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1.
Phys Rev Lett ; 129(20): 201801, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36461983

RESUMO

This Letter presents the results from the MiniBooNE experiment within a full "3+1" scenario where one sterile neutrino is introduced to the three-active-neutrino picture. In addition to electron-neutrino appearance at short baselines, this scenario also allows for disappearance of the muon-neutrino and electron-neutrino fluxes in the Booster Neutrino Beam, which is shared by the MicroBooNE experiment. We present the 3+1 fit to the MiniBooNE electron-(anti)neutrino and muon-(anti)neutrino data alone and in combination with MicroBooNE electron-neutrino data. The best-fit parameters of the combined fit with the exclusive charged-current quasielastic analysis (inclusive analysis) are Δm^{2}=0.209 eV^{2}(0.033 eV^{2}), |U_{e4}|^{2}=0.016(0.500), |U_{µ4}|^{2}=0.500(0.500), and sin^{2}(2θ_{µe})=0.0316(1.0). Comparing the no-oscillation scenario to the 3+1 model, the data prefer the 3+1 model with a Δχ^{2}/d.o.f.=24.7/3(17.3/3), a 4.3σ(3.4σ) preference assuming the asymptotic approximation given by Wilks's theorem.

2.
Phys Rev Lett ; 121(22): 221801, 2018 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-30547637

RESUMO

The MiniBooNE experiment at Fermilab reports results from an analysis of ν_{e} appearance data from 12.84×10^{20} protons on target in neutrino mode, an increase of approximately a factor of 2 over previously reported results. A ν_{e} charged-current quasielastic event excess of 381.2±85.2 events (4.5σ) is observed in the energy range 200

3.
Phys Rev Lett ; 120(14): 141802, 2018 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-29694148

RESUMO

We report the first measurement of monoenergetic muon neutrino charged current interactions. MiniBooNE has isolated 236 MeV muon neutrino events originating from charged kaon decay at rest (K^{+}→µ^{+}ν_{µ}) at the NuMI beamline absorber. These signal ν_{µ}-carbon events are distinguished from primarily pion decay in flight ν_{µ} and ν[over ¯]_{µ} backgrounds produced at the target station and decay pipe using their arrival time and reconstructed muon energy. The significance of the signal observation is at the 3.9σ level. The muon kinetic energy, neutrino-nucleus energy transfer (ω=E_{ν}-E_{µ}), and total cross section for these events are extracted. This result is the first known-energy, weak-interaction-only probe of the nucleus to yield a measurement of ω using neutrinos, a quantity thus far only accessible through electron scattering.

4.
Oncogenesis ; 2: e64, 2013 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-23958854

RESUMO

Dishevelled (Dvl) is a key regulator of Wnt signaling both in the canonical and non-canonical pathways. Here we report the identification of a regulatory domain of ubiquitination (RDU) in the C-terminus of Dvl. Mutations in the RDU resulted in accumulation of polyubiquitinated forms of Dvl, which were mainly K63 linked. Small interfering RNA-based screening identified Usp14 as a mediator of Dvl deubiquitination. Genetic and chemical suppression of Usp14 activity caused an increase in Dvl polyubiquitination and significantly impaired downstream Wnt signaling. These data suggest that Usp14 functions as a positive regulator of the Wnt signaling pathway. Consistently, tissue microarray analysis of colon cancer revealed a strong correlation between the levels of Usp14 and ß-catenin, which suggests an oncogenic role for Usp14 via enhancement of Wnt/ß-catenin signaling.

5.
Phys Rev Lett ; 110(16): 161801, 2013 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-23679593

RESUMO

The MiniBooNE experiment at Fermilab reports results from an analysis of ν[over ¯](e) appearance data from 11.27×10(20) protons on target in the antineutrino mode, an increase of approximately a factor of 2 over the previously reported results. An event excess of 78.4±28.5 events (2.8σ) is observed in the energy range 200

6.
Ann Oncol ; 24(4): 889-94, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23136230

RESUMO

BACKGROUND: Some reports suggest that patients with synchronous multiple foci of nonsmall-cell lung cancers (NSCLC) distributed in multiple lobes have a poor prognosis, even when there is no extrathoracic metastasis. The vast majority of such patients do not receive surgical treatment. For those who undergo surgery, prognostic factors are unclear. PATIENTS AND METHODS: We systematically reviewed the literature on surgery for synchronous NSCLC in multiple lobes published between 1990 and 2011. Individual patient data were used to obtain adjusted hazard ratios (HRs) in each dataset and pooled analyses were carried out. RESULTS: Six studies contributed 467 eligible patients for analysis. The median overall survival was 52.0 months [95% confidence interval 45.6-63.7]. Male gender and advanced age were associated with a decreased survival: HRs 1.64 (1.22, 2.22) and 1.40 (1.20, 1.80) per 20-year increment, respectively. Patients with cancers distributed in one lung had a higher mortality risk than those with bilateral disease: HRs 1.45 (1.06, 2.00). N1 or N2 had a decreased survival compared with N0: HRs 1.68 (1.12, 2.51) and 1.94 (1.33, 2.82), respectively. There was a trend toward increased mortality among patients with different histology: HRs 1.29 (0.96, 1.75). CONCLUSION: Advanced age, male gender, nodal involvement, and unilateral tumor location were poor prognostic factors.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Linfonodos/patologia , Neoplasias Primárias Múltiplas/cirurgia , Prognóstico , Fatores Etários , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/patologia , Fatores Sexuais , Resultado do Tratamento
7.
Phys Rev Lett ; 103(6): 061802, 2009 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-19792551

RESUMO

The MiniBooNE Collaboration reports a search for nu_{micro} and nu[over]_{micro} disappearance in the Deltam;{2} region of 0.5-40 eV;{2}. These measurements are important for constraining models with extra types of neutrinos, extra dimensions, and CPT violation. Fits to the shape of the nu_{micro} and nu[over]_{micro} energy spectra reveal no evidence for disappearance at the 90% confidence level (C.L.) in either mode. The test of nu[over]_{micro} disappearance probes a region below Deltam;{2} = 40 eV;{2} never explored before.

8.
Phys Rev Lett ; 103(8): 081801, 2009 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-19792715

RESUMO

Using high statistics samples of charged-current numu interactions, the MiniBooNE [corrected] Collaboration reports a measurement of the single-charged-pion production to quasielastic cross section ratio on mineral oil (CH2), both with and without corrections for hadron reinteractions in the target nucleus. The result is provided as a function of neutrino energy in the range 0.4 GeV

9.
Phys Rev Lett ; 102(21): 211801, 2009 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-19519094

RESUMO

We report the first observation of off-axis neutrino interactions in the MiniBooNE detector from the NuMI beam line at Fermilab. The MiniBooNE detector is located 745 m from the NuMI production target, at 110 mrad angle (6.3 degrees) with respect to the NuMI beam axis. Samples of charged-current quasielastic numicro and nue interactions are analyzed and found to be in agreement with expectation. This provides a direct verification of the expected pion and kaon contributions to the neutrino flux and validates the modeling of the NuMI off-axis beam.

10.
Phys Rev Lett ; 102(10): 101802, 2009 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-19392103

RESUMO

The MiniBooNE Collaboration observes unexplained electronlike events in the reconstructed neutrino energy range from 200 to 475 MeV. With 6.46x10;{20} protons on target, 544 electronlike events are observed in this energy range, compared to an expectation of 415.2+/-43.4 events, corresponding to an excess of 128.8+/-20.4+/-38.3 events. The shape of the excess in several kinematic variables is consistent with being due to either nu_{e} and nu[over ]_{e} charged-current scattering or nu_{mu} neutral-current scattering with a photon in the final state. No significant excess of events is observed in the reconstructed neutrino energy range from 475 to 1250 MeV, where 408 events are observed compared to an expectation of 385.9+/-35.7 events.

11.
Phys Rev Lett ; 100(3): 032301, 2008 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-18232974

RESUMO

The observation of neutrino oscillations is clear evidence for physics beyond the standard model. To make precise measurements of this phenomenon, neutrino oscillation experiments, including MiniBooNE, require an accurate description of neutrino charged current quasielastic (CCQE) cross sections to predict signal samples. Using a high-statistics sample of nu_(mu) CCQE events, MiniBooNE finds that a simple Fermi gas model, with appropriate adjustments, accurately characterizes the CCQE events observed in a carbon-based detector. The extracted parameters include an effective axial mass, M_(A)(eff)=1.23+/-0.20 GeV, that describes the four-momentum dependence of the axial-vector form factor of the nucleon, and a Pauli-suppression parameter, kappa=1.019+/-0.011. Such a modified Fermi gas model may also be used by future accelerator-based experiments measuring neutrino oscillations on nuclear targets.

12.
Phys Rev Lett ; 98(23): 231801, 2007 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-17677898

RESUMO

The MiniBooNE Collaboration reports first results of a search for nu e appearance in a nu mu beam. With two largely independent analyses, we observe no significant excess of events above the background for reconstructed neutrino energies above 475 MeV. The data are consistent with no oscillations within a two-neutrino appearance-only oscillation model.

13.
Arch Environ Contam Toxicol ; 46(4): 542-50, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15253053

RESUMO

We reviewed the U.S. Geological Survey National Wildlife Health Center (NWHC) mortality database from 1980 to 2000 to identify cases of poisoning caused by organophosphorus and carbamate pesticides. From the 35,022 cases from which one or more avian carcasses were submitted to the NWHC for necropsy, we identified 335 mortality events attributed to anticholinesterase poisoning, 119 of which have been included in earlier reports. Poisoning events were classified as confirmed (n = 205) when supported by findings of > or =50% inhibition of cholinesterase (ChE) activity in brain tissue and the detection of a specific pesticide in the gastrointestinal contents of one or more carcasses. Suspected poisonings (n = 130) were defined as cases where brain ChE activity was > or =50% inhibited or a specific pesticide was identified in gastrointestinal contents. The 335 avian mortality events occurred in 42 states. Washington, Virginia, and Ohio had the highest frequency of events, with 24 (7.2%), 21 (6.3%), and 20 (6.0%) events, respectively. A total of 8877 carcasses of 103 avian species in 12 orders was recovered. Because carcass counts underestimate total mortality, this represents the minimum actual mortality. Of 24 different pesticides identified, the most frequent were famphur (n = 59: 18%), carbofuran (n = 52; 15%), diazinon (n = 40; 12%), and fenthion (n = 17; 5.1%). Falconiformes were reported killed most frequently (49% of all die-offs) but Anseriformes were found dead in the greatest numbers (64% of 8877 found dead). The majority of birds reported killed by famphur were Passeriformes and Falconiformes, with the latter found dead in 90% of famphur-related poisoning events. Carbofuran and famphur were involved in mortality of the greatest variety of species (45 and 33, respectively). Most of the mortality events caused by diazinon involved waterfowl.


Assuntos
Doenças das Aves , Aves , Inibidores da Colinesterase/intoxicação , Praguicidas/intoxicação , Acetilcolinesterase/metabolismo , Animais , Doenças das Aves/induzido quimicamente , Doenças das Aves/enzimologia , Doenças das Aves/mortalidade , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Encéfalo/patologia , Intoxicação/enzimologia , Intoxicação/mortalidade , Intoxicação/veterinária , Estudos Retrospectivos , Estados Unidos/epidemiologia
15.
Arch Environ Contam Toxicol ; 41(3): 364-8, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11503074

RESUMO

The Coeur d'Alene River basin in Idaho has been contaminated by mine tailings that have impaired the health of wildlife since the early 1900s. In other parts of the world, virtually all lead poisoning of waterfowl is caused by the ingestion of manmade lead artifacts, primarily spent lead shotshell pellets or, occasionally, fishing sinkers. However, in the Coeur d'Alene River basin in Idaho, nonartifactual lead poisoning was the ultimate cause of death of most of 219 (77%) of 285 waterfowl carcasses that had been found sick or dead from 1992 through 1997. The majority of these 219 waterfowl (172 tundra swans [Cygnus columbianus], 33 Canada geese [Branta canadensis], and 14 other species) were poisoned by ingesting river sediment that was contaminated with lead. The next most common cause of death (20 instances, 7%) was lead poisoning accompanied by ingested shotshell pellets. The remaining 46 waterfowl succumbed to trauma, infectious diseases (aspergillosis, avian cholera, tuberculosis), or miscellaneous problems, or the cause of death was not determined.


Assuntos
Aves , Intoxicação por Chumbo/veterinária , Mineração , Animais , Animais Selvagens , Exposição Ambiental , Feminino , Sedimentos Geológicos/química , Masculino , Dinâmica Populacional , Poluentes Químicos da Água
17.
Mol Cell ; 7(6): 1143-52, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11430818

RESUMO

Substrates enter the proteasome core particle (CP) through a channel that opens upon association with the regulatory particle (RP). Using yeast mutants, we show that channel opening is mediated by the ATPase domain of Rpt2, one of six ATPases in the RP. To test whether degradation products exit through this channel, we analyzed their size distribution. Their median length from an open-channel CP mutant was 40% greater than that from the wild-type. Thus, channel opening may enhance the yield of peptides long enough to function in antigen presentation. These experiments demonstrate that gating of the RP channel controls both substrate entry and product release, and is specifically regulated by an ATPase in the base of the RP.


Assuntos
Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Cisteína Endopeptidases/metabolismo , Ativação do Canal Iônico/fisiologia , Complexos Multienzimáticos/metabolismo , Peptídeo Hidrolases/metabolismo , Adenosina Trifosfatases/química , Sequência de Aminoácidos , Apresentação de Antígeno/fisiologia , Cisteína Endopeptidases/química , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Ativação do Canal Iônico/efeitos dos fármacos , Dados de Sequência Molecular , Complexos Multienzimáticos/química , Peptídeo Hidrolases/química , Canais de Potássio/farmacologia , Complexo de Endopeptidases do Proteassoma , Estrutura Quaternária de Proteína , Especificidade por Substrato , Leveduras
18.
Biochimie ; 83(3-4): 325-32, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11295493

RESUMO

The core particle (CP) of the yeast proteasome is composed of four heptameric rings of subunits arranged in a hollow, barrel-like structure. We have found that the CP is autoinhibited by the N-terminal tails of the outer (alpha) ring subunits. Crystallographic analysis showed that deletion of the tail of the alpha3 subunit opens a channel into the proteolytically active interior chamber of the CP, thus derepressing peptide hydrolysis. In the latent state of the particle, the tails prevent substrate entry by imposing topological closure on the CP. Inhibition by the alpha subunit tails is relieved upon binding of the regulatory particle to the CP to form the proteasome holoenzyme. Opening of the CP channel by assembly of the holoenzyme is regulated by the ATPase domain of Rpt2, one of 17 subunits in the RP. Thus, open-channel mutations in CP subunits suppress the closed-channel phenotype of an rpt2 mutant. These results identify a specific mechanism for allosteric regulation of the CP by the RP.


Assuntos
Adenosina Trifosfatases/metabolismo , Motivos de Aminoácidos/genética , Complexos Multienzimáticos/metabolismo , Peptídeo Hidrolases/genética , Peptídeo Hidrolases/metabolismo , Complexo de Endopeptidases do Proteassoma , Regulação Alostérica/fisiologia , Motivos de Aminoácidos/fisiologia , Cristalografia por Raios X , Ativação Enzimática , Holoenzimas/química , Holoenzimas/genética , Holoenzimas/metabolismo , Humanos , Modelos Moleculares , Complexos Multienzimáticos/química , Complexos Multienzimáticos/genética , Mutagênese Sítio-Dirigida/genética , Peptídeo Hidrolases/química , Subunidades Proteicas , Transporte Proteico/fisiologia , Alinhamento de Sequência , Relação Estrutura-Atividade , Leveduras/enzimologia
19.
Nat Struct Biol ; 7(11): 1062-7, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11062564

RESUMO

The core particle (CP) of the yeast proteasome is composed of four heptameric rings of subunits arranged in a hollow, barrel-like structure. We report that the CP is autoinhibited by the N-terminal tails of the outer (alpha) ring subunits. Crystallographic analysis showed that deletion of the tail of the alpha 3-subunit opens a channel into the proteolytically active interior chamber of the CP, thus derepressing peptide hydrolysis. In the latent state of the particle, the tails prevent substrate entry by imposing topological closure on the CP. Inhibition by the alpha-subunit tails is relieved upon binding of the regulatory particle to the CP to form the proteasome holoenzyme.


Assuntos
Cisteína Endopeptidases/química , Cisteína Endopeptidases/metabolismo , Complexos Multienzimáticos/química , Complexos Multienzimáticos/metabolismo , Saccharomyces cerevisiae/enzimologia , Motivos de Aminoácidos/genética , Sequência de Aminoácidos , Sequência Conservada , Cristalografia por Raios X , Cisteína Endopeptidases/genética , Holoenzimas/química , Holoenzimas/genética , Holoenzimas/metabolismo , Humanos , Hidrólise , Modelos Moleculares , Dados de Sequência Molecular , Complexos Multienzimáticos/antagonistas & inibidores , Complexos Multienzimáticos/genética , Mutação/genética , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/metabolismo , Complexo de Endopeptidases do Proteassoma , Estrutura Quaternária de Proteína , Subunidades Proteicas , Saccharomyces cerevisiae/genética , Alinhamento de Sequência , Relação Estrutura-Atividade
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