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This paper presents the development of an all-in-one probe to simultaneously measure all components of the generalized Ohm's law in reversed-field pinch plasmas and tokamaks. The polyhedral configuration of the Mach probe is achieved through the specific arrangement, angle, and depth of the collimator channel apertures drilled into the surface of a hollow boron nitride cylinder encasing it. This probe includes a central Mach probe to assess the ion velocity field in three dimensions. Initial tests at the RELAX and Madison Symmetric Torus machines have confirmed the probe's effectiveness, revealing an octahedron form similar to a tetrahedron. The probe seems to function correctly and is expected to facilitate the empirical validation of two-fluid equilibria at the periphery of toroidal plasmas.
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We report on a measurement of astrophysical tau neutrinos with 9.7 yr of IceCube data. Using convolutional neural networks trained on images derived from simulated events, seven candidate ν_{τ} events were found with visible energies ranging from roughly 20 TeV to 1 PeV and a median expected parent ν_{τ} energy of about 200 TeV. Considering backgrounds from astrophysical and atmospheric neutrinos, and muons from π^{±}/K^{±} decays in atmospheric air showers, we obtain a total estimated background of about 0.5 events, dominated by non-ν_{τ} astrophysical neutrinos. Thus, we rule out the absence of astrophysical ν_{τ} at the 5σ level. The measured astrophysical ν_{τ} flux is consistent with expectations based on previously published IceCube astrophysical neutrino flux measurements and neutrino oscillations.
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The T2K experiment presents new measurements of neutrino oscillation parameters using 19.7(16.3)×1020 protons on target (POT) in (anti-)neutrino mode at the far detector (FD). Compared to the previous analysis, an additional 4.7×1020 POT neutrino data was collected at the FD. Significant improvements were made to the analysis methodology, with the near-detector analysis introducing new selections and using more than double the data. Additionally, this is the first T2K oscillation analysis to use NA61/SHINE data on a replica of the T2K target to tune the neutrino flux model, and the neutrino interaction model was improved to include new nuclear effects and calculations. Frequentist and Bayesian analyses are presented, including results on sin2θ13 and the impact of priors on the δCP measurement. Both analyses prefer the normal mass ordering and upper octant of sin2θ23 with a nearly maximally CP-violating phase. Assuming the normal ordering and using the constraint on sin2θ13 from reactors, sin2θ23=0.561-0.032+0.021 using Feldman-Cousins corrected intervals, and Δm322=2.494-0.058+0.041×10-3eV2 using constant Δχ2 intervals. The CP-violating phase is constrained to δCP=-1.97-0.70+0.97 using Feldman-Cousins corrected intervals, and δCP=0,π is excluded at more than 90% confidence level. A Jarlskog invariant of zero is excluded at more than 2σ credible level using a flat prior in δCP, and just below 2σ using a flat prior in sinδCP. When the external constraint on sin2θ13 is removed, sin2θ13=28.0-6.5+2.8×10-3, in agreement with measurements from reactor experiments. These results are consistent with previous T2K analyses.
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The origin of high-energy cosmic rays, atomic nuclei that continuously impact Earth's atmosphere, is unknown. Because of deflection by interstellar magnetic fields, cosmic rays produced within the Milky Way arrive at Earth from random directions. However, cosmic rays interact with matter near their sources and during propagation, which produces high-energy neutrinos. We searched for neutrino emission using machine learning techniques applied to 10 years of data from the IceCube Neutrino Observatory. By comparing diffuse emission models to a background-only hypothesis, we identified neutrino emission from the Galactic plane at the 4.5σ level of significance. The signal is consistent with diffuse emission of neutrinos from the Milky Way but could also arise from a population of unresolved point sources.
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A supermassive black hole, obscured by cosmic dust, powers the nearby active galaxy NGC 1068. Neutrinos, which rarely interact with matter, could provide information on the galaxy's active core. We searched for neutrino emission from astrophysical objects using data recorded with the IceCube neutrino detector between 2011 and 2020. The positions of 110 known gamma-ray sources were individually searched for neutrino detections above atmospheric and cosmic backgrounds. We found that NGC 1068 has an excess of [Formula: see text] neutrinos at tera-electron volt energies, with a global significance of 4.2σ, which we interpret as associated with the active galaxy. The flux of high-energy neutrinos that we measured from NGC 1068 is more than an order of magnitude higher than the upper limit on emissions of tera-electron volt gamma rays from this source.
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We present a search for an unstable sterile neutrino by looking for a resonant signal in eight years of atmospheric ν_{µ} data collected from 2011 to 2019 at the IceCube Neutrino Observatory. Both the (stable) three-neutrino and the 3+1 sterile neutrino models are disfavored relative to the unstable sterile neutrino model, though with p values of 2.8% and 0.81%, respectively, we do not observe evidence for 3+1 neutrinos with neutrino decay. The best-fit parameters for the sterile neutrino with decay model from this study are Δm_{41}^{2}=6.7_{-2.5}^{+3.9} eV^{2}, sin^{2}2θ_{24}=0.33_{-0.17}^{+0.20}, and g^{2}=2.5π±1.5π, where g is the decay-mediating coupling. The preferred regions of the 3+1+decay model from short-baseline oscillation searches are excluded at 90% C.L.
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We report a search for nonstandard neutrino interactions (NSI) using eight years of TeV-scale atmospheric muon neutrino data from the IceCube Neutrino Observatory. By reconstructing incident energies and zenith angles for atmospheric neutrino events, this analysis presents unified confidence intervals for the NSI parameter ε_{µτ}. The best-fit value is consistent with no NSI at a p value of 25.2%. With a 90% confidence interval of -0.0041≤ε_{µτ}≤0.0031 along the real axis and similar strength in the complex plane, this result is the strongest constraint on any NSI parameter from any oscillation channel to date.
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We present an all-sky 90% confidence level upper limit on the cosmic flux of relativistic magnetic monopoles using 2886 days of IceCube data. The analysis was optimized for monopole speeds between 0.750c and 0.995c, without any explicit restriction on the monopole mass. We constrain the flux of relativistic cosmic magnetic monopoles to a level below 2.0×10^{-19} cm^{-2} s^{-1} sr^{-1} over the majority of the targeted speed range. This result constitutes the most strict upper limit to date for magnetic monopoles with ßâ³0.8 and up to ßâ¼0.995 and fills the gap between existing limits on the cosmic flux of nonrelativistic and ultrarelativistic magnetic monopoles.
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Electron antineutrino appearance is measured by the T2K experiment in an accelerator-produced antineutrino beam, using additional neutrino beam operation to constrain parameters of the Pontecorvo-Maki-Nakagawa-Sakata (PMNS) mixing matrix. T2K observes 15 candidate electron antineutrino events with a background expectation of 9.3 events. Including information from the kinematic distribution of observed events, the hypothesis of no electron antineutrino appearance is disfavored with a significance of 2.40σ and no discrepancy between data and PMNS predictions is found. A complementary analysis that introduces an additional free parameter which allows non-PMNS values of electron neutrino and antineutrino appearance also finds no discrepancy between data and PMNS predictions.
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The T2K experiment measures muon neutrino disappearance and electron neutrino appearance in accelerator-produced neutrino and antineutrino beams. With an exposure of 14.7(7.6)×10^{20} protons on target in the neutrino (antineutrino) mode, 89 ν_{e} candidates and seven anti-ν_{e} candidates are observed, while 67.5 and 9.0 are expected for δ_{CP}=0 and normal mass ordering. The obtained 2σ confidence interval for the CP-violating phase, δ_{CP}, does not include the CP-conserving cases (δ_{CP}=0, π). The best-fit values of other parameters are sin^{2}θ_{23}=0.526_{-0.036}^{+0.032} and Δm_{32}^{2}=2.463_{-0.070}^{+0.071}×10^{-3} eV^{2}/c^{4}.
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The aim of the present study was to examine the correlation between the results of lymphocyte proliferative test (LPT) specific to food allergens and allergic skin diseases in dogs. Investigations were performed in 138 dogs with allergic skin diseases diagnosed in a private animal hospital. Of the 138 animals, 97 cases had positive reactions in LPT specific to food allergens. Of these 97 dogs, 67 animals were diagnosed with canine atopic dermatitis (CAD), but 30 dogs did not have IgE antibodies to environmental allergens. As 14 dogs out of 30 animals showed a positive result, 12 dogs underwent elimination diet trial based on the test results and all of them showed improvement in the pruritus score. Therefore, we conclude that LPT is an effective diagnostic test for allergic skin disease. Results of the lymphocyte test are useful in the identification of food allergens for the elimination diet trial.
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Alérgenos/farmacologia , Dermatite/veterinária , Doenças do Cão/metabolismo , Hipersensibilidade Alimentar/veterinária , Linfócitos/efeitos dos fármacos , Animais , Proliferação de Células , Dermatite/imunologia , Cães , Feminino , Imunoglobulina E/metabolismo , Linfócitos/citologia , Masculino , Estudos RetrospectivosRESUMO
BACKGROUND: A variety of skin diseases, such as atopic dermatitis, senile xerosis or psoriasis tends to worsen during the dry winter season. These skin diseases are also characterized by itch sensation. OBJECTIVES: To evaluate the generation of histamine in the dermis of hairless mice kept under various conditions of environmental humidity. MATERIALS AND METHODS: We carried out the quantification of mast cell population and evaluated the histamine content in the epidermis, dermis and serum of the mice kept under various conditions of environmental humidity. RESULTS: Histamine content in the dermis of the mice kept in a low environmental humidity (relative humidity < 10%) for 3 and 5 days was significantly higher than that of the mice kept in a high environmental humidity (relative humidity > 80%) for the same period of time. No significant difference was observed on the histamine content in the epidermis between the two humidity groups. The number of mast cells in the dermis of the mice kept in the low environmental humidity was significantly higher than that of the mice kept in the high environmental humidity. Topical application of petrolatum reduced the level of histamine in the dermis of the mice under the low environmental humidity. CONCLUSIONS: These results suggest that a low environmental humidity increases mast cell number and dermal histamine content.
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Histamina/análise , Umidade , Mastócitos/citologia , Pele/citologia , Animais , Contagem de Células , Meio Ambiente , Epiderme/química , Resposta Galvânica da Pele , Glicerol/farmacologia , Camundongos , Camundongos Pelados , Vaselina/farmacologia , Pele/química , Pele/efeitos dos fármacosRESUMO
In open heart surgery, the efficacy of temporary pacing to control perioperative cardiac dysrhythmias is well known. However, a temporary pacing wire is not routinely attached during minimally invasive direct coronary artery bypass because of its less invasiveness. In case of off-pump coronary artery bypass (OPCAB) with mediansternotomy, is it also unnecessary? We report 2 patients undergoing OPCAB without postoperative temporary pacing wire who suffered from possibly fatal rhythm disturbances after operation, and needed long hospitalization. After these experiences, we routinely attach a temporary pacing wire during OPCAB with mediansternotomy. We believe, in case of OPCAB, a temporary pacing wire is as effective as in conventional CABG.
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Estimulação Cardíaca Artificial , Ponte de Artéria Coronária/métodos , Doença das Coronárias/cirurgia , Idoso , Estimulação Cardíaca Artificial/métodos , Feminino , Humanos , Masculino , Procedimentos Cirúrgicos Minimamente InvasivosRESUMO
OBJECTIVE AND DESIGN: The characteristics of the antihistamine effect of the new antiallergic compound TAK-427 were investigated. MATERIALS AND METHODS: In vitro binding assay of [(3)H] pyrilamine was performed using recombinant human histamine H(1) receptors (rhH(1)R). In vivo studies were performed in male ICR mice or Hartley guinea pigs. Drugs were administered orally 1 h before examinations. Determinations were made of histamine-induced skin reaction, ex vivo measured radioligand binding to brain and lung H(1) receptors, pentobarbital-induced sleeping time, passive cutaneous anaphylaxis (PCA) reaction, and antigen-induced itch-scratch responses (ISRs). RESULTS: TAK-427 inhibited ligand binding to rhH(1)R with an IC(50) value of 17.3 nmol/l. TAK-427 inhibited histamine-induced skin reactions in guinea pigs and mice with an ID(50) value of 0.884 and 0.450 mg/kg, p.o., respectively; significant inhibition associated with 10 mg/kg of TAK-427 was still observed 24 h after dosing in guinea pigs. TAK-427 showed as high selectivity for peripheral H(1) receptors as terfenadine and epinastine did, which was evaluated by ex vivo measured radioligand binding. Even at 300 mg/kg, TAK-427 did not affect pentobarbital-induced sleeping time in mice. TAK-427 significantly inhibited PCA in mice and guinea pigs, and also inhibited antigen-induced ISRs in guinea pigs. CONCLUSIONS: These results suggest that TAK-427 may have a long-lasting antihistamine activity with minimum sedative side effect and suppress acute phase allergic reactions.
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Antagonistas dos Receptores Histamínicos , Imidazóis/farmacologia , Piridazinas/farmacologia , Algoritmos , Animais , Comportamento Animal/efeitos dos fármacos , Ligação Competitiva/efeitos dos fármacos , Encéfalo/metabolismo , Cobaias , Antagonistas dos Receptores Histamínicos H1/farmacologia , Humanos , Hipnóticos e Sedativos/farmacologia , Imidazóis/metabolismo , Imidazóis/farmacocinética , Masculino , Camundongos , Camundongos Endogâmicos ICR , Ovalbumina/imunologia , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Pentobarbital/farmacologia , Prurido/prevenção & controle , Piridazinas/metabolismo , Piridazinas/farmacocinética , Ensaio Radioligante , Receptores Histamínicos H1/metabolismo , Proteínas Recombinantes/metabolismo , Sono/efeitos dos fármacos , Fatores de TempoRESUMO
A 84-year-old female with a ruptured, detached, and entrapped cutting balloon was successfully undergone the surgical removal under beating heart. But the left anterior descending coronary artery (LAD) was severely dissected by ruptured cutting balloon. So we had to anastomose left internal thoracic artery (LITA) to the distal part of LAD. Postoperative coronary angiography showed the narrowing of LAD and the effective revascularization was not obtained. We must recognize that the intima of the coronary artery is impaired by the ruptured cutting balloon more severely than we expected.
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Angioplastia Coronária com Balão/instrumentação , Procedimentos Cirúrgicos Cardíacos , Doença das Coronárias/cirurgia , Vasos Coronários/lesões , Remoção de Dispositivo , Idoso , Idoso de 80 Anos ou mais , Doença das Coronárias/terapia , Feminino , Humanos , Ruptura , StentsRESUMO
Cisplatin (CDDP) is a potent DNA-damaging anticancer agent, and its cytotoxic action is exerted by the induction of apoptosis. However, activation of the transcription factor NF-kappaB results in protection against apoptosis. We examined the molecular mechanisms involved in the induction of apoptosis by CDDP as regards both suppression of NF-kappaB and activation of caspases. Human oral squamous carcinoma cells (B88) were employed in this study. We found that CDDP treatment affected neither NF-kappaB activity nor the expression levels of antiapoptotic proteins, including TRAF-1, TRAF-2, and cFLIP, in B88 cells. However, two apoptosome molecules, cytochrome c and Apaf-1, were significantly augmented in the cytoplasm by CDDP treatment. Further, the activation of caspase-9 and caspase-3, downstream molecules leading to mitochondria-mediated apoptosis, were detected after treatment with CDDP. Finally, apoptosis was also clearly observed, as evidenced by cleavage of PARP through the activation of caspase-3. These findings suggest that CDDP exerts its apoptotic action by the mitochondria-mediated activation of caspases but not by the activation of caspases due to the inhibition of NF-kappaB activity that follows the suppression of antiapoptotic proteins.
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Antineoplásicos/farmacologia , Apoptose , Carcinoma de Células Escamosas/patologia , Cisplatino/farmacologia , Mitocôndrias/efeitos dos fármacos , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Caspases/metabolismo , Divisão Celular/efeitos dos fármacos , Grupo dos Citocromos c/metabolismo , Relação Dose-Resposta a Droga , Humanos , Mitocôndrias/fisiologia , Neoplasias Bucais/tratamento farmacológico , NF-kappa B/fisiologia , Receptores do Fator de Necrose Tumoral/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais CultivadasRESUMO
OBJECTIVE AND DESIGN: We investigated the effects of the thromboxane (TX) A2 antagonist seratrodast, the peptide leukotriene (p-LT) antagonist pranlukast, the antihistaminic drug terfenadine and the glucocorticoid dexamethasone on antigen-induced sneezing, biphasic nasal blockage and nasal hyperresponsiveness to histamine using a guinea pig model of allergic rhinitis. SUBJECTS: Male Hartley guinea pigs were used. TREATMENT: Intranasally sensitized guinea pigs were challenged once every week for 13 weeks by inhalation of Japanese cedar pollen as the antigen. Dexamethasone and other agents were administered orally 3 and 1 h, respectively, before the 4th, 6th and 13th challenge. METHODS: Sneezing frequency and the change in specific airway resistance (sRaw) were measured at these challenges. Two days after the 13th challenge, nasal responsiveness to histamine was evaluated by measuring sRaw after intranasal instillation of increasing doses of histamine. Moreover, the levels of TXB2, p-LTs and histamine were estimated in nasal cavity lavage fluid (NCLF) collected at the 13th challenge. RESULTS: Only terfenadine (10 mg/kg) significantly inhibited sneezing at any challenge time. Seratrodast (3 and 10 mg/ kg), pranlukast (30 mg/kg) and dexamethasone (10 mg/kg), but not terfenadine, suppressed both the early and late phase elevation of sRaw (biphasic nasal blockage), although the degree of inhibition on the early phase response varied with the challenge time. In contrast, the development of nasal hyperresponsiveness to histamine was inhibited by only dexamethasone. Furthermore, biphasic increases in TXB2, p-LTs and histamine in NCLF were observed after the challenge in sensitized animals. CONCLUSIONS: These results suggest that TXA2 and p-LTs, but not histamine, play important roles in both the early and the late phase nasal blockage in this model of allergic rhinitis.
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Leucotrienos/fisiologia , Obstrução Nasal/fisiopatologia , Rinite Alérgica Sazonal/fisiopatologia , Tromboxano A2/fisiologia , Animais , Antialérgicos/farmacologia , Antiasmáticos/farmacologia , Anti-Inflamatórios/farmacologia , Benzoquinonas/farmacologia , Cromonas/farmacologia , Dexametasona/farmacologia , Cobaias , Ácidos Heptanoicos/farmacologia , Histamina/farmacologia , Liberação de Histamina/efeitos dos fármacos , Masculino , Cavidade Nasal/patologia , Obstrução Nasal/tratamento farmacológico , Obstrução Nasal/etiologia , Rinite Alérgica Sazonal/tratamento farmacológico , Espirro , Terfenadina/farmacologia , Irrigação TerapêuticaRESUMO
OBJECTIVE AND DESIGN: We characterized the leukocyte kinetics after antigen challenge, and investigated the effects of the thromboxane (TX) A2 antagonist seratrodast, the peptide leukotriene (p-LT) antagonist pranlukast, the antihistaminic drug terfenadine and the glucocorticoid dexamethasone on this leukocyte response in a guinea pig model of allergic rhinitis. SUBJECTS: Male Hartley guinea pigs were used. TREATMENT: Intranasally sensitized guinea pigs were challenged once every week for 15 weeks by inhalation of Japanese cedar pollen as the antigen. Dexamethasone and other agents were administered orally 3 and 1 h, respectively, before the 15th challenge. METHODS: The time-related changes in the numbers of differential leukocytes in nasal cavity lavage fluid (NCLF) and in peripheral blood after pollen inhalation challenge were investigated. The effects of the drugs on the antigen-induced changes in the leukocyte counts were evaluated. In addition, histopathological examination of the nasal mucosa was also performed 5 h after the challenge. RESULTS: There was a marked increase in the number of leukocytes in NCLF, especially of eosinophils, which peaked at 5 h, after antigen challenge in this model. This response was also accompanied by the peripheral blood eosinophilia and neutrophilia. Seratrodast (30 mg/kg), pranlukast (30 mg/kg) and dexamethasone (10 mg/kg) inhibited the eosinophilia in all of the blood, the nasal mucosa and NCLF seen 5 h after the antigen challenge. Terfenadine (10 mg/kg) had no apparent effect on the blood and the mucosal eosinophilia, although it tended to suppress the eosinophil accumulation in NCLF. CONCLUSIONS: These results suggest that the present model is useful for analyzing the mechanisms of antigen-induced eosinophilic inflammation in allergic rhinitis and that both TXA2 and p-LTs, but not histamine, contribute to the antigen-induced eosinophilia in this model of allergic rhinitis.
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Antialérgicos/farmacologia , Antígenos/imunologia , Leucócitos/patologia , Rinite Alérgica Sazonal/patologia , Administração Intranasal , Animais , Antiasmáticos/farmacologia , Anti-Inflamatórios/farmacologia , Antígenos/administração & dosagem , Benzoquinonas/farmacologia , Cromonas/farmacologia , Dexametasona/farmacologia , Cobaias , Ácidos Heptanoicos/farmacologia , Cinética , Contagem de Leucócitos , Antagonistas de Leucotrienos , Masculino , Cavidade Nasal/patologia , Terfenadina/farmacologia , Irrigação Terapêutica , Tromboxano A2/antagonistas & inibidoresRESUMO
A 1-year-old infant with complete atrioventricular block was successfully treated with the pacemaker implantation using steroid-eluting epicardial pacing lead by the subxyphoid approach. Pacing threshold after implantation were measured frequently to use the function named "Capture management" of the generator (Medtronic: Kappa, Model 701). The postoperative pacing threshold were kept lower and stabilized after 5 weeks.
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Estimulação Cardíaca Artificial/métodos , Marca-Passo Artificial , Eletrocardiografia , Humanos , Lactente , Masculino , Pericárdio , EsteroidesRESUMO
Canine cationic trypsin was purified by salting-out, gel filtration and affinity chromatography. Purity was confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The molecular weight was ca. 28kDa by SDS-PAGE. Thirty hybridomas were obtained which produced mAb to canine cationic trypsin by the cell fusion technique. Twenty-two of these recognized cationic trypsin only, while eight hybridomas recognized both cationic and anionic trypsin. Several of the anti-canine cationic trypsin mAb were purified by salting-out and DEAE ion-change chromatography using ascites fluid of immunized BALB/c mice. The mAb proved to have very high specificity to canine cationic trypsin as shown by immunoblotting and it may be possible to use them to develop clinical assays.