Inference of RNA decay rate from transcriptional profiling highlights the regulatory programs of Alzheimer's disease.

The abundance of mRNA is mainly determined by the rates of RNA transcription and decay. Here, we present a method for unbiased estimation of differential mRNA decay rate from RNA-sequencing data by modeling the kinetics of mRNA metabolism. We show that in all primary human tissues tested, and particularly in the central nervous system, many pathways are regulated at the mRNA stability level. We present a parsimonious regulatory model consisting of two RNA-binding proteins and four microRNAs that modulate the mRNA stability landscape of the brain, which suggests a new link between RBFOX proteins and Alzheimer's disease. We show that downregulation of RBFOX1 leads to destabilization of mRNAs encoding for synaptic transmission proteins, which may contribute to the loss of synaptic function in Alzheimer's disease. RBFOX1 downregulation is more likely to occur in older and female individuals, consistent with the association of Alzheimer's disease with age and gender."mRNA abundance is determined by the rates of transcription and decay. Here, the authors propose a method for estimating the rate of differential mRNA decay from RNA-seq data and model mRNA stability in the brain, suggesting a link between mRNA stability and Alzheimer's disease.

Discovery of 6.035GHz Hydroxyl Maser Flares in IRAS18566+0408

We report the discovery of 6.035GHz hydroxyl (OH) maser flares toward the massive star forming region IRAS18566+0408 (G37.55+0.20), which is the only region known to show periodic formaldehyde (4.8 GHz H2CO) and methanol (6.7 GHz CH3OH) maser flares. The observations were conducted between October 2008 and January 2010 with the 305m Arecibo Telescope in Puerto Rico. We detected two flare events, one in March 2009, and one in September to November 2009. The OH maser flares are not simultaneous with the H2CO flares, but may be correlated with CH3OH flares from a component at corresponding velocities. A possible correlated variability of OH and CH3OH masers in IRAS18566+0408 is consistent with a common excitation mechanism (IR pumping) as predicted by theory.Comment: Accepted for publication in the Astrophysical Journa

Fire retardant foams developed to suppress fuel fires

Heat insulating polyurethane foam retards and suppresses fuel fires. Uniformly dispersed in the foam is a halogenated polymer capable of splitting off hydrogen halide upon heating and charring of the polyurethane

Masses of Nearby Supermassive Black Holes with Very-Long Baseline Interferometry

Dynamical mass measurements to date have allowed determinations of the mass M and the distance D of a number of nearby supermassive black holes. In the case of Sgr A*, these measurements are limited by a strong correlation between the mass and distance scaling roughly as M ~ D^2. Future very-long baseline interferometric (VLBI) observations will image a bright and narrow ring surrounding the shadow of a supermassive black hole, if its accretion flow is optically thin. In this paper, we explore the prospects of reducing the correlation between mass and distance with the combination of dynamical measurements and VLBI imaging of the ring of Sgr A*. We estimate the signal to noise ratio of near-future VLBI arrays that consist of five to six stations, and we simulate measurements of the mass and distance of Sgr A* using the expected size of the ring image and existing stellar ephemerides. We demonstrate that, in this best-case scenario, VLBI observations at 1 mm can improve the error on the mass by a factor of about two compared to the results from the monitoring of stellar orbits alone. We identify the additional sources of uncertainty that such imaging observations have to take into account. In addition, we calculate the angular diameters of the bright rings of other nearby supermassive black holes and identify the optimal targets besides Sgr A* that could be imaged by a ground-based VLBI array or future space-VLBI missions allowing for refined mass measurements.Comment: 8 pages, 4 figures, 2 tables, refereed version, accepted for publication in Ap

EVLA Observations of OH Masers in ON 1

This Letter reports on initial Expanded Very Large Array (EVLA) observations of the 6035 MHz masers in ON 1. The EVLA data are of good quality, lending confidence in the new receiver system. Nineteen maser features, including six Zeeman pairs, are detected. The overall distribution of 6035 MHz OH masers is similar to that of the 1665 MHz OH masers. The spatial resolution is sufficient to unambiguously determine that the magnetic field is strong (~ -10 mG) at the location of the blueshifted masers in the north, consistent with Zeeman splitting detected in 13441 MHz OH masers in the same velocity range. Left and right circularly polarized ground-state features dominate in different regions in the north of the source, which may be due to a combination of magnetic field and velocity gradients. The combined distribution of all OH masers toward the south is suggestive of a shock structure of the sort previously seen in W3(OH).Comment: 4 pages using emulateapj.cls including 2 tables and 2 color figure

Systematic discovery of structural elements governing stability of mammalian messenger RNAs.

Decoding post-transcriptional regulatory programs in RNA is a critical step towards the larger goal of developing predictive dynamical models of cellular behaviour. Despite recent efforts, the vast landscape of RNA regulatory elements remains largely uncharacterized. A long-standing obstacle is the contribution of local RNA secondary structure to the definition of interaction partners in a variety of regulatory contexts, including--but not limited to--transcript stability, alternative splicing and localization. There are many documented instances where the presence of a structural regulatory element dictates alternative splicing patterns (for example, human cardiac troponin T) or affects other aspects of RNA biology. Thus, a full characterization of post-transcriptional regulatory programs requires capturing information provided by both local secondary structures and the underlying sequence. Here we present a computational framework based on context-free grammars and mutual information that systematically explores the immense space of small structural elements and reveals motifs that are significantly informative of genome-wide measurements of RNA behaviour. By applying this framework to genome-wide human mRNA stability data, we reveal eight highly significant elements with substantial structural information, for the strongest of which we show a major role in global mRNA regulation. Through biochemistry, mass spectrometry and in vivo binding studies, we identified human HNRPA2B1 (heterogeneous nuclear ribonucleoprotein A2/B1, also known as HNRNPA2B1) as the key regulator that binds this element and stabilizes a large number of its target genes. We created a global post-transcriptional regulatory map based on the identity of the discovered linear and structural cis-regulatory elements, their regulatory interactions and their target pathways. This approach could also be used to reveal the structural elements that modulate other aspects of RNA behaviour

Impact of incomplete ventricular coverage on diagnostic performance of myocardial perfusion imaging.

In the context of myocardial perfusion imaging (MPI) with cardiac magnetic resonance (CMR), there is ongoing debate on the merits of using technically complex acquisition methods to achieve whole-heart spatial coverage, rather than conventional 3-slice acquisition. An adequately powered comparative study is difficult to achieve given the requirement for two separate stress CMR studies in each patient. The aim of this work is to draw relevant conclusions from SPECT MPI by comparing whole-heart versus simulated 3-slice coverage in a large existing dataset. SPECT data from 651 patients with suspected coronary artery disease who underwent invasive angiography were analyzed. A computational approach was designed to model 3-slice MPI by retrospective subsampling of whole- heart data. For both whole-heart and 3-slice approaches, the diagnostic performance and the stress total perfusion deficit (TPD) score-a measure of ischemia extent/severity-were quantified and compared. Diagnostic accuracy for the 3-slice and whole-heart approaches were similar (area under the curve: 0.843 vs. 0.855, respectively; P = 0.07). The majority (54%) of cases missed by 3-slice imaging had primarily apical ischemia. Whole-heart and 3-slice TPD scores were strongly correlated (R2 = 0.93, P < 0.001) but 3-slice TPD showed a small yet significant bias compared to whole-heart TPD (- 1.19%; P < 0.0001) and the 95% limits of agreement were relatively wide (- 6.65% to 4.27%). Incomplete ventricular coverage typically acquired in 3-slice CMR MPI does not significantly affect the diagnostic accuracy. However, 3-slice MPI may fail to detect severe apical ischemia and underestimate the extent/severity of perfusion defects. Our results suggest that caution is required when comparing the ischemic burden between 3-slice and whole-heart datasets, and corroborate the need to establish prognostic thresholds specific to each approach

Homogenization of the one-dimensional wave equation

We present a method for two-scale model derivation of the periodic homogenization of the one-dimensional wave equation in a bounded domain. It allows for analyzing the oscillations occurring on both microscopic and macroscopic scales. The novelty reported here is on the asymptotic behavior of high frequency waves and especially on the boundary conditions of the homogenized equation. Numerical simulations are reported