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We report a search for time variations of the solar ^{8}B neutrino flux using 5804 live days of Super-Kamiokande data collected between May 31, 1996, and May 30, 2018. Super-Kamiokande measured the precise time of each solar neutrino interaction over 22 calendar years to search for solar neutrino flux modulations with unprecedented precision. Periodic modulations are searched for in a dataset comprising five-day interval solar neutrino flux measurements with a maximum likelihood method. We also applied the Lomb-Scargle method to this dataset to compare it with previous reports. The only significant modulation found is due to the elliptic orbit of the Earth around the Sun. The observed modulation is consistent with astronomical data: we measured an eccentricity of (1.53±0.35)%, and a perihelion shift of (-1.5±13.5) days.
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We report a search for cosmic-ray boosted dark matter with protons using the 0.37 megaton×years data collected at Super-Kamiokande experiment during the 1996-2018 period (SKI-IV phase). We searched for an excess of proton recoils above the atmospheric neutrino background from the vicinity of the Galactic Center. No such excess is observed, and limits are calculated for two reference models of dark matter with either a constant interaction cross section or through a scalar mediator. This is the first experimental search for boosted dark matter with hadrons using directional information. The results present the most stringent limits on cosmic-ray boosted dark matter and exclude the dark matter-nucleon elastic scattering cross section between 10^{-33}cm^{2} and 10^{-27}cm^{2} for dark matter mass from 1 MeV/c^{2} to 300 MeV/c^{2}.
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This corrects the article DOI: 10.1103/PhysRevLett.130.031802.
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The aim of this study was to evaluate the association between eosinophils in ascites and the diagnosis of intestinal anisakidosis in patients with peritoneal signs on physical examination. We reviewed retrospectively 16 patients diagnosed with intestinal anisakidosis, evaluated between 2012 and 2015. All patients had ingested raw anchovies. The analysis of ascites fluid in ten of these patients was compared with that of 15 patients with ascites and other abdominal pathology (except liver cirrhosis). All patients had an increased number of white blood cells in the ascites fluid. The eosinophil count was significantly higher in patients with intestinal anisakidosis (P < 0.01). All patients had a good outcome. Increased eosinophils in ascites fluid is strongly associated with the diagnosis of intestinal anisakidosis.
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Anisaquíase/complicações , Anisaquíase/patologia , Ascite/etiologia , Eosinofilia/etiologia , Eosinófilos/patologia , Abdome/patologia , Adulto , Animais , Ascite/patologia , Eosinofilia/patologia , Feminino , Humanos , Intestinos/patologia , Japão , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
A search for boosted dark matter using 161.9 kt yr of Super-Kamiokande IV data is presented. We search for an excess of elastically scattered electrons above the atmospheric neutrino background, with a visible energy between 100 MeV and 1 TeV, pointing back to the Galactic center or the Sun. No such excess is observed. Limits on boosted dark matter event rates in multiple angular cones around the Galactic center and Sun are calculated. Limits are also calculated for a baseline model of boosted dark matter produced from cold dark matter annihilation or decay. This is the first experimental search for boosted dark matter from the Galactic center or the Sun interacting in a terrestrial detector.
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BACKGROUND: Many perforated peptic ulcers (PPUs) require surgical repair due to diffuse peritonitis. However, few studies have examined the clinical effects of postoperative drainage after PPU repair. This study aimed to investigate the drain insertion rates in patients who underwent PPU repair in Japan, and to clarify the impact of drain insertion on the postoperative clinical course. METHODS: A retrospective nationwide cohort study was performed using administrative claims data of patients who had undergone PPU repair between 2010 and 2016. These patients were divided into two groups based on whether or not they had received a postoperative abdominal drain. Using propensity score matching, we compared the incidences of postoperative interventions for abdominal complications between both groups. RESULTS: A total of 4869 patients from 324 hospitals were analyzed. At the hospital level, drains were placed in all PPU repair patients in 229 (70.7%) hospitals. At the patient level, 4401 patients (90.4%) had drains inserted. The drain group was associated with a higher emergency admission rate, poorer preoperative shock status, longer anesthetic time, and a higher amount of intra-abdominal irrigation. In the propensity score-matched patients, the drain group had a significantly lower incidence of postoperative interventions than the no-drain group (1.9 vs. 5.6%; risk ratio = 0.35; 95% confidence interval 0.16-0.73; P = 0.003). CONCLUSION: Postoperative drainage was performed in the majority of patients who underwent PPU repair in Japan. Drainage following PPU repair may facilitate patient recovery by reducing the need for postoperative interventions.
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Drenagem , Úlcera Péptica Perfurada/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Adulto , Idoso , Bases de Dados Factuais , Drenagem/efeitos adversos , Drenagem/estatística & dados numéricos , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Complicações Pós-Operatórias/etiologia , Pontuação de Propensão , Estudos RetrospectivosRESUMO
Search results for nucleon decays pâe^{+}X, pâµ^{+}X, nâνγ (where X is an invisible, massless particle) as well as dinucleon decays npâe^{+}ν, npâµ^{+}ν, and npâτ^{+}ν in the Super-Kamiokande experiment are presented. Using single-ring data from an exposure of 273.4 kton·yr, a search for these decays yields a result consistent with no signal. Accordingly, lower limits on the partial lifetimes of τ_{pâe^{+}X}>7.9×10^{32} yr, τ_{pâµ^{+}X}>4.1×10^{32} yr, τ_{nâνγ}>5.5×10^{32} yr, τ_{npâe^{+}ν}>2.6×10^{32} yr, τ_{npâµ^{+}ν}>2.2×10^{32} yr, and τ_{npâτ^{+}ν}>2.9×10^{31} yr at a 90% confidence level are obtained. Some of these searches are novel.
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Super-Kamiokande (SK) can search for weakly interacting massive particles (WIMPs) by detecting neutrinos produced from WIMP annihilations occurring inside the Sun. In this analysis, we include neutrino events with interaction vertices in the detector in addition to upward-going muons produced in the surrounding rock. Compared to the previous result, which used the upward-going muons only, the signal acceptances for light (few-GeV/c^{2}-200-GeV/c^{2}) WIMPs are significantly increased. We fit 3903 days of SK data to search for the contribution of neutrinos from WIMP annihilation in the Sun. We found no significant excess over expected atmospheric-neutrino background and the result is interpreted in terms of upper limits on WIMP-nucleon elastic scattering cross sections under different assumptions about the annihilation channel. We set the current best limits on the spin-dependent WIMP-proton cross section for WIMP masses below 200 GeV/c^{2} (at 10 GeV/c^{2}, 1.49×10^{-39} cm^{2} for χχâbb[over ¯] and 1.31×10^{-40} cm^{2} for χχâτ^{+}τ^{-} annihilation channels), also ruling out some fraction of WIMP candidates with spin-independent coupling in the few-GeV/c^{2} mass range.
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It remains poorly understood how symptoms in allergic rhinitis are most severe during overnight or early in the morning. The circadian clock consisting of a network of several 'clock genes' including Clock drives daily rhythms in physiology. This study showed that allergen-induced surface CD203c expression on basophils in seasonal allergic rhinitis caused by Japanese cedar pollen exhibited a time-of-day-dependent variation associated with temporal variations in canonical circadian clock gene expression. We also found that bone-marrow-derived basophils (BM basophils) generated from wild-type mice exhibited a time-of-day-dependent variation in IgE-mediated IL-4 and histamine production, which was not observed in BM basophils generated from Clock-mutated mice. Therefore, allergen-specific basophil reactivity shows daily variations depending on the circadian clock activity in basophils, which could partly explain temporal symptomatic variations in allergic rhinitis. Additionally, circadian variations in CD203c expression should be considered for interpretation of this biomarker in clinical research.
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Alérgenos/imunologia , Basófilos/imunologia , Basófilos/metabolismo , Relógios Circadianos/genética , Rinite Alérgica Sazonal/genética , Rinite Alérgica Sazonal/imunologia , Adulto , Animais , Proteínas CLOCK/genética , Proteínas CLOCK/metabolismo , Regulação da Expressão Gênica , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Mutação , Proteínas Circadianas Period/genética , Proteínas Circadianas Period/metabolismo , Diester Fosfórico Hidrolases/genética , Diester Fosfórico Hidrolases/metabolismo , Pólen/imunologia , Pirofosfatases/genética , Pirofosfatases/metabolismo , Fatores de Tempo , Adulto JovemRESUMO
The trilepton nucleon decay modes pâe+νν and pâµ+νν violate |Δ(B-L)| by two units. Using data from a 273.4 kt yr exposure of Super-Kamiokande a search for these decays yields a fit consistent with no signal. Accordingly, lower limits on the partial lifetimes of τpâe+νν>1.7×10(32) years and τpâµ+νν>2.2×10(32) years at a 90% confidence level are obtained. These limits can constrain Grand Unified Theories which allow for such processes.
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We present the results of searches for nucleon decay via nâν[over ¯]π0 and pâν[over ¯]π+ using data from a combined 172.8 kt·yr exposure of Super-Kamiokande-I,-II, and-III. We set lower limits on the partial lifetime for each of these modes: τnâν[over ¯]π0>1.1×10(33) years and τpâν[over ¯]π+>3.9×10(32) years at a 90% confidence level.
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A search for the dinucleon decay pp â K+ K+ has been performed using 91.6 kton·yr data from Super-Kamiokande-I. This decay provides a sensitive probe of the R-parity-violating parameter λ112''. A boosted decision tree analysis found no signal candidates in the data. The expected background was 0.28±0.19 atmospheric neutrino induced events and the estimated signal detection efficiency was 12.6%±3.2%. A lower limit of 1.7×10(32) years has been placed on the partial lifetime of the decay O16 â C14K+ K+ at 90% C.L. A corresponding upper limit of 7.8×10(-9) has been placed on the parameter λ112''.
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We report an indication that the elastic scattering rate of solar B8 neutrinos with electrons in the Super-Kamiokande detector is larger when the neutrinos pass through Earth during nighttime. We determine the day-night asymmetry, defined as the difference of the average day rate and average night rate divided by the average of those two rates, to be [-3.2 ± 1.1(stat) ± 0.5(syst)]%, which deviates from zero by 2.7 σ. Since the elastic scattering process is mostly sensitive to electron-flavored solar neutrinos, a nonzero day-night asymmetry implies that the flavor oscillations of solar neutrinos are affected by the presence of matter within the neutrinos' flight path. Super-Kamiokande's day-night asymmetry is consistent with neutrino oscillations for 4 × 10(-5) eV(2) ≤ Δm 2(21) ≤ 7 × 10(-5) eV(2) and large mixing values of θ12, at the 68% C.L.
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BACKGROUND: S100A7/psoriasin is a member of the S100 protein family and is encoded in the epidermal differentiation complex, which contains genes for markers of epidermal differentiation. S100A7/psoriasin is overexpressed in hyperproliferative skin diseases, where it is believed not only to exhibit antimicrobial functions, but also to induce immunomodulatory activities, including chemotaxis and cytokine/chemokine production. OBJECTIVES: To evaluate the effect of S100A7/psoriasin on keratinocyte differentiation and regulation of the tight junction (TJ) barrier. METHODS: Expression of differentiation markers and TJ proteins in human keratinocytes was determined by real-time polymerase chain reaction and Western blot. The changes in TJ barrier function were assessed by transepithelial electrical resistance and paracellular permeability assays. Glycogen synthase kinase-3 (GSK-3) and mitogen-activated protein kinase (MAPK) activation was analysed by Western blot, whereas ß-catenin and E-cadherin activation was evaluated by Western blot and immunofluorescence. RESULTS: S100A7/psoriasin enhanced the expression of several differentiation markers and selectively increased the expression of TJ proteins (e.g. claudins and occludin), which are known to strengthen the TJ barrier. Furthermore, S100A7/psoriasin increased ß-catenin and E-cadherin accumulation at cell-cell contact, and enhanced transepithelial electrical resistance while reducing the paracellular permeability of keratinocyte layers. The data suggest that S100A7/psoriasin-mediated regulation of the TJ barrier was via both the GSK-3 and MAPK pathways, as evidenced by the inhibitory effects of inhibitors for GSK-3 and MAPKs. CONCLUSIONS: Our finding that S100A7/psoriasin regulates differentiation and strengthens TJ barrier function provides novel evidence that, in addition to antimicrobial and immunoregulatory activities, S100A7/psoriasin is involved in skin innate immunity.
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Antígenos de Diferenciação/efeitos dos fármacos , Queratinócitos/efeitos dos fármacos , Proteínas S100/farmacologia , Pele/efeitos dos fármacos , Junções Íntimas/efeitos dos fármacos , Caderinas/metabolismo , Células Cultivadas , Dextranos/metabolismo , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Humanos , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Proteína A7 Ligante de Cálcio S100 , Proteínas de Junções Íntimas/metabolismo , beta Catenina/metabolismoRESUMO
In this study, we applied a photothermal microscope to study the process of malignant melanoma formation. We analyzed benign papilloma tumors, their metastatic carcinomas, and metastatic melanoma on the preparation of mouse skin using a gray-level co-occurrence matrix (GLCM) method. Based on the analysis of nine GLCM parameters investigated, the characteristics during the degenerative and metastatic processes are clarified by the investigation. The determination of characteristic parameters corresponding to three processes before, during, and after the degeneration indicated that this investigation enables the detection of the malignant transformation and related processes.
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Melanoma , Microscopia , Neoplasias Cutâneas , Animais , Camundongos , Melanoma/patologia , Neoplasias Cutâneas/patologiaRESUMO
Super-Kamiokande atmospheric neutrino data were fit with an unbinned maximum likelihood method to search for the appearance of tau leptons resulting from the interactions of oscillation-generated tau neutrinos in the detector. Relative to the expectation of unity, the tau normalization is found to be 1.42 ± 0.35(stat)(-0.12)(+0.14)(syst) excluding the no-tau-appearance hypothesis, for which the normalization would be zero, at the 3.8σ level. We estimate that 180.1 ± 44.3(stat)(-15.2)(+17.8) (syst) tau leptons were produced in the 22.5 kton fiducial volume of the detector by tau neutrinos during the 2806 day running period. In future analyses, this large sample of selected tau events will allow the study of charged current tau neutrino interaction physics with oscillation produced tau neutrinos.
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The genes Tlx1 (Hox11), Enx (Hox11L2, Tlx-2) and Rnx (Hox11L2, Tlx-3) constitute a family of orphan homeobox genes. In situ hybridization has revealed considerable overlap in their expression within the nervous system, but Rnx is singularly expressed in the developing dorsal and ventral region of the medulla oblongata. Tlx1-deficient and Enx-deficient mice display phenotypes in tissues where the mutated gene is singularly expressed, resulting in asplenogenesis and hyperganglionic megacolon, respectively. To determine the developmental role of Rnx, we disrupted the locus in mouse embryonic stem (ES) cells. Rnx deficient mice developed to term, but all died within 24 hours after birth from a central respiratory failure. The electromyographic activity of intercostal muscles coupled with the C4 ventral root activity assessed in a medulla-spinal cord preparation revealed a high respiratory rate with short inspiratory duration and frequent apnea. Furthermore, a coordinate pattern existed between the abnormal activity of inspiratory neurons in the ventrolateral medulla and C4 motorneuron output, indicating a central respiratory defect in Rnx mice. Thus, Rnx is critical for the development of the ventral medullary respiratory centre and its deficiency results in a syndrome resembling congenital central hypoventilation.
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Anormalidades Múltiplas/genética , Genes Homeobox , Proteínas de Homeodomínio/fisiologia , Hipoventilação/genética , Proteínas Oncogênicas/fisiologia , Animais , Apneia/congênito , Apneia/genética , Cianose/genética , Eletromiografia , Desenvolvimento Embrionário e Fetal/genética , Genes Letais , Genótipo , Idade Gestacional , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Hipoventilação/congênito , Hibridização In Situ , Músculos Intercostais/fisiopatologia , Bulbo/metabolismo , Camundongos , Camundongos Knockout , Neurônios Motores/patologia , Neurônios/patologia , Proteínas Oncogênicas/deficiência , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismo , Proteínas do Grupo Polycomb , Proteínas Repressoras/genética , Proteínas Repressoras/fisiologia , Centro Respiratório/embriologia , Centro Respiratório/patologia , Medula Espinal/metabolismoRESUMO
AIMS/HYPOTHESIS: Despite advances in pharmacological treatments, diabetes with hypertension continues to be a major public health problem with high morbidity and mortality rates. We recently identified a circulating peptide coupling factor 6 (CF6), which binds to the plasma membrane ATP synthase (ecto-F(1)F(o) complex), resulting in intracellular acidosis. We investigated whether overexpression of CF6 contributes to diabetes and hypertension by intracellular acidosis. METHODS: Transgenic mice overexpressing CF6 (also known as ATP5J) were generated, and physiological, biochemical and molecular biology studies were performed. RESULTS: CF6 overexpression elicited a sustained decrease in intracellular pH in tissues (aorta, kidney, skeletal muscle and liver, with the exception of adipose tissue) that express its receptor, the ß-subunit of ecto-F(1)F(o) complex. Consistent with the receptor distribution, phospho-insulin receptor ß, phosphoinositide 3-kinase activity and the phospho-Akt1:total Akt1 ratio were all decreased in the skeletal muscle and the liver in transgenic compared with wild-type mice, resulting in a decrease of plasma membrane-bound GLUT4 and an increase in hepatic glucose production. Under a high-sucrose diet, transgenic mice had insulin resistance and mild glucose intolerance; under a high-salt diet, they had elevated blood pressure with increased renal RAS-related C3 botulinum substrate 1 (RAC1)-GTP, which is an activator of mineralocorticoid receptor. CONCLUSIONS/INTERPRETATION: Through its action on the ß-subunit of ecto-F(1)F(o) complex, which results in intracellular acidosis, CF6 plays a crucial role in the development of insulin resistance and hypertension. This finding might advance our understanding of the mechanisms underlying diabetes and hypertension, possibly also providing a novel therapeutic target against cardiovascular disease.
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Intolerância à Glucose/metabolismo , Hipertensão/metabolismo , ATPases Mitocondriais Próton-Translocadoras/metabolismo , Fatores Acopladores da Fosforilação Oxidativa/metabolismo , ATPases Translocadoras de Prótons/metabolismo , Acidose/metabolismo , Animais , Pressão Sanguínea , Citoplasma/metabolismo , Modelos Animais de Doenças , Teste de Tolerância a Glucose , Hepatócitos/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Hipertensão/genética , Resistência à Insulina , Camundongos , Camundongos Transgênicos , Neuropeptídeos/metabolismo , Proteínas rac de Ligação ao GTP/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismoRESUMO
BACKGROUND: ATP2A2 encoding the sarcoplasmic/endoplasmic reticulum Ca(2+) -ATPase2 (SERCA2) is a Darier disease (DD)-related gene. Ultraviolet (UV) B irradiation downregulates ATP2A2/SERCA2 expression in keratinocytes, whereas cyclooxygenase-2 (COX-2) expression is dramatically upregulated by UVB. OBJECTIVES: To analyse the involvement of COX-2 in ATP2A2/SERCA2 expression. METHODS: Keratinocytes were transfected with COX-2 siRNA or treated with COX-2 inhibitor, celecoxib, to evaluate the effect of COX-2 on ATP2A2/SERCA2 expression. Quantitative real-time polymerase chain reaction, Western blotting analysis and reporter assay were used to determine the amount of mRNA, protein level and transcription activity, respectively. RESULTS: COX-2 knockdown by siRNA resulted in upregulation of ATP2A2 transcription. Treatment by celecoxib rescued UVB-mediated suppression of the ATP2A2 transcription and SERCA2 protein expression. Simple addition of prostaglandin (PG) E(2) , which is a product of COX-2 enzyme, reduced the amounts of ATP2A2 mRNA and SERCA2 protein in keratinocytes. CONCLUSIONS: UVB downregulates ATP2A2/SERCA2 expression via induction of COX-2 expression and subsequent increase of PGE(2) production in keratinocytes. Considering that DD is caused by the decreased function of SERCA2 due to the reduced expression of the ATP2A2 gene, this finding shows the possibility that COX-2 inhibition may be useful to prevent and/or treat DD.