RNA major groove modifications improve siRNA stability and biological activity

RNA 5-methyl and 5-propynyl pyrimidine analogs were substituted into short interfering RNAs (siRNAs) to probe major groove steric effects in the active RNA-induced silencing complex (RISC). Synthetic RNA guide strands containing varied combinations of propynyl and methyl substitution revealed that all C-5 substitutions increased the thermal stability of siRNA duplexes containing them. Cellular gene suppression experiments using luciferase targets in HeLa cells showed that the bulky 5-propynyl modification was detrimental to RNA interference activity, despite its stabilization of the helix. Detrimental effects of this substitution were greatest at the 5′-half of the guide strand, suggesting close steric approach of proteins in the RISC complex with that end of the siRNA/mRNA duplex. However, substitutions with the smaller 5-methyl group resulted in gene silencing activities comparable to or better than that of wild-type siRNA. The major groove modifications also increased the serum stability of siRNAs

Hearing of malaria mosquitoes is modulated by a beta-adrenergic-like octopamine receptor which serves as insecticide target

Malaria mosquitoes acoustically detect their mating partners within large swarms that form transiently at dusk. Indeed, male malaria mosquitoes preferably respond to female flight tones during swarm time. This phenomenon implies a sophisticated context- and time-dependent modulation of mosquito audition, the mechanisms of which are largely unknown. Using transcriptomics, we identify a complex network of candidate neuromodulators regulating mosquito hearing in the species Anopheles gambiae. Among them, octopamine stands out as an auditory modulator during swarm time. In-depth analysis of octopamine auditory function shows that it affects the mosquito ear on multiple levels: it modulates the tuning and stiffness of the flagellar sound receiver and controls the erection of antennal fibrillae. We show that two α- and β-adrenergic-like octopamine receptors drive octopamine's auditory roles and demonstrate that the octopaminergic auditory control system can be targeted by insecticides. Our findings highlight octopamine as key for mosquito hearing and mating partner detection and as a potential novel target for mosquito control

The Close AGN Reference Survey (CARS): Locating the [O III] wing component in luminous local Type 1 AGN

Context. The strong asymmetry in the optical [O III] λ5007 emission line is one of the best signatures of active galactic nuclei (AGN) driven warm (∼104 K) ionized gas outflows on host galaxy scales. While large spectroscopic surveys such as the sloan digital sky survey (SDSS) have characterized the kinematics of [O III] for large samples of AGN, estimating the associated energetics requires spatially resolving these outflows with, for example, integral field unit (IFU) studies. Aims. As part of the Close AGN Reference Survey, we obtained spatially resolved IFU spectroscopy for a representative sample of 39 luminous type 1 AGN at 0.01 < z < 0.06 with the multi unit spectroscopic explorer and the visible multi object spectrograph IFUs at the very large telescope to infer the spatial location of the ionized gas outflows. Methods. We compared the 2D light distributions of the [O III] wing to that of the Hβ broad emission line region, a classical point source (PSF). We then used the PSF to distinguish between the unresolved and resolved [O III] wing emission. We further determined its location using spectro-astrometry for the point-like sources. Results. The [O III] wing is spatially unresolved in 23 out of the 36 AGN with > 80% of the flux associated with a point-like source. We measured < 100 pc offsets in the spatial location of the outflow from the AGN nucleus using the spectro-astrometry technique for these sources. For the other 13 AGN, the [O III] wing emission is resolved and possibly extended on several kiloparsec scales. Conclusions. We conclude that [O III] wing emission can be compact or extended in an unbiased luminous AGN sample, where both cases are likely to appear. Electron density in the compact [O III] wing regions (median ne ∼ 1900 cm−3) is nearly a magnitude higher than in the extended ones (median ne ∼ 500 cm−3). The presence of spatially extended and compact [O III] wing emission is unrelated to the AGN bolometric luminosity and to inclination effects, which means other features such as time delays, or mechanical feedback (radio jets) may shape the ionized gas outflow properties

The MURALES survey. IV. Searching for nuclear outflows in 3C radio galaxies at z < 0.3 with MUSE observations

We analyze VLT/MUSE observations of 37 radio galaxies from the Third Cambridge catalogue (3C) with redshift $<$0.3 searching for nuclear outflows of ionized gas. These observations are part of the MURALES project (a MUse RAdio Loud Emission line Snapshot survey), whose main goal is to explore the feedback process in the most powerful radio-loud AGN. We applied a nonparametric analysis to the [O~III] $\lambda$5007 emission line, whose asymmetries and high-velocity wings reveal signatures of outflows. We find evidence of nuclear outflows in 21 sources, with velocities between $\sim$400 - 1000 km s$^{-1}$, outflowing masses of $\sim 10^5-10^7$ M$_\odot$, and a kinetic energy in the range $\sim 10^{53} - 10^{56}$ erg. In addition, evidence for extended outflows is found in the 2D gas velocity maps of 13 sources of the subclasses of high-excitation (HEG) and broad-line (BLO) radio galaxies, with sizes between 0.4 and 20 kpc. We estimate a mass outflow rate in the range 0.4 - 30 M$_\odot$ yr$^{-1}$ and an energy deposition rate of ${\dot E}_{kin} \sim 10^{42}-10^{45}$ erg s$^{-1}$. Comparing the jet power, the nuclear luminosity of the active galactic nucleus, and the outflow kinetic energy rate, we find that outflows of HEGs and BLOs are likely radiatively powered, while jets likely only play a dominant role in galaxies with low excitation. The low loading factors we measured suggest that these outflows are driven by momentum and not by energy. Based on the gas masses, velocities, and energetics involved, we conclude that the observed ionized outflows have a limited effect on the gas content or the star formation in the host. In order to obtain a complete view of the feedback process, observations exploring the complex multiphase structure of outflows are required.Comment: 40 pages; accepted for publication on A&A

Design and construction of the MicroBooNE Cosmic Ray Tagger system

The MicroBooNE detector utilizes a liquid argon time projection chamber (LArTPC) with an 85 t active mass to study neutrino interactions along the Booster Neutrino Beam (BNB) at Fermilab. With a deployment location near ground level, the detector records many cosmic muon tracks in each beam-related detector trigger that can be misidentified as signals of interest. To reduce these cosmogenic backgrounds, we have designed and constructed a TPC-external Cosmic Ray Tagger (CRT). This sub-system was developed by the Laboratory for High Energy Physics (LHEP), Albert Einstein center for fundamental physics, University of Bern. The system utilizes plastic scintillation modules to provide precise time and position information for TPC-traversing particles. Successful matching of TPC tracks and CRT data will allow us to reduce cosmogenic background and better characterize the light collection system and LArTPC data using cosmic muons. In this paper we describe the design and installation of the MicroBooNE CRT system and provide an overview of a series of tests done to verify the proper operation of the system and its components during installation, commissioning, and physics data-taking

Ionization Electron Signal Processing in Single Phase LArTPCs II. Data/Simulation Comparison and Performance in MicroBooNE

The single-phase liquid argon time projection chamber (LArTPC) provides a large amount of detailed information in the form of fine-grained drifted ionization charge from particle traces. To fully utilize this information, the deposited charge must be accurately extracted from the raw digitized waveforms via a robust signal processing chain. Enabled by the ultra-low noise levels associated with cryogenic electronics in the MicroBooNE detector, the precise extraction of ionization charge from the induction wire planes in a single-phase LArTPC is qualitatively demonstrated on MicroBooNE data with event display images, and quantitatively demonstrated via waveform-level and track-level metrics. Improved performance of induction plane calorimetry is demonstrated through the agreement of extracted ionization charge measurements across different wire planes for various event topologies. In addition to the comprehensive waveform-level comparison of data and simulation, a calibration of the cryogenic electronics response is presented and solutions to various MicroBooNE-specific TPC issues are discussed. This work presents an important improvement in LArTPC signal processing, the foundation of reconstruction and therefore physics analyses in MicroBooNE.Comment: 54 pages, 36 figures; the first part of this work can be found at arXiv:1802.0870

A Deep Neural Network for Pixel-Level Electromagnetic Particle Identification in the MicroBooNE Liquid Argon Time Projection Chamber

We have developed a convolutional neural network (CNN) that can make a pixel-level prediction of objects in image data recorded by a liquid argon time projection chamber (LArTPC) for the first time. We describe the network design, training techniques, and software tools developed to train this network. The goal of this work is to develop a complete deep neural network based data reconstruction chain for the MicroBooNE detector. We show the first demonstration of a network's validity on real LArTPC data using MicroBooNE collection plane images. The demonstration is performed for stopping muon and a $\nu_\mu$ charged current neutral pion data samples

Calibration of the charge and energy loss per unit length of the MicroBooNE liquid argon time projection chamber using muons and protons

We describe a method used to calibrate the position- and time-dependent response of the MicroBooNE liquid argon time projection chamber anode wires to ionization particle energy loss. The method makes use of crossing cosmic-ray muons to partially correct anode wire signals for multiple effects as a function of time and position, including cross-connected TPC wires, space charge effects, electron attachment to impurities, diffusion, and recombination. The overall energy scale is then determined using fully-contained beam-induced muons originating and stopping in the active region of the detector. Using this method, we obtain an absolute energy scale uncertainty of 2% in data. We use stopping protons to further refine the relation between the measured charge and the energy loss for highly-ionizing particles. This data-driven detector calibration improves both the measurement of total deposited energy and particle identification based on energy loss per unit length as a function of residual range. As an example, the proton selection efficiency is increased by 2% after detector calibration

Reconstruction and measurement of (100) MeV energy electromagnetic activity from π0 arrow γγ decays in the MicroBooNE LArTPC

We present results on the reconstruction of electromagnetic (EM) activity from photons produced in charged current νμ interactions with final state π0s. We employ a fully-automated reconstruction chain capable of identifying EM showers of (100) MeV energy, relying on a combination of traditional reconstruction techniques together with novel machine-learning approaches. These studies demonstrate good energy resolution, and good agreement between data and simulation, relying on the reconstructed invariant π0 mass and other photon distributions for validation. The reconstruction techniques developed are applied to a selection of νμ + Ar → μ + π0 + X candidate events to demonstrate the potential for calorimetric separation of photons from electrons and reconstruction of π0 kinematics