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Scattering of high energy particles from nucleons probes their structure, as was done in the experiments that established the non-zero size of the proton using electron beams1. The use of charged leptons as scattering probes enables measuring the distribution of electric charges, which is encoded in the vector form factors of the nucleon2. Scattering weakly interacting neutrinos gives the opportunity to measure both vector and axial vector form factors of the nucleon, providing an additional, complementary probe of their structure. The nucleon transition axial form factor, FA, can be measured from neutrino scattering from free nucleons, νµn â µ-p and [Formula: see text], as a function of the negative four-momentum transfer squared (Q2). Up to now, FA(Q2) has been extracted from the bound nucleons in neutrino-deuterium scattering3-9, which requires uncertain nuclear corrections10. Here we report the first high-statistics measurement, to our knowledge, of the [Formula: see text] cross-section from the hydrogen atom, using the plastic scintillator target of the MINERvA11 experiment, extracting FA from free proton targets and measuring the nucleon axial charge radius, rA, to be 0.73 ± 0.17 fm. The antineutrino-hydrogen scattering presented here can access the axial form factor without the need for nuclear theory corrections, and enables direct comparisons with the increasingly precise lattice quantum chromodynamics computations12-15. Finally, the tools developed for this analysis and the result presented are substantial advancements in our capabilities to understand the nucleon structure in the weak sector, and also help the current and future neutrino oscillation experiments16-20 to better constrain neutrino interaction models.
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Neutrino-induced charged-current single π^{+} production in the Δ(1232) resonance region is of considerable interest to accelerator-based neutrino oscillation experiments. In this Letter, high statistic differential cross sections are reported for the semiexclusive reaction ν_{µ}Aâµ^{-}π^{+}+ nucleon(s) on scintillator, carbon, water, iron, and lead targets recorded by MINERvA using a wideband ν_{µ} beam with ⟨E_{ν}⟩≈6 GeV. Suppression of the cross section at low Q^{2} and enhancement of low T_{π} are observed in both light and heavy nuclear targets compared with phenomenological models used in current neutrino interaction generators. The cross sections per nucleon for iron and lead compared with CH across the kinematic variables probed are 0.8 and 0.5 respectively, a scaling which is also not predicted by current generators.
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MINERvA has measured the ν_{µ}-induced coherent π^{+} cross section simultaneously in hydrocarbon (CH), graphite (C), iron (Fe), and lead (Pb) targets using neutrinos from 2 to 20 GeV. The measurements exceed the predictions of the Rein-Sehgal and Berger-Sehgal PCAC based models at multi-GeV ν_{µ} energies and at produced π^{+} energies and angles, E_{π}>1 GeV and θ_{π}<10°. Measurements of the cross-section ratios of Fe and Pb relative to CH reveal the effective A scaling to increase from an approximate A^{1/3} scaling at few GeV to an A^{2/3} scaling for E_{ν}>10 GeV.
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This Letter presents the first simultaneous measurement of the quasielasticlike neutrino-nucleus cross sections on C, water, Fe, Pb, and scintillator (hydrocarbon or CH) as a function of longitudinal and transverse muon momentum. The ratio of cross sections per nucleon between Pb and CH is always above unity and has a characteristic shape as a function of transverse muon momentum that evolves slowly as a function of longitudinal muon momentum. The ratio is constant versus longitudinal momentum within uncertainties above a longitudinal momentum of 4.5 GeV/c. The cross section ratios to CH for C, water, and Fe remain roughly constant with increasing longitudinal momentum, and the ratios between water or C to CH do not have any significant deviation from unity. Both the overall cross section level and the shape for Pb and Fe as a function of transverse muon momentum are not reproduced by current neutrino event generators. These measurements provide a direct test of nuclear effects in quasielasticlike interactions, which are major contributors to long-baseline neutrino oscillation data samples.
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Neutrino charged-current quasielastic-like scattering, a reaction category extensively used in neutrino oscillation measurements, probes nuclear effects that govern neutrino-nucleus interactions. This Letter reports the first measurement of the triple-differential cross section for ν_{µ} quasielastic-like reactions using the hydrocarbon medium of the MINERvA detector exposed to a wideband beam spanning 2≤E_{ν}≤20 GeV. The measurement maps the correlations among transverse and longitudinal muon momenta and summed proton kinetic energies, and compares them to predictions from a state-of-art simulation. Discrepancies are observed that likely reflect shortfalls with modeling of pion and nucleon intranuclear scattering and/or spectator nucleon ejection from struck nuclei. The separate determination of leptonic and hadronic variables can inform experimental approaches to neutrino-energy estimation.
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The ovicidal and larvicidal effect of a full aqueous extract (FE) and two phases: an aqueous (Aq-Ph) and an ethyl acetate (EtOAc-Ph) from Ruta chalepensis (Rc) stems and leaves against Haemonchus contortus (Hc) were assessed. The egg hatching inhibition (EHI) assay and larval mortality (LM) test were performed by triplicate in 96-well micro-titration plates (n=4 wells). The FE against Hc eggs and larvae was assessed at 1.25, 2.5, 5, 10 and 20 mg/mL; and 30, 60, 90, 120,150 and 200 mg/ mL, respectively. The ovicidal effect of Aq-F and EtOAc-F was assessed at 1.25, 2.5, 5, 10 and 20 mg/mL. Plates were incubated at 28 °C for 48 (ovicidal assay) and 72 h (larvicidal assay). The EHI results were considered based on the mean number of eggs hatching failure after 48 h exposure. The LM was recorded after 72 h exposure to the Rc phases and expressed as mortality percentage. The Rc FE caused 96 and 100% EHI at 10 and 20 mg/mL, respectively; meanwhile, 74% LM was recorded at 200 mg/mL (p<0.05). The Aq-Ph showed 78.5% EHI at 2.5 mg/mL. Likewise, the EtOAc-Ph caused 100% EHI in almost all concentrations. Eighteen compounds including alkaloids, cumarins, triterpens, flavonoids, tannins, saponins and sterols were identified by GC-MS analysis. The results indicate that the aqueous extract from Rc possesses bioactive compounds with in vitro nematocidal activity against Hc; mainly in the EtOAc-Ph. Further studies should be performed to elucidate those compounds searching for alternative methods of control of the sheep haemonchosis.
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BACKGROUND: COVID-19 pandemic causes high global morbidity and mortality and better medical treatments to reduce mortality are needed. OBJECTIVE: To determine the added benefit of cyclosporine A (CsA), to low-dose steroid treatment, in patients with COVID-19. METHODS: Open-label, non randomized pilot study of patients with confirmed infection of SARS-CoV-2 hospitalized from April to May 2020 at a single centre in Puebla, Mexico. Patients were assigned to receive either steroids or CsA plus steroids. Pneumonia severity was assessed by clinical, laboratory, and lung tomography. The death rate was evaluated at 28 days. RESULTS: A total of 209 adult patients were studied, 105 received CsA plus steroids (age 55.3 ± 13.3; 69% men), and 104 steroids alone (age 54.06 ± 13.8; 61% men). All patients received clarithromycin, enoxaparin and methylprednisolone or prednisone up to 10 days. Patient's death was associated with hypertension (RR = 3.5) and diabetes (RR = 2.3). Mortality was 22 and 35% for CsA and control groups (P = 0.02), respectively, for all patients, and 24 and 48.5% for patients with moderate to severe disease (P = 0.001). Higher cumulative clinical improvement was seen for the CsA group (Nelson Aalen curve, P = 0.001, log-rank test) in moderate to severe patients. The Cox proportional hazard analysis showed the highest HR improvement value of 2.15 (1.39-3.34, 95%CI, P = 0.0005) for CsA treatment in moderate to severe patients, and HR = 1.95 (1.35-2.83, 95%CI, P = 0.0003) for all patients. CONCLUSION: CsA used as an adjuvant to steroid treatment for COVID-19 patients showed to improve outcomes and reduce mortality, mainly in those with moderate to severe disease. Further investigation through controlled clinical trials is warranted.
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Tratamento Farmacológico da COVID-19 , Ciclosporina/uso terapêutico , Glucocorticoides/uso terapêutico , Metilprednisolona/uso terapêutico , Prednisona/uso terapêutico , COVID-19/mortalidade , COVID-19/patologia , Ciclosporina/efeitos adversos , Quimioterapia Combinada , Feminino , Glucocorticoides/administração & dosagem , Humanos , Pulmão/patologia , Masculino , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Projetos Piloto , Prednisona/administração & dosagem , Resultado do TratamentoRESUMO
BACKGROUND: While cancer is common, its incidence varies widely by tissue. These differences are attributable to variable risk factors, such as environmental exposure, genetic inheritance, and lifetime number of stem cell divisions in a tissue. Folate deficiency is generally associated with increased risk for colorectal cancer (CRC) and acute lymphocytic leukemia (ALL). Conversely, high folic acid (FA) intake has also been associated with higher CRC risk. OBJECTIVE: Our objective was to compare the effect of folate intake on mutant frequency (MF) and types of mutations in the colon and bone marrow of mice. METHODS: Five-week-old MutaMouse male mice were fed a deficient (0 mg FA/kg), control (2 mg FA/kg), or supplemented (8 mg FA/kg) diet for 20 wk. Tissue MF was assessed using the lacZ mutant assay and comparisons made by 2-factor ANOVA. LacZ mutant plaques were sequenced using next-generation sequencing, and diet-specific mutation profiles within each tissue were compared by Fisher's exact test. RESULTS: In the colon, the MF was 1.5-fold and 1.3-fold higher in mice fed the supplemented diet compared with mice fed the control (P = 0.001) and deficient (P = 0.008) diets, respectively. This contrasted with the bone marrow MF in the same mice where the MF was 1.7-fold and 1.6-fold higher in mice fed the deficient diet compared with mice fed the control (P = 0.02) and supplemented (P = 0.03) diets, respectively. Mutation profiles and signatures (mutation context) were tissue-specific. CONCLUSIONS: Our data indicate that dietary folate intake affects mutagenesis in a tissue- and dose-specific manner in mice. Mutation profiles were generally tissue- but not dose-specific, suggesting that altered cellular folate status appears to interact with endogenous mutagenic mechanisms in each tissue to create a permissive context in which specific mutation types accumulate. These data illuminate potential mechanisms underpinning differences in observed associations between folate intake/status and cancer.
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Ácido Fólico/administração & dosagem , Taxa de Mutação , Animais , Medula Óssea/efeitos dos fármacos , Medula Óssea/metabolismo , Colo/efeitos dos fármacos , Colo/metabolismo , Relação Dose-Resposta a Droga , Ácido Fólico/efeitos adversos , Ácido Fólico/sangue , Deficiência de Ácido Fólico/sangue , Deficiência de Ácido Fólico/genética , Sequenciamento de Nucleotídeos em Larga Escala , Óperon Lac/efeitos dos fármacos , Masculino , Camundongos , Camundongos Mutantes , Camundongos Transgênicos , Mutagênese , Especificidade de ÓrgãosRESUMO
BACKGROUND: The number of patients waiting for a lung transplant worldwide greatly exceeds the number of available donors. Ex vivo lung perfusion is a useful tool that allows marginal donor lungs to be evaluated and reconditioned for a successful lung transplantation. AIM: To describe the first Chilean and Latin American experience in ex vivo lung perfusion for marginal donor lungs before transplantation. MATERIAL AND METHODS: Descriptive analysis of all ex vivo lung perfusion conducted for marginal donor lungs at a private clinic, from April 2019 to October 2020. High risk donor lungs and rejected lungs from other transplantation centers were included. The "Toronto Protocol" was used for ex vivo lung perfusion. Donor lung characteristics and recipient outcomes were studied. RESULTS: During the study period, five ex vivo lung perfusions were performed. All lungs were reconditioned and transplanted. No complications were associated. There were no primary graft dysfunctions and only one chronic allograft dysfunction. There was no mortality during the first year. The median arterial oxygen partial pressure/fractional inspired oxygen ratio increased from 266 mm Hg in the donor lung to 419 after 3 hours of ex vivo lung perfusion (p = 0.043). CONCLUSIONS: ex vivo lung perfusion is a safe and useful tool that allows marginal donor lungs to be reconditioned and successfully transplanted.
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Transplante de Pulmão , Circulação Extracorpórea , Humanos , América Latina , Pulmão/cirurgia , Perfusão , Doadores de TecidosRESUMO
Chagas disease, caused by the hemoflagelate parasite Trypanosoma cruzi, is one of the most prevalent endemic parasitoses, affecting 7-8 million people. Due to the complexity of the infection, no vaccines are available at present. The extraordinary adjuvant capacity of bacille Calmette-Guérin (BCG) was explored in this work to develop a vaccine candidate to protect against T. cruzi infection using the recombinant BCG (rBCG) vaccine platform. Three antigens of the parasite corresponding to the N and C terminal fragments of the enzyme trans-sialidase (NT-TS and CT-TS, respectively) and a fragment of the cruzipain enzyme (CZf) were cloned into the vectors pUS997 and pUS2000 and transformed into the BCG Pasteur strain. In vaccinated mice, rBCG expressing NT-TS in pUS2000 plasmid provided the highest protection and the lowest parasitemia after challenging BALB/c mice with a 50% lethal dose of parasites. When mice vaccinated with pUS2000-NT-TS were challenged with a 100% lethal dose of parasite, high levels of protection were also obtained, together with a low degree of cardiac lesions 120 days after infection. In immunized mice with pUS2000-NT-TS/rBCG clone, the proliferation of CD4+ cells from splenocytes stimulated with the TS antigen was significant; this stimulation increased interferon (IFN)-γ and interleukin (IL)-17 within CD4⺠T lymphocytes (LTCD4+ ) cells and IFN-γ and CD107 expression within LTCD8+ cells. Therefore, pUS2000-NT-TS/rBCG conferred high levels of protection, which correlated with an immune response orientated towards a T helper type 1 (Th1)/Th17 profile, together with an LTC-specific response, indicating that rBCG is a promising platform to develop vaccines against T. cruzi.
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Doença de Chagas/imunologia , Mycobacterium bovis/imunologia , Vacinas Protozoárias/imunologia , Células Th1/imunologia , Células Th17/imunologia , Vacinas Sintéticas/imunologia , Adjuvantes Imunológicos , Animais , Antígenos de Protozoários/genética , Antígenos de Protozoários/imunologia , Células Cultivadas , Clonagem Molecular , Cisteína Endopeptidases/genética , Modelos Animais de Doenças , Humanos , Imunização , Camundongos , Neuraminidase/genética , Proteínas de Protozoários/genética , Trypanosoma cruzi/fisiologiaRESUMO
We measure neutrino charged-current quasielasticlike scattering on hydrocarbon at high statistics using the wideband Neutrinos at the Main Injector beam with neutrino energy peaked at 6 GeV. The double-differential cross section is reported in terms of muon longitudinal (p_{â¥}) and transverse (p_{â¥}) momentum. Cross section contours versus lepton momentum components are approximately described by a conventional generator-based simulation, however, discrepancies are observed for transverse momenta above 0.5 GeV/c for longitudinal momentum ranges 3-5 and 9-20 GeV/c. The single differential cross section versus momentum transfer squared (dσ/dQ_{QE}^{2}) is measured over a four-decade range of Q^{2} that extends to 10 GeV^{2}. The cross section turnover and falloff in the Q^{2} range 0.3-10 GeV^{2} is not fully reproduced by generator predictions that rely on dipole form factors. Our measurement probes the axial-vector content of the hadronic current and complements the electromagnetic form factor data obtained using electron-nucleon elastic scattering. These results help oscillation experiments because they probe the importance of various correlations and final-state interaction effects within the nucleus, which have different effects on the visible energy in detectors.
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Final-state kinematic imbalances are measured in mesonless production of ν_{µ}+Aâµ^{-}+p+X in the MINERvA tracker. Initial- and final-state nuclear effects are probed using the direction of the µ^{-}-p transverse momentum imbalance and the initial-state momentum of the struck neutron. Differential cross sections are compared to predictions based on current approaches to medium modeling. These models underpredict the cross section at intermediate intranuclear momentum transfers that generally exceed the Fermi momenta. As neutrino interaction models need to correctly incorporate the effect of the nucleus in order to predict neutrino energy resolution in oscillation experiments, this result points to a region of phase space where additional cross section strength is needed in current models, and demonstrates a new technique that would be suitable for use in fine-grained liquid argon detectors where the effect of the nucleus may be even larger.
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This corrects the article DOI: 10.1103/PhysRevLett.116.071802.
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We report on multinucleon effects in low momentum transfer (<0.8 GeV/c) antineutrino interactions on plastic (CH) scintillator. These data are from the 2010-2011 antineutrino phase of the MINERvA experiment at Fermilab. The hadronic energy spectrum of this inclusive sample is well described when a screening effect at a low energy transfer and a two-nucleon knockout process are added to a relativistic Fermi gas model of quasielastic, Δ resonance, and higher resonance processes. In this analysis, model elements introduced to describe previously published neutrino results have quantitatively similar benefits for this antineutrino sample. We present the results as a double-differential cross section to accelerate the investigation of alternate models for antineutrino scattering off nuclei.
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The start-up phase of a membrane bioreactor (MBR) for municipal wastewater treatment was studied to determine the effect of temperature on the organic matter removal and heterotrophic kinetics. The MBR system was analyzed during four start-up phases with values of hydraulic retention time (HRT) of 6 h and 10 h, mixed liquor suspended solids (MLSS) concentrations of 4,000 mg L-1 and 7,000 mg L-1 in the steady state, and temperature values of 11.5, 14.2, 22.9 and 30.1 °C. The influence of temperature on the biological process of organic matter removal was determined through the Arrhenius equation and Monod model. At the most favorable operation conditions of HRT (10 h) and MLSS (7,000 mg L-1) corresponding to phase 4, the effect of these variables dominated over the temperature. Heterotrophic biomass from phase 2 (HRT = 10 h, MLSS = 4,000 mg L-1 and T = 30.1 °C) had the highest values of chemical oxygen demand (COD) degradation rate (rsu,H), implying less time to remove organic matter and shorter duration of the start-up phase.
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Reatores Biológicos/microbiologia , Membranas Artificiais , Modelos Teóricos , Temperatura , Purificação da Água/métodos , Análise da Demanda Biológica de Oxigênio , Biomassa , Cinética , Esgotos/química , Águas Residuárias/químicaRESUMO
Neuroinflammation is the hallmark of several infectious and neurodegenerative diseases. Synthetic glucocorticoids (GCs) are the first-line immunosuppressive drugs used for controlling neuroinflammation. A delayed diffusion of GCs molecules and the high systemic doses required for brain-specific targeting lead to severe undesirable effects, particularly when lifelong treatment is required. Therefore, there is an urgent need for improving this current therapeutic approach. The intranasal (i.n.) route is being employed increasingly for drug delivery to the brain via the olfactory system. In this study, the i.n. route is compared to the intravenous (i.v.) administration of GCs with respect to their effectiveness in controlling neuroinflammation induced experimentally by systemic lipopolysaccharide (LPS) injection. A statistically significant reduction in interleukin (IL)-6 levels in the central nervous system (CNS) in the percentage of CD45+ /CD11b+ /lymphocyte antigen 6 complex locus G6D [Ly6G+ and in glial fibrillary acidic protein (GFAP) immunostaining was observed in mice from the i.n.-dexamethasone (DX] group compared to control and i.v.-DX-treated animals. DX treatment did not modify the percentage of microglia and perivascular macrophages as determined by ionized calcium binding adaptor molecule 1 (Iba1) immunostaining of the cortex and hippocampus. The increased accumulation of DX in brain microvasculature in DX-i.n.-treated mice compared with controls and DX-IV-treated animals may underlie the higher effectiveness in controlling neuroinflammation. Altogether, these results indicate that IN-DX administration may offer a more efficient alternative than systemic administration to control neuroinflammation in different neuropathologies.
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Córtex Cerebral , Hipocampo , Lipopolissacarídeos/toxicidade , Microglia , Doenças Neurodegenerativas , Administração Intranasal , Animais , Antígenos Ly/imunologia , Antígeno CD11b/imunologia , Proteínas de Ligação ao Cálcio/imunologia , Córtex Cerebral/imunologia , Córtex Cerebral/patologia , Proteína Glial Fibrilar Ácida/imunologia , Hipocampo/imunologia , Hipocampo/patologia , Interleucina-6/imunologia , Antígenos Comuns de Leucócito/imunologia , Masculino , Camundongos , Proteínas dos Microfilamentos/imunologia , Microglia/imunologia , Microglia/patologia , Doenças Neurodegenerativas/induzido quimicamente , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/imunologia , Doenças Neurodegenerativas/patologiaRESUMO
The Ashkenazi Jewish (AJ) population has an increased risk for a variety of recessive diseases due to historical founder effects and genetic drift. For some, the disease-causing founder mutations have been identified and well-characterized, but for others, further study is necessary. The purpose of this study is to assess the carrier frequencies of 85 pathogenic variants causative of 29 recessive conditions in the AJ population. Up to 3000 AJ individuals were genotyped by Luminex MagPlex® -TAG™ bead array or Agena Bioscience™ MassARRAY assays. We identified seven conditions with carrier frequencies higher than 1 in 100, nine between 1 in 100 and 1 in 200, and four between 1 in 200 and 1 in 500. Variants in nine conditions had a detected carrier rate of less than 1 in 500 or were not identified in approximately 2000 AJ individuals. We assessed the combined AJ carrier frequency for 18 relatively prevalent diseases to be 1 in 6, and the risk of AJ individuals to be a carrier couple for one of these 18 diseases as 1 in 441. We note additional recessive genetic conditions should be considered for AJ carrier screening panels.
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Genes Recessivos , Doenças Genéticas Inatas/genética , Genética Populacional , Judeus/genética , Feminino , Efeito Fundador , Triagem de Portadores Genéticos , Doenças Genéticas Inatas/epidemiologia , Predisposição Genética para Doença , Testes Genéticos , Genótipo , Heterozigoto , Humanos , Masculino , MutaçãoRESUMO
Colloidal silver nanocubes in solution were analyzed by the Z-scan technique in the resonant and non-resonant regimes. Three different systems with particle sizes of 56, 99 and 215 nm, and concentrations of 0.378, 0.831 and 0.715 mg/mL, respectively, were obtained by the polyol method. Nonlinear excitation of the samples was performed with laser pulses of 26 ps, at a repetition rate of 10 Hz, and using three different wavelenghts (355, 532 and 1064 nm), exciting only the electronic part of the optical nonlinearity, and avoiding induced thermal loading of the samples. Whenever observable, samples showed saturable absorption for all wavelengths, which was dependent, in general, on concentration and incident intensity. For samples featuring sizes of 55 and 99 nm, saturable absorption could be observed for wavelengths close to their dipolar surface plasmon resonances; while, for samples with sizes of 99 and 215 nm, saturable absorption and positive nonlinear optical refraction (only for size of 215 nm) could be observed at 1064 nm. Besides, for some samples, nonlinear optical response followed the incident intensity profile at wavelengths close to resonance. On the contrary, for wavelengths out of resonance, the nonlinear optical behavior showed to be nonlocal, ie, its profile was narrower than the incident one.
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Neutral-current production of K^{+} by atmospheric neutrinos is a background in searches for the proton decay pâK^{+}ν[over ¯]. Reactions such as νpâνK^{+}Λ are indistinguishable from proton decays when the decay products of the Λ are below detection threshold. Events with K^{+} are identified in MINERvA by reconstructing the timing signature of a K^{+} decay at rest. A sample of 201 neutrino-induced neutral-current K^{+} events is used to measure differential cross sections with respect to the K^{+} kinetic energy, and the non-K^{+} hadronic visible energy. An excess of events at low hadronic visible energy is observed relative to the prediction of the neut event generator. Good agreement is observed with the cross section prediction of the genie generator. A search for photons from π^{0} decay, which would veto a neutral-current K^{+} event in a proton decay search, is performed, and a 2σ deficit of detached photons is observed relative to the genie prediction.
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Charged-current ν_{µ} interactions on carbon, iron, and lead with a final state hadronic system of one or more protons with zero mesons are used to investigate the influence of the nuclear environment on quasielasticlike interactions. The transferred four-momentum squared to the target nucleus, Q^{2}, is reconstructed based on the kinematics of the leading proton, and differential cross sections versus Q^{2} and the cross-section ratios of iron, lead, and carbon to scintillator are measured for the first time in a single experiment. The measurements show a dependence on the atomic number. While the quasielasticlike scattering on carbon is compatible with predictions, the trends exhibited by scattering on iron and lead favor a prediction with intranuclear rescattering of hadrons accounted for by a conventional particle cascade treatment. These measurements help discriminate between different models of both initial state nucleons and final state interactions used in the neutrino oscillation experiments.