Recent results from deuterium experiments on the Large Helical Device and their contribution to fusion reactor development

In recent deuterium experiments on the Large Helical Device (LHD), we succeeded in expanding the temperature domain to higher regions for both electron and ion temperatures. Suppression of the Energetic particle driven resistive InterChange mode (EIC) by a moderate electron temperature increase is a key technique to extend the high temperature domain of LHD plasmas. We found a clear isotope effect in the formation of the Internal Transport Barrier (ITB) in high temperature plasmas. A new technique to measure the hydrogen isotope fraction was developed in the LHD in order to investigate the behavior of the isotope mixing state. The technique revealed that the non-mixing and the mixing states of hydrogen isotopes can be realized in plasmas. In deuterium plasmas, we also succeeded simultaneously realizing the formation of the Edge Transport Barrier (ETB) and the divertor detachment. It is found that Resonant Magnetic Perturbation (RMP) plays an important role in the simultaneous formation of the ETB and the detachment. Contributions to fusion reactor development from the engineering point of view, i.e. Negative-ion based Neutral Beam Injector (N-NBI) research and the mass balance study of tritium, are also discussed

Pharmacokinetics and Disposition of Contezolid in Humans—Resolution of a Disproportionate Human Metabolite for Clinical Development

Contezolid (MRX-I), a novel oxazolidinone antibiotic, was recently approved for the treatment of serious Gram-positive infections. The pharmacokinetics and disposition of [ 14 C]contezolid were investigated in a single-dose human mass balance study. Cross-species comparison of plasma exposure for contezolid and metabolites was performed, and the safety of the disproportionate metabolite in human was evaluated with additional nonclinical studies. After an oral administration of 99.1 μCi/602 mg dose of [ 14 C]contezolid, approximately 91.5% of the radioactivity was recovered in 0–168 h postdose, mainly in urine and followed by feces. The principal metabolic pathway of contezolid in human comprised an oxidative ring opening of 2,3-dihydropyridin-4-one fragment into polar metabolites MRX445-1 and MRX459, with recovery of approximately 48% and 15% of the dose, respectively, in urine and feces. Contezolid, MRX445-1, and MRX459 accounted for 68.0%, 19.5%, and 4.84% of the plasma exposure of the total radioactivity, respectively. Metabolites MRX445-1 and MRX459 were observed in disproportionately higher amounts in human plasma as compared to that rat or dog, the rodent and nonrodent species used for the general nonclinical safety assessment of this molecule. This discrepancy was resolved with additional nonclinical studies, wherein the primary metabolite, MRX445-1, was further characterized. The no observed adverse effect level (NOAEL) of MRX445-1 was determined as 360 mg/kg/day in 14-day repeat-dose test in pregnant and non-pregnant SD rats. Furthermore, MRX445-1 exhibited no antibacterial activity in vitro. Thus, MRX445-1 is not expected to exert clinically relevant pharmacology and toxicity.

Effect of Inoculum Pretreatment on Alcohol Production from Volatile Fatty Acids through an Anaerobic Solventogenic Process

1AbstractBackgroundProduction of alcohols from wastes through biological processes is environmentally and economically interesting, since they can be valorized as drop-in liquid fuels, which have a high market value. Using microbial mixed cultures in such processes is of great interest since it confers more stability, a higher resistance to both toxicity and contamination, and an increased substrate flexibility. However, there is still a lack of fundamental knowledge on such microbial populations used as inoculum in solventogenic processes. This work evaluates the effect of four different physicochemical pretreatments (acidic, thermal, acidic-thermal and thermal-acidic) on an anaerobic inoculum used for alcohols production from volatile fatty acids.ResultsAll experiments were conducted in single batches using acetate and butyrate as substrates, at 30°C and with a pressurized headspace of pure H2 at 2182 mBar. Higher productions of both ethanol and butanol were achieved with both thermal and acidic-thermal pretreatments of the inoculum. The highest concentrations of ethanol and butanol produced were respectively of 122 mg.L−1 and 97 mg.L−1 for the thermal pretreatment (after 710 hours), and of 87 mg.L−1 and 143 mg.L−1 for the acidic-thermal pretreatment (after 210 hours). Butyrate was consumed and acetate was produced in all assays. A mass balance study indicated that the inoculum provided part of the substrate. Thermodynamic data indicated that a high H2 partial pressure favored solventogenic metabolic pathways. Finally, sequencing data showed that both thermal and acidic-thermal pretreatments selected mainly the bacterial genera Pseudomonas, Brevundimonas and Clostridium.ConclusionThe acidic-thermal pretreatment selected a bacterial community more adapted to the conversion of acetate and butyrate into ethanol and butanol, respectively. A higher production of ethanol was achieved with the thermal pretreatment, but at a slower rate. The thermal-acidic pretreatment was unstable, showing a huge variability between replicates. The acidic pretreatment showed the lowest alcohol production, almost negligible as compared to the control assay.

Mass Balance Study of the Engineered Cationic Antimicrobial Peptide, WLBU2, Following a Single Intravenous Dose of 14C-WLBU2 in Mice.

Background: To address multidrug resistance we developed engineered cationic antimicrobial peptides (eCAPs). Lead eCAP WLBU2 displays potent activity against drug-resistant bacteria and effectively treats lethal bacterial infections in mice reducing bacterial loads to undetectable levels in diverse organs. Background: To address multidrug resistance we developed engineered cationic antimicrobial peptides (eCAPs). Lead eCAP WLBU2 displays potent activity against drug-resistant bacteria and effectively treats lethal bacterial infections in mice reducing bacterial loads to undetectable levels in diverse organs. Objective: To support development of WLBU2, we conducted a mass balance study. Methods: CD1 mice were administered 10, 15, 20 and 30 mg/kg QDx5 WLBU2 or a single dose of [14C]-WLBU2 at 15 mg/kg IV. Tolerability, tissue distribution and excretion were evaluated with liquid scintillation and HPLCradiochromatography. Results: The maximum tolerated dose of WLBU2 is 20 mg/kg IV. We could account for greater than >96% of the radioactivity distributed within mouse tissues at 5 and 15 min. By 24 h, only ~40-50% of radioactivity remained in the mice. The greatest % of the dose was present in liver, accounting for ~35% of radioactivity at 5 and 15 min, and ~ 8% of radioactivity remained at 24 h. High radioactivity was also present in kidneys, plasma, red blood cells and lungs, while less than 0.2% of radioactivity was present in brain, fat, or skeletal muscle. Urinary and fecal excretion accounted for 12.5 and 2.2% of radioactivity at 24 h. Conclusion: WLBU2 distributes widely to mouse tissues and is rapidly cleared with a terminal radioactivity half-life of 22 h, a clearance of 27.4 mL/h/kg, and a distribution volume of 0.94 L/kg. At 2-100 µg-eq/g, the concentrations of 14CWLBU2 appear high enough in the tissues to account for inhibition of microbial growth.

Spatially distributed mass balance of 14 Icelandic glaciers, 1945−2017. Trends and link with climate.

<p>Excluding the three largest ice caps, Icelandic glaciers have, until recently, received limited attention in terms of mass balance observations over the last century. In this study, mass balance estimates from 1945 to 2017 are presented, in decadal time spans, for 14 glaciers (total area 1054 km<sup>2</sup>) subject to different climatic forcing in Iceland. The mass balances are derived from airborne and spaceborne stereo imagery and airborne lidar, and correlated with precipitation and air temperature by a first order equation including a reference-surface correction term. This permits statistical modelling of annual mass balances and to temporally homogenize the mass balances for a region-wide, multidecadal mass balance study. The mean (standard deviation) mass balances of the target glaciers were −0.43 (0.17) m w.e. a<sup>−1</sup> in 1945−1960, 0.01 (0.21) m w.e. a<sup>−1</sup> in 1960−1980, 0.10 (0.23) m w.e. a<sup>−1</sup> in 1980−1994, −0.98 (0.44) m w.e. a<sup>−1</sup> in 1994−2004, −1.23 (0.57) m w.e. a<sup>−1</sup> in 2004−2010 and 0.06 (0.35) m w.e. a<sup>−1</sup> in 2010−2017. The majority of mass loss occured in 1994−2010, accounting for 22.5±1.6 Gt (1.4±0.1 Gt a<sup>−1</sup>). High decadal mass-balance variability is found on glaciers located at the south and west coasts,<br>in contrast to the glaciers located inland, north and northwest. These patterns are likely explained by the proximity to warm (south and west) versus cold (northwest) oceanic currents.</p>