Investigating the impact of the molecular charge-exchange rate on detached SOLPS-ITER simulations

Plasma-molecular interactions generate molecular ions which react with the plasma and contribute to detachment through molecular activated recombination (MAR), reducing the ion target flux, and molecular activated dissociation (MAD), both of which create excited atoms. Hydrogenic emission from these atoms have been detected experimentally in detached TCV, JET and MAST-U deuterium plasmas. The TCV findings, however, were in disagreement with SOLPS-ITER simulations for deuterium indicating a molecular ion density ($D_2^+$) that was insufficient to lead to significant hydrogenic emission, which was attributed to underestimates of the molecular charge exchange rate ($D_2 + D^+ \rightarrow D_2^+ + D$) for deuterium (obtained by rescaling the hydrogen rates by their isotope mass). In this work, we have performed new SOLPS-ITER simulations with the default rate setup and a modified rate setup where ion isotope mass rescaling was disabled. This increased the $D_2^+$ content by $> \times 100$. By disabling ion isotope mass rescaling: 1) the total ion sinks are more than doubled due to the inclusion of MAR; 2) the additional MAR causes the ion target flux to roll-over during detachment; 3) the total $D\alpha$ emission in the divertor increases during deep detachment by roughly a factor four; 4) the neutral atom density in the divertor is doubled due to MAD, leading to a 50\% increase in neutral pressure; 5) total hydrogenic power loss is increased by up to 60\% due to MAD. These differences result in an improved agreement between the experiment and the simulations in terms of spectroscopic measurements, ion source/sink inferences and the occurrence of an ion target flux roll-over

SOLPS-ITER validation with TCV L-mode discharges editors-pick

This work presents a quantitative test of SOLPS-ITER simulations against tokamak a configuration variable (TCV) L-mode experiments. These simulations account for drifts, currents, kinetic neutrals, and carbon impurities providing the most complete edge transport simulations for TCV to date. The comparison is performed on nominally identical discharges carried out to assess the effectiveness of TCV's divertor baffles in the framework of the European Plasma Exhaust program and employs numerous edge diagnostics providing a detailed code-experiment benchmark for TCV. The simulations show a qualitative consistency, but the quantitative differences remain, which are assessed herein. It is found that, for a given separatrix density, the simulations most notably yield a colder, and denser, divertor state with a higher divertor neutral pressure than measured

Communications Biophysics

Contains reports on five research projects.National Science Foundation (Grant G-16526)National Institutes of Health (Grant MH-04737-02

Rab27a and Rab27b control different steps of the exosome secretion pathway

Exosomes are secreted membrane vesicles that share structural and biochemical characteristics with intraluminal vesicles of multivesicular endosomes (MVEs). Exosomes could be involved in intercellular communication and in the pathogenesis of infectious and degenerative diseases. The molecular mechanisms of exosome biogenesis and secretion are, however, poorly understood. Using an RNA interference (RNAi) screen, we identified five Rab GTPases that promote exosome secretion in HeLa cells. Among these, Rab27a and Rab27b were found to function in MVE docking at the plasma membrane. The size of MVEs was strongly increased by Rab27a silencing, whereas MVEs were redistributed towards the perinuclear region upon Rab27b silencing. Thus, the two Rab27 isoforms have different roles in the exosomal pathway. In addition, silencing two known Rab27 effectors, Slp4 (also known as SYTL4, synaptotagmin-like 4) and Slac2b (also known as EXPH5, exophilin 5), inhibited exosome secretion and phenocopied silencing of Rab27a and Rab27b, respectively. Our results therefore strengthen the link between MVEs and exosomes, and introduce ways of manipulating exosome secretion in vivo

PrP Expression, PrPSc Accumulation and Innervation of Splenic Compartments in Sheep Experimentally Infected with Scrapie

BACKGROUND: In prion disease, the peripheral expression of PrP(C) is necessary for the transfer of infectivity to the central nervous system. The spleen is involved in neuroinvasion and neural dissemination in prion diseases but the nature of this involvement is not known. The present study undertook the investigation of the spatial relationship between sites of PrP(Sc) accumulation, localisation of nerve fibres and PrP(C) expression in the tissue compartments of the spleen of scrapie-inoculated and control sheep. METHODOLOGY/PRINCIPAL FINDINGS: Laser microdissection and quantitative PCR were used to determine PrP mRNA levels and results were compared with immunohistochemical protocols to distinguish PrP(C) and PrP(Sc) in tissue compartments of the spleen. In sheep experimentally infected with scrapie, the major sites of accumulation of PrP(Sc) in the spleen, namely the lymphoid nodules and the marginal zone, expressed low levels of PrP mRNA. Double immunohistochemical labelling for PrP(Sc) and the pan-nerve fibre marker, PGP, was used to evaluate the density of innervation of splenic tissue compartments and the intimacy of association between PrP(Sc) and nerves. Some nerve fibres were observed to accompany blood vessels into the PrP(Sc)-laden germinal centres. However, the close association between nerves and PrP(Sc) was most apparent in the marginal zone. Other sites of close association were adjacent to the wall of the central artery of PALS and the outer rim of germinal centres. CONCLUSIONS/SIGNIFICANCE: The findings suggest that the degree of PrP(Sc) accumulation does not depend on the expression level of PrP(C). Though several splenic compartments may contribute to neuroinvasion, the marginal zone may play a central role in being the compartment with most apparent association between nerves and PrP(Sc)

Exosome-Producing Follicle Associated Epithelium Is Not Involved in Uptake of PrPd from the Gut of Sheep (Ovis aries): An Ultrastructural Study

In natural or experimental oral scrapie infection of sheep, disease associated prion protein (PrPd) often first accumulates in Peyer's patch (PP) follicles. The route by which infectivity reaches the follicles is unknown, however, intestinal epithelial cells may participate in intestinal antigenic presentation by delivering exosomes as vehicles of luminal antigens. In a previous study using an intestinal loop model, following inoculation of scrapie brain homogenate, inoculum associated PrPd was detected by light microscopy shortly (15 minutes to 3.5 hours) after inoculation in the villous lacteals and sub-mucosal lymphatics. No PrPd was located within the follicle-associated epithelium (FAE), sub-FAE domes or the PP follicles. To evaluate this gut loop model and the transportation routes in more detail, we used electron microscopy (EM) to study intestinal tissues exposed to scrapie or control homogenates for 15 minutes to 10 days. In addition, immuno-EM was used to investigate whether exosomes produced in the FAE may possess small amounts of PrPd that were not detectable by light microscopy. This study showed that the integrity of the intestinal epithelium was sustained in the intestinal loop model. Despite prominent transcytotic activity and exosome release from the FAE of the ileal PP in sheep, these structures were not associated with transportation of PrPd across the mucosa. The study did not determine how infectivity reaches the follicles of PPs. The possibility that the infectious agent is transported across the FAE remains a possibility if it occurs in a form that is undetectable by the methods used in this study. Infectivity may also be transported via lymph to the blood and further to all other lymphoid tissues including the PP follicles, but the early presence of PrPd in the PP follicles during scrapie infection argues against such a mechanism

Differences in Immunoglobulin Light Chain Species Found in Urinary Exosomes in Light Chain Amyloidosis (AL)

Renal involvement is a frequent consequence of plasma cell dyscrasias. The most common entities are light chain amyloidosis, monoclonal immunoglobulin deposition disease and myeloma cast nephropathy. Despite a common origin, each condition has its own unique histologic and pathophysiologic characteristic which requires a renal biopsy to distinguish. Recent studies have shown urinary exosomes containing kidney-derived membrane and cytosolic proteins that can be used to probe the proteomics of the entire urinary system from the glomerulus to the bladder. In this study, we analyzed urine exosomes to determine the differences between exosomes from patients with light chain amyloidosis, multiple myeloma, monoclonal gammopathy of undetermined significance, and non-paraproteinemia related kidney disease controls. In patients with light chain amyloidosis, multiple myeloma and monoclonal gammopathy of undetermined significance, immunoreactive proteins corresponding to monomeric light chains were found in exosomes by western blot. In all of the amyloidosis samples with active disease, high molecular weight immunoreactive species corresponding to a decamer were found which were not found in exosomes from the other diseases or in amyloidosis exosomes from patients in remission. Few or no light chains monomeric bands were found in non-paraproteinemia related kidney disease controls. Our results showed that urinary exosomes may have tremendous potential in furthering our understanding of the pathophysiology and diagnosis of plasma cell dyscrasia related kidney diseases

Plasma miRNA as Biomarkers for Assessment of Total-Body Radiation Exposure Dosimetry

The risk of radiation exposure, due to accidental or malicious release of ionizing radiation, is a major public health concern. Biomarkers that can rapidly identify severely-irradiated individuals requiring prompt medical treatment in mass-casualty incidents are urgently needed. Stable blood or plasma-based biomarkers are attractive because of the ease for sample collection. We tested the hypothesis that plasma miRNA expression profiles can accurately reflect prior radiation exposure. We demonstrated using a murine model that plasma miRNA expression signatures could distinguish mice that received total body irradiation doses of 0.5 Gy, 2 Gy, and 10 Gy (at 6 h or 24 h post radiation) with accuracy, sensitivity, and specificity of above 90%. Taken together, these data demonstrate that plasma miRNA profiles can be highly predictive of different levels of radiation exposure. Thus, plasma-based biomarkers can be used to assess radiation exposure after mass-casualty incidents, and it may provide a valuable tool in developing and implementing effective countermeasures

Langmuir probe electronics upgrade on the tokamak a configuration variable

A detailed description of the Langmuir probe electronics upgrade for TCV (Tokamak a Configuration Variable) is presented. The number of amplifiers and corresponding electronics has been increased from 48 to 120 in order to simultaneously connect all of the 114 Langmuir probes currently mounted in the TCV divertor and main-wall tiles. Another set of 108 amplifiers is ready to be installed in order to connect 80 new probes, built in the frame of the TCV divertor upgrade. Technical details of the amplifier circuitry are discussed as well as improvements over the first generation of amplifiers developed at SPC (formerly CRPP) in 1993/1994 and over the second generation developed in 2012/2013. While the new amplifiers have been operated successfully for over a year, it was found that their silicon power transistors can be damaged during some off-normal plasma events. Possible solutions are discussed. (C) 2019 Author(s)