for a hybrid protein containing a DnaJ domain in place of its Ggamma exon 1 domain, joined to the Ggamma10 second exon domain. The predicted mRNA is expressed in humans, and the protein coded by it is readily translated in vitro. This protein does not form a functional G protein betagamma dimer, but it could generate a chaperone-like protein related to its DNA-J domain. These studies suggest that alternative splicing is not a prominent mechanism for generating G protein subunit diversity from within the human or mouse genomes. Instead, each of the known 12 gamma subunit genes generate transcripts with one prevalent protein.

G protein-coupled receptor (GPCR)-Galpha fusion proteins were first characterized more than 10 years ago as a strategy for studying receptor-G protein signaling. A large number of studies have used this approach to characterize receptor coupling to members of the Gs, Gi, and Gq families of Galpha subunits, but this strategy has not been widely used to study Galpha12 and Galpha13. As described in the article by Zhang et al. in this issue of Molecular Pharmacology (p. 1433) characterization of the signaling properties of thromboxane A2 receptor (TPalpha) -Galpha12 and -Galpha13 fusion constructs demonstrates the applicability of this strategy to members of this unique family of Galpha subunits, and how this strategy can be used to resolve otherwise difficult problems of receptor pharmacology associated with these proteins. The general strategy of making receptor-Galpha fusion constructs has wide applicability to a number of research problems, but there are perhaps also "hidden messages" in how different receptor-Galpha subunit fusion pairs behave.

High power quasi-continuous operation, as foreseen, e.g. in the stellarator W7-X, makes it necessary to actively cool all in-vessel components and thus also the front end of any periscopes used to observe the plasma in the ultravoilet (UV) to infrared (IR) spectral range. In this environment, not only the shutters which are required to prevent the windows from building-up coatings with poor transmission properties during boronisation and glow discharge cleaning, but also the faceplate of the periscope and, in particular, the observation windows need to be actively cooled. An ANSYS ® study of a prototype of such a complete actively cooled periscope head, consisting of a faceplate, three windows and a rotating shutter, is being presented. Furthermore, in a follow up of a detailed theoretical investigation of the suitability of the various window materials available for the different spectral regions, using the finite element code ANSYS ® , an experimental study of the prototype design of a window which can be actively cooled by water or gas (e.g. compressed air) is being presented. For the qualification of the window design, a special high heat load vacuum chamber equipped with a Boralectric ® infrared heater was used, which allows to study its properties up to heat loads of 50 kW/m 2 , using initially the window material with the worst overall design properties, namely fused silica. Our sealing design was successfully tested not only with water (over 70 heat cycles) and compressed air cooling but also with helium at a static pressure of 30 bar for central window temperatures of 400 °C.

The Gβ and Gγ subunit of the heterotrimeric G proteins form a functional dimer that is stable once assembled in vivo or in vitro. The requirements, mechanism, and specificity of dimer formation are still incompletely understood, but represent important biochemical processes involved in the specificity of cellular signaling through G proteins. Here, seven Gβ and 12 FLAG-epitope-tagged Gγ subunits were separately synthesized in vitro using a rabbit reticulocyte lysate expression system. The translation products were combined and dimers isolated by immunoprecipitation. Gβ1 and Gβ4 formed dimers with all Gγ subunit isoforms, generally with Gβ/Gγ stoichiometries between 0.2:1 and 0.5:1. Gβ5, Gβ5L, and Gβ3s did not form significant amounts of dimer with any of the γ subunit isoforms. Gβ2 and Gβ3 formed dimers with selected Gγ isoforms to levels intermediate between that of Gβ1/Gβ4 and Gβ3s/Gβ5/Gβ5L. We also expressed selected Gβγ in HEK293 cells and measured PLCβ2 activity. Gβγ dimer-dependent increases in IP3 ...

Large molybdenum mirrors have been exposed in the SOL of TEXTOR in order to simulate conditions relevant for ITER optical components. Distortions of the reflectivity - increase as well as decrease - are found in the erosion and deposition dominated areas, respectively. The changes are most pronounced in the near UV and level off in the IR and can partly be attributed to observed surface changes. A novel periscope system was installed and mirrors exposed in a pilot experiment to simulate the transmission of light to distant sensors in ITER.

The alpha subunit of the heterotrimeric G protein Gs (Gsalpha) is involved in numerous physiological processes and is a primary determinant of cellular responses to extracellular signals. Genetic variations in the Gsalpha gene may play an important role in complex diseases and drug responses. To characterize the genetic diversity in this locus, we resequenced exons and flanking introns of the gene in 44 genomic samples and analysed the haplotype structure of the gene in an additional 50 African-Americans and 50 Caucasians. Significant differences in allele frequency for nearly all the genotyped single nucleotide polymorphism (SNPs) were detected between the two ethnic groups. Linkage disequilibrium (LD) analysis of this locus revealed two haplotype blocks characterized by strong LD and reduced haplotype diversity, especially in Caucasians. Between the two blocks is a narrow (approximately 3 kb) recombination hotspot centred on exons 4 and 5, and a widely used genetic marker in association studies in this region (rs7121) was in linkage equilibrium with the rest of the gene. The haplotype structure of the GNAS locus warrants reevaluation of previous association studies that used marker rs7121 and affects choice of SNP markers to be used in future studies of this locus.

A Ser to Asn mutation at position 54 of the alpha subunit of G(s) (designated N54-alpha(s)) was characterized after transient expression of it with various components of the receptor-adenylyl cyclase pathway in COS-1, COS-7, and HEK 293 cells. Previous studies of the N54-alpha(s) mutant revealed that it has a conditional dominant negative phenotype that prevents hormone-stimulated increases in cAMP without interfering with the regulation of basal cAMP levels (Cleator, J. H., Mehta, N. D., Kurtz, D. K., Hildebrandt, J. D. (1999) FEBS Lett. 243, 205-208). Experiments reported here were conducted to localize the mechanism of the dominant negative effect of the mutant. Competition studies conducted with activated alpha(s)* (Q212L) showed that the N54 mutant did not work down-stream by blocking the interaction of endogenous alpha(s) with adenylyl cyclase. The co-expression of wild type or N54-alpha(s) along with the thyroid-stimulating hormone (TSH) receptor and adenylyl cyclase isotypes differing with respect to betagamma stimulation (AC II or AC III) revealed that the phenotype of the mutant is not dependent upon the presence of adenylyl cyclase isoforms regulated by betagamma. These studies ruled out a downstream site of action of the mutant. To investigate an upstream site of action, N54-alpha(s) was co-expressed with either the TSH receptor that activates both alpha(s) and alpha(q) or with the alpha(1B)-adrenergic receptor that activates only alpha(q). N54-alpha(s) failed to inhibit alpha(1B)-adrenergic receptor stimulation of inositol 1,4,5-trisphosphate production but did inhibit TSH stimulation of inositol 1,4,5-trisphosphate. These results show that G(s) and G(q) compete for activation by the TSH receptor. They also indicate that the N54 protein has a dominant negative phenotype by blocking upstream receptor interactions with normal G proteins. This phenotype is different from that seen in analogous mutants of other G protein alpha subunits and suggests that either regulation or protein-protein interactions differ among G protein alpha subunits.

In order to derive plasma energy outflux from thermographic measurements an inverse heat conduction problem must be solved. A solution method for the time-dependent three-dimensional heat conduction equation is presented which improves an analytical Green's function solution by a numerical iteration method to include nonlinear effects. The measured temperature excursion of a graphite surface irradiated by laser heat flux pulses can be well described by the model calculations.

The power exhaust from a burning plasma is a key problem in the design of future fusion reactors. Presently employed divertor materials restrict the stationary heat flux to 10 MW m−2. This paper deals with the power load onto the divertor target of W7-AS. The divertor experiments of W7-AS serve as a testbed for W7-X, since this is also equipped with a modular island divertor and its edge structure is similar to that of the W7-AS. The heat flux onto the divertor target is determined by means of infrared thermography. In W7-AS divertor discharges, bunches of edge localized modes (ELMs) with an overall duration of a few milliseconds expel plasma, mostly at the transition from high to low confinement regimes or during density ramps. The heat flux and energy loss they produce is comparable to strong ELMs (type I ELMs) in a tokamak. These bunches of ELMs induce further asymmetries of the heat flux deposition onto the divertor targets.

The research on divertors for stellarators is at the beginning. Extensive studies are being prepared on large helical device (LHD) and W7-X. W7-AS is now being operated with an open island divertor (ID) which serves as a test bed for the W7-X diverter. The divertor enables access to a new NBI-heated, high-density operating regime with improved confinement properties. This regime-the high-density H-mode (HDH)-displays no evident mode activity, is extant above a threshold density and characterized by flat density profiles. high-energy- and low-impurity-confinement times and edge-localized radiation. Impurity accumulation, normally associated with ELM-free H-modes, is avoided. Quasi-steady-state discharges with n e up to 4 x 10 20 m -3 , edge radiation levels up to 90% and plasma partial detachment at the divertor targets can be simultaneously realized. The accessibility to other improved confinement modes in W7-AS (conventional H-mode anti OC-mode) is not restricted by the divertor. The results provide a promising basis for future experiments, in particular on W7-X, and recommend the ID as a serious candidate for solving the plasma exhaust problem in stellarators.

Heterotrimeric G proteins transduce signals from activated transmembrane G protein-coupled receptors to appropriate downstream effectors within cells. Signaling specificity is achieved in part by the specific α, β, and γ subunits that compose a given heterotrimer. Additional structural and functional diversity in these subunits is generated at the level of posttranslational modification, offering alternate regulatory mechanisms for G protein signaling. Presented here is the identification of a variant of the γ 2 subunit of G protein heterotrimer purified from bovine brain and the demonstration that this RDTASIA γ 2 variant, containing unique amino acid sequence at its N terminus, is a substrate for ubiquitylation and degradation via the N-end rule pathway. Although N-end-dependent degradation has been shown to have important functions in peptide import, chromosome segregation, angiogenesis, and cardiovascular development, the identification of cellular substrates in mammalian systems has remained elusive. The isolation of RDTASIA γ 2 from a native tissue represents identification of a mammalian N-end rule substrate from a physiological source, and elucidates a mechanism for the targeting of G protein γ subunits for ubiquitylation and degradation.

Plasma sprayed B4C-layers considered as wall coatings for the W7X stellarator have been studied during and after exposure to TEXTOR and after arcing experiments in vacuum. Arcing through the B4C layer occurred favoured by high power fluxes and not restricted to less stable phases. But this arcing implies an especially noisy scrape-off layer (SOL). Instead of moving retrograde in the external magnetic field, the arc spot on the B4C-layer sticks to the same location for its whole lifetime. Consequently, the arc erodes the entire B4C layer, finally burning down to the Cu substrate. In the neighbourhood of craters the surface contains Cu originating from those craters. This material, hauled to the surface by the arc, is subject to subsequent erosion, transport, and redeposition by the SOL-plasma. The behaviour of arcs on B4C is most probably caused by the peculiar temperature dependences of the electrical and heat conductivity of B4C. 2003 Elsevier Science B.V. All rights reserved.

Thermography is applied on the stellarator W7-AS to monitor the thermal load of the recently installed divertor targets. A three dimensional numerical code was developed to evaluate power fluxes arriving at the targets from the measured temporal evolution of the surface temperature distribution. Values of the thermal conductivity of the used CFC-target material for all three directions are required for this evaluation and determined by observing the propagation of controlled heat pulses applied by an infrared laser. The evaluation of the thermographic measurements during plasma operation shows characteristic spatial and temporal features of the arrived heat fluxes. Significant features in high density regimes like plasma detachment from the divertor target plates or strongly enhanced localised plasma radiation (MARFE) has been observed by the installed infrared cameras. The implications of these observations for the thermographic system for W7-X are shortly addressed.

The new island divertor in W7-AS enables quasi steady-state operation with NBI at very high density including scenarios with stable detachment from the targets. Experiments with reversed B-field indicate that the interaction zones on the targets are affected in first order by E×B drifts. Stable detachment is restricted to magnetic field configurations with sufficiently large separation between x-points and targets and not too small field line pitch inside the islands. It is always partial in the sense that it does not extend over the full target area. This inhomogeneity is ascribed to an in/out asymmetry of the electron temperature at the upstream separatrix position.

A promisingnew operational reg ime on the Wendelstein stellarator W7-AS has been discovered, fulfillingthe conditions of optimal core behavior in combination with edge parameters suitable for successful divertor scenarios. This regime, the high density H-mode (HDH), displays no systematically evident mode activity, and is edge localized mode (ELM)-free. It is extant above a power-dependent threshold density and characterized by flat density profiles, high energy- and low impurity-confinement times and edge-localized radiation. Impurity accumulation, normally as

Application of ion beam analysis techniques in the studies of material transport and fuel inventory in the controlled fusion devices is exemplified. Enhanced proton scattering on the carbon isotopes 12C(p,p)12C, 13C(p,p)13C and secondary ion mass spectrometry allowed for determination of carbon erosion and re-deposition on the wall components following the experiments with a tracer (13CH4) injection into the plasma edge at the TEXTOR tokamak. For the assessment of the deuterium fuel accumulation in the plasma facing components depth profiling by means of nuclear reaction analysis, 3He(d,p)4He, was performed. Advantages and limitations of those nuclear methods in solving experimental problems are addressed.

A new method for the determination of massive erosion and deposition on plasma facing components has been developed and was tested successfully on a graphite tile of the ALT-II limiter of TEXTOR. The surface profile of the tile was measured before and after exposure to plasma discharges with an optical profiler, erosion or deposition is determined from the difference of the two profiles. The profiles were determined relative to specially machined holes, which provide stable reference points. An accuracy of about 1 μm can be achieved. After exposure for 7625 plasma seconds a maximum erosion of 28 μm carbon is observed in erosion dominated areas, while a maximum deposition of about 40 μm is observed in net redeposition areas. The composition and structure of the redeposited layers were investigated with secondary ion mass spectroscopy and scanning electron microscopy.

Carbon sources and the sinks have been quantified in TEXTOR and are discussed in terms of short and long range transport. The major source (22 g/h) is the graphite belt limiter, but part (10 g/h) of the carbon is directly re-deposited after short range transport. Long range transport causes flake formation on obstacles and neutralisers, but little and deuterium rich (D/C≈0.7) deposition in remote areas. The rest is leaving via the pumps in gaseous form. This behaviour is different from that in JET where large amounts of deuterium rich deposits were found in the louvers. Tungsten is favoured for the ITER divertors because of its low sputtering yield for hydrogen, but melting and erosion by carbon may be an additional concern. The short range transport of tungsten has been investigated in a well defined experiment and quantitatively re-constructed by means of the ERO-TEXTOR code. Code validation is necessary in order to increase the confidence and the applicability to JET and ITER.

In ASDEX Upgrade, tungsten was employed as plasma facing material at the central column heat shield in the plasma main chamber. The campaign averaged tungsten erosion flux was determined by measuring the difference of the W-layer thickness before and after the experimental campaign using ion beam analysis methods. The observed lateral variation and the total amount of eroded tungsten are attributed to erosion by impact of ions from the scrape-off layer plasma. Migration and redeposition of eroded tungsten were investigated by quantitative analysis of deposited tungsten on collector probes and wall samples. The obtained results, as well as the spectroscopically observed low tungsten plasma penetration probability, indicate that a major fraction of the eroded tungsten migrates predominantly through direct transport channels in the outer plasma scrape-off layer without entering the confined plasma.

Stellarators have the intrinsic property of steady state operation. However, on present-day stellarators the pulse length is usually not only limited due to technical reasons, but also by physical problems. Lack of density control and a subsequent radiation collapse terminate the discharges quite often at high densities. To improve the control of the plasma-wall interaction, the island divertor concept was developed for optimized stellarators. To test this divertor concept on W7-AS, all limiters were removed and replaced by ten divertor modules. In subsequent divertor experiments a promising new plasma operational regime has been discovered which is termed 'high density H-mode' (HDH-mode). During the transition into that regime a clear reduction of ELM-like events and turbulent fluctuations is observed. The HDH-mode combines good energy confinement with very low impurity confinement resulting in low core radiation, but high edge-localized radiation. Consequently, stationary discharges at densities of typically 2 x 10 20 m -3 can be performed within the accessible pulse length of about 1 s. At densities above 3 x 10 20 m -3 a controlled transition from attached to partially detached plasmas is observed. The still edge-localized radiation reaches 90% of the heating power so that the power load onto the divertor target plates is further reduced. At a lower toroidal field of 0.9 T average β-values could be raised from earlier 2% to more than 3% in magnetic field configurations with rather smooth flux surfaces at the plasma boundary. The recently obtained results render excellent prospects for W7-X, the larger superconducting successor experiment of W7-AS.

The distribution and properties in brain of the alpha subunits of the major bovine brain Go isoforms, GoA, GoB and GoC, were characterized. The alpha(o)A and alpha(o)B isoforms arise from alternative splicing of RNAs from a single alpha(o) gene, whereas alpha(o)C is a deamidated form of alpha(o)A. All three Go isoforms purify from brain with different populations of betagamma dimers. This variable subunit composition of Go heterotrimers is likely a consequence of their functional differences. This study examined the biochemical properties of the alpha(o) isoforms to see if these properties explain the variable betagamma composition of their heterotrimers. The brain distribution of alpha(o)B differed substantially from that of alpha(o)A and alpha(o)C, as did its guanine nucleotide binding properties. The unique subunit composition of GoB can be explained by its expression in different brain regions. The alpha(o)A and alpha(o)C showed slight differences in guanine nucleotide binding properties but no preference for particular betagamma dimers when reassociated with a heterogeneous betagamma pool. The alpha(o)C protein occurred in a constant ratio to alpha(o)A throughout the brain, but was a much larger percent of total brain alpha(o) than previously thought, approximately 35%. These results suggest that alpha(o)A is a precursor of alpha(o)C and that the association of G(o)alpha subunits with different betagamma dimers reflects the function of an adaptive, G-protein signaling mechanism in brain.

W7-AS has recently been equipped with ten open divertor modules in order to experimentally evaluate the island divertor concept. First results are reported in this paper. The new divertors enable access to a new NBI-heated, very high density (up to e = 3.5 × 1020 m-3) operating regime with promising confinement properties. The energy confinement time increases steeply with density and then saturates. In contrast, the particle and impurity confinement times decrease with increasing density. This allows full density control and quasi-steady-state operation also under conditions of partial detachment from the divertor targets. Radiated power fractions are low to moderate in attached regimes and reach up to about 90% in detachment scenarios. The radiation always stays peaked at the edge. The extremely high densities necessitated the development of non-standard heating techniques for central heating. For the first time efficient heating of an NBI target plasma by electron Bernstein waves (140 GHz, second harmonic) is achieved. In addition, this heating scenario enables fine tuning of the upstream boundary conditions for divertor operation.

13 CH 4 was injected into 18 consecutive ohmic discharges (108 s) through a hole in a graphite block equipped with an aluminium plate. CH and CII radical emission adjacent the hole was observed by spectroscopy, while the incremental grow of the deposit was measured in situ by colorimetry. SIMS depth profiling yielded the fractions of 13 C and of the 12 C out of the background. Ratios up to 13 C / C ≈0.42 were found although the deposition efficiency for 13 C was only about 0.2%. H and D were co-deposited up to ratios of 0.4 and 0.2, respectively, as measured by NRA and ERDA. The results can be simulated quantitatively by means of the ERO-TEXTOR code if high re-erosion is assumed for the hydrogen rich radicals CH x + . Within the interaction depth the 13 C/C ratio seems to become quasi-stationary. 13 C transported to obstacles creates a ratio of 13 C / C ≈0.27 after 108 s.

In NBI discharges with density ramps in W7-AS, the quiescent H-mode is restricted to the same ranges of the edge rotational transform as in ECRH discharges and occurs above threshold densities ≥ 10 20 m 3 which increase with heating power. Higher power needs higher density for stabilization. The approach to the quiescent H-mode often occurs, with increasing density and decreasing power flow through the edge, from grassy through dithering states to bursts of ELMs and, in a few cases, quasi-periodic ELMs. This goes parallel with increasing radial gradients of the plasma pressure and E-field at the edge. Higher heating power reduces in particular the T i gradients and hence the E-field gradients, which effect can be compensated by higher density. The correlations found are fairly consistent when an E x B flow shear decorrelation of the turbulent transport is assumed.

A polished graphite sample with a tungsten layer on the plasma-facing surface was exposed to the scrape-off plasma of TEXTOR-94 for about 200 s of discharge time. The plasma exposure caused a contamination layer with a thickness up to 300 nm consisting mainly of the deposited plasma impurity carbon and the tungsten substrate material. The processes and conditions involved in the growth of such mixed material layers are examined. In accompanying experiments, the penetration of carbon into tungsten by diffusion and ion implantation at different temperatures has been measured. The influence of synergistic effects on the carbon penetration into tungsten by the simultaneous impact of carbon and hydrogen ions was studied by irradiation of tungsten with CH 3 ions. The discussion also includes processes such as non-uniform deposition, preferential erosion and prompt local redeposition.

3D modeling on W7-AS suggests that to obtain divertor plasma detachment, upstream separatrix densities nes in the range of 10 20 m −3 will be necessary. This paper investigates the ratio of nes to the line-averaged density n e under a variety of conditions – P heat ∼0.4–2 MW , n e ∼0.2–2.7×10 20 m −3 – for inner-limiter plasma configurations in preparation for the upcoming divertor phase. n es / n e ranges from 0.05 for the quiescent H-mode H* (Pecrh∼0.4 MW) up to ∼0.35 for high-power (Pnbi∼2 MW), heavily fueled discharges where nes approaches 1020 m−3 within a density ramp. For P nbi MW , n es / n e declines with increasing n e as the H-mode threshold density n e thr approaches. L–H–L switching transitions cause n es / n e to alternate between higher and lower values. The attainment of H* implies reduced n es / n e and incipient radiation collapse of the core plasma. n e thr and n es / n e both increase with heating power by which means detachment-relevant nes can be attained, albeit at n e close to the density limit. These phenomena in detail exhibit a sensitive dependence on ιa – even a 1% change results in evident and reproducible plasma behavior.

Core, edge and scrape-off-layer plasma behaviour is studied principally under conditions of an a = 5/9 boundary island configuration - which is relevant for the upcoming W7-AS divertor campaign - but for now with ten inboard sector limiters. The major focus is on compatibility between good core confinement and attainment of high recycling at the limiter. At low input power Pin0.4 MW, operation at densities necessary to attain effective divertor action in the future invariably leads to a transition to the ELM-free H-mode accompanied by lower edge densities and increased core radiation until radiation collapse ensues. Thereby, enhancement factors in E of nearly two above the international stellarator confinement scaling are transiently achieved. The threshold density ethr, necessary to attain the H-mode increases with heating power, such that at 2 MW NBI heating power the H-mode is completely suppressed and peak densities at the limiter exceeding 1.5 × 1020 m-3 are realized. The efficacy of newly-installed control coils designed to manipulate the island geometry is tested. Their influence on the core plasma is verified. Due to geometrical effects associated with the mutual shadowing of the inboard limiters, statements regarding the influence on island physics must await the divertor configuration.

Go is the major G protein in bovine brain, with at least three isoforms, GoA, GoB, and GoC. Whereas αoA and αoB arise from a single Goα gene as alternatively spliced mRNAs, αoA and αoC are thought to differ by covalent modification. To test the hypothesis that αoA and αoC have different N-terminal lipid modifications, proteolytic fragments of αo isoforms were immunoprecipitated with an N terminus-specific antibody and analyzed by matrix-assisted laser desorption ionization mass spectrometry. The major masses observed in immunoprecipitates were the same for all three αoisoforms and corresponded to the predicted mass of a myristoylated N-terminal fragment. Structural differences between αoAand αoC were also compared before and after limited tryptic proteolysis using SDS-polyacrylamide gel electrophoresis containing 6 m urea. Based upon the αosubunit fragments produced under activating and nonactivating conditions, differences between αoA and αoCwere localized to a C-terminal fragment of the protein. This region, involved in receptor and effector interactions, implies divergent signaling roles for these two αo proteins. Finally, the structural difference between αoA and αoCis associated with a difference of at most 2 daltons based upon measurements by electrospay ionization mass spectrometry.

The structural differences between two major forms of the alpha subunit of the heterotrimeric G protein GO were found to be due to deamidation of either of two Asn residues near the C-terminus of the proteins, in a region involved in receptor recognition. GO is the most abundant heterotrimeric G protein in mammalian brain. Two forms of the protein, GOA and GOB, are known to be generated by alternative splicing of a single GOalpha gene. A third isoform, alphaOC, represents about 1/3 of the alphaO protein in brain and is related to alphaOA, from which it is thought to be generated by protein modification. Mass spectrometry and chemical derivatization of tryptic fragments of the proteins were used to localize the structural difference between alphaOA and alphaOC to a C-terminal peptide. Sequence analysis of a C-terminal chymotryptic fragment both by ion trap mass spectrometry and by Edman degradation identified Asn346 and Asn347 of alphaOA as alternative deamidation sites in alphaOC. These structural differences have immediate implications for G protein function, as they occur in a conformationally sensitive part of the protein involved in receptor recognition and activation. Since Asn347 is a conserved residue present in most G protein alpha subunits outside the alphas family, these observations may have general significance for many G proteins. Deamidation may be a component of a novel process for modifying or adapting cellular responses mediated by G proteins.

The assessment of the genetic stability of an expression-system used for the production of recombinant drugs and the verification of the nucleotide sequence of expression plasmids makes it necessary to estimate a limit of detection for variant sequences. Therefore, a series of experiments was performed in which defined mixtures of two different plasmid-DNAs were subjected to nucleotide sequence analysis using an automatic sequencer (ABI 377) and PCR-based sequencing reactions. A plasmid, pGR201 (Fig. 1a), encoding recombinant non-glycosylated human prourokinase (Saruplase), was spiked in varying ratios (90:10; 80:20; 70:30; 60:40) with a related plasmid, pSJ41 (Fig. 1a), differing in a single base-substitution and a cluster of multiple mutations, respectively. Each of these mixtures was sequenced six times in a 50 bp-region covering the variant sequences in order to estimate a limit of detection for point mutations and clusters of multiple mutations. The results are of general interest since we a...

The heterotrimeric G proteins are extensively involved in the regulation of cells by extracellular signals. The receptors that control them are often the targets of drugs. There are many isoforms of each of the three subunits that make up these proteins. Thus far, genes for at least sixteen alpha subunits, five beta subunits, and eleven gamma subunits have been identified. In addition, some of these proteins have splice variants or are differentially modified. Based upon what is already known, there are well over a thousand possible G protein heterotrimer combinations. The role of subunit diversity in heterotrimer formation and its effect on signaling by G proteins are still not well understood. However, many current lines of research are leading toward an understanding of these roles. The functional significance of subunit heterogeneity is related to the mechanisms used by G proteins to transmit and integrate the many signals coming into cells through this system. Described here are the basic mechanisms by which G proteins integrate cellular responses, the possible role of subunit heterogeneity in these mechanisms, and the evidence for and against their physiological significance. Recent studies suggest the likely possibility that subunit heterogeneity plays an important role in signaling by G proteins. This role has the potential to extend substantially the flexibility of G proteins in mediating cellular responses to extracellular signals. However, the details of this are yet to be worked out, and they are the subject of many different avenues of research.

Receptor activation of heterotrimeric G proteins dissociates G alpha from the G betagamma complex, allowing both to regulate effectors. Little is known about the effector-interaction regions of G betagamma. We had used molecular modeling to dock a peptide encoding the region of residues 956-982 of adenylyl cyclase (AC) 2 onto Gbeta to identify residues on Gbeta that may interact with effectors. Based on predictions from the model, we synthesized peptides encoding sequences of residues 86-105 (Gbeta 86-105) and 115-135 (Gbeta 115-135) from Gbeta. The Gbeta 86-105 peptide inhibited G betagamma stimulation of AC2 and blocked G betagamma inhibition of AC1 and by itself inhibited calmodulin-stimulated AC1, thus displaying partial agonist activity. Substitution of Met-101 with Asn in this peptide resulted in the loss of both the inhibitory and partial agonist activities. Most activities of the Gbeta 115-135 peptide were similar to those of Gbeta 86-105 but Gbeta 115-135 was less efficacious in blocking G betagamma inhibition of AC1. Substitution of Tyr-124 with Val in the Gbeta 115-135 peptide diminished all of its activities. These results identify the region encoded by amino acids 84-143 of Gbeta as a surface that is involved in transmitting signals to effectors.

In order to study impurity transport and radiation behavior nitrogen has been injected into the scrape-off plasma of limiter-dominated discharges by gas puffing or into natural magnetic islands at the plasma edge of separatrix-dominated discharges by a reciprocating erosion probe. Strong radiative plasma edge cooling with a reduction of the power flux to the limiter could be obtained. The accompanied degradation of the energy confinement and the observed decrease of the central electron temperature can partly be explained by the reduction of the effective heating power. At high plasma densities and sufficiently strong impurity injection phenomena well known from tokamaks, like plasma shrinking, plasma detachment from the limiters and MARFE's were transiently observed.