3,412 research outputs found
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
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