Clostridium perfringens epsilon toxin induces blood brain barrier permeability via caveolae-dependent transcytosis and requires expression of MAL.

Clostridium perfringens epsilon toxin (ETX) is responsible for causing the economically devastating disease, enterotoxaemia, in livestock. It is well accepted that ETX causes blood brain barrier (BBB) permeability, however the mechanisms involved in this process are not well understood. Using in vivo and in vitro methods, we determined that ETX causes BBB permeability in mice by increasing caveolae-dependent transcytosis in brain endothelial cells. When mice are intravenously injected with ETX, robust ETX binding is observed in the microvasculature of the central nervous system (CNS) with limited to no binding observed in the vasculature of peripheral organs, indicating that ETX specifically targets CNS endothelial cells. ETX binding to CNS microvasculature is dependent on MAL expression, as ETX binding to CNS microvasculature of MAL-deficient mice was not detected. ETX treatment also induces extravasation of molecular tracers including 376Da fluorescein salt, 60kDA serum albumin, 70kDa dextran, and 155kDA IgG. Importantly, ETX-induced BBB permeability requires expression of both MAL and caveolin-1, as mice deficient in MAL or caveolin-1 did not exhibit ETX-induced BBB permeability. Examination of primary murine brain endothelial cells revealed an increase in caveolae in ETX-treated cells, resulting in dynamin and lipid raft-dependent vacuolation without cell death. ETX-treatment also results in a rapid loss of EEA1 positive early endosomes and accumulation of large, RAB7-positive late endosomes and multivesicular bodies. Based on these results, we hypothesize that ETX binds to MAL on the apical surface of brain endothelial cells, causing recruitment of caveolin-1, triggering caveolae formation and internalization. Internalized caveolae fuse with early endosomes which traffic to late endosomes and multivesicular bodies. We believe that these multivesicular bodies fuse basally, releasing their contents into the brain parenchyma

Singlet fission spin dynamics from molecular structure: a modular computational pipeline

Singlet fission, which has applications in areas ranging form solar energy to quantum information, relies critically on transitions within a multi-spin manifold. These transitions are driven by fluctuations in the spin-spin exchange interaction, which have been linked to changes in nuclear geometry or exciton migration. Whilst simple calculations have supported this mechanism, to date little effort has been made to model realistic fluctuations which are informed by the actual structure and properties of physical materials. In this paper, we develop a modular computational pipeline for calculating singlet fission spin dynamics by way of electronic structural calculations, molecular dynamics, and numerical models of spin dynamics. The outputs of this pipeline aid in the interpretation of measured spin dynamics and allow us to place constraints on geometric fluctuations which are consistent with these observations.Comment: 23 pages (including SI), 7 Figure

High-Power Hall Propulsion Development at NASA Glenn Research Center

The NASA Office of the Chief Technologist Game Changing Division is sponsoring the development and testing of enabling technologies to achieve efficient and reliable human space exploration. High-power solar electric propulsion has been proposed by NASA's Human Exploration Framework Team as an option to achieve these ambitious missions to near Earth objects. NASA Glenn Research Center is leading the development of mission concepts for a solar electric propulsion Technical Demonstration Mission. The mission concepts are highlighted in this paper but are detailed in a companion paper. There are also multiple projects that are developing technologies to support a demonstration mission and are also extensible to NASA's goals of human space exploration. Specifically, the In-Space Propulsion technology development project at the NASA Glenn has a number of tasks related to high-power Hall thrusters including performance evaluation of existing Hall thrusters; performing detailed internal discharge chamber, near-field, and far-field plasma measurements; performing detailed physics-based modeling with the NASA Jet Propulsion Laboratory's Hall2De code; performing thermal and structural modeling; and developing high-power efficient discharge modules for power processing. This paper summarizes the various technology development tasks and progress made to date

High-Power Hall Propulsion Development at NASA Glenn Research Center

The NASA Office of the Chief Technologist Game Changing Division is sponsoring the development and testing of enabling technologies to achieve efficient and reliable human space exploration. High-power solar electric propulsion has been proposed by NASA's Human Exploration Framework Team as an option to achieve these ambitious missions to near Earth objects. NASA Glenn Research Center (NASA Glenn) is leading the development of mission concepts for a solar electric propulsion Technical Demonstration Mission. The mission concepts are highlighted in this paper but are detailed in a companion paper. There are also multiple projects that are developing technologies to support a demonstration mission and are also extensible to NASA's goals of human space exploration. Specifically, the In-Space Propulsion technology development project at NASA Glenn has a number of tasks related to high-power Hall thrusters including performance evaluation of existing Hall thrusters; performing detailed internal discharge chamber, near-field, and far-field plasma measurements; performing detailed physics-based modeling with the NASA Jet Propulsion Laboratory's Hall2De code; performing thermal and structural modeling; and developing high-power efficient discharge modules for power processing. This paper summarizes the various technology development tasks and progress made to dat

Time-series spectroscopy of the rapidly oscillating Ap star HR 3831

We present time-series spectroscopy of the rapidly oscillating Ap star HR 3831. This star has a dominant pulsation period of 11.7 minutes and a rotation period of 2.85 days. We have analysed 1400 intermediate-resolution spectra of the wavelength region 6100--7100 AA obtained over one week, using techniques similar to those we applied to another roAp star, Alpha Cir. We confirm that the H-alpha velocity amplitude of HR 3831 is modulated with rotation phase. Such a modulation was predicted by the oblique pulsator model, and rules out the spotted pulsator model. However, further analysis of H-alpha and other lines reveal rotational modulations that cannot easily be explained using the oblique pulsator model. In particular, the phase of the pulsation as measured by the width of the H-alpha line varies with height in the line. The variation of the H-alpha bisector shows a very similar pattern to that observed in Alpha Cir, which we have previously attributed to a radial node in the stellar atmosphere. However, the striking similarities between the two stars despite the much shorter period of Alpha Cir (6.8 min) argues against this interpretation unless the structure of the atmosphere is somewhat different between the two stars. Alternatively, the bisector variation is a signature of the degree l of the mode and not the overtone value n. High-resolution studies of the metal lines in roAp stars are needed to understand fully the form of the pulsation in the atmosphere.Comment: 13 pages, 20 figures, accepted by MNRA

Type II Quasars from the Sloan Digital Sky Survey: V. Imaging host galaxies with the Hubble Space Telescope

Type II quasars are luminous Active Galactic Nuclei whose centers are obscured by large amounts of gas and dust. In this paper we present 3-band HST images of nine type II quasars with redshifts 0.2 < z < 0.4 selected from the Sloan Digital Sky Survey based on their emission line properties. The intrinsic luminosities of these AGN are estimated to be -24 > M_B > -26, but optical obscuration allows their host galaxies to be studied unencumbered by bright nuclei. Each object has been imaged in three continuum filters (`UV', `blue' and `yellow') placed between the strong emission lines. The spectacular, high quality images reveal a wealth of details about the structure of the host galaxies and their environments. Six of the nine galaxies in the sample are ellipticals with de Vaucouleurs light profiles, one object has a well-defined disk component and the remaining two have marginal disks. Stellar populations of type II quasar hosts are more luminous (by a median of 0.3-0.7 mag, depending on the wavelength) and bluer (by about 0.4 mag) than are M* galaxies at the same redshift. When smooth fits to stellar light are subtracted from the images, we find both positive and negative residuals that become more prominent toward shorter wavelengths. We argue that the negative residuals are due to kpc-scale dust obscuration, while most positive residuals are due to the light from the nucleus scattered off interstellar material in the host galaxy. Scattered light makes a significant contribution to the broad band continuum emission and can be the dominant component of the extended emission in the UV in extreme cases.Comment: 51 pages, including 12 grey scale figures, 4 color figures, 5 tables. In press in AJ. Version with higher-resolution images available at http://www.astro.princeton.edu/~nadia/qso2.html. (Minor changes in response to the referee report

Large Variations in Volcanic Aerosol Forcing Efficiency Due to Eruption Source Parameters and Rapid Adjustments

The relationship between volcanic stratospheric aerosol optical depth (SAOD) and volcanic radiative forcing is key to quantify volcanic climate impacts. In their fifth assessment report, the Intergovernmental Panel on Climate Change used one scaling factor between volcanic SAOD and volcanic forcing based on climate model simulations of the 1991 Mt. Pinatubo eruption, which may not be appropriate for all eruptions. Using a large-ensemble of aerosol-chemistry-climate simulations of eruptions with different sulfur dioxide emissions, latitudes, emission altitudes and seasons, we find that the effective radiative forcing (ERF) is on average 20% less than the instantaneous radiative forcing, predominantly due to a positive shortwave cloud adjustment. In our model, the volcanic SAOD-ERF relationship is non-unique and varies widely depending on time since an eruption, eruption latitude and season due to differences in aerosol dispersion and incoming solar radiation. Our revised SAOD-ERF relationships suggest that volcanic forcing has been previously overestimated