Heritable Sperm Chromatin Epigenetics: A Break to Remember

Sperm chromatin not only has a unique structure to condense and protect the paternal DNA in transit, but also provides epigenetic information that supports embryonic development. Most of the unique sperm nuclear architecture is formed during the sweeping postmeiotic chromatin remodeling events in spermiogenesis, where the majority of nucleosomes are removed and replaced by protamines. The remaining histones and other chromatin proteins are located in structurally and transcriptionally relevant positions in the genome and carry diverse post-translational modifications relevant to the control of embryonic gene expression. How such postmeiotic chromatin-based programming of sperm epigenetic information proceeds, and how susceptible the process is to modulation by exogenous factors are key questions for understanding the inheritance of acquired epigenetic marks through the male germ line. We propose that transient DNA strand breaks mediated by topoisomerase II beta and the subsequent activation of DNA damage response pathways result in defined post-translational modifications of histones in spermiogenesis. These pathways, likely along with others, may contribute to chromatin remodeling in elongating spermatids, influence chromatin-based intergenerational inheritance of epigenetic information, and may be defective in pathologies of abnormal male gametogenesis and infertility

Proton Motive Force-Dependent Hoechst 33342 Transport by the ABC Transporter LmrA of Lactococcus lactis

The fluorescent compound Hoechst 33342 is a substrate for many multidrug resistance (MDR) transporters and is widely used to characterize their transport activity. We have constructed mutants of the adenosine triphosphate (ATP) binding cassette (ABC)-type MDR transporter LmrA of Lactococcus lactis that are defective in ATP hydrolysis. These mutants and wild-type LmrA exhibited an atypical behavior in the Hoechst 33342 transport assay. In membrane vesicles, Hoechst 33342 transport was shown to be independent of the ATPase activity of LmrA, and it was not inhibited by orthovanadate but sensitive to uncouplers that collapse the proton gradient and to N,N'-dicyclohexylcarbodiimide, an inhibitor of the F0F1-ATPase. In contrast, transport of Hoechst 33342 by the homologous, heterodimeric MDR transporter LmrCD showed a normal ATP dependence and was insensitive to uncouplers of the proton gradient. With intact cells, expression of LmrA resulted in an increased rate of Hoechst 33342 influx while LmrCD caused a decrease in the rate of Hoechst 33342 influx. Cellular toxicity assays using a triple knockout strain, i.e., L. lactis ΔlmrA ΔlmrCD, demonstrate that expression of LmrCD protects cells against the growth inhibitory effects of Hoechst 33342, while in the presence of LmrA, cells are more susceptible to Hoechst 33342. Our data demonstrate that the LmrA-mediated Hoechst 33342 transport in membrane vesicles is influenced by the transmembrane pH gradient due to a pH-dependent partitioning of Hoechst 33342 into the membrane.

Determination of muon momentum in the MicroBooNE LArTPC using an improved model of multiple Coulomb scattering

We discuss a technique for measuring a charged particle's momentum by means of multiple Coulomb scattering (MCS) in the MicroBooNE liquid argon time projection chamber (LArTPC). This method does not require the full particle ionization track to be contained inside of the detector volume as other track momentum reconstruction methods do (range-based momentum reconstruction and calorimetric momentum reconstruction). We motivate use of this technique, describe a tuning of the underlying phenomenological formula, quantify its performance on fully contained beam-neutrino-induced muon tracks both in simulation and in data, and quantify its performance on exiting muon tracks in simulation. Using simulation, we have shown that the standard Highland formula should be re-tuned specifically for scattering in liquid argon, which significantly improves the bias and resolution of the momentum measurement. With the tuned formula, we find agreement between data and simulation for contained tracks, with a small bias in the momentum reconstruction and with resolutions that vary as a function of track length, improving from about 10% for the shortest (one meter long) tracks to 5% for longer (several meter) tracks. For simulated exiting muons with at least one meter of track contained, we find a similarly small bias, and a resolution which is less than 15% for muons with momentum below 2 GeV/c. Above 2 GeV/c, results are given as a first estimate of the MCS momentum measurement capabilities of MicroBooNE for high momentum exiting tracks

Convolutional Neural Networks Applied to Neutrino Events in a Liquid Argon Time Projection Chamber

We present several studies of convolutional neural networks applied to data coming from the MicroBooNE detector, a liquid argon time projection chamber (LArTPC). The algorithms studied include the classification of single particle images, the localization of single particle and neutrino interactions in an image, and the detection of a simulated neutrino event overlaid with cosmic ray backgrounds taken from real detector data. These studies demonstrate the potential of convolutional neural networks for particle identification or event detection on simulated neutrino interactions. We also address technical issues that arise when applying this technique to data from a large LArTPC at or near ground level

The Pandora multi-algorithm approach to automated pattern recognition of cosmic-ray muon and neutrino events in the MicroBooNE detector

The development and operation of Liquid-Argon Time-Projection Chambers for neutrino physics has created a need for new approaches to pattern recognition in order to fully exploit the imaging capabilities offered by this technology. Whereas the human brain can excel at identifying features in the recorded events, it is a significant challenge to develop an automated, algorithmic solution. The Pandora Software Development Kit provides functionality to aid the design and implementation of pattern-recognition algorithms. It promotes the use of a multi-algorithm approach to pattern recognition, in which individual algorithms each address a specific task in a particular topology. Many tens of algorithms then carefully build up a picture of the event and, together, provide a robust automated pattern-recognition solution. This paper describes details of the chain of over one hundred Pandora algorithms and tools used to reconstruct cosmic-ray muon and neutrino events in the MicroBooNE detector. Metrics that assess the current pattern-recognition performance are presented for simulated MicroBooNE events, using a selection of final-state event topologies.Comment: Preprint to be submitted to The European Physical Journal

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

Measurement of cosmic-ray reconstruction efficiencies in the MicroBooNE LArTPC using a small external cosmic-ray counter

The MicroBooNE detector is a liquid argon time projection chamber at Fermilab designed to study short-baseline neutrino oscillations and neutrino-argon interaction cross-section. Due to its location near the surface, a good understanding of cosmic muons as a source of backgrounds is of fundamental importance for the experiment. We present a method of using an external 0.5 m (L) x 0.5 m (W) muon counter stack, installed above the main detector, to determine the cosmic-ray reconstruction efficiency in MicroBooNE. Data are acquired with this external muon counter stack placed in three different positions, corresponding to cosmic rays intersecting different parts of the detector. The data reconstruction efficiency of tracks in the detector is found to be $\epsilon_{\mathrm{data}}=(97.1\pm0.1~(\mathrm{stat}) \pm 1.4~(\mathrm{sys}))\%$, in good agreement with the Monte Carlo reconstruction efficiency $\epsilon_{\mathrm{MC}} = (97.4\pm0.1)\%$. This analysis represents a small-scale demonstration of the method that can be used with future data coming from a recently installed cosmic-ray tagger system, which will be able to tag $\approx80\%$ of the cosmic rays passing through the MicroBooNE detector.Comment: 19 pages, 12 figure

Noise Characterization and Filtering in the MicroBooNE Liquid Argon TPC

The low-noise operation of readout electronics in a liquid argon time projection chamber (LArTPC) is critical to properly extract the distribution of ionization charge deposited on the wire planes of the TPC, especially for the induction planes. This paper describes the characteristics and mitigation of the observed noise in the MicroBooNE detector. The MicroBooNE's single-phase LArTPC comprises two induction planes and one collection sense wire plane with a total of 8256 wires. Current induced on each TPC wire is amplified and shaped by custom low-power, low-noise ASICs immersed in the liquid argon. The digitization of the signal waveform occurs outside the cryostat. Using data from the first year of MicroBooNE operations, several excess noise sources in the TPC were identified and mitigated. The residual equivalent noise charge (ENC) after noise filtering varies with wire length and is found to be below 400 electrons for the longest wires (4.7 m). The response is consistent with the cold electronics design expectations and is found to be stable with time and uniform over the functioning channels. This noise level is significantly lower than previous experiments utilizing warm front-end electronics.Comment: 36 pages, 20 figure

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

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