Deletion of the trpc4 gene and its role in simple and complex strategic learning

The TRPC4 ion channel is expressed extensively in corticolimbic and a subpopulation of midbrain dopamine neurons. While TRPC4 knockout (KO) rats exhibit reduced sociability and social exploration, little is known about the role of TRPC4 in motivation and learning. To identify a function for TRPC4 channels in learning processes  we tested TRPC4 KO and normal wild type (WT) rats. TRPC4 KO and WT rats exhibited no differences in Y-­maze learning or simple discrimination learning. Furthermore, on a more complex serial reversal shift task designed  to assess strategic learning where the reward and non-­reward cues were repeatedly reversed between training sessions both TRPC4 KO and WT rats   performed equally well. Finally, we found no   performance differences when using a conditional reversal shift task where a tone signals the reversal of reward and non-reward cues within sessions. These data suggest that although TRPC4 channels may play a role in social interaction/anxiety  they exert a minimal role in simple and complex strategic learning

PBFA Z: A 20-MA z-pinch driver for plasma radiation sources

Sandia National Laboratories is completing a major modification to the PBFA-II facility. PBFA Z will be a z-pinch driver capable of delivering up to 20 MA to a z-pinch load. It optimizes the electrical coupling to the implosion energy of z pinches at implosion velocities of {approximately} 40 cm/{mu}s. Design constraints resulted in an accelerator with a 0.12-{Omega} impedance, a 10.25-nH inductance, and a 120-ns pulse width. The design required new water transmission lines, insulator stack, and vacuum power feeds. Current is delivered to the z-pinch load through four, self-magnetically-insulated vacuum transmission lines and a double post-hole convolute. A variety of design codes are used to model the power flow. These predict a peak current of 20 MA to a z-pinch load having a 2-cm length, a 2-cm radius, and a 15--mg mass, coupling 1.5 MJ into kinetic energy. We present 2-D Rad-Hydro calculations showing MJ x-ray outputs from tungsten wire-array z pinches

Reactive Oxygen Species Stimulate Insulin Secretion in Rat Pancreatic Islets: Studies Using Mono-Oleoyl-Glycerol

Chronic exposure (24–72 hrs) of pancreatic islets to elevated glucose and fatty acid leads to glucolipoxicity characterized by basal insulin hypersecretion and impaired glucose-stimulated insulin secretion (GSIS). Our aim was to determine the mechanism for basal hypersecretion of insulin. We used mono-oleoyl-glycerol (MOG) as a tool to rapidly increase lipids in isolated rat pancreatic ß-cells and in the clonal pancreatic ß-cell line INS-1 832/13. MOG (25–400 µM) stimulated basal insulin secretion from ß-cells in a concentration dependent manner without increasing intracellular Ca2+ or O2 consumption. Like GSIS, MOG increased NAD(P)H and reactive oxygen species (ROS). The mitochondrial reductant ß-hydroxybutyrate (ß-OHB) also increased the redox state and ROS production, while ROS scavengers abrogated secretion. Diazoxide (0.4 mM) did not prevent the stimulatory effect of MOG, confirming that the effect was independent of the KATP-dependent pathway of secretion. MOG was metabolized to glycerol and long-chain acyl-CoA (LC-CoA), whereas, acute oleate did not similarly increase LC-CoA. Inhibition of diacylglycerol kinase (DGK) did not mimic the effect of MOG on insulin secretion, indicating that MOG did not act primarily by inhibiting DGK. Inhibition of acyl-CoA synthetase (ACS) reduced the stimulatory effect of MOG on basal insulin secretion by 30% indicating a role for LC-CoA. These data suggest that basal insulin secretion is stimulated by increased ROS production, due to an increase in the mitochondrial redox state independent of the established components of GSIS

Reactive Oxygen Species Stimulate Insulin Secretion in Rat Pancreatic Islets: Studies Using Mono-Oleoyl-Glycerol

Chronic exposure (24–72 hrs) of pancreatic islets to elevated glucose and fatty acid leads to glucolipoxicity characterized by basal insulin hypersecretion and impaired glucose-stimulated insulin secretion (GSIS). Our aim was to determine the mechanism for basal hypersecretion of insulin. We used mono-oleoyl-glycerol (MOG) as a tool to rapidly increase lipids in isolated rat pancreatic ß-cells and in the clonal pancreatic ß-cell line INS-1 832/13. MOG (25–400 µM) stimulated basal insulin secretion from ß-cells in a concentration dependent manner without increasing intracellular Ca2+ or O2 consumption. Like GSIS, MOG increased NAD(P)H and reactive oxygen species (ROS). The mitochondrial reductant ß-hydroxybutyrate (ß-OHB) also increased the redox state and ROS production, while ROS scavengers abrogated secretion. Diazoxide (0.4 mM) did not prevent the stimulatory effect of MOG, confirming that the effect was independent of the KATP-dependent pathway of secretion. MOG was metabolized to glycerol and long-chain acyl-CoA (LC-CoA), whereas, acute oleate did not similarly increase LC-CoA. Inhibition of diacylglycerol kinase (DGK) did not mimic the effect of MOG on insulin secretion, indicating that MOG did not act primarily by inhibiting DGK. Inhibition of acyl-CoA synthetase (ACS) reduced the stimulatory effect of MOG on basal insulin secretion by 30% indicating a role for LC-CoA. These data suggest that basal insulin secretion is stimulated by increased ROS production, due to an increase in the mitochondrial redox state independent of the established components of GSIS

Magnetic Tower Outflows from a Radial Wire Array Z-pinch

We present the first results of high energy density laboratory astrophysics experiments which explore the evolution of collimated outflows and jets driven by a toroidal magnetic field. The experiments are scalable to astrophysical flows in that critical dimensionless numbers such as the Mach number, the plasma beta and the magnetic Reynolds number are all in the astrophysically appropriate ranges. Our experiments use the MAGPIE pulsed power machine and allow us to explore the role of magnetic pressure in creating and collimating the outflow as well as showing the creation of a central jet within the broader outflow cavity. We show that currents flow along this jet and we observe its collimation to be enhanced by the additional hoop stresses associated with the generated toroidal field. Although at later times the jet column is observed to go unstable, the jet retains its collimation. We also present simulations of the magnetic jet evolution using our two-dimensional resistive magneto-hydrodynamic (MHD) laboratory code. We conclude with a discussion of the astrophysical relevance of the experiments and of the stability properties of the jet.Comment: Accepted by MNRAS. 17 pages without figures. Full version with figures can be found at http://www.pas.rochester.edu/~afrank/labastro/MF230rv.pd

Analysis of radially resolved spectra and potential for lasing in Mo wire array Z pinches

Measurements of radially resolved L-shell Mo spectra from wire array pinches on Sandia's Z generator are presented and analyzed using a collisional-radiative model. The spectra indicate large radial gradients in density over the {approx}8-mm-diameter plasma column, but only the emission from the {approx}2 mm central region of the pinch appears to be influenced by opacity. Population inversions and significant gain factors for 100-200 {angstrom} transitions in Ne-like Mo are predicted to exist at the diagnosed plasma conditions

Spectroscopic diagnosis of foam z-pinch plasmas on SATURN

Solid and annular silicon aerogel and agar foams were shot on the accelerator SATURN to study plasma initiation, acceleration, and stagnation. SATURN delivers 7 MA with a 50 nsec rise time to these foam loads. We fielded several spectroscopic diagnostics to measure plasma parameters throughout the z-pinch discharge. A spatially resolved single frame time-gated EUV spectrometer measured the extent of plasma ablation off the surface foam. A time integrated crystal spectrometer showed that characteristic K shell radiation of silicon in the aerogel and of S and Na impurities in the agar were all attenuated when the foam loads were coated with a conductive layer of gold. The time resolved pinhole camera showed that in general the quality of the pinch implosions was poor but improved with increasing efforts to improve current continuity such as prepulse and conductive coatings

One- and two-dimensional density and temperature measurements of an argon-neon Z-pinch plasma at stagnation

In order to benchmark and improve current 2D radiation magnetohydrodynamic (MHD) models of Z-pinch plasmas, we have performed experiments which characterize the plasma -conditions at stagnation. In the experiments the SATURN pulsed power facility at Sandia National Laboratory was used to create an imploding -Ar-Ne plasma. An absolutely calibrated, high resolution space- and time- resolving Johann crystal spectrometer was used to infer the electron temperature Te from the slope of the hydrogenlike Ne free-bound continuum, and the ion density ni from the Stark broadening of the Ar heliunlike Rydberg series. 2D electron temperature profiles of the plasma are obtained from a set of imaging crystals also focused on the Ne free-bound continuum. We shot two types of gas nozzles in the experiment, annular and uniform fill which varies the amount of mass in the plasma. 2D local thermodynamic equilibrium (LTE) and non-LTE MM models predict a radiating region denser and cooler than measured

Fast resistive bolometry

Resistive bolometry is an accurate, robust, spectrally broadband technique for measuring absolute x-ray fluence and flux. Bolometry is an independent technique for x-ray measurements that is based on a different set of physical properties than other diagnostics such as x-ray diodes, photoconducting detectors, and P-I-N diodes. Bolometers use the temperature-driven change in element resistivity to determine the total deposited energy. The calibration of such a device is based on fundamental material properties and its physical dimensions. We describe the use of nickel and gold bolometers to measure x rays generated by high-power z pinches on Sandia's Saturn and Z accelerators. The Sandia bolometer design described herein has a pulse response of {approximately}1 ns. We describe in detail the fabrication, fielding, and data analysis issues leading to highly accurate x-ray measurements. The fundamental accuracy of resistive bolometry will be discussed

Metformin Enhances Autophagy and Normalizes Mitochondrial Function to Alleviate Aging-Associated Inflammation

Age is a non-modifiable risk factor for the inflammation that underlies age-associated diseases; thus, anti-inflammaging drugs hold promise for increasing health span. Cytokine profiling and bioinformatic analyses showed that Th17 cytokine production differentiates CD4+ T cells from lean, normoglycemic older and younger subjects, and mimics a diabetes-associated Th17 profile. T cells from older compared to younger subjects also had defects in autophagy and mitochondrial bioenergetics that associate with redox imbalance. Metformin ameliorated the Th17 inflammaging profile by increasing autophagy and improving mitochondrial bioenergetics. By contrast, autophagy-targeting siRNA disrupted redox balance in T cells from young subjects and activated the Th17 profile by activating the Th17 master regulator, STAT3, which in turn bound IL-17A and F promoters. Mitophagy-targeting siRNA failed to activate the Th17 profile. We conclude that metformin improves autophagy and mitochondrial function largely in parallel to ameliorate a newly defined inflammaging profile that echoes inflammation in diabetes