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  • 1
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    Spatially regulated editing of genetic information within a neuron (2020)
    Oxford University Press
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    Publication Date: 2022-05-26
    Description: © The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Vallecillo-Viejo, I. C., Liscovitch-Brauer, N., Diaz Quiroz, J. F., Montiel-Gonzalez, Maria F., Nemes, Sonya E., Rangan, K. J., Levinson, S. R., Eisenberg, E., & Rosenthal, J. J. C. Spatially regulated editing of genetic information within a neuron. Nucleic Acids Research, (2020): gkaa172, doi: 10.1093/nar/gkaa172.
    Description: In eukaryotic cells, with the exception of the specialized genomes of mitochondria and plastids, all genetic information is sequestered within the nucleus. This arrangement imposes constraints on how the information can be tailored for different cellular regions, particularly in cells with complex morphologies like neurons. Although messenger RNAs (mRNAs), and the proteins that they encode, can be differentially sorted between cellular regions, the information itself does not change. RNA editing by adenosine deamination can alter the genome’s blueprint by recoding mRNAs; however, this process too is thought to be restricted to the nucleus. In this work, we show that ADAR2 (adenosine deaminase that acts on RNA), an RNA editing enzyme, is expressed outside of the nucleus in squid neurons. Furthermore, purified axoplasm exhibits adenosine-to-inosine activity and can specifically edit adenosines in a known substrate. Finally, a transcriptome-wide analysis of RNA editing reveals that tens of thousands of editing sites (〉70% of all sites) are edited more extensively in the squid giant axon than in its cell bodies. These results indicate that within a neuron RNA editing can recode genetic information in a region-specific manner.
    Description: National Science Foundation (NSF) [IOS1557748 to J.R.]; United States–Israel Binational Science Foundation [BSF2013094 to J.R. and E.E.]; The Grass Foundation grant in support of the Doryteuthis pealeii Genome Project, and a gift by Mr. Edward Owens. Funding for open access charge: United States–Israel Binational Science Foundation [BSF2013094].
    Repository Name: Woods Hole Open Access Server
    Type: Article
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  • 2
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    The collimation of magnetic jets by disc winds (2016)
    Oxford University Press
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    Publication Date: 2016-07-15
    Description: The collimation of a Poynting-flux dominated jet by a wind emanating from the surface of an accretion flow is computed using a semi-analytic model. The injection of the disc wind is treated as a boundary condition in the equatorial plane, and its evolution is followed by invoking a prescribed geometry of streamlines. Solutions are obtained for a wide range of disc wind parameters. It is found that jet collimation generally occurs when the total wind power exceeds about 10 percents of the jet power. For moderate wind powers, we find gradual collimation. For strong winds, we find rapid collimation followed by focusing of the jet, after which it remains narrow over many Alfvén crossing times before becoming conical. We estimate that in the later case, the jet's magnetic field may be dissipated by the current-driven kink instability over a distance of a few hundreds gravitational radii. We apply the model to M87 and show that the observed parabolic shape of the radio jet within the Bondi radius can be reproduced provided that the wind injection zone extends to several hundreds gravitational radii, and that its total power is about one-third of the jet power. The radio spectrum can be produced by synchrotron radiation of relativistically hot, thermal electrons in the sheath flow surrounding the inner jet.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 3
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    The effect of Compton drag on the dynamics of dissipative Poynting-dominated flows: implications for the unification of radio loud AGN (2016)
    Oxford University Press
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    Publication Date: 2016-03-24
    Description: The dynamics of a dissipative Poynting-dominated flow subject to a radiation drag due to Compton scattering of ambient photons by relativistic electrons accelerated in reconnecting current sheets is studied. It is found that the efficiency at which magnetic energy is converted to radiation is limited to a maximum value of c = 3 l dis 0 /4( 0 + 1), where 0 is the initial magnetization of the flow and l dis ≤ 1 the fraction of initial Poynting flux that can dissipate. The asymptotic Lorentz factor satisfies ≥ 0 (1 + l dis 0 /4), where 0 is the initial Lorentz factor. This limit is approached in cases where the cooling time is shorter than the local dissipation time. A somewhat smaller radiative efficiency is expected if radiative losses are dominated by synchrotron and Synchrotron Self-Compton emissions. It is suggested that under certain conditions magnetic field dissipation may occur in two distinct phases: On small scales, asymmetric magnetic fields that are advected into the polar region and dragged out by the outflow dissipate to a more stable configuration. The dissipated energy is released predominantly as gamma rays. On much larger scales, the outflow encounters a flat density profile medium and re-collimates. This leads to further dissipation and wobbling of the jet head by the kink instability, as found recently in 3D magnetohydrodynamic simulations. Within the framework of a model proposed recently to explain the dichotomy of radio loud active galactic nuclei (AGN), this scenario can account for the unification of gamma-ray blazars with Fanaroff–Riley type I and Fanaroff–Riley type II radio sources.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 4
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    Measuring the Stringency of Environmental Regulations (2016)
    Oxford University Press
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    Publication Date: 2016-02-03
    Description: Do environmental regulations discourage investment, reduce labor demand, or alter patterns of international trade? To answer these important policy questions, we need ways to measure the stringency of environmental regulations empirically. While creating measures of stringency is often characterized as a data collection challenge, we identify four fundamental conceptual obstacles to evaluating these measures: multidimensionality, simultaneity, industrial composition, and capital vintage. We then describe recent approaches used by researchers to measure the stringency of environmental regulations, primarily in the United States, and evaluate their success in light of these obstacles. We find that few approaches come close to being the ideal—a theoretically motivated, tractable, single measure that captures environmental regulatory stringency empirically.
    Keywords: F18 - Trade and Environment, L51 - Economics of Regulation, Q52 - Pollution Control Costs ; Distributional Effects ; Employment Effects, Q58 - Government Policy
    Print ISSN: 1750-6816
    Electronic ISSN: 1750-6824
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Political Science , Economics
    Published by Oxford University Press
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  • 5
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    CNV analysis in a large schizophrenia sample implicates deletions at 16p12.1 and SLC1A1 and duplications at 1p36.33 and CGNL1 (2014)
    Oxford University Press
    Details
    Publication Date: 2014-02-20
    Description: Large and rare copy number variants (CNVs) at several loci have been shown to increase risk for schizophrenia. Aiming to discover novel susceptibility CNV loci, we analyzed 6882 cases and 11 255 controls genotyped on Illumina arrays, most of which have not been used for this purpose before. We identified genes enriched for rare exonic CNVs among cases, and then attempted to replicate the findings in additional 14 568 cases and 15 274 controls. In a combined analysis of all samples, 12 distinct loci were enriched among cases with nominal levels of significance ( P 〈 0.05); however, none would survive correction for multiple testing. These loci include recurrent deletions at 16p12.1, a locus previously associated with neurodevelopmental disorders ( P = 0.0084 in the discovery sample and P = 0.023 in the replication sample). Other plausible candidates include non-recurrent deletions at the glutamate transporter gene SLC1A1, a CNV locus recently suggested to be involved in schizophrenia through linkage analysis, and duplications at 1p36.33 and CGNL1 . A burden analysis of large (〉500 kb), rare CNVs showed a 1.2% excess in cases after excluding known schizophrenia-associated loci, suggesting that additional susceptibility loci exist. However, even larger samples are required for their discovery.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 6
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    On the origin of short GRBs with extended emission and long GRBs without associated SN (2014)
    Oxford University Press
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    Publication Date: 2014-08-18
    Description: The Burst and Transient Source Experiment classifies cosmological gamma-ray bursts (GRBs) into short (less than 2 s) and long (over 2 s) events, commonly attributed to mergers of compact objects and, respectively, peculiar core-collapse supernovae. This standard classification has recently been challenged by the Swift discovery of short GRBs showing extended emission (SGRBEE) and nearby long GRBs without an accompanying supernovae (LGRBN). Both show an initial hard pulse, characteristic of SGRBs, followed by a long duration soft tail. We here consider the spectral peak energy ( E p, i )–radiated energy ( E iso ) correlation and the redshift distributions to probe the astronomical and physical origin of these different classes of GRBs. We consider Swift events of 15 SGRBs, 7 SGRBEEs, 3 LGRBNs and 230 LGRBs detected by Swift . The spectral-energy properties of the initial pulse of both SGRBEE and LGRBNs are found to coincide with those of SGRBs. A Monte Carlo simulation shows that the redshift distributions of SGRBs, SGRBEE and LGRBNs fall outside the distribution of LGRBs at 4.75, 4.67 and 4.31, respectively. A distinct origin of SGRBEEs with respect to LGRBs is also supported by the elliptical host galaxies of the SGRBEE events 050509B and 050724. This combined evidence supports the hypothesis that SGRBEE and LGRBNs originate in mergers as SGRBs. Moreover, long/soft tail of SGRB and LGRBNs satisfy the same E p, i - E iso Amati correlation holding for normal LGRBs. This fact points to rapidly rotating black holes as a common long-lived inner engine produced by different astronomical progenitors (mergers and supernovae).
    Print ISSN: 1745-3925
    Electronic ISSN: 1745-3933
    Topics: Physics
    Published by Oxford University Press
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  • 7
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    Reconstruction of small-scale galaxy cluster substructure with lensing flexion (2016)
    Oxford University Press
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    Publication Date: 2016-10-15
    Description: We present reconstructions of galaxy-cluster-scale mass distributions from simulated gravitational lensing data sets including strong lensing, weak lensing shear, and measurements of quadratic image distortions – flexion. The lensing data is constructed to make a direct comparison between mass reconstructions with and without flexion. We show that in the absence of flexion measurements, significant galaxy-group scale substructure can remain undetected in the reconstructed mass profiles, and that the resulting profiles underestimate the aperture mass in the substructure regions by ~25–40 per cent. When flexion is included, subhaloes down to a mass of ~3  x  10 12 M can be detected at an angular resolution smaller than 10 arcsec. Aperture masses from profiles reconstructed with flexion match the input distribution values to within an error of ~13 per cent, including both statistical error and scatter. This demonstrates the important constraint that flexion measurements place on substructure in galaxy clusters and its utility for producing high-fidelity mass reconstructions.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 8
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    Reconfinement of highly magnetized jets: implications for HST-1 in M87 (2016)
    Oxford University Press
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    Publication Date: 2016-12-10
    Description: Stationary features are occasionally observed in active galactic nucleus jets. A notable example is the HST-1 knot in M87. Such features are commonly interpreted as reconfinement shocks in hydrodynamic jets or focusing nozzles in Poynting jets. In this paper, we compute the structure and Lorentz factor of a highly magnetized jet confined by external pressure having a profile that flattens abruptly at some radius. We find the development of strong oscillations upon transition from the steeper to the flatter pressure profile medium. Analytic formula is derived for the location of the nodes of these oscillations. We apply the model to the M87 jet and show that if the jet remains magnetically dominated up to sub-kiloparsec scales, then focusing is expected. The location of the HST-1 knot can be reconciled with recent measurements of the pressure profile around the Bondi radius if the jet luminosity satisfies L j ~= 10 43  erg s –1 . However, we find that magnetic domination at the collimation break implies a Lorentz factor in excess of 10 2 , atypical to Fanaroff–Riley type I sources. A much lower value of the asymptotic Lorentz factor would require substantial loading close to the black hole. In that case, HST-1 may be associated with a collimation nozzle of a hydrodynamic flow.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 9
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    A penalized Bayesian approach to predicting sparse protein-DNA binding landscapes (2014)
    Oxford University Press
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    Publication Date: 2014-02-26
    Description: Motivation: Cellular processes are controlled, directly or indirectly, by the binding of hundreds of different DNA binding factors (DBFs) to the genome. One key to deeper understanding of the cell is discovering where, when and how strongly these DBFs bind to the DNA sequence. Direct measurement of DBF binding sites (BSs; e.g. through ChIP-Chip or ChIP-Seq experiments) is expensive, noisy and not available for every DBF in every cell type. Naive and most existing computational approaches to detecting which DBFs bind in a set of genomic regions of interest often perform poorly, due to the high false discovery rates and restrictive requirements for prior knowledge. Results: We develop SparScape, a penalized Bayesian method for identifying DBFs active in the considered regions and predicting a joint probabilistic binding landscape. Using a sparsity-inducing penalization, SparScape is able to select a small subset of DBFs with enriched BSs in a set of DNA sequences from a much larger candidate set. This substantially reduces the false positives in prediction of BSs. Analysis of ChIP-Seq data in mouse embryonic stem cells and simulated data show that SparScape dramatically outperforms the naive motif scanning method and the comparable computational approaches in terms of DBF identification and BS prediction. Availability and implementation: SparScape is implemented in C++ with OpenMP (optional at compilation) and is freely available at ‘ www.stat.ucla.edu/~zhou/Software.html ’ for academic use. Contact: zhou@stat.ucla.edu Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 10
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    Relativistic shock breakout from a stellar wind (2018)
    Oxford University Press
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    Publication Date: 2018-03-13
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press on behalf of The Royal Astronomical Society.
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