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In this study we assessed the role of HDAC in mediating lipopolysaccharide (LPS)-induced transendothelial hyperpermeability and acute lung injury (ALI). We demonstrate that HDAC inhibition protects against LPS-mediated EBD. Inhibition of multiple HDAC by the general inhibitors panobinostat or trichostatin provided protection against LPS-induced transendothelial hyperpermeability, acetylated and suppressed Hsp90 chaperone function, and attenuated RhoA activity and signaling crucial to endothelial barrier function. Treatment with the HDAC3-selective inhibitor RGFP-966 or the HDAC6-selective inhibitor tubastatin A provided partial protection against LPS-mediated transendothelial hyperpermeability. Similarly, knock down of HDAC3 and HDAC6 by specific small-interfering RNAs provided significant protection against LPS-induced EBD. Furthermore, combined pharmacological inhibition of both HDAC3 and -6 attenuated the inflammation, capillary permeability, and structural abnormalities associated with LPS-induced ALI in mice. Together these data indicate that HDAC mediate increased transendothelial hyperpermeability caused by LPS and that inhibition of HDAC protects against LPS-mediated EBD and ALI by suppressing Hsp90-dependent RhoA activity and signaling.

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A key parameter in modeling differential spacecraft charging is the resistivity of insulating materials. This parameter determines how charge will accumulate and redistribute across the spacecraft, as well as the time scale for charge transport and dissipation. ASTM constant voltage methods are shown to provide inaccurate resistivity measurements for materials with resistivities greater than ~10 17 Ω-cm or with long polarization decay times such as are found in many polymers. These data have been shown to often be inappropriate for spacecraft charging applications, and have been found to underestimate charging effects by one to four orders of magnitude for many materials. The charge storage decay method is shown to be the preferred method to determine the resistivities of such highly insulating materials. A review is presented of methods to measure the resistivity of highly insulating materials-including the electrometerresistance method, the electrometer-constant voltage method, and the charge storage method. The different methods are found to be appropriate for different resistivity ranges and for different charging circumstances. A simple, macroscopic, physics-based model of these methods allows separation of the polarization current and dark current components from long duration measurements of resistivity over day-to month-long time scales. Model parameters are directly related to the magnitude of charge transfer and storage and the rate of charge transport. The model largely explains the observed differences in resistivity found using the different methods and provides a framework for recommendations for the appropriate test method for spacecraft materials with different resistivities and applications..

Abstract-Electron-induced electron yields of high-resistivity, high-yield materials -ceramic polycrystalline aluminum oxide and the polymer polyimide (Kapton HN), -were made by using a low-fluence, pulsed incident electron beam and charge neutralization electron source to minimize charge accumulation. Large changes in energy-dependent total yield curves and yield decay curves were observed, even for incident electron fluences of <3 fC/mm 2 . The evolution of the electron yield as charge accumulates in the material is modeled in terms of electron recapture based on an extended Chung-Everhart model of the electron emission spectrum. This model is used to explain anomalies measured in highly insulating, high-yield materials, and to provide a method for determining the limiting yield spectra of uncharged dielectrics. Relevance of these results to spacecraft charging is also discussed.

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A traditional constant voltage conductivity test method was used to measure how the conductivity of highly insulating low-density polyethylene polymer films depends on applied electric field, repeated and prolonged electric field exposure, and sample temperature. The strength of the applied voltage was varied to determine the electric field dependence. At low electric field, the resistivity was measured from cryogenic temperatures to well above the glass transition temperature. Comparisons were made with a variety of models of the conduction mechanisms common in insulators, including transient polarization and diffusion and steady-state thermally activated hopping conductivity and variable range hopping conductivity, to determine which mechanisms were active for LDPE and to provide a better picture of its electrical behavior.

Electron emission and concomitant charge accumulation near the surface of insulators is central to understanding spacecraft charging. We present a study of changes in electron emission yields as a result of internal charge build up due to electron dose. Evolution of total, backscattered and secondary yield results over a broad range of incident energies are presented for two representative insulators, Kapton TM and Al 2 O 3. Reliable yield curves for un-charged insulators are measured and quantifiable changes in yields are observed due to <100 fC/mm 2 fluences. We find excellent agreement with a phenomenological argument based on insulator charging predicted by the yield curve; this includes a decrease in the rate of change of the yield as incident energies approach the crossover energies and as accumulated internal charge reduces the landing energy to asymptotically approach a steady state surface charge and unity yield. We also find that the exponential decay of yield curves with fluence exhibit an energy dependant decay constant, α(E). Finally, we discuss physics based models for this energy dependence. To understand fluence and energy dependence of these charging processes requires knowledge of how charge is deposited within the insulator, the mechanisms for charge trapping and transport within the insulator, and how the profile of trapped charge affects the transport and emission of charges from insulators.