Astrocyte IKKß/NF-κB signaling is required for diet-induced obesity and hypothalamic inflammation.

OBJECTIVE: Obesity and high fat diet (HFD) consumption in rodents is associated with hypothalamic inflammation and reactive gliosis. While neuronal inflammation promotes HFD-induced metabolic dysfunction, the role of astrocyte activation in susceptibility to hypothalamic inflammation and diet-induced obesity (DIO) remains uncertain. METHODS: Metabolic phenotyping, immunohistochemical analyses, and biochemical analyses were performed on HFD-fed mice with a tamoxifen-inducible astrocyte-specific knockout of IKKß (GfapCreERIkbkbfl/fl, IKKß-AKO), an essential cofactor of NF-κB-mediated inflammation. RESULTS: IKKß-AKO mice with tamoxifen-induced IKKß deletion prior to HFD exposure showed equivalent HFD-induced weight gain and glucose intolerance as Ikbkbfl/fl littermate controls. In GfapCreERTdTomato marker mice treated using the same protocol, minimal Cre-mediated recombination was observed in the mediobasal hypothalamus (MBH). By contrast, mice pretreated with 6 weeks of HFD exposure prior to tamoxifen administration showed substantially increased recombination throughout the MBH. Remarkably, this treatment approach protected IKKß-AKO mice from further weight gain through an immediate reduction of food intake and increase of energy expenditure. Astrocyte IKKß deletion after HFD exposure-but not before-also reduced glucose intolerance and insulin resistance, likely as a consequence of lower adiposity. Finally, both hypothalamic inflammation and astrocytosis were reduced in HFD-fed IKKß-AKO mice. CONCLUSIONS: These data support a requirement for astrocytic inflammatory signaling in HFD-induced hyperphagia and DIO susceptibility that may provide a novel target for obesity therapeutics.

Magnetic diagnostic suite of the C-2 field-reversed configuration experiment confinement vessel.

Magnetic measurements are a fundamental part of determining the size and shape of field-reversed configuration (FRC) plasmas in the C-2 device. The magnetic probe suite consists of 44 in-vessel and ex-vessel probes constructed using various technologies: ultra-high vacuum compatible mineral-insulated cable, nested triple axis coils hand-wound on ceramic bobbins, and commercial chip inductors mounted on printed circuit boards. Together, these probes measure the three-dimensional excluded flux profile of the FRC, which approximates the shape of the separatrix between the confined plasma volume and the scrape-off layer. High accuracy is achieved by using the extensive probe measurements to compensate for non-ideal effects such as flux leakage through the vacuum vessel and bulk motion of the FRC towards the wall. A subset of the probes is also used as a set of Mirnov arrays that provide sensitive detection of perturbations and oscillations of the FRC.

Field reversed configuration confinement enhancement through edge biasing and neutral beam injection.

Field reversed configurations (FRCs) with high confinement are obtained in the C-2 device by combining plasma gun edge biasing and neutral beam injection. The plasma gun creates an inward radial electric field that counters the usual FRC spin-up. The n = 2 rotational instability is stabilized without applying quadrupole magnetic fields. The FRCs are nearly axisymmetric, which enables fast ion confinement. The plasma gun also produces E × B shear in the FRC edge layer, which may explain the observed improved particle transport. The FRC confinement times are improved by factors 2 to 4, and the plasma lifetimes are extended from 1 to up to 4 ms.

Dynamic formation of a hot field reversed configuration with improved confinement by supersonic merging of two colliding high-ß compact toroids.

A hot stable field-reversed configuration (FRC) has been produced in the C-2 experiment by colliding and merging two high-ß plasmoids preformed by the dynamic version of field-reversed θ-pinch technology. The merging process exhibits the highest poloidal flux amplification obtained in a magnetic confinement system (over tenfold increase). Most of the kinetic energy is converted into thermal energy with total temperature (T{i}+T{e}) exceeding 0.5 keV. The final FRC state exhibits a record FRC lifetime with flux confinement approaching classical values. These findings should have significant implications for fusion research and the physics of magnetic reconnection.

COBRA-STAR, a five frame point-projection x-ray imaging system for 1 MA scale wire-array Z pinches.

A new imaging system for 1 MA scale wire-array Z-pinch experiments that produces up to five high-resolution x-ray images per experimental pulse has been developed. Calibrated areal density measurements of the Z-pinch plasma can be obtained from each pulse. The system substitutes five molybdenum (Mo) X pinches for the normal copper return-current conductors to provide point sources of x-rays for point-projection radiography. Each backlighting X pinch consists of four Mo wires, the x-ray burst timing of which was controlled by varying the wire diameter (mass) from 10.2 to 30 microm in the five X pinches. Typical images have a 16x8 mm2 field of view at the wire array and a magnification of about 6.5:1 on the x-ray-sensitive film. Titanium (Ti) filters in front of the films transmit continuum radiation in the spectral range of 3-5 keV. Inclusion on the Ti of a step wedge having known thickness increments of the same material as the wires enables the calibrated areal density measurements to be made of the exploding wire plasmas. Here, we used tungsten (W) step wedges with step thicknesses ranging from 0.015 to 1.1 microm to obtain accurate (+/-10%) areal density measurements of W plasmas from the spatial profile of film exposure. When imaging arrays that produce intense radiation pulses, a plastic monofilament "quencher" is placed on axis to avoid film saturation. Images have subnanosecond temporal resolution and about 7 microm spatial resolution.

Wide band focusing x-ray spectrograph with spatial resolution.

A new, wide spectral bandwidth x-ray spectrograph, the wide-bandwidth focusing spectrograph with spatial resolution (WB-FSSR), based on spherically bent mica crystals, is described. The wide bandwidth is achieved by combining three crystals to form a large aperture dispersive element. Since the WB-FSSR covers a wide spectral band, it is very convenient for application as a routine diagnostic tool in experiments in which the desired spectral coverage is different from one test to the next. The WB-FSSR has been tested in imploding wire-array experiments on a 1 MA pulsed power machine, and x-ray spectra were recorded in the 1-20 A spectral band using different orders of mica crystal reflection. Using a two mirror-symmetrically placed WB-FSSR configuration, it was also possible to distinguish between a real spectral shift and a shift of recorded spectral lines caused by the spatial distribution of the radiating plasma. A spectral resolution of about 2000 was demonstrated and a spatial resolution of approximately 100 microm was achieved in the spectral band of 5-10 A in second order of mica reflection. A simple method of numerical analysis of spectrograph capability is proposed.