Characterization of Quasi-Keplerian, Differentially Rotating, Free-Boundary Laboratory Plasmas.

We present results from pulsed-power driven differentially rotating plasma experiments designed to simulate physics relevant to astrophysical disks and jets. In these experiments, angular momentum is injected by the ram pressure of the ablation flows from a wire array Z pinch. In contrast to previous liquid metal and plasma experiments, rotation is not driven by boundary forces. Axial pressure gradients launch a rotating plasma jet upward, which is confined by a combination of ram, thermal, and magnetic pressure of a surrounding plasma halo. The jet has subsonic rotation, with a maximum rotation velocity 23±3 km/s. The rotational velocity profile is quasi-Keplerian with a positive Rayleigh discriminant κ^{2}∝r^{-2.8±0.8} rad^{2}/s^{2}. The plasma completes 0.5-2 full rotations in the experimental time frame (∼150 ns).

Ion-temperature determination with a baffled Langmuir probe.

An electrostatic Langmuir probe for real-time measurements of parameters in magnetized plasma is tested in fully ionized, barium, Q-machine plasma. The small-diameter, long-length, tungsten wire sensor, i.e., the probe tip, oriented with its cylindrical axis perpendicular to the magnetic field (B), is partially shielded by ceramic baffles, or masks, that form sensor-access slots between the baffles. Adjusting the azimuthal orientation of the slots, by rotating the probe about its cylindrical axis, changes the fraction of proximity gyro-orbiting electrons, relative to the fraction of proximity gyro-orbiting ions, that can access the recessed sensor along the magnetic field. Thus, the ratio between the electron and ion saturation currents, Ie sat and Ii sat, can be adjusted without having affected the probe bias voltage Vb. When optimally shielded (Ie sat/Ii sat=1), accurate, real-time measurements of space potential Vs can be acquired. When maximally shielded (Ie sat/Ii sat≪1), accurate, real-time measurements of ion temperature Ti can be acquired. Subtracting the floating potential Vf of an optimally shielded baffled probe from Vf of a maximally shielded baffled probe yields Ti (and its fluctuation phase) in real time.

Factors influencing the commercialization of inertial fusion energy.

Managing the IFE pathway to fusion electricity will involve management of commericalization scope, schedule, cost and risk. The technology pathway to economical fusion power comprises the commercialization scope. Industry assumes commercialization risk in fielding its own pre-pilot plant research programme for this compact-fusion pathway without the benefit of a federally coordinated IFE research and development programme. The cost of commercializing the mass-production of inexpensive targets and insisting on high reliability, availability, maintainability and inspectability has a major impact on the economics of commercializing fusion power plants. Schedule vulnerability for inertial fusion energy arises from the sensitivity of time-based roadmap stages to uncertainties in the pace of scientific understanding and technology development, as well as to unexpected and inexplicable changes of the budgeting process. Rather than rely on a time-based roadmap, a milestone-based roadmap is maximally appropriate, especially for industry and investors who are particularly well-suited to taking the risks associated with reaching the target milestones provided by the government. Milestones must be identified and optimally sequenced and the necessary resources must be delineated. Progress on the above factors, since the outcomes of recent U.S., U.K. and EUROfusion roadmapping exercises were released, are reported. This article is part of a discussion meeting issue 'Prospects for high gain inertial fusion energy (part 2)'.

Prospects for high gain inertial fusion energy: an introduction to the first special edition.

A European consortium of 15 laboratories across nine nations have worked together under the EUROFusion Enabling Research grants for the past decade with three principle objectives. These are: (a) investigating obstacles to ignition on megaJoule-class laser facilities; (b) investigating novel alternative approaches to ignition, including basic studies for fast ignition (both electron and ion-driven), auxiliary heating, shock ignition etc.; and (c) developing technologies that will be required in the future for a fusion reactor. The Hooke discussion meeting in March 2020 provided an opportunity to reflect on the progress made in inertial confinement fusion research world-wide to date. This first edition of two special issues seeks to identify paths forward to achieve high fusion energy gain. This article is part of a discussion meeting issue 'Prospects for high gain inertial fusion energy (part 1)'.

Control of current and voltage oscillations in a short dc discharge making use of external auxiliary electrode.

A dc discharge with a hot cathode is subject to current and voltage plasma oscillations, which have deleterious effects on its operation. The oscillations can be inhibited by installing an auxiliary electrode, placed outside of anode. By collecting a modest current through a small opening in anode, we show that the discharge becomes stable, in a certain pressure range. This method of avoiding current oscillations can be used, for example, for high current stabilizers.

Magnetically insulated baffled probe for real-time monitoring of equilibrium and fluctuating values of space potentials, electron and ion temperatures, and densities.

By restricting the electron-collection area of a cold Langmuir probe compared to the ion-collection area, the probe floating potential can become equal to the space potential, and thus conveniently monitored, rather than to a value shifted from the space potential by an electron-temperature-dependent offset, i.e., the case with an equal-collection-area probe. This design goal is achieved by combining an ambient magnetic field in the plasma with baffles, or shields, on the probe, resulting in species-selective magnetic insulation of the probe collection area. This permits the elimination of electron current to the probe by further adjustment of magnetic insulation which results in an ion-temperature-dependent offset when the probe is electrically floating. Subtracting the floating potential of two magnetically insulated baffled probes, each with a different degree of magnetic insulation, enables the electron or ion temperature to be measured in real time.

Observation of inverse ion-cyclotron damping induced by parallel-velocity shear.

The generation of broadband multiharmonic spectra of electrostatic ion-cyclotron waves is demonstrated in a magnetized laboratory plasma in which shear in the magnetic-field-aligned (parallel) ion flow and a relative parallel electron drift are present. Shear correlates with an increased number of harmonics and a decreased electron drift speed. Wave and particle measurements indicate that cyclotron damping is reduced and even becomes negative. The fluctuations in the time domain are spiky, similar to electric-field fluctuations observed both in Earth's auroral zone and in numerical simulations.

Experimental verification of the shear-modified ion-acoustic instability.

The predicted shear-induced shift of the wave phase velocity, the essence of the shear-modified ion-acoustic (SMIA) instability mechanism that reduces ion Landau damping for otherwise damped ion-acoustic waves [V. Gavrishchaka et al., 80, 728 (1998)], is verified with direct measurements in a strongly magnetized laboratory plasma. The SMIA growth rate is shown to increase with increasing shear, as predicted. SMIA wave propagation is shown to be possible at both small and large angles to the magnetic field, consistent with space observations of ion-acoustic-like waves.

Macrophages and their subpopulations following allogenic bone marrow transplantation for chronic myeloid leukaemia.

A morphometric and immunohistochemical study was performed on 354 bone marrow trephine biopsies derived from 126 patients with chronic myeloid leukaemia (CML) before and after allogeneic bone marrow transplantation (BMT). The purpose of this investigation was to evaluate the macrophage population, including several subsets and their dynamics in the posttransplant period. In addition to the total CD68+ resident (mature) macrophages the so-called activated fraction identified by its capacity to express alpha-D-galactosyl residues, the pseudo-Gaucher cells (PGCs) and the iron-laden histiocytic reticular cells were also considered. Following immuno- and lectin-histochemical staining morphometric analysis was carried out on sequential postgraft bone marrow specimens at standardized intervals. Compared to the normal bone marrow and calculated per haematopoiesis (cellularity) an overall decrease of about 40-50% in the quantity of CD68+ macrophages and the BSA-I+ subpopulation was detectable in the early posttransplant period (9-45 days after BMT). Noteworthy was the temporal recurrence of PGCs in the engrafted bone marrow, which was not associated with a clonally transformed cell population or leukaemic relapse. Reappearance of postgraft PGCs was most prominent in the first 2 months after BMT. This conspicuous feature was presumed to be functionally associated with a pronounced degradation of cell debris following pretransplant myelo-ablative therapy (scavenger macrophages). Evidence for an activation of the BSA-I+ macrophage subset was derived from the identical carbohydrate-binding capacity shown by the PGCs. In the regenerating haematopoiesis shortly after BMT a significant correlation between the number of BSA-I+ macrophages and erythroid precursor cells was determinable. This result implicates a close functional relationship between postgraft reconstitution of erythropoietic islets and centrally localized activated macrophages. In conclusion, findings emerging from this study included the reappearance of PCGs in the engrafted bone marrow independently of a leukaemic relapse and the significant association of the activated BSA-I+ macrophage subset with the recovery of erythropoiesis.

Carcinogen activation by sulfate conjugate formation.

The foregoing pages presented a substantial body of data that established that sulfotransferase conjugation can transform many xenobiotics into agents that can modify cellular macromolecules. However, activation by sulfation is rarely the only metabolic pathway that is open to these compounds; other pathways can become more important in response to a variety of factors. This metabolic switching can be produced by substrate concentration, cofactor availability, kinetic factors that dictate the velocity of the various possible conjugation reactions, and, in some cases, competition between Phase-I and Phase-II metabolism. Also, it is important to realize that demonstration of activation by sulfate ester formation in vitro does not necessarily mean that a similar activation process will occur in vivo. Experience also teaches that argument by analogy can be very misleading in the case of sulfate activation. Small structural differences can upset the delicate balance between sulfate activation and the various other competing pathways. Nevertheless, sulfation is an important mechanism by which a number of chemicals are transformed to their activated forms.

Alkylation of DNA by 1,3-dialkyl-3-acyltriazenes: correlation of biological activity with chemical behavior.

The reactions of calf thymus DNA with four 1,3-dialkyl-3-acyltriazenes were studied alone or in the presence of pig liver esterase in pH 7.4 phosphate buffer for varying lengths of time. The best alkylating agent in the absence of esterase was determined to be 1,3-dimethyl-3-carbethoxytriazene (DMC), followed in order by 1-(2-hydroxyethyl)-3-methyl-3-carbethoxytriazene (HMC), 1-(2-hydroxyethyl)-3-methyl-3-acetyltriazene (HMA), and 1-(2- chloroethyl)-3-methyl-3-carbethoxytriazene (CMC). This order is the same as that for the rate of decomposition of the various acyltriazenes in pH 7.5 phosphate buffer. The extent of calf thymus DNA alkylation by CMC was found to be dependent on both the reaction buffer and the ionic strength of the medium. Alkylation by CMC alone in low ionic strength glycine buffer produced large quantities of 7-(2-chloroethyl)guanine and 7-(2-hydroxyethyl)guanine. The products of DNA alkylation observed at neutral pH are consistent with N(2)-N(3) heterolysis of the triazene, resulting in the N(1) alkyldiazonium ion as the sole alkylating species. In the presence of esterase, CMC showed an enhanced rate of product formation. Furthermore, the product distribution shifted dramatically from mainly hydroxyethylation to predominantly methylation. CMC is postulated to undergo initial enzymatic deacylation, leading to two different alkyldiazonium ions which competitively alkylate DNA. HMC, on the other hand, was little affected by the esterase. The enzyme-catalyzed reaction showed a small increase in methylation and a smaller decrease in hydroxyethylation.(ABSTRACT TRUNCATED AT 250 WORDS)

Activation of a beta-hydroxyalkylnitrosamine to alkylating agents: evidence for the involvement of a sulfotransferase.

N-Nitrosomethyl(2-hydroxyethyl)amine (NMHEA), when administered by gavage, is a strong liver carcinogen in F344 female rats, but a weak liver carcinogen in male rats. After repeated exposure to NMHEA, either in drinking water or by gavage, female rats accumulated higher levels of DNA-guanine adducts than did their male counterparts, suggesting a correlation with the observed disparity in carcinogenicity. NMHEA has been shown to alkylate rat liver DNA in vivo in a dose-dependent manner. Chemical investigations of NMHEA suggest that it becomes a strong electrophile when a good leaving group is substituted on the hydroxyl. We have proposed that NMHEA is activated to its ultimate carcinogenic form by conjugation with sulfate. The sulfate ester was postulated to undergo rapid cyclization to 3-methyl-1,2,3-oxadizolinium ion, which has previously been found to be a potent methylating agent in vitro. The effect of sulfotransferase inhibitors on the DNA alkylation in rats by NMHEA was studied in vivo. Dichloronitrophenol, a powerful inhibitor of phenol sulfotransferase, had little effect on the methylation and O6-hydroxyethylation of DNA guanine in female rats, while depressing the hydroxyethylation of the N-7 position of guanine. Dichloronitrophenol, however, dramatically enhanced the methylation of DNA in male rats. It also slightly inhibited the N-nitrosodimethylamine-induced methylation of DNA. On the other hand, propylene glycol, an alcohol sulfotransferase inhibitor, had a profound inhibitory effect on DNA methylation induced by NMHEA, very little effect on the formation of N7-(2-hydroxyethyl)guanine, but a very strong effect on the O6-hydroxyethylguanine lesions. NMHEA-induced alkylation was also studied in male and female brachymorphic mice, which are deficient in the ability to synthesize the sulfate donor 3'-phosphoadenosine 5'-phosphosulfate required for sulfotransferase activity, and their heterozygous siblings. No significant differences were seen between the heterozygous and brachymorphic mice in overall levels of alkylation, except in the case of 7-hydroxyethylation. In contrast to rats, male mice showed higher levels of formation of all DNA guanine adducts than did the females. However, propylene glycol was found to depress all the levels of alkylation in the brachymorphic mice, except for N7-(2-hydroxyethyl)guanine, as was observed in rats.(ABSTRACT TRUNCATED AT 400 WORDS)

1,3-Dialkyltriazenes: reactive intermediates and DNA alkylation.

The reactions of calf thymus (ct) DNA with 1,3-dimethyltriazene (DMT), N-methyl-N-nitrosourea (MNU), 1,3-diethyltriazene (DET), N-ethyl-N-nitrosourea (ENU), and 1-ethyl-3-methyltriazene (MET) were studied as a function of concentration of the alkylating agents, of various buffers, and of ionic strength. The amount of alkylation at the 7- and O6-positions of guanine increased linearly with dose over a 10-fold concentration range. The slopes of the DMT and MNU curves were identical as were those of DET and ENU. These data suggest that both types of compounds alkylate DNA via a similar intermediate, presumably the corresponding alkanediazonium ion. MET methylates and ethylates DNA, the amount of each product being a function of the competitive formation of the two diazonium ions possible from MET. The MET product ratios could be reproduced by an appropriate mixture of DET and DMT. The alkylation of DNA by DMT and by MET is very sensitive to ionic strength, to the nature of the buffer, and to the identity of the salt used to balance ionic strength. In general, the reaction is favored by low ionic strength, by amine rather than oxy acid buffers, and by doubly charged inert anions. The alkylation of DNA is inversely proportional to the logarithm of the ionic strength over a wide range. The mutagenic activity of triazenes in Salmonella typhimurium is correlated very well with the ability of the triazenes to form adducts, particularly O6-guanine adducts.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism of DNA binding by the oesophageal carcinogen N-nitroso-N-methylaniline.

N-Nitroso-N-methylaniline (NMA) is a strong oesophageal carcinogen in rats but exhibits few overt genotoxic effects. Previous work from our laboratory established that NMA is readily metabolized by cytochrome P450-catalysed N-demethylation to produce the benzenediazonium ion (BDI), a relatively stable but reactive electrophilic agent. We have also shown that BDI reacts with DNA to form an acid-labile adduct. We have now shown that BDI, generated chemically or by the metabolism of NMA in vitro, reacts with DNA to form a triazene coupling product at the N6-position of adenine residues. This adduct has also been shown to be produced in the liver DNA of rats treated with NMA. Procedures for the isolation of DNA and for analysis of the adduct are presented.

Stereoselectivity in the microsomal conversion of N-nitrosodimethylamine to formaldehyde.

The possibility that N-nitrosodimethylamine (NDMA) might be metabolized preferentially at either the syn (relative to the nitroso oxygen) or the anti methyl group has been examined by comparing the rates of formaldehyde production when unlabeled NDMA, its fully deuteriated analogue (NDMA-d6), and (Z)- or (E)-N-nitrosomethyl(methyl-d3)amine (NDMA-d3) were incubated in turn at concentrations of 0-2.4 mM with acetone-induced rat liver microsomes. The Km values for the conversion of (Z)- and (E)-NDMA-d3 to formaldehyde were identical to each other within experimental error (32 +/- 2 and 35 +/- 1 microM, respectively) but different from those for NDMA (24 +/- 6 microM) and NDMA-d6 (116 +/- 3 microM); similar Vmax values were observed for the four isotopic variants [7.5-8.1 nmol/(mg of protein.min)]. The observed similarity of kinetic parameters for (Z)- and (E)-NDMA-d3 suggested that the isotopic composition of the methyl group is an energetically more important determinant of its rate of oxidation at the NDMA demethylase active site than is its orientation relative to the nitroso oxygen atom. The absence of syn vs anti stereospecificity was confirmed via product isolation studies, in which the formaldehyde generated from each of the four isotopomers was trapped as the dimedone adduct and assayed for deuterium content by mass spectrometry; again, a strong preference for metabolism at CH3 vs CD3 regardless of stereochemistry was observed, though the data on CH2O generation suggested that there may be a slight net excess of anti attack. The results indicate that the microsomal enzymes employed display little regioselectivity in metabolizing the syn vs anti methyl groups of NDMA.

Evidence for an unstable DNA adduct from N-nitroso-N-methylaniline.

N-Nitroso-N-methylaniline (NMA) is an esophageal carcinogen in F344 rats. Attempts to detect binding of NMA to DNA or RNA have not been successful. NMA is not mutagenic in the standard Ames bacterial assay, and it did not induce sister chromatid exchanges in mammalian cells. NMA forms the benzenediazonium ion (BDI) during metabolism. This ion has been known to react with aromatic amines, such as adenine, to form triazene coupling products. The purpose of this research was to demonstrate that a triazene adduct, which would be expected to be hydrolytically unstable, was formed by coupling with the adenine residues in DNA. Liver DNA from a rat treated with NMA or from in vitro reactions of BDI with DNA was treated with sodium borohydride. This reaction was shown to result in the reduction of 6-(1-phenyltriazeno)purine to 6-hydrazinopurine (N6-aminoadenine). The hydrolysate of the DNA, presumably containing the hydrazine, was treated with 4-(dimethylamino)naphthaldehyde, and the resulting hydrazone was isolated by reverse-phase HPLC using fluorescence detection. The identity of the adduct was demonstrated by high-resolution mass spectrometry. These data suggest strongly that NMA forms an unstable triazene adduct with adenine in DNA both in vitro and in vivo.

Alkylation of DNA in rats by N-nitrosomethyl-(2-hydroxyethyl)amine: dose response and persistence of the alkylated lesions in vivo.

The in vivo alkylation of DNA by N-nitrosomethyl-(2-hydroxyethyl)amine (NMHEA) was examined in male and female F-344/N rats. NMHEA is a strong hepatocarcinogen in female rats when administered by gavage but a weaker hepatocarcinogen in male rats. Groups of 5 rats of each sex were treated by gavage with various doses of NMHEA dissolved in corn oil. After 4 h the animals were sacrificed and the livers, lungs, and kidneys were removed. The DNA from each liver was isolated and the neutral thermal and mild acid hydrolysates were separated by high-performance liquid chromatography. The alkylated guanines were quantified by fluorescence spectroscopy. NMHEA gives rise to four fluorescent alkylated guanines, 7- and O6-methylguanines, and 7- and O6-hydroxyethylguanines. The dose-response data revealed that all four lesions increased with dose. There was approximately 10x more methylation than hydroxyethylation at the 7 position of guanine. There was less O6 alkylation, but both methylation and hydroxyethylation were observed at all of the doses studied. The overall alkylation was the same in males and females at the 10- and 20-mg/kg doses, but at higher doses the females exhibited significantly higher levels of alkylation than males. The level of alkylation of DNA isolated from non-target tissues, lung, and kidney was low. The persistence of these lesions in vivo was studied at a dose of 25 mg/kg. Groups of five animals each were sacrificed at various times from 0 to 96 h. There was no significant difference between the sexes in persistence of any of the lesions in the liver. The 7-alkylguanines disappeared slowly over the observation period. 7-Methylguanine was present at 30% of the maximum level after 96 h, while 7-hydroxyethylguanine appeared to be more stable. The O6-alkylguanines were removed rapidly from the liver, being at base level by 48 h. The rapid removal of O6-hydroxyethylguanine suggests a repair process independent of O6-alkylguanine-DNA guanine alkyl transferase: an excision repair is postulated. In vitro alkylation of calf thymus DNA by N-nitrosomethyl-(2-tosyloxyethyl)amine, a surrogate for the putative O-sulfate conjugate of NMHEA, resulted in exclusive methylation of DNA-guanine at both the 7 and O6 positions; no hydroxyethylation was detected. In vitro alkylation of calf thymus DNA with 2-hydroxyethyl-ethylnitrosourea resulted in exclusive hydroxyethylation of DNA-guanine at the 7 and O6 positions.(ABSTRACT TRUNCATED AT 400 WORDS)

Home blood transfusions: the medical, economic, and legal issues surrounding a new treatment procedure.

Blood transfusions have almost always been confined to hospital settings in the past. Recent medical care trends have shifted some therapies (e.g., renal dialysis, hemophilia treatment) into the patient's home. Transfusions are now being given in increasing numbers to stable patients in their homes. This paper examines the medical aspects, the economic issues, and the legal implications of such transfusions. Candidates for home transfusion must be carefully chosen primarily according to the medical guidelines for such treatment. Any legal issues must be satisfactorily answered before approval is given. The paper concludes that if done properly, home transfusions can be safe, cost-effective, and convenient for a carefully selected segment of patients.