Controlled sulfur-based engineering confers mouldability to phosphorothioate antisense oligonucleotides

Phosphorothioates (PS) have proven their effectiveness in the area of therapeutic oligonucleotides with applications spanning from cancer treatment to neurodegenerative disorders. Initially, PS substitution was introduced for the antisense oligonucleotides (PS ASOs) because it confers an increased nuclease resistance meanwhile ameliorates cellular uptake and in-vivo bioavailability. Thus, PS oligonucleotides have been elevated to a fundamental asset in the realm of gene silencing therapeutic methodologies. But, despite their wide use, little is known on the possibly different structural changes PS-substitutions may provoke in DNA·RNA hybrids. Additionally, scarce information and significant controversy exists on the role of phosphorothioate chirality in modulating PS properties. Here, through comprehensive computational investigations and experimental measurements, we shed light on the impact of PS chirality in DNA-based antisense oligonucleotides; how the different phosphorothioate diastereomers impact DNA topology, stability and flexibility to ultimately disclose pro-Sp S and pro-Rp S roles at the catalytic core of DNA Exonuclease and Human Ribonuclease H; two major obstacles in ASOs-based therapies. Altogether, our results provide full-atom and mechanistic insights on the structural aberrations PS-substitutions provoke and explain the origin of nuclease resistance PS-linkages confer to DNA·RNA hybrids; crucial information to improve current ASOs-based therapies.© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research

Distribución espacial de mortalidad en nogal pecanero en la región centro sur del estado de Chihuahua

Gran parte de la economía de la región centro sur del estado de Chihuahua depende de la agriculcultura. Es una zona semidesértica que utiliza agua de los ríos Conchos y San Pedro para el riego de los cultivos. De éstos, uno de los principales es el cultivo del nogal pecanero. Sin embargo, su producción se puede ver afectada por plagas y enfermedades además de que pueden causar la muerte de los nogales. En este estudio se presenta la distribución espacial de huertas en las que se buscó la presencia de nogales muertos o muriendo, así como sus principales causales: pudrición texana (Phymatotrichum omnivorum), nematodo agallador (Meloidogyne spp), gallina ciega (Phyllophaga spp) y gusano barrenador del tronco (Euplatypus spp). El municipio que más huertas nogaleras presenta es el de Meoqui, sin embargo, es el que menor problemas de mortalidad existen, y Delicias en el que el problema es mayor, al igual que los agentes etiológicos estudiados: Phymatotrichum omnivorum, Meloidogyne spp, Phyllophaga spp y Euplatypus spp tendiendo a concentrarse en su frontera noreste

The First Quiescent Galaxies in TNG300

We identify the first quiescent galaxies in TNG300, the largest volume of the IllustrisTNG cosmological simulation suite, and explore their quenching processes and time evolution to z=0. We find that the first quiescent galaxies with stellar masses M_* > 3 x 10^{10} M_sun and specific star formation rates sSFR < 10^{-11} yr^{-1} emerge at z~4.2 in TNG300. Suppression of star formation in these galaxies begins with a thermal mode of AGN feedback at z~6, and a kinetic feedback mode acts in each galaxy by z~4.7 to complete the quenching process, which occurs on a time-scale of ~0.35 Gyr. Surprisingly, we find that the majority of these galaxies are not the main progenitors of their z=0 descendants; instead, four of the five galaxies fall into more massive galaxies in subsequent mergers at a range of redshifts 2.5 < z < 0.2. By z=0, these descendants are the centres of galaxy clusters with average stellar masses of 8 x 10^{11} M_sun. We make predictions for the first quenched galaxies to be located by the James Webb Space Telescope (JWST).Comment: 6 pages, 4 figure

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

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

Water Network Optimization with Wastewater Regeneration Models

The conventional water network synthesis approach greatly simplifies wastewater treatment units by using fixed recoveries, creating a gap for their applicability to industrial processes. This work describes a unifying approach combining various technologies capable of removing all the major types of contaminants through the use of more realistic models. The following improvements are made over the typical superstructure-based water network models. First, unit-specific shortcut models are developed in place of the fixed contaminant removal model to describe contaminant mass transfer in wastewater treatment units. Shortcut wastewater treatment cost functions are also incorporated into the model. In addition, uncertainty in mass load of contaminants is considered to account for the range of operating conditions. Furthermore, the superstructure is modified to accommodate realistic potential structures. We present a modified Lagrangean-based decomposition algorithm in order to solve the resulting nonconvex mixed-integer nonlinear programming (MINLP) problem efficiently. Several examples are presented to illustrate the effectiveness and limitations of the algorithm for obtaining the global optimal solutions.The authors would like to acknowledge financial support from the National Science Foundation for financial support under grant CBET-1437668, the program “Estancias de movilidad en el extranjero “Jose Castillejo” para jóvenes doctores” (JC2011-0051) of the Spanish Ministerio de Educación, and from the University of Alicante (GRE11-19)

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