First Search for Dark-Trident Processes Using the MicroBooNE Detector.

We present a first search for dark-trident scattering in a neutrino beam using a dataset corresponding to 7.2×10^{20} protons on target taken with the MicroBooNE detector at Fermilab. Proton interactions in the neutrino target at the main injector produce π^{0} and η mesons, which could decay into dark-matter (DM) particles mediated via a dark photon A^{'}. A convolutional neural network is trained to identify interactions of the DM particles in the liquid-argon time projection chamber (LArTPC) exploiting its imagelike reconstruction capability. In the absence of a DM signal, we provide limits at the 90% confidence level on the squared kinematic mixing parameter ϵ^{2} as a function of the dark-photon mass in the range 10≤M_{A^{'}}≤400 MeV. The limits cover previously unconstrained parameter space for the production of fermion or scalar DM particles χ for two benchmark models with mass ratios M_{χ}/M_{A^{'}}=0.6 and 2 and for dark fine-structure constants 0.1≤α_{D}≤1.

First Measurement of η Meson Production in Neutrino Interactions on Argon with MicroBooNE.

We present a measurement of η production from neutrino interactions on argon with the MicroBooNE detector. The modeling of resonant neutrino interactions on argon is a critical aspect of the neutrino oscillation physics program being carried out by the DUNE and Short Baseline Neutrino programs. η production in neutrino interactions provides a powerful new probe of resonant interactions, complementary to pion channels, and is particularly suited to the study of higher-order resonances beyond the Δ(1232). We measure a flux-integrated cross section for neutrino-induced η production on argon of 3.22±0.84(stat)±0.86(syst) 10^{-41} cm^{2}/nucleon. By demonstrating the successful reconstruction of the two photons resulting from η production, this analysis enables a novel calibration technique for electromagnetic showers in GeV accelerator neutrino experiments.

Search for Heavy Neutral Leptons in Electron-Positron and Neutral-Pion Final States with the MicroBooNE Detector.

We present the first search for heavy neutral leptons (HNLs) decaying into νe^{+}e^{-} or νπ^{0} final states in a liquid-argon time projection chamber using data collected with the MicroBooNE detector. The data were recorded synchronously with the NuMI neutrino beam from Fermilab's main injector corresponding to a total exposure of 7.01×10^{20} protons on target. We set upper limits at the 90% confidence level on the mixing parameter |U_{µ4}|^{2} in the mass ranges 10≤m_{HNL}≤150 MeV for the νe^{+}e^{-} channel and 150≤m_{HNL}≤245 MeV for the νπ^{0} channel, assuming |U_{e4}|^{2}=|U_{τ4}|^{2}=0. These limits represent the most stringent constraints in the mass range 35

First Double-Differential Measurement of Kinematic Imbalance in Neutrino Interactions with the MicroBooNE Detector.

We report the first measurement of flux-integrated double-differential quasielasticlike neutrino-argon cross sections, which have been made using the Booster Neutrino Beam and the MicroBooNE detector at Fermi National Accelerator Laboratory. The data are presented as a function of kinematic imbalance variables which are sensitive to nuclear ground-state distributions and hadronic reinteraction processes. We find that the measured cross sections in different phase-space regions are sensitive to different nuclear effects. Therefore, they enable the impact of specific nuclear effects on the neutrino-nucleus interaction to be isolated more completely than was possible using previous single-differential cross section measurements. Our results provide precision data to help test and improve neutrino-nucleus interaction models. They further support ongoing neutrino-oscillation studies by establishing phase-space regions where precise reaction modeling has already been achieved.

First Measurement of Quasielastic Λ Baryon Production in Muon Antineutrino Interactions in the MicroBooNE Detector.

We present the first measurement of the cross section of Cabibbo-suppressed Λ baryon production, using data collected with the MicroBooNE detector when exposed to the neutrinos from the main injector beam at the Fermi National Accelerator Laboratory. The data analyzed correspond to 2.2×10^{20} protons on target running in neutrino mode, and 4.9×10^{20} protons on target running in anti-neutrino mode. An automated selection is combined with hand scanning, with the former identifying five candidate Λ production events when the signal was unblinded, consistent with the GENIE prediction of 5.3±1.1 events. Several scanners were employed, selecting between three and five events, compared with a prediction from a blinded Monte Carlo simulation study of 3.7±1.0 events. Restricting the phase space to only include Λ baryons that decay above MicroBooNE's detection thresholds, we obtain a flux averaged cross section of 2.0_{-1.7}^{+2.2}×10^{-40} cm^{2}/Ar, where statistical and systematic uncertainties are combined.

First Constraints on Light Sterile Neutrino Oscillations from Combined Appearance and Disappearance Searches with the MicroBooNE Detector.

We present a search for eV-scale sterile neutrino oscillations in the MicroBooNE liquid argon detector, simultaneously considering all possible appearance and disappearance effects within the 3+1 active-to-sterile neutrino oscillation framework. We analyze the neutrino candidate events for the recent measurements of charged-current ν_{e} and ν_{µ} interactions in the MicroBooNE detector, using data corresponding to an exposure of 6.37×10^{20} protons on target from the Fermilab booster neutrino beam. We observe no evidence of light sterile neutrino oscillations and derive exclusion contours at the 95% confidence level in the plane of the mass-squared splitting Δm_{41}^{2} and the sterile neutrino mixing angles θ_{µe} and θ_{ee}, excluding part of the parameter space allowed by experimental anomalies. Cancellation of ν_{e} appearance and ν_{e} disappearance effects due to the full 3+1 treatment of the analysis leads to a degeneracy when determining the oscillation parameters, which is discussed in this Letter and will be addressed by future analyses.

Search for an Excess of Electron Neutrino Interactions in MicroBooNE Using Multiple Final-State Topologies.

We present a measurement of ν_{e} interactions from the Fermilab Booster Neutrino Beam using the MicroBooNE liquid argon time projection chamber to address the nature of the excess of low energy interactions observed by the MiniBooNE Collaboration. Three independent ν_{e} searches are performed across multiple single electron final states, including an exclusive search for two-body scattering events with a single proton, a semi-inclusive search for pionless events, and a fully inclusive search for events containing all hadronic final states. With differing signal topologies, statistics, backgrounds, reconstruction algorithms, and analysis approaches, the results are found to be either consistent with or modestly lower than the nominal ν_{e} rate expectations from the Booster Neutrino Beam and no excess of ν_{e} events is observed.

Scintillation light detection in the 6-m drift-length ProtoDUNE Dual Phase liquid argon TPC.

DUNE is a dual-site experiment for long-baseline neutrino oscillation studies, neutrino astrophysics and nucleon decay searches. ProtoDUNE Dual Phase (DP) is a 6  ×  6  ×  6 m 3 liquid argon time-projection-chamber (LArTPC) that recorded cosmic-muon data at the CERN Neutrino Platform in 2019-2020 as a prototype of the DUNE Far Detector. Charged particles propagating through the LArTPC produce ionization and scintillation light. The scintillation light signal in these detectors can provide the trigger for non-beam events. In addition, it adds precise timing capabilities and improves the calorimetry measurements. In ProtoDUNE-DP, scintillation and electroluminescence light produced by cosmic muons in the LArTPC is collected by photomultiplier tubes placed up to 7 m away from the ionizing track. In this paper, the ProtoDUNE-DP photon detection system performance is evaluated with a particular focus on the different wavelength shifters, such as PEN and TPB, and the use of Xe-doped LAr, considering its future use in giant LArTPCs. The scintillation light production and propagation processes are analyzed and a comparison of simulation to data is performed, improving understanding of the liquid argon properties.

First Measurement of Energy-Dependent Inclusive Muon Neutrino Charged-Current Cross Sections on Argon with the MicroBooNE Detector.

We report a measurement of the energy-dependent total charged-current cross section σ(E_{ν}) for inclusive muon neutrinos scattering on argon, as well as measurements of flux-averaged differential cross sections as a function of muon energy and hadronic energy transfer (ν). Data corresponding to 5.3×10^{19} protons on target of exposure were collected using the MicroBooNE liquid argon time projection chamber located in the Fermilab booster neutrino beam with a mean neutrino energy of approximately 0.8 GeV. The mapping between the true neutrino energy E_{ν} and reconstructed neutrino energy E_{ν}^{rec} and between the energy transfer ν and reconstructed hadronic energy E_{had}^{rec} are validated by comparing the data and Monte Carlo (MC) predictions. In particular, the modeling of the missing hadronic energy and its associated uncertainties are verified by a new method that compares the E_{had}^{rec} distributions between data and a MC prediction after constraining the reconstructed muon kinematic distributions, energy, and polar angle to those of data. The success of this validation gives confidence that the missing energy in the MicroBooNE detector is well modeled and underpins first-time measurements of both the total cross section σ(E_{ν}) and the differential cross section dσ/dν on argon.

Search for Neutrino-Induced Neutral-Current Δ Radiative Decay in MicroBooNE and a First Test of the MiniBooNE Low Energy Excess under a Single-Photon Hypothesis.

We report results from a search for neutrino-induced neutral current (NC) resonant Δ(1232) baryon production followed by Δ radiative decay, with a ⟨0.8⟩ GeV neutrino beam. Data corresponding to MicroBooNE's first three years of operations (6.80×10^{20} protons on target) are used to select single-photon events with one or zero protons and without charged leptons in the final state (1γ1p and 1γ0p, respectively). The background is constrained via an in situ high-purity measurement of NC π^{0} events, made possible via dedicated 2γ1p and 2γ0p selections. A total of 16 and 153 events are observed for the 1γ1p and 1γ0p selections, respectively, compared to a constrained background prediction of 20.5±3.65(syst) and 145.1±13.8(syst) events. The data lead to a bound on an anomalous enhancement of the normalization of NC Δ radiative decay of less than 2.3 times the predicted nominal rate for this process at the 90% confidence level (C.L.). The measurement disfavors a candidate photon interpretation of the MiniBooNE low-energy excess as a factor of 3.18 times the nominal NC Δ radiative decay rate at the 94.8% C.L., in favor of the nominal prediction, and represents a greater than 50-fold improvement over the world's best limit on single-photon production in NC interactions in the sub-GeV neutrino energy range.

Progressive secondary exo-focal dopaminergic neurodegeneration occurs in not directly connected midbrain nuclei after pure motor-cortical stroke.

Transsynaptic anterograde and retrograde degeneration of neurons and neural fibers are assumed to trigger local excitotoxicity and inflammatory processes. These processes in turn are thought to drive exo-focal neurodegeneration in remote areas connected to the infarcted tissue after ischemic stroke. In the case of middle cerebral artery occlusion (MCAO), in which striato-nigral connections are affected, the hypothesis of inflammation-induced remote neurodegeneration is based on the temporal dynamics of an early appearance of inflammatory markers in midbrain followed by dopaminergic neuronal loss. To test the hypothesis of a direct transsynaptic mediation of secondary exo-focal post-ischemic neurodegeneration, we used a photochemical induction of a stroke (PTS) in Sprague-Dawley rats restricted to motor cortex (MC), thereby sparing the striatal connections to dopaminergic midbrain nuclei. To dissect the temporal dynamics of post-ischemic neurodegeneration, we analyzed brain sections harvested at day 7 and 14 post stroke. Here, an unexpectedly pronounced and widespread loss of dopaminergic neurons occurred 14 days after stroke also affecting dopaminergic nuclei that are not directly coupled to MC. Since the pattern of neurodegeneration in case of a pure motor stroke is similar to a major stroke including the striatum, it is unlikely that direct synaptic coupling is a prerequisite for delayed secondary exo-focal post ischemic neurodegeneration. Furthermore, dopaminergic neurodegeneration was already detected by Fluoro-Jade C staining at day 7, coinciding with a solely slight inflammatory response. Thus, inflammation cannot be assumed to be the primary driver of exo-focal post-ischemic cell death. Moreover, nigral substance P (SP) expression indicated intact striato-nigral innervation after PTS, whereas opposing effects on SP expression after striatal infarcts argue against a critical role of SP in neurodegenerative or inflammatory processes during exo-focal neurodegeneration.

Combination of light-driven co-delivery of chemodrugs and plasmonic-induced heat for cancer therapeutics using hybrid protein nanocapsules.

BACKGROUND: Improving the water solubility of hydrophobic drugs, increasing their accumulation in tumor tissue and allowing their simultaneous action by different pathways are essential issues for a successful chemotherapeutic activity in cancer treatment. Considering potential clinical application in the future, it will be promising to achieve such purposes by developing new biocompatible hybrid nanocarriers with multimodal therapeutic activity. RESULTS: We designed and characterised a hybrid nanocarrier based on human serum albumin/chitosan nanoparticles (HSA/chitosan NPs) able to encapsulate free docetaxel (DTX) and doxorubicin-modified gold nanorods (DOXO-GNRs) to simultaneously exploit the complementary chemotherapeutic activities of both antineoplasic compounds together with the plasmonic optical properties of the embedded GNRs for plasmonic-based photothermal therapy (PPTT). DOXO was assembled onto GNR surfaces following a layer-by-layer (LbL) coating strategy, which allowed to partially control its release quasi-independently release regarding DTX under the use of near infrared (NIR)-light laser stimulation of GNRs. In vitro cytotoxicity experiments using triple negative breast MDA-MB-231 cancer cells showed that the developed dual drug encapsulation approach produces a strong synergistic toxic effect to tumoral cells compared to the administration of the combined free drugs; additionally, PPTT enhances the cytostatic efficacy allowing cell toxicities close to 90% after a single low irradiation dose and keeping apoptosis as the main cell death mechanism. CONCLUSIONS: This work demonstrates that by means of a rational design, a single hybrid nanoconstruct can simultaneously supply complementary therapeutic strategies to treat tumors and, in particular, metastatic breast cancers with good results making use of its stimuli-responsiveness as well as its inherent physico-chemical properties.

Toll-Like Receptors as Therapeutic Targets in Central Nervous System Tumors.

In recent years, progress has been made in understanding the pathological, genetic, and molecular heterogeneity of central nervous system (CNS) tumors. However, improvements in risk classification, prognosis, and treatment have not been sufficient. Currently, great importance has been placed to the tumor microenvironment and the immune system, which are very important components that influence the establishment and development of tumors. Toll-like receptors (TLRs) are innate immunite system sensors of a wide variety of molecules, such as those associated with microorganisms and danger signals. TLRs are expressed on many cells, including immune cells and nonimmune cells such as neurons and cancer cells. In the tumor microenvironment, activation of TLRs plays dual antitumoral (dendritic cells, cytotoxic T cells, and natural killer cells activation) and protumoral effects (tumor cell proliferation, survival, and resistance to chemotherapy) and constitutes an area of opportunities and challenges in the development of new therapeutic strategies. Several clinical trials have been carried out, and others are currently in process; however, the results obtained to date have been contradictory and have not led to a definitive position about the use of TLR agonists in adjuvant therapy during the treatment of central nervous system (CNS) tumors. In this review, we focus on recent advances in TLR agonists as immunotherapies for treatment of CNS tumors.

[Bilateral Wallerian degeneration of pontocerebellar fibres secondary to pontine infarction]. / Degeneracion walleriana bilateral de haces pontocerebelosos secundaria a infarto protuberancial.

TITLE: Degeneracion walleriana bilateral de haces pontocerebelosos secundaria a infarto protuberancial.

Pathogenic Compound Heterozygous Mutations in a Mexican Mestizo Patient with Niemann-Pick Disease Type B.

Niemann-Pick disease (NPD) type B is a lysosomal storage disorder caused by a deficiency of acid sphingomyelinase (ASM). We report the clinical follow-up of a 16-year-old Mexican mestizo woman with a NPD type B phenotype who presented hepatosplenomegaly, persitstenly low high-density lipoprotein (HDL) cholesterol and thrombocytopenia, without central nervous system involvement. After of a dengue fever episode with severe anemia and pancytopenia, leading to a bone marrow study n which foamy histiocytes were noticed and diagnosis of NiemannPick disease was suspected; and confirmed by biochemical and molecular tests. The missense c.1343 A>G (p.Tyr448Cys, formerly Y446C) and c. 1426C>T (p.Arg476Trp, formerly R474W) mutations in the SMPD1 gene were identified. These mutations have never been reported in the Mexican population. Since the c.1343 A>G (Y446C) mutation has been previously reported in a Japanese patient with NPD type A, we suggest an attenuator effect of c.1426C>T (R474W) allele (previously associated with the NPD type B phenotype). In conclusion, this is the first description of the concomitant occurrence of Y446C and R476W mutations in a Mexican patient with NPD type B, showing the importance of increased awareness and availability of specialized diagnostic tests in the diagnosis of rare inherited metabolic diseases.