105 research outputs found
Observations of stress-coupled grain boundary migration in nanocrystalline thin films
Stress-coupled grain boundary migration has been shown to be an active deformation mechanism in a number of nanocrystalline metals. Ex situ tensile and hardness testing have proven to be valuable tools in uncovering the existence of stress-coupled grain boundary migration and ascertaining the role of shear stress, but these ex situ -experiments cannot provided detailed information about the microstructure as it evolves. In contrast, emerging in situ techniques such as TEM-based Precession Assisted Crystal Orientation Mapping and SEM-based Transmission Kikuchi Diffraction now allow for nanoscale observations of individual grains and grain boundaries. -Conducting in situ mechanical tests in conjunction with orientation mapping provides quantitative mechanistic information about grain boundary migration and greatly facilitates comparisons with computer simulations. Key parameters of interest to this study include the effect of grain boundary character and chemistry on the coupling factor, grain boundary mobility, and attendant mechanical response of nanocrystalline metals
On the origin of X-shaped radio galaxies
After a brief, critical review of the leading explanations proposed for the
small but important subset of radio galaxies showing an X-shaped morphology
(XRGs) we propose a generalized model, based on the jet-shell interaction and
spin-flip hypotheses. The most popular scenarios for this intriguing phenomenon
invoke either hydrodynamical backflows and over-pressured cocoons or rapid jet
reorientations, presumably from the spin-flips of central engines following the
mergers of pairs of galaxies, each of which contains a supermassive black hole
(SMBH). We confront these models with a number of key observations and thus
argue that none of the models is capable of explaining the entire range of
salient observational properties of XRGs, although some of the arguments raised
in the literature against the spin-flip scenario are probably not tenable. We
then propose here a new scenario which also involves galactic mergers but would
allow the spin of the central engine to maintain its direction. Motivated by
the detailed multi-band observations of the nearest radio galaxy, Centaurus A,
this new model emphasizes the role of interactions between the jets and the
shells of stars and gas that form and rotate around the merged galaxy and can
cause temporary deflections of the jets, occasionally giving rise to an
X-shaped radio structure. Although each of the models is likely to be relevant
to a subset of XRGs, the bulk of the evidence indicates that most of them are
best explained by the jet-shell interaction or spin-flip hypotheses.Comment: 19 pages, major revision including two Appendices and a Table,
accepted in Research in Astronomy and Astrophysic
Detection of intrinsic source structure at ~3 Schwarzschild radii with Millimeter-VLBI observations of SAGITTARIUS A*
We report results from very long baseline interferometric (VLBI) observations
of the supermassive black hole in the Galactic center, Sgr A*, at 1.3 mm (230
GHz). The observations were performed in 2013 March using six VLBI stations in
Hawaii, California, Arizona, and Chile. Compared to earlier observations, the
addition of the APEX telescope in Chile almost doubles the longest baseline
length in the array, provides additional {\it uv} coverage in the N-S
direction, and leads to a spatial resolution of 30 as (3
Schwarzschild radii) for Sgr A*. The source is detected even at the longest
baselines with visibility amplitudes of 4-13% of the total flux density.
We argue that such flux densities cannot result from interstellar refractive
scattering alone, but indicate the presence of compact intrinsic source
structure on scales of 3 Schwarzschild radii. The measured nonzero
closure phases rule out point-symmetric emission. We discuss our results in the
context of simple geometric models that capture the basic characteristics and
brightness distributions of disk- and jet-dominated models and show that both
can reproduce the observed data. Common to these models are the brightness
asymmetry, the orientation, and characteristic sizes, which are comparable to
the expected size of the black hole shadow. Future 1.3 mm VLBI observations
with an expanded array and better sensitivity will allow a more detailed
imaging of the horizon-scale structure and bear the potential for a deep
insight into the physical processes at the black hole boundary.Comment: 11 pages, 5 figures, accepted to Ap
Exploring the Mode of Action of Bioactive Compounds by Microfluidic Transcriptional Profiling in Mycobacteria
10.1371/journal.pone.0069191PLoS ONE87-POLN
Lysyl-tRNA synthetase as a drug target in malaria and cryptosporidiosis
Malaria and cryptosporidiosis, caused by apicomplexan parasites, remain major drivers of global child mortality. New drugs for the treatment of malaria and cryptosporidiosis, in particular, are of high priority; however, there are few chemically validated targets. The natural product cladosporin is active against blood- and liver-stage; Plasmodium falciparum; and; Cryptosporidium parvum; in cell-culture studies. Target deconvolution in; P. falciparum; has shown that cladosporin inhibits lysyl-tRNA synthetase (; Pf; KRS1). Here, we report the identification of a series of selective inhibitors of apicomplexan KRSs. Following a biochemical screen, a small-molecule hit was identified and then optimized by using a structure-based approach, supported by structures of both; Pf; KRS1 and; C. parvum; KRS (; Cp; KRS). In vivo proof of concept was established in an SCID mouse model of malaria, after oral administration (ED; 90; = 1.5 mg/kg, once a day for 4 d). Furthermore, we successfully identified an opportunity for pathogen hopping based on the structural homology between; Pf; KRS1 and; Cp; KRS. This series of compounds inhibit; Cp; KRS and; C. parvum; and; Cryptosporidium hominis; in culture, and our lead compound shows oral efficacy in two cryptosporidiosis mouse models. X-ray crystallography and molecular dynamics simulations have provided a model to rationalize the selectivity of our compounds for; Pf; KRS1 and; Cp; KRS vs. (human); Hs; KRS. Our work validates apicomplexan KRSs as promising targets for the development of drugs for malaria and cryptosporidiosis
An Upstream Open Reading Frame Controls Translation of var2csa, a Gene Implicated in Placental Malaria
Malaria, caused by the parasite Plasmodium falciparum, is responsible for substantial morbidity, mortality and economic losses in tropical regions of the world. Pregnant women are exceptionally vulnerable to severe consequences of the infection, due to the specific adhesion of parasite-infected erythrocytes in the placenta. This adhesion is mediated by a unique variant of PfEMP1, a parasite encoded, hyper-variable antigen placed on the surface of infected cells. This variant, called VAR2CSA, binds to chondroitin sulfate A on syncytiotrophoblasts in the intervillous space of placentas. VAR2CSA appears to only be expressed in the presence of a placenta, suggesting that its expression is actively repressed in men, children or non-pregnant women; however, the mechanism of repression is not understood. Using cultured parasite lines and reporter gene constructs, we show that the gene encoding VAR2CSA contains a small upstream open reading frame that acts to repress translation of the resulting mRNA, revealing a novel form of gene regulation in malaria parasites. The mechanism underlying this translational repression is reversible, allowing high levels of protein translation upon selection, thus potentially enabling parasites to upregulate expression of this variant antigen in the presence of the appropriate host tissue
A ring-like accretion structure in M87 connecting its black hole and jet
The nearby radio galaxy M87 is a prime target for studying black hole
accretion and jet formation^{1,2}. Event Horizon Telescope observations of M87
in 2017, at a wavelength of 1.3 mm, revealed a ring-like structure, which was
interpreted as gravitationally lensed emission around a central black hole^3.
Here we report images of M87 obtained in 2018, at a wavelength of 3.5 mm,
showing that the compact radio core is spatially resolved. High-resolution
imaging shows a ring-like structure of 8.4_{-1.1}^{+0.5} Schwarzschild radii in
diameter, approximately 50% larger than that seen at 1.3 mm. The outer edge at
3.5 mm is also larger than that at 1.3 mm. This larger and thicker ring
indicates a substantial contribution from the accretion flow with absorption
effects in addition to the gravitationally lensed ring-like emission. The
images show that the edge-brightened jet connects to the accretion flow of the
black hole. Close to the black hole, the emission profile of the jet-launching
region is wider than the expected profile of a black-hole-driven jet,
suggesting the possible presence of a wind associated with the accretion flow.Comment: 50 pages, 18 figures, 3 tables, author's version of the paper
published in Natur
First M87 Event Horizon Telescope Results. IV. Imaging the Central Supermassive Black Hole
We present the first Event Horizon Telescope (EHT) images of M87, using observations from April 2017 at 1.3 mm wavelength. These images show a prominent ring with a diameter of similar to 40 mu as, consistent with the size and shape of the lensed photon orbit encircling the "shadow" of a supermassive black hole. The ring is persistent across four observing nights and shows enhanced brightness in the south. To assess the reliability of these results, we implemented a two-stage imaging procedure. In the first stage, four teams, each blind to the others' work, produced images of M87 using both an established method (CLEAN) and a newer technique (regularized maximum likelihood). This stage allowed us to avoid shared human bias and to assess common features among independent reconstructions. In the second stage, we reconstructed synthetic data from a large survey of imaging parameters and then compared the results with the corresponding ground truth images. This stage allowed us to select parameters objectively to use when reconstructing images of M87. Across all tests in both stages, the ring diameter and asymmetry remained stable, insensitive to the choice of imaging technique. We describe the EHT imaging procedures, the primary image features in M87, and the dependence of these features on imaging assumptions
First M87 Event Horizon Telescope Results. VI. The Shadow and Mass of the Central Black Hole
We present measurements of the properties of the central radio source in M87 using Event Horizon Telescope data obtained during the 2017 campaign. We develop and fit geometric crescent models (asymmetric rings with interior brightness depressions) using two independent sampling algorithms that consider distinct representations of the visibility data. We show that the crescent family of models is statistically preferred over other comparably complex geometric models that we explore. We calibrate the geometric model parameters using general relativistic magnetohydrodynamic (GRMHD) models of the emission region and estimate physical properties of the source. We further fit images generated from GRMHD models directly to the data. We compare the derived emission region and black hole parameters from these analyses with those recovered from reconstructed images. There is a remarkable consistency among all methods and data sets. We find that >50% of the total flux at arcsecond scales comes from near the horizon, and that the emission is dramatically suppressed interior to this region by a factor >10, providing direct evidence of the predicted shadow of a black hole. Across all methods, we measure a crescent diameter of 42 +/- 3 mu as and constrain its fractional width to b
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