More than a Historical Sidenote: The Nuclear Ambitions of the Shah of Iran

Scholarly work on nuclear proliferation tends to relegate the atomic aspirations of the Shah to the role of a framing device for the nuclear ambitions of the Islamic Republic of Iran. This approach is lacking, as it overlooks a large body of primary source material which portends to an alarming interest in, and potential movement towards nuclear weapons on the part of the Iranian ruler. This article will examine whether the Shah took any concrete steps towards developing nuclear weapons. In arguing that Mohammad Reza Pahlavi did so, two arguments are made. Firstly, that the Shah’s nuclear energy programme, when completed, would have allowed for nuclear weapons to be developed. Secondly, there were multiple efforts by the Shah to procure weapon systems which are key in a functioning nuclear deterrent

Escherichia coli TatA and TatB Proteins Have N-out, C-in Topology in Intact Cells

The twin arginine protein transport (Tat) system translocates folded proteins across the cytoplasmic membrane of prokaryotes and the thylakoid membrane of chloroplasts. In Escherichia coli, TatA, TatB, and TatC are essential components of the machinery. A complex of TatB and TatC acts as the substrate receptor, whereas TatA is proposed to form the Tat transport channel. TatA and TatB are related proteins that comprise an N-terminal transmembrane helix and an adjacent amphipathic helix. Previous studies addressing the topological organization of TatA have given conflicting results. In this study, we have addressed the topological arrangement of TatA and TatB in intact cells by labeling of engineered cysteine residues with the membrane-impermeable thiol reagent methoxypolyethylene glycol maleimide. Our results show that TatA and TatB share an N-out, C-in topology, with no evidence that the amphipathic helices of either protein are exposed at the periplasmic side of the membrane. We further show that the N-out, C-in topology of TatA is fixed and is not affected by the absence of other Tat components or by the overproduction of a Tat substrate. These data indicate that topological reorganization of TatA is unlikely to accompany Tat-dependent protein transport

Human Patient-Derived Brain Tumor Models to Recapitulate Ependymoma Tumor Vasculature.

Despite in vivo malignancy, ependymoma lacks cell culture models, thus limiting therapy development. Here, we used a tunable three-dimensional (3D) culture system to approximate the ependymoma microenvironment for recapitulating a patient\u27s tumor in vitro. Our data showed that the inclusion of VEGF in serum-free, mixed neural and endothelial cell culture media supported the in vitro growth of all four ependymoma patient samples. The growth was driven by Nestin and Ki67 double-positive cells in a putative cancer stem cell niche, which was manifested as rosette-looking clusters in 2D and spheroids in 3D. The effects of extracellular matrix (ECM) such as collagen or Matrigel superseded that of the media conditions, with Matrigel resulting in the greater enrichment of Nestin-positive cells. When mixed with endothelial cells, the 3D co-culture models developed capillary networks resembling the in vivo ependymoma vasculature. The transcriptomic analysis of two patient cases demonstrated the separation of in vitro cultures by individual patients, with one patient\u27s culture samples closely clustered with the primary tumor tissue. While VEGF was found to be necessary for preserving the transcriptomic features of in vitro cultures, the presence of endothelial cells shifted the gene\u27s expression patterns, especially genes associated with ECM remodeling. The homeobox genes were mostly affected in the 3D in vitro models compared to the primary tumor tissue and between different 3D formats. These findings provide a basis for understanding the ependymoma microenvironment and enabling the further development of patient-derived in vitro ependymoma models for personalized medicine

Bolocam Survey for 1.1 mm Dust Continuum Emission in the c2d Legacy Clouds. II. Ophiuchus

We present a large-scale millimeter continuum map of the Ophiuchus molecular cloud. Nearly 11 square degrees, including all of the area in the cloud with visual extinction more than 3 magnitudes, was mapped at 1.1 mm with Bolocam on the Caltech Submillimeter Observatory (CSO). By design, the map also covers the region mapped in the infrared with the Spitzer Space Telescope. We detect 44 definite sources, and a few likely sources are also seen along a filament in the eastern streamer. The map indicates that dense cores in Ophiuchus are very clustered and often found in filaments within the cloud. Most sources are round, as measured at the half power point, but elongated when measured at lower contour levels, suggesting spherical sources lying within filaments. The masses, for an assumed dust temperature of 10 K, range from 0.24 to 3.9 solar masses, with a mean value of 0.96 solar masses. The total mass in distinct cores is 42 solar masses, 0.5 to 2% of the total cloud mass, and the total mass above 4 sigma is about 80 solar masses. The mean densities in the cores are quite high, with an average of 1.6 x 10^6 per cc, suggesting short free-fall times. The core mass distribution can be fitted with a power law with slope of 2.1 plus or minus 0.3 for M>0.5 solar masses, similar to that found in other regions, but slightly shallower than that of some determinations of the local IMF. In agreement with previous studies, our survey shows that dense cores account for a very small fraction of the cloud volume and total mass. They are nearly all confined to regions with visual extinction at least 9 mag, a lower threshold than found previously.Comment: 47 pages, 16 figures, accepted for Ap

The Dust Emissivity Spectral Index in the Starless Core TMC-1C

In this paper we present a dust emission map of the starless core TMC-1C taken at 2100 microns. Along with maps at 160, 450, 850 and 1200 microns, we study the dust emissivity spectral index from the (sub)millimeter spectral energy distribution, and find that it is close to the typically assumed value of beta = 2. We also map the dust temperature and column density in TMC-1C, and find that at the position of the dust peak (A_V ~ 50), the line-of-sight-averaged temperature is ~7 K. Employing simple Monte Carlo modeling, we show that the data are consistent with a constant value for the emissivity spectral index over the whole map of TMC-1C.Comment: 11 pages, including 5 pages of figures. Accepted to Ap

FusorSV: an algorithm for optimally combining data from multiple structural variation detection methods.

Comprehensive and accurate identification of structural variations (SVs) from next generation sequencing data remains a major challenge. We develop FusorSV, which uses a data mining approach to assess performance and merge callsets from an ensemble of SV-calling algorithms. It includes a fusion model built using analysis of 27 deep-coverage human genomes from the 1000 Genomes Project. We identify 843 novel SV calls that were not reported by the 1000 Genomes Project for these 27 samples. Experimental validation of a subset of these calls yields a validation rate of 86.7%. FusorSV is available at https://github.com/TheJacksonLaboratory/SVE . Genome Biol 2018 Mar 20; 19(1):38

The Twin-Arginine Translocation Pathway in α-Proteobacteria Is Functionally Preserved Irrespective of Genomic and Regulatory Divergence

The twin-arginine translocation (Tat) pathway exports fully folded proteins out of the cytoplasm of Gram-negative and Gram-positive bacteria. Although much progress has been made in unraveling the molecular mechanism and biochemical characterization of the Tat system, little is known concerning its functionality and biological role to confer adaptive skills, symbiosis or pathogenesis in the α-proteobacteria class. A comparative genomic analysis in the α-proteobacteria class confirmed the presence of tatA, tatB, and tatC genes in almost all genomes, but significant variations in gene synteny and rearrangements were found in the order Rickettsiales with respect to the typically described operon organization. Transcription of tat genes was confirmed for Anaplasma marginale str. St. Maries and Brucella abortus 2308, two α-proteobacteria with full and partial intracellular lifestyles, respectively. The tat genes of A. marginale are scattered throughout the genome, in contrast to the more generalized operon organization. Particularly, tatA showed an approximately 20-fold increase in mRNA levels relative to tatB and tatC. We showed Tat functionality in B. abortus 2308 for the first time, and confirmed conservation of functionality in A. marginale. We present the first experimental description of the Tat system in the Anaplasmataceae and Brucellaceae families. In particular, in A. marginale Tat functionality is conserved despite operon splitting as a consequence of genome rearrangements. Further studies will be required to understand how the proper stoichiometry of the Tat protein complex and its biological role are achieved. In addition, the predicted substrates might be the evidence of role of the Tat translocation system in the transition process from a free-living to a parasitic lifestyle in these α-proteobacteria