3,602 research outputs found

    Scintillation counter with MRS APD light readout

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    START, a high-efficiency and low-noise scintillation detector for ionizing particles, was developed for the purpose of creating a high-granular system for triggering cosmic muons. Scintillation light in START is detected by MRS APDs (Avalanche Photo-Diodes with Metal-Resistance-Semiconductor structure), operated in the Geiger mode, which have 1 mm^2 sensitive areas. START is assembled from a 15 x 15 x 1 cm^3 scintillating plastic plate, two MRS APDs and two pieces of wavelength-shifting optical fiber stacked in circular coils inside the plastic. The front-end electronic card is mounted directly on the detector. Tests with START have confirmed its operational consistency, over 99% efficiency of MIP registration and good homogeneity. START demonstrates a low intrinsic noise of about 10^{-2} Hz. If these detectors are to be mass-produced, the cost of a mosaic array of STARTs is estimated at a moderate level of 2-3 kUSD/m^2.Comment: 6 pages, 5 figure

    Post-sigh sleep apneas in mice: Systematic review and data-driven definition

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    Sleep apneas can be categorized as post-sigh (prevailing in non-rapid eye movement sleep) or spontaneous (prevailing in rapid eye movement sleep) according to whether or not they are preceded by an augmented breath (sigh). Notably, the occurrence of these apnea subtypes changes differently in hypoxic/hypercapnic environments and in some genetic diseases, highlighting the importance of an objective discrimination. We aim to: (a) systematically review the literature comparing the criteria used in categorizing mouse sleep apneas; and (b) provide data-driven criteria for this categorization, with the final goal of reducing experimental variability in future studies. Twenty-two wild-type mice, instrumented with electroencephalographic/electromyographic electrodes, were placed inside a whole-body plethysmographic chamber to quantify sleep apneas and sighs. Wake\u2013sleep states were scored on 4-s epochs based on electroencephalographic/electromyographic signals. Literature revision showed that highly different criteria were used for post-sigh apnea definition, the intervals for apnea occurrence after sigh ranging from 1 breath up to 20 s. In our data, the apnea occurrence rate during non-rapid eye movement sleep was significantly higher than that calculated before the sigh only in the 1st and 2nd 4-s epochs following a sigh. These data suggest that, in mice, apneas should be categorized as post-sigh only if they start within 8 s from a sigh; the choice of shorter or longer time windows might underestimate or slightly overestimate their occurrence rate, respectively

    Antimicrobial susceptibility of bacteria isolated from the lower respiratory tract of inpatients with pneumonia in Brazilian hospitals: results from the SENTRY surveillance program, 1997 and 1998

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    Background: Nosocomial pneumonia is the most common fatal nosocomial infection with attributable mortality rates ranging from 30 to 60% and a rapid initiation of optimal antimicrobial therapy is important to obtain treatment success. SENTRY is a comprehensive antimicrobial surveillance study involving a great number of medical centers distributed worldwide. Objective: To evaluate the antimicrobial susceptibility of bacterial isolates collected from the lower respiratory tract of inpatients with pneumonia. Material & methods: The authors report the antimicrobial susceptibility of 525 isolates collected in 11 Brazilian hospitals, as part of the SENTRY program. The isolates were tested for susceptibility by broth micro-dilution against a large number of drugs. Results: The five most frequently isolated species were (n/%): Pseudomonas aeruginosa (158/30.1%), Staphylococcus aureus (103/19.6%), Acinetobacter spp. (68/13.0%), Klebsiella spp. (50/9.5%), and Enterobacter spp. (44/8.4%). These five species represented more than 80% of all isolates. P. aeruginosa demonstrated high rates of resistance to most antimicrobial agents tested. The highest susceptibility rates were shown by piperacillin/tazobactam (71.5%) and meropenem (69.0%). Acinetobacter spp. also showed very high rates of resistance. The most active compounds against this species were imipenem and meropenem (80.9% susceptibility) followed by tetracycline (63.2% susceptibility). Cephalosporin susceptibilities among Klebsiella spp were very low and 36.0% of isolates were considered ESBL producers based on increased MICs, > 2 mug/mL) to ceftriaxone or ceftazidime or aztreonam. Ceftriaxone was active against only 56.8% of Enterobacter spp. isolates (MIC50 1 mug/mL), while cefepime was active against 88.6% of these isolates (MIC, ou =2mig/mL para ceftriaxona ou ceftazidima, indicando produção de ESBL, foram encontrados em 36,0% das amostras. Os antimicrobianos mais ativos contra Klebsiella spp. foram os carbapenens (100% de sensibilidade) e as quinolonas (92,0% de sensibilidade). Ceftriaxona foi ativa contra somente 56,8% das amostras de Enterobacter spp. (MIC50, 1mig/mL), enquanto a cefepima foi ativa contra 88,6% destes isolados (MIC50, <= 0,12mig/mL). A resistência à oxacilina foi detectada em 43,7% dos isolados de S. aureus. As drogas mais ativas contra essa espécie foram: vancomicina, teicoplanina, quinupristin-dalfopristin e linezolida. Conclusões: Os resultados do presente estudo mostraram alta prevalência de Acinetobacter spp. e altas taxas de resistência entre bacilos gram-negativos quando comparados com resultados de estudos norte-americanos e europeus.Universidade Federal de São Paulo (UNIFESP)Universidade de Iowa Faculdade de Medicina Departmento de PatologiaLaboratório Santa LuziaLaboratório LâminaUNIFESPSciEL

    Looking for pathways related to COVID-19: confirmation of pathogenic mechanisms by SARS-CoV-2-host interactome

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    In the last months, many studies have clearly described several mechanisms of SARS-CoV-2 infection at cell and tissue level, but the mechanisms of interaction between host and SARS-CoV-2, determining the grade of COVID-19 severity, are still unknown. We provide a network analysis on protein–protein interactions (PPI) between viral and host proteins to better identify host biological responses, induced by both whole proteome of SARS-CoV-2 and specific viral proteins. A host-virus interactome was inferred, applying an explorative algorithm (Random Walk with Restart, RWR) triggered by 28 proteins of SARS-CoV-2. The analysis of PPI allowed to estimate the distribution of SARS-CoV-2 proteins in the host cell. Interactome built around one single viral protein allowed to define a different response, underlining as ORF8 and ORF3a modulated cardiovascular diseases and pro-inflammatory pathways, respectively. Finally, the network-based approach highlighted a possible direct action of ORF3a and NS7b to enhancing Bradykinin Storm. This network-based representation of SARS-CoV-2 infection could be a framework for pathogenic evaluation of specific clinical outcomes. We identified possible host responses induced by specific proteins of SARS-CoV-2, underlining the important role of specific viral accessory proteins in pathogenic phenotypes of severe COVID-19 patients

    PML as a potential predictive factor of oxaliplatin/fluoropyrimidine-based first line chemotherapy efficacy in colorectal cancer patients

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    PML regulates a wide range of pathways involved in tumorigenesis, such as apoptosis, which is also one of the main mechanisms through which oxaliplatin and fluoropyrimidine exert their antineoplastic activity. The present study aims to investigate PML expression as a predictive factor of oxaliplatin/fluoropyrimidine therapy efficacy. EXPERIMENTAL DESIGN: 74 metastatic colorectal cancer patients who received oxaliplatin/floropyrimidine-based first line therapy have been included in this retrospective study. PML expression was assessed by immunohistochemistry. RESULTS: PML down-regulation was detected in 39 (52.7%) patients (14 complete and 25 partial PML loss). RR was significantly lower (25.6%) in patients with PML down-regulation than in patients with preserved PML expression (60%) (P\u2009=\u20090.006). Median TTP was 5.5 months when PML was down-regulated versus 11.9 months in case of preserved PML expression (P\u2009<\u20090.0001). A statistical significant difference was also detected in OS (15.6 and 24.5 months respectively, P\u2009=\u20090.003). The impact of PML down-regulation on TTP and OS was statistically significant also in a multivariate model. CONCLUSIONS: This study represents the first evidence of a possible correlation between PML protein expression and outcome of metastatic colorectal cancer patients treated with oxaliplatin/fluoropyrimidine-based first line therapy

    New data on OZI rule violation in bar{p}p annihilation at rest

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    The results of a measurement of the ratio R = Y(phi pi+ pi-) / Y(omega pi+ pi-) for antiproton annihilation at rest in a gaseous and in a liquid hydrogen target are presented. It was found that the value of this ratio increases with the decreasing of the dipion mass, which demonstrates the difference in the phi and omega production mechanisms. An indication on the momentum transfer dependence of the apparent OZI rule violation for phi production from the 3S1 initial state was found.Comment: 11 pages, 3 PostScript figures, submitted to Physics Letter

    Measurements of the reaction pˉp→ϕη\bar{p}p \to \phi \eta of antiproton annihilation at rest at three hydrogen target densities

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    The proton-antiproton annihilation at rest into the ϕη\phi\eta final state was measured for three different target densities: liquid hydrogen, gaseous hydrogen at NTP and at a low pressure of 5 mbar. The yield of this reaction in the liquid hydrogen target is smaller than in the low-pressure gas target. The branching ratios of the ϕη\phi\eta channel were calculated on the basis of simultaneous analysis of the three data samples. The branching ratio for annihilation into ϕη\phi\eta from the 3S1^3S_1 protonium state turns out to be about ten times smaller as compared to the one from the 1P1^1P_1 state.Comment: 10 pages, 3 Postscript figures. Accepted by Physics Letters

    Dicer and Drosha expression and response to Bevacizumab-based therapy in advanced colorectal cancer patients

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    PURPOSE: The miRNA-regulating enzymes Dicer and Drosha exhibit aberrant expression in several cancer types. Dicer and Drosha play a crucial role during the angiogenetic process in vitro and, for Dicer, in vivo. We aimed to investigate the potential role of Dicer and Drosha in predicting response to Bevacizumab-based therapy in advanced colorectal cancer (CRC) patients. METHODS: Dicer and Drosha mRNA levels were analysed in formalin-fixed paraffin-embedded specimens from patients affected by advanced CRC treated with or without Bevacizumab-containing regimens (n=116 and n=50, respectively) and from patients with diverticulosis as control group (n=20). The experimental data were obtained using qRT-PCR, analysed comparing Dicer and Drosha expression levels in tumour samples versus normal mucosa and then compared to clinical outcome. RESULTS: The tumour samples from Bevacizumab-treated patients showed a significantly higher Drosha expression (P<.001) versus normal mucosa, while Dicer levels did not differ. Intriguingly, we found that low Dicer levels predicted a longer progression-free survival (PFS) (P<.0001) and overall survival (OS) (P=.009). In addition, low Dicer levels were associated with better response to Bevacizumab-based treatments versus high Dicer levels (1.7% complete responses and 53.4% partial responses versus 0% and 32.7%, respectively; P=.0067). Multivariate analysis identified three independent predictors of improved OS: high performance status (PS) (relative risk (RR) 1.45; P=.011), lower organs involvement (RR 0.79; P=.034) and low Dicer expression (RR 0.71; P=.008). Conversely, Drosha levels were not associated with prognosis and outcome associated with treatment. In non-Bevacizumab-treated patients, Dicer and Drosha expression did not correlate with outcome. CONCLUSION: These findings suggest that low Dicer mRNA levels seem to be independent predictors of favourable outcome and response in patients affected by advanced CRCs treated with Bevacizumab-based therapy
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