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Copper-dependent halogenase catalyses unactivated C−H bond functionalization
Carbon–hydrogen (C–H) bonds are the foundation of essentially every organic molecule, making them an ideal place to do chemical synthesis. The key challenge is achieving selectivity for one particular C(sp 3 )−H bond. In recent years, metalloenzymes have been found to perform C(sp 3 )−H bond functionalization. Despite substantial progresses in the past two decades, enzymatic halogenation and pseudohalogenation of unactivated C(sp 3 )−H—providing a functional handle for further modification—have been achieved with only non-haem iron/α-ketoglutarate-dependent halogenases, and are therefore limited by the chemistry possible with these enzymes. Here, in this work, we report the discovery and characterization of a previously unknown halogenase ApnU, part of a protein family containing domain of unknown function 3328 (DUF3328). ApnU uses copper in its active site to catalyse iterative chlorinations on multiple unactivated C(sp 3 )−H bonds. By taking advantage of the softer copper centre, we demonstrate that ApnU can catalyse unprecedented enzymatic C(sp 3 )−H bond functionalization such as iodination and thiocyanation. Using biochemical characterization and proteomics analysis, we identified the functional oligomeric state of ApnU as a covalently linked homodimer, which contains three essential pairs—one interchain and two intrachain—of disulfide bonds. The metal-coordination active site in ApnU consists of binuclear type II copper centres, as revealed by electron paramagnetic resonance spectroscopy. This discovery expands the enzymatic capability of C(sp 3 )−H halogenases and provides a foundational understanding of this family of binuclear copper-dependent oxidative enzymes.
Joint neutrino oscillation analysis from the T2K and NOvA experiments
The landmark discovery that neutrinos have mass and can change type (or flavour) as they propagate—a process called neutrino oscillation—has opened up a rich array of theoretical and experimental questions being actively pursued today. Neutrino oscillation remains the most powerful experimental tool for addressing many of these questions, including whether neutrinos violate charge-parity (CP) symmetry, which has possible connections to the unexplained preponderance of matter over antimatter in the Universe. Oscillation measurements also probe the mass-squared differences between the different neutrino mass states (Δ$m^2$), whether there are two light states and a heavier one (normal ordering) or vice versa (inverted ordering), and the structure of neutrino mass and flavour mixing. Here we carry out the first joint analysis of datasets from NOvA and T2K, the two currently operating long-baseline neutrino oscillation experiments (hundreds of kilometres of neutrino travel distance), taking advantage of our complementary experimental designs and setting new constraints on several neutrino sector parameters. This analysis provides new precision on the $Δm_{32}^2$ mass difference, finding $-2.43_{−0.03}^{+0.04}$ x $10^{-13}$ $\textrm{eV}^2$ in the normal ordering and $-2.43^{+0.03}_{-0.04}$ x $10^{-13}$ $\textrm{eV}^2$ in the inverted ordering, as well as a 3σ interval on δ CP of [−1.38π, 0.30π] in the normal ordering and [−0.92π, −0.04π] in the inverted ordering. The data show no strong preference for either mass ordering, but notably, if inverted ordering were assumed true within the three-flavour mixing model, then our results would provide evidence of CP symmetry violation in the lepton sector.
Monte Carlo method for constructing confidence intervals with unconstrained and constrained nuisance parameters in the NOvA experiment
Measuring observables to constrain models using maximum-likelihood estimation is fundamental to many physics experiments. Wilks' theorem provides a simple way to construct confidence intervals on model parameters, but it only applies under certain conditions. These conditions, such as nested hypotheses and unbounded parameters, are often violated in neutrino oscillation measurements and other experimental scenarios. Monte Carlo methods can address these issues, albeit at increased computational cost. In the presence of nuisance parameters, however, the best way to implement a Monte Carlo method is ambiguous. Furthermore, this paper documents the method selected by the NOvA experiment, the profile construction. It presents the toy studies that informed the choice of method, details of its implementation, and tests performed to validate it. It also includes some practical considerations which may be of use to others choosing to use the profile construction.
Explanation of the seasonal variation of cosmic multiple muon events observed with the NOvA Near Detector
The flux of cosmic ray muons at the Earth’s surface exhibits seasonal variations due to changes in the temperature of the atmosphere affecting the production and decay of mesons in the upper atmosphere. Using 1473 live days of data collected by the NuMI Off-axis 𝜈 𝑒 Appearance (NOvA) Near Detector during 2018–2022, we studied the seasonal pattern in the multiple-muon event rate. The data confirm an anticorrelation between the multiple-muon event rate and effective atmospheric temperature, consistent across all the years of data. Previous analyses from MINOS and NOvA saw a similar anticorrelation but did not include an explanation. We find that this anticorrelation is driven by altitude–geometry effects as the average muon production height changes with the season. This has been studied with a CORSIKA cosmic ray simulation package by varying atmospheric parameters, and provides an explanation to a longstanding discrepancy between the seasonal phases of single and multiple-muon events.
Expanding neutrino oscillation parameter measurements in NOvA using a Bayesian approach
NOvA is a long-baseline neutrino oscillation experiment that measures oscillations in charged-current ν μ → ν μ (disappearance) and ν μ → ν e (appearance) channels, and their antineutrino counterparts, using neutrinos of energies around 2 GeV over a distance of 810 km. In this work we reanalyze the dataset first examined in our previous paper [] using an alternative statistical approach based on Bayesian Markov chain Monte Carlo. We measure oscillation parameters consistent with the previous results. We also extend our inferences to include the first NOvA measurements of the reactor mixing angle θ 13 , where we find 0.071 ≤ sin 2 2 θ 13 ≤ 0.107 , and the Jarlskog invariant, where we observe no significant preference for the C P -conserving value J = 0 over values favoring C P violation. We use these results to examine the effects of constraints from short-baseline measurements of θ 13 using antineutrinos from nuclear reactors when making NOvA measurements of θ 23 . Our long-baseline measurement of θ 13 is shown to be consistent with the reactor measurements, supporting the general applicability and robustness of the Pontecorvo-Maki-Nakagawa-Sakata framework for neutrino oscillations. Published by the American Physical Society 2024
Measurement of 𝑑 2 𝜎/𝑑|$\vec{q}$|𝑑𝐸 avail in charged current 𝜈 𝜇 -nucleus interactions at ⟨𝐸 𝜈 ⟩=1.86 GeV using the NOvA Near Detector
Double- and single-differential cross sections for inclusive charged-current 𝜈 𝜇 -nucleus scattering are reported for the kinematic domain 0 to 2 GeV/𝑐 in three-momentum transfer and 0 to 2 GeV in available energy, at a mean 𝜈 𝜇 energy of 1.86 GeV. The measurements are based on an estimated 995,760 𝜈 𝜇 charged-current (CC) interactions in the scintillator medium of the NOvA Near Detector. The subdomain populated by 2-particle-2-hole (2p2h) reactions is identified by the cross section excess relative to predictions for 𝜈 𝜇 -nucleus scattering that are constrained by a data control sample. Models for 2-particle-2-hole processes are rated by 𝜒 2 comparisons of the predicted-versus-measured 𝜈 𝜇 CC inclusive cross section over the full phase space and in the restricted subdomain. Shortfalls are observed in neutrino generator predictions obtained using the theory-based València and SuSAv2 2p2h models.
Search for 𝐶𝑃-Violating Neutrino Nonstandard Interactions with the NOvA Experiment
This Letter reports a search for charge-parity (𝐶𝑃) symmetry violating nonstandard interactions (NSI) of neutrinos with matter using the NOvA Experiment, and examines their effects on the determination of the standard oscillation parameters. Data from 𝜈 𝜇 ($\bar{𝜈}$ 𝜇 ) → 𝜈 𝜇 ($\bar{𝜈}$ 𝜇 ) and 𝜈 𝜇 ($\bar{𝜈}$ 𝜇 ) → 𝜈 𝑒 ( $\bar{𝜈}$ 𝑒 ) oscillation channels are used to measure the effect of the NSI parameters 𝜖 𝑒𝜇 and 𝜖 𝑒𝜏 . With 90% CL the magnitudes of the NSI couplings are constrained to be |𝜖 𝑒𝜇 | ≲0.3 and |𝜖 𝑒𝜏 | ≲ 0.4. A degeneracy at |𝜖 𝑒𝜏 | ≈ 1.8 is reported, and we observe that the presence of NSI limits sensitivity to the standard 𝐶𝑃 phase 𝛿 𝐶𝑃 .
Dual-Baseline Search for Active-to-Sterile Neutrino Oscillations in NOvA
We report a search for neutrino oscillations to sterile neutrinos under a model with three active and one sterile neutrinos (3+1 model). This analysis uses the NOvA detectors exposed to the NuMI beam, running in neutrino mode. The data exposure, 13.6 × 10 20 protons on target, doubles that previously analyzed by NOvA, and the analysis is the first to use 𝜈 𝜇 charged-current interactions in conjunction with neutral-current interactions. Neutrino samples in the near and far detectors are fitted simultaneously, enabling the search to be carried out over a Δ𝑚$^{2}_{41}$ range extending 2 (3) orders of magnitude above (below) 1 eV 2 . NOvA finds no evidence for active-to-sterile neutrino oscillations under the 3+1 model at 90% confidence level. New limits are reported in multiple regions of parameter space, excluding some regions currently allowed by IceCube at 90% confidence level. We additionally set the most stringent limits for anomalous 𝜈 𝜏 appearance for Δ𝑚$^{2}_{41}$ ≤ 3 eV 2 .
Ionization-based search for magnetic monopoles using the NOvA Far Detector
We report a search for highly ionizing magnetic monopoles in the cosmic-ray flux using a 2713-day dataset collected during 2015–2025 with the NOvA Far Detector, a 14-kt segmented detector located on Earth’s surface in Minnesota, United States. The search is sensitive to monopoles across a wide range of speeds, 7 × 10 −4 < 𝛽 < 0.995, and is sensitive to masses as low as 2 × 10 5 GeV for the fastest monopoles. No signal was observed. With the detector’s large surface area and minimal overburden, we achieve the strongest flux limits reported to date in several regions of speed and mass. For heavy monopoles with masses above 10 13 GeV that are able to reach the detector from above or—crossing Earth—from below, we find a flux limit 𝜙 90% < 2 × 10 −16 cm −2 s −1 sr −1 (90% confidence level) for monopoles with 0.005 < 𝛽 < 0.8. Across the same range of speeds, we report a limit 𝜙 90% < 8 × 10 −16 cm −2 s −1 sr −1 for light monopoles with masses above 10 8 GeV that can reach the detector from above.
Measurement of 𝜋 0 production in $\bar{v}_μ$ charged-current interactions in the NOvA near detector
We present a high-statistics measurement of muon antineutrino-induced charged-current neutral pion production on a hydrocarbon target using the NOvA near detector. The differential cross sections as functions of the momenta and angles of the outgoing pion and muon, the squared four-momentum transfer, and the invariant mass of the hadronic system at an average neutrino energy of 2 GeV are measured and compared with predictions from various neutrino interaction models. The results agree with the GENIE prediction but suggest that other models underestimate the cross section in the Δ(1232) resonance region. These results represent the most precise measurement of antineutrino-induced neutral pion production to date.
Precision Measurement of Neutrino Oscillation Parameters with 10 Years of Data from the NOvA Experiment
This Letter reports measurements of muon-neutrino disappearance and electron-neutrino appearance and the corresponding antineutrino processes between the two NOvA detectors in the NuMI neutrino beam. These measurements use a dataset with double the neutrino mode beam exposure that was previously analyzed, along with improved simulation and analysis techniques. A joint fit to these samples in the three-flavor paradigm results in the most precise single-experiment constraint on the atmospheric neutrino mass-splitting, $Δm^2_{32}= 2.431^{+0.036}_{-0.034} (-2.479^{+0.036}_{-0.036}) \times 10^{-3}$~eV$^2$ if the mass ordering is Normal (Inverted). In both orderings, a region close to maximal mixing with $\sin^2θ_{23}=0.55_{+0.06}^{-0.02}$ is preferred. The NOvA data show a mild preference for the Normal mass ordering with a Bayes factor of 2.4 (corresponding to 70% of the posterior probability), indicating that the Normal ordering is 2.4 times more probable than the Inverted ordering. When incorporating a 2D $Δm^2_{32}\textrm{--}\sin^2 2θ_{13}$ constraint based on Daya Bay data, this preference strengthens to a Bayes factor of 6.6 (87\%).
Low energy neutrino detection with a compact water-based liquid scintillator detector
In this study, the conceptual design and physics simulations of a near-field Water-based Liquid Scintillator (WbLS) detector placed 100 m from the Akkuyu Nuclear Power Plant (ANPP), currently under construction and aiming at being Turkey’s first nuclear power plant, is presented. The ANPP is an excellent opportunity for neutrino studies and the development of an R &D program for neutrino detectors in Turkey. The Reactor Neutrino Experiments of Turkey (RNET) program includes a compact detector with a 2.5-ton volume of WbLS and a ~ 30% photo-coverage, and the program is planned to be expanded with a medium-size 30-ton detector that will be an international testbed for WbLS and new detector technologies through low energy neutrino studies. In the following, the focus will be on the smaller ~2.5 ton detector, instrumented with 8-in. high quantum efficiency PMTs and two layers of cosmic veto paddles, covering all sides of the detector, to track and veto cosmic particles. Inverse Beta Decay (IBD) events from electron anti-neutrinos generated in the reactor core are simulated using the RAT-PAC simulation package and several liquids with different percentages of Liquid Scintillator (LS) and Gadolinium (Gd) are investigated.
A Measurement of the Electron Antineutrino Charged-Current Inclusive Cross Section with NOvA [Poster]
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Technology Acceptance Workshop Meeting Proceedings, April 20-29, 2022
The Renewable Energy Wildlife Institute and the National Renewable Energy Laboratory convened a virtual workshop facilitated by the Consensus Building Institute in April 2022 to identify recommendations on how to accelerate the rate of research and development, evaluation, and adoption of technologies for monitoring or minimizing wildlife impacts from wind energy. The workshop drew on expertise from stakeholder groups including technology developers, federal agencies, conservation nonprofits, and the wind industry. Over the course of four sessions, participants discussed incentives and barriers to technology development beginning with early field testing and validation, through full-scale experimental deployment, and finally broad-scale acceptance and commercial deployment.
Research and Development Studies for Reactor Neutrino Experiments in Turkey (RNET)
The program of the Reactor Neutrino Experiments of Turkey includes a small portable Water-based liquid scintillator detector to detect neutrinos from the Akkuyu nuclear power plant, planned to begin operating in 2023. The small near-field detector will weigh about 2-3 tons and will be placed less than 100 meters from the reactor cores. The Reactor Neutrino Experiments of Turkey program also includes a medium-size 30-ton Water-based liquid scintillator detector, which will be placed 1-2 km away from the reactor cores and will be used as a far detector. Both detectors and their responses to neutrino interactions were simulated using a GEANT4-based RAT-PAC simulation package. Here, we will share the technical and physical details of both detectors, and discuss the ongoing R&D effort for neutrino studies in Turkey.
Reexamining Fat: Exploring Diversity, Plasticity, Development, Functional Implication, and Therapeutic Options
Obesity has become so prevalent in many developed countries that it is increasingly perceived as a new norm, despite decades of interventions and drug development. Although research continues to explore novel strategies, no single approach to date has demonstrated sustained success in reducing its population-level dominance. This underscores the need to better evaluate and integrate the growing body of knowledge surrounding obesity’s multifaceted nature. Stamped under one ‘fat’ name, adipose tissue varies by color, location, morphology, composition, and function. This variability suggests a level of complexity that demands deeper investigation. Although the relevance and roles of different adipose types have been extensively discussed throughout the literature, their interdependence, synergy, and collective impact on the body remain to be fully expounded. This review aims to further consolidate and elucidate the available information on the different adipose tissue types and their association with obesity and metabolic health. We also discuss existing and emerging therapeutic strategies, highlighting their respective strengths and limitations.
Search for Accelerator-Produced Sub-GeV Dark Matter with the NOvA Near Detector
The NuMI facility at Fermilab produces a high-intensity beam of muon neutrinos and antineutrinos, designed to study neutrino oscillations. This beam may also be a source of dark matter particles produced through a light mediator. We search for dark matter particles with masses between 1 and 200 MeV that interact with Standard Model particles via a vector portal, producing forward-scattered single-electron events in the NOvA near detector. We set limits on the dark-visible coupling based on an exposure of 2.55x10^21 protons of 120 GeV energy on the NuMI target. For the dark matter mass range 10-20 MeV, this analysis sets the tightest constraints on the coupling to date.