265 research outputs found
Recommended from our members
Redox-dependent gating of VDAC by mitoNEET.
MitoNEET is an outer mitochondrial membrane protein essential for sensing and regulation of iron and reactive oxygen species (ROS) homeostasis. It is a key player in multiple human maladies including diabetes, cancer, neurodegeneration, and Parkinson's diseases. In healthy cells, mitoNEET receives its clusters from the mitochondrion and transfers them to acceptor proteins in a process that could be altered by drugs or during illness. Here, we report that mitoNEET regulates the outer-mitochondrial membrane (OMM) protein voltage-dependent anion channel 1 (VDAC1). VDAC1 is a crucial player in the cross talk between the mitochondria and the cytosol. VDAC proteins function to regulate metabolites, ions, ROS, and fatty acid transport, as well as function as a "governator" sentry for the transport of metabolites and ions between the cytosol and the mitochondria. We find that the redox-sensitive [2Fe-2S] cluster protein mitoNEET gates VDAC1 when mitoNEET is oxidized. Addition of the VDAC inhibitor 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS) prevents both mitoNEET binding in vitro and mitoNEET-dependent mitochondrial iron accumulation in situ. We find that the DIDS inhibitor does not alter the redox state of MitoNEET. Taken together, our data indicate that mitoNEET regulates VDAC in a redox-dependent manner in cells, closing the pore and likely disrupting VDAC's flow of metabolites
Unforeseen Computed Tomography Resimulation for Initial Radiation Planning: Associated Factors and Clinical Impact
Purpose: Repeat computed tomography (CT) simulation is problematic because of additional expense of clinic resources, patient inconvenience, additional radiation exposure, and treatment delay. We investigated the factors and clinical impact of unplanned CT resimulations in our network. Methods and Materials: We used the billing records of 18,170 patients treated at 5 clinics. A total of 213 patients were resimulated before their first treatment. The disease site, location, use of 4- dimensional CT (4DCT), contrast, image fusion, and cause for resimulation were recorded. Odds ratios determined statistical significance. Results: Our total rate of resimulation was 1.2%. Anal/colorectal (P \u3c .001) and head and neck (P \u3c .001) disease sites had higher rates of resimulation. Brain (P Z .001) and lung/thorax (P Z .008) had lower rates of resimulation. The most common causes for resimulation were setup change (11.7%), change in patient anatomy (9.8%), and rectal filling (8.5%). The resimulation rate for 4DCTs was 3.03% compared with 1.0% for non-4DCTs (P \u3c .001). Median time between simulations was 7 days. Conclusions: The most common sites for resimulation were anal/colorectal and head and neck, largely because of change in setup or changes in anatomy. The 4DCT technique correlated with higher resimulation rates. The resimulation rate was 1.2%, and median treatment delay was 7 days. Further studies are warranted to limit the rate of resimulation
Astrometry with the Wide-Field InfraRed Space Telescope
The Wide-Field InfraRed Space Telescope (WFIRST) will be capable of
delivering precise astrometry for faint sources over the enormous field of view
of its main camera, the Wide-Field Imager (WFI). This unprecedented combination
will be transformative for the many scientific questions that require precise
positions, distances, and velocities of stars. We describe the expectations for
the astrometric precision of the WFIRST WFI in different scenarios, illustrate
how a broad range of science cases will see significant advances with such
data, and identify aspects of WFIRST's design where small adjustments could
greatly improve its power as an astrometric instrument.Comment: version accepted to JATI
The Infrared Imaging Spectrograph (IRIS) for TMT: Data Reduction System
IRIS (InfraRed Imaging Spectrograph) is the diffraction-limited first light
instrument for the Thirty Meter Telescope (TMT) that consists of a
near-infrared (0.84 to 2.4 m) imager and integral field spectrograph
(IFS). The IFS makes use of a lenslet array and slicer for spatial sampling,
which will be able to operate in 100's of different modes, including a
combination of four plate scales from 4 milliarcseconds (mas) to 50 mas with a
large range of filters and gratings. The imager will have a field of view of
3434 arcsec with a plate scale of 4 mas with many selectable
filters. We present the preliminary design of the data reduction system (DRS)
for IRIS that need to address all of these observing modes. Reduction of IRIS
data will have unique challenges since it will provide real-time reduction and
analysis of the imaging and spectroscopic data during observational sequences,
as well as advanced post-processing algorithms. The DRS will support three
basic modes of operation of IRIS; reducing data from the imager, the lenslet
IFS, and slicer IFS. The DRS will be written in Python, making use of
open-source astronomical packages available. In addition to real-time data
reduction, the DRS will utilize real-time visualization tools, providing
astronomers with up-to-date evaluation of the target acquisition and data
quality. The quicklook suite will include visualization tools for 1D, 2D, and
3D raw and reduced images. We discuss the overall requirements of the DRS and
visualization tools, as well as necessary calibration data to achieve optimal
data quality in order to exploit science cases across all cosmic distance
scales.Comment: 13 pages, 2 figures, 6 tables, Proceeding 9913-165 of the SPIE
Astronomical Telescopes + Instrumentation 201
Cholesterol accumulation promotes photoreceptor senescence and retinal degeneration
PURPOSE: Dysregulated cholesterol metabolism is critical in the pathogenesis of AMD. Cellular senescence contributes to the development of numerous age-associated diseases. In this study, we investigated the link between cholesterol burden and the cellular senescence of photoreceptors.
METHODS: Retinas from rod-specific ATP binding cassette subfamily A member 1 (Abca1) and G member 1 (Abcg1) (Abca1/g1-rod/-rod) knockout mice fed with a high-fat diet were analyzed for the signs of cellular senescence. Real-time quantitative PCR and immunofluorescence were used to characterize the senescence profile of the retina and cholesterol-treated photoreceptor cell line (661W). Inducible elimination of p16(Ink4a)-positive senescent cells (INK-ATTAC) mice or the administration of senolytic drugs (dasatinib and quercetin: D&Q) were used to examine the impact of senolytics on AMD-like phenotypes in Abca1/g1-rod/-rod retina.
RESULTS: Increased accumulation of senescent cells as measured by markers of cellular senescence was found in Abca1/g1-rod/-rod retina. Exogenous cholesterol also induced cellular senescence in 661W cells. Selective elimination of senescent cells in Abca1/g1-rod/-rod;INK-ATTAC mice or by administration of D&Q improved visual function, lipid accumulation in retinal pigment epithelium, and Bruch\u27s membrane thickening.
CONCLUSIONS: Cholesterol accumulation promotes cellular senescence in photoreceptors. Eliminating senescent photoreceptors improves visual function in a model of retinal neurodegeneration, and senotherapy offers a novel therapeutic avenue for further investigation
The Infrared Imaging Spectrograph (IRIS) for TMT: motion planning with collision avoidance for the on-instrument wavefront sensors
The InfraRed Imaging Spectrograph (IRIS) will be a first-light client instrument for the Narrow Field Infrared Adaptive Optics System (NFIRAOS) on the Thirty Meter Telescope. IRIS includes three configurable tip/tilt (TT) or tip/tilt/focus (TTF) On-Instrument Wavefront Sensors (OIWFS). These sensors are positioned over natural guide star (NGS) asterisms using movable polar-coordinate pick-ofi arms (POA) that patrol an approximately 2-arcminute circular field-of-view (FOV). The POAs are capable of colliding with one another, so an algorithm for coordinated motion that avoids contact is required. We have adopted an approach in which arm motion is evaluated using the gradient descent of a scalar potential field that includes an attractive component towards the goal configuration (locations of target stars), and repulsive components to avoid obstacles (proximity to adjacent arms). The resulting vector field is further modified by adding a component transverse to the repulsive gradient to avoid problematic local minima in the potential. We present path planning simulations using this computationally inexpensive technique, which exhibit smooth and efficient trajectories
The Infrared Imaging Spectrograph (IRIS) for TMT: Instrument Overview
We present an overview of the design of IRIS, an infrared (0.84 - 2.4 micron)
integral field spectrograph and imaging camera for the Thirty Meter Telescope
(TMT). With extremely low wavefront error (<30 nm) and on-board wavefront
sensors, IRIS will take advantage of the high angular resolution of the narrow
field infrared adaptive optics system (NFIRAOS) to dissect the sky at the
diffraction limit of the 30-meter aperture. With a primary spectral resolution
of 4000 and spatial sampling starting at 4 milliarcseconds, the instrument will
create an unparalleled ability to explore high redshift galaxies, the Galactic
center, star forming regions and virtually any astrophysical object. This paper
summarizes the entire design and basic capabilities. Among the design
innovations is the combination of lenslet and slicer integral field units, new
4Kx4k detectors, extremely precise atmospheric dispersion correction, infrared
wavefront sensors, and a very large vacuum cryogenic system.Comment: Proceedings of the SPIE, 9147-76 (2014
The SPLASH Survey: Kinematics of Andromeda's Inner Spheroid
The combination of large size, high stellar density, high metallicity, and
Sersic surface brightness profile of the spheroidal component of the Andromeda
galaxy (M31) within R_proj ~ 20 kpc suggest that it is unlike any subcomponent
of the Milky Way. In this work we capitalize on our proximity to and external
view of M31 to probe the kinematical properties of this "inner spheroid." We
employ a Markov chain Monte Carlo (MCMC) analysis of resolved stellar
kinematics from Keck/DEIMOS spectra of 5651 red giant branch stars to
disentangle M31's inner spheroid from its stellar disk. We measure the mean
velocity and dispersion of the spheroid in each of five spatial bins after
accounting for a locally cold stellar disk as well as the Giant Southern Stream
and associated tidal debris. For the first time, we detect significant spheroid
rotation (v_rot ~ 50 km/s) beyond R_proj ~ 5 kpc. The velocity dispersion
decreases from about 140 km/s at R_proj = 7 kpc to 120 km/s at R_proj = 14 kpc,
consistent to 2 sigma with existing measurements and models. We calculate the
probability that a given star is a member of the spheroid and find that the
spheroid has a significant presence throughout the spatial extent of our
sample. Lastly, we show that the flattening of the spheroid is due to velocity
anisotropy in addition to rotation. Though this suggests that the inner
spheroid of M31 more closely resembles an elliptical galaxy than a typical
spiral galaxy bulge, it should be cautioned that our measurements are much
farther out (2 - 14 r_eff) than for the comparison samples.Comment: Accepted for publication in Ap
Infrared Nonlinear Optics
Contains reports on six research projects.Defense Advanced Research Projects Agency Universities Research Initiative (Contract N00014-46-K-0760)Strategic Defense Initiative/Innovative Science & Technology, managed by the U.S. Naval Research Laboratory (Contract N00014-87-K-2031)National Science Foundation (Grant EET-87-18417
An overview of the NIRSPEC upgrade for the Keck II telescope
NIRSPEC is a 1-5 micron echelle spectrograph in use on the Keck II Telescope
since 1999. The spectrograph is capable of both moderate (R~2,000) and high
(R~25,000) resolution observations and has been a workhorse instrument across
many astronomical fields, from planetary science to extragalactic observations.
In the latter half of 2018, we will upgrade NIRSPEC to improve the sensitivity
and stability of the instrument and increase its lifetime. The major components
of the upgrade include replacing the spectrometer and slit-viewing camera
detectors with Teledyne H2RG arrays and replacing all transputer-based
electronics. We present detailed design, testing, and analysis of the upgraded
instrument, including the finalized optomechanical design of the new 1-5 micron
slit-viewing camera, final alignment and assembly of the science array,
electronics systems, and updated software design.Comment: Proceedings of the 2018 SPIE Astronomical Telescopes &
Instrumentatio
- …