Heavy impurity transport in tokamaks subject to plasma rotation, NTV and the influence of saturated ideal MHD perturbations

Strongly peaked tungsten accumulation is a common feature of high performance plasma scenarios in JET with the ITER-like wall, particularly during MHD activity induced by m⁄n = 1⁄1 continuous modes. This study investigates the effect of 1⁄1 long living internal kink modes on heavy impurity transport in the presence of strong flows and NTV ambipolar electric field. A novel formulation which includes these effects is presented and applied in the VENUS-LEVIS code in order to follow tungsten ions in a saturated JET-like 1⁄1 internal kinked toroidally rotating plasma configuration. The synergy between 3D magnetic fields, strong flows and NTV is seen to cause tungsten accumulation in contrast to what is observed in similar axisymmetric configurations. Rapid inward transport of impurities in JET plasmas following the triggering of continuous 1⁄1 modes is explained by the work presented here, and we use the same theory to postulate why outward transport can occur in kinked ASDEX-U plasmas.

Glial Chloride Homeostasis Under Transient Ischemic Stress

High water permeabilities permit rapid adjustments of glial volume upon changes in external and internal osmolarity, and pathologically altered intracellular chloride concentrations ([Cl–]int) and glial cell swelling are often assumed to represent early events in ischemia, infections, or traumatic brain injury. Experimental data for glial [Cl–]int are lacking for most brain regions, under normal as well as under pathological conditions. We measured [Cl–]int in hippocampal and neocortical astrocytes and in hippocampal radial glia-like (RGL) cells in acute murine brain slices using fluorescence lifetime imaging microscopy with the chloride-sensitive dye MQAE at room temperature. We observed substantial heterogeneity in baseline [Cl–]int, ranging from 14.0 ± 2.0 mM in neocortical astrocytes to 28.4 ± 3.0 mM in dentate gyrus astrocytes. Chloride accumulation by the Na+-K+-2Cl– cotransporter (NKCC1) and chloride outward transport (efflux) through K+-Cl– cotransporters (KCC1 and KCC3) or excitatory amino acid transporter (EAAT) anion channels control [Cl–]int to variable extent in distinct brain regions. In hippocampal astrocytes, blocking NKCC1 decreased [Cl–]int, whereas KCC or EAAT anion channel inhibition had little effect. In contrast, neocortical astrocytic or RGL [Cl–]int was very sensitive to block of chloride outward transport, but not to NKCC1 inhibition. Mathematical modeling demonstrated that higher numbers of NKCC1 and KCC transporters can account for lower [Cl–]int in neocortical than in hippocampal astrocytes. Energy depletion mimicking ischemia for up to 10 min did not result in pronounced changes in [Cl–]int in any of the tested glial cell types. However, [Cl–]int changes occurred under ischemic conditions after blocking selected anion transporters. We conclude that stimulated chloride accumulation and chloride efflux compensate for each other and prevent glial swelling under transient energy deprivation.

Proton Transport in Cancer Cells: The Role of Carbonic Anhydrases

Intra- and extracellular pH regulation is a pivotal function of all cells and tissues. Net outward transport of H+ is a prerequisite for normal physiological function, since a number of intracellular processes, such as metabolism and energy supply, produce acid. In tumor tissues, distorted pH regulation results in extracellular acidification and the formation of a hostile environment in which cancer cells can outcompete healthy local host cells. Cancer cells employ a variety of H+/HCO3−-coupled transporters in combination with intra- and extracellular carbonic anhydrase (CA) isoforms, to alter intra- and extracellular pH to values that promote tumor progression. Many of the transporters could closely associate to CAs, to form a protein complex coined “transport metabolon”. While transport metabolons built with HCO3−-coupled transporters require CA catalytic activity, transport metabolons with monocarboxylate transporters (MCTs) operate independently from CA catalytic function. In this article, we assess some of the processes and functions of CAs for tumor pH regulation and discuss the role of intra- and extracellular pH regulation for cancer pathogenesis and therapeutic intervention.

Adaptive Response of HK-2 Cells to High Levels of COM Crystals Highlights CaSR as an Enhancer of Crystal Adhesion

Background: Calcium oxalate monohydrate (COM) is an aetiologic factor for urolithiasis. However, how Human Kidney-2 (HK-2) cells respond to a high COM has not yet been completely elucidated.Materials and methods: A gel-based proteomics approach was applied to investigate COM-induced cellular proteomic changes. The COM-induced upregulation of calcium-sensing receptor (CaSR) in HK-2 cells was studied. Surface phospholipids (PS), which play a role in urolithiasis formation by mediating adhesion of HK-2 cells, were labelled in the inner or outer leaflet of the plasma membrane of HK-2 cells with fluorescent nitrobenzoxadiazole (NBD) to form NBD-PS to detect transmembrane movements of PS. After labelling, HK-2 cells were exposed to COM in the presence of the CaSR-specific agonist gadolinium chloride (GdCl3) or the CaSR-specific antagonist NPS2390. Inward and outward transmembrane movements of PS were tracked with a fluorescence quenching assay. Surface-expressed PS was detected by an annexin V binding assay. Changes in aminophospholipid translocase (APLT), oxidative stress (OS), levels of apoptosis-related proteins in HK-2 cells and crystal adhesion were also assessed.Results: COM increased CaSR and surface-expressed PS levels, decreased APLT activity, impaired inward transport of PS, and enhanced outward transport of PS. However, pretreatment with GdCl3 further effectively inhibited the inward movement of PS and APLT activity and increased surface-expressed PS levels compared with COM treatment alone. In contrast, NPS2390 promoted the inward movement of PS and APLT activity and decreased surface-expressed PS levels compared with COM treatment alone. COM increased OS, apoptosis of HK-2 cells and crystal adhesion onto cells, and this increase was further enhanced by GdCl3 pretreatment but attenuated by NPS2390 treatment.Conclusions: These results strongly suggest that COM-induced CaSR generation may affect crystal adhesion by regulating PS externalization, apoptosis and OS in HK-2 cells.

Chondrules reveal large-scale outward transport of inner Solar System materials in the protoplanetary disk

Dynamic models of the protoplanetary disk indicate there should be large-scale material transport in and out of the inner Solar System, but direct evidence for such transport is scarce. Here we show that the ε50Ti-ε54Cr-Δ17O systematics of large individual chondrules, which typically formed 2 to 3 My after the formation of the first solids in the Solar System, indicate certain meteorites (CV and CK chondrites) that formed in the outer Solar System accreted an assortment of both inner and outer Solar System materials, as well as material previously unidentified through the analysis of bulk meteorites. Mixing with primordial refractory components reveals a “missing reservoir” that bridges the gap between inner and outer Solar System materials. We also observe chondrules with positive ε50Ti and ε54Cr plot with a constant offset below the primitive chondrule mineral line (PCM), indicating that they are on the slope ∼1.0 in the oxygen three-isotope diagram. In contrast, chondrules with negative ε50Ti and ε54Cr increasingly deviate above from PCM line with increasing δ18O, suggesting that they are on a mixing trend with an ordinary chondrite-like isotope reservoir. Furthermore, the Δ17O-Mg# systematics of these chondrules indicate they formed in environments characterized by distinct abundances of dust and H2O ice. We posit that large-scale outward transport of nominally inner Solar System materials most likely occurred along the midplane associated with a viscously evolving disk and that CV and CK chondrules formed in local regions of enhanced gas pressure and dust density created by the formation of Jupiter.

Environmental interactions during the extreme rain event associated with ex-tropical cyclone Oswald (2013)

Tropical cyclone (TC) Oswald made landfall over north-east Australia as a minimal or Category 1 TC on the Australian scale on 21 January 2013. As it moved southward, it intensified over land and produced extreme rainfall for nearly 7 days. Tornadoes were reported and confirmed. Tragically, seven people died and insurance estimates were ~$1 billion. It is demonstrated that the event was associated with an interaction between the ex-Oswald circulation and an amplifying Rossby wave, which propagated north-eastward from high latitudes. Diagnoses showed that as the wave amplified and broke, a potential vorticity (PV) anomaly (PVA) extended to mid-levels, moved equatorward, merged with or axisymmetrised the ex-Oswald circulation through mid-levels. Backward trajectories from locations regularly scattered within the mid-level circulation illustrated that the storm transitioned from an isolated vortex into a circulation which was strongly influenced by its environment for at least 5 days. During this interaction, PV was advected from the environment towards the storm through mid-levels. The heavy rain coincided with the commencement and maintenance of this PV injection. The PV injection is quantified and shown to be consistent with PV advection by the mean radial flow. In addition, eddy angular momentum convergence in the mid- to upper levels coincided with an intensification of the circulation through this region. This was first related to outward transport of anticyclonic momentum by the asymmetric outflow at upper levels, followed by inward transport of cyclonic momentum by the asymmetric inflow. It is shown that the environmental interaction had an impact on vortex structure changes, rainfall and tornado development. We propose that the environmental processes influenced the ascent within the storm (1) via differential vorticity advection and baroclinic forcing, as the mid- to upper level PVA approached the circulation and (2) by low- to mid-level warm air advection.

Climate Warming–Related Strengthening of the Tropical Hydrological Cycle

The authors estimate climate warming–related twenty-first-century changes of moisture transports from the descending into the ascending regions in the tropics. Unlike previous studies that employ time and space averaging, here homogeneous high horizontal and vertical resolution data from an Intergovernmental Panel on Climate Change Fourth Assessment Report (IPCC AR4) climate model are used. This allows for estimating changes in much greater detail (e.g., the estimation of the distribution of ascending and descending regions, changes in the vertical profile, and separating changes of the inward and outward transports). Low-level inward and midlevel outward moisture transports of the convective regions in the tropics are found to increase in a simulated anthropogenically warmed climate as compared to a simulated twentieth-century atmosphere, indicating an intensification of the hydrological cycle. Since an increase of absolute inward transport exceeds the absolute increase of outward transport, the resulting budget is positive, meaning that more water is projected to converge in the moist tropics. The intensification is found mainly to be due to the higher amount of water in the atmosphere, while the contribution of weakening wind counteracts this response marginally. In addition the changing statistical properties of the vertical profile of the moisture transport are investigated and the importance of the substantial outflow of moisture from the moist tropics at midlevels is demonstrated.

FC29-05 - Season, sunlight, and brain serotonin function

IntroductionMany experience low mood and energy during winter. Brain serotonin is involved in the regulation of many physiologic and pathologic functions that vary with season. Seasonal variations in peripheral serotonergic markers have been described in clinical and nonclinical populations, and a postmortem study shows seasonal differences in hypothalamic serotonin concentration.AimWe investigated the molecular background of seasonal changes in serotonin function by conducting a series of studies on serotonin transporter (5-HTT) density and function in depression and health.MethodsIn a large study in drug-free patients with seasonal affective disorder (SAD) we aimed at detecting state-related alterations in 5-HTT-mediated inward and outward transport in platelets. Another study in healthy subjects aimed at detecting seasonal variations in 5-HTT binding in the living human brain using [11C] DASB positron emission tomography. Regional 5-HTT binding, an index of 5-HTT density, was assessed in a large sample of drug-naïve healthy volunteers, and was related to meteorological and astronomical data.ResultsIn patients with SAD we showed that the 5-HTT is in a hyperfunctional state during winter depression, and normalizes after light therapy and in natural summer remission. In healthy subjects, 5-HTT binding was higher in autumn/winter as compared to spring/summer. Regional 5-HTT binding correlated negatively with daily sunshine, such that higher values occurred at times of lesser light.ConclusionsSince high 5-HTT density is associated with low synaptic serotonin levels, regulation of 5-HTT density and 5-HTT function by light is a mechanism that may explain seasonal changes in normal and pathologic behaviours.