3,022 research outputs found

    Disentangling protostellar evolutionary stages in clustered environments using Spitzer-IRS spectra and comprehensive SED modeling

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    When studying the evolutionary stages of protostars that form in clusters, the role of any intracluster medium cannot be neglected. High foreground extinction can lead to situations where young stellar objects (YSOs) appear to be in earlier evolutionary stages than they actually are, particularly when using simple criteria like spectral indices. To address this issue, we have assembled detailed SED characterizations of a sample of 56 Spitzer-identified candidate YSOs in the clusters NGC 2264 and IC 348. For these, we use spectra obtained with the Infrared Spectrograph onboard the Spitzer Space Telescope and ancillary multi-wavelength photometry. The primary aim is twofold: 1) to discuss the role of spectral features, particularly those due to ices and silicates, in determining a YSO's evolutionary stage, and 2) to perform comprehensive modeling of spectral energy distributions (SEDs) enhanced by the IRS data. The SEDs consist of ancillary optical-to-submillimeter multi-wavelength data as well as an accurate description of the 9.7 micron silicate feature and of the mid-infrared continuum derived from line-free parts of the IRS spectra. We find that using this approach, we can distinguish genuine protostars in the cluster from T Tauri stars masquerading as protostars due to external foreground extinction. Our results underline the importance of photometric data in the far-infrared/submillimeter wavelength range, at sufficiently high angular resolution to more accurately classify cluster members. Such observations are becoming possible now with the advent of the Herschel Space Observatory.Comment: Accepted for publication in Ap

    PHYSICAL CONNECTION BETWEEN BVRF SEGMENTS BASED ON LEVELING ASSOCIATED WITH GRAVIMETRY

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    Considering the efforts to establish Global Reference Systems linked to the geopotential space, new alternatives are sought to address the problems found in the classic national vertical networks. The Brazilian Vertical Reference Frame (BVRF) was materialized in two different segments with independent datums (Imbituba and Santana tide gauges) due to the terrain difficulties for conventional leveling. The 2018 BVRF realization, in the geopotential space, still remains without interoperability between its segments. We analyze alternatives for physical connection based on the new precepts of the International Association of Geodesy (IAG) involving the geopotential space. Some proposed solutions for physical connection based on GPS leveling associated with gravimetry are presented. These solutions were developed with the aim of evidencing the discrepancy between the two BVRF segments, now carried out in terms of geopotential numbers and normal heights. The results indicate differences ranging from about 45 cm to 140 cm between the two segments depending on the strategy employed. Comparisons with previous determinations based on indirect strategies and involving previous BVRF realizations are made

    Análise populacional e funcional dos polimorfismos genéticos CYP2D6*4 e CYP2C19*17 do citocromo P450 e C3435T do gene MDR1

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    A variabilidade da resposta aos fármacos deve-se, em grande parte, a fatores genéticos. Polimorfismos em genes que codificam enzimas metabolizadoras de xenobióticos, como as enzimas CYP2D6 e CYP2C19 do citocromo P450 (CYP450), e em genes codificantes de proteínas que promovem o seu efluxo, como o gene MDR1, codificante da glicoproteína-P (Pgp), podem afetar a eficácia de um tratamento farmacológico ou a sua toxicidade, determinando assim a variabilidade interindividual na resistência a fármacos. Como tal, e porque os genes que codificam estas proteínas são extremamente polimórficos torna-se necessária uma análise genética e funcional aprofundada. Com o intuito de prever a incidência de algumas variações genéticas na população Portuguesa, procedeu-se ao estudo dos polimorfismos CYP2D6*4 e CYP2C19*17, do CYP450, e C3435T do gene MDR1. Estes polimorfismos foram pesquisados quer por PCR-RFLP quer por High Resolution Melting (HRM) em amostras de DNA genómico extraído de dadores voluntários do Instituto Superior de Ciências da Saúde - Norte. Os resultados obtidos permitiram identificar diferentes genótipos, tendo-se verificado uma frequência de 7,4% para o polimorfismo CYP2C19*17, de 7,7% para o polimorfismo CYP2D6*4 e, por último, de 13,0% para o polimorfismo C3435T. De forma a complementar o estudo populacional, o polimorfismo C3435T do gene MDR1 foi também genotipado em linhas celulares tumorais de adenocarcinoma do intestino, HCT-15, HT29-MTX e Caco-2, com o objetivo de determinar a influência da presença do polimorfismo na funcionalidade da Pgp. Assim, foram realizados ensaios de resistência à doxorrubicina, um fármaco antitumoral substrato da Pgp, que permitissem avaliar uma possível relação entre a presença/ausência dos polimorfismos e diferentes perfis de metabolização. Os resultados obtidos demonstraram que a linha celular HCT-15 de genótipo TT apresentou uma maior resistência ao fármaco do que as restantes linhas de genótipo CT. Foi também observado que a linha HCT-15 apresentava uma maior expressão da Pgp, e que esta era induzida após exposição ao fármaco, o que poderá estar associado à presença do polimorfismo C3435T. Contudo, a existência de um perfil genético e metabólico diferente nas linhas celulares utilizadas impossibilita a determinação do papel específico do polimorfismo C3435T na funcionalidade do gene MDR1 por esta abordagem. Assim, com o intuito de relacionar a presença do polimorfismo com o efluxo da doxorrubicina, efetuou-se a expressão heteróloga do gene MDR1 na presença e na ausência do polimorfismo na estirpe Saccharomyces cerevisiae AD1-8 desprovida dos principais transportadores de fármacos. Os resultados obtidos demonstraram que a proteína apresentava funcionalidade neste sistema heterólogo, demonstrando assim que a levedura S. cerevisiae constitui um bom modelo para estudos funcionais de polimorfismos do gene MDR1 humano

    Tuberculin skin testing versus interferon-gamma release assay among users of a public health unit in Northeast Portugal

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    he screening of groups with a high risk for developing tuberculosis (TB) is a priority in order to control this disease. Since there is no gold standard for the diagnosis of latent TB infection (LTBI), both the tuberculin skin test (TST) and the interferon-gamma release assays (IGRA) have been used for this purpose. The aim of this study was to determine the proportion of LTBI by using the TST and the IGRA tests, and to assess the risk factors related with discordant results between tests across several risk groups advised for screening in Northeast Portugal. Data were collected from the database of patients with suspected LTBI and advised for the screening in a public health unit (January 2014 to December 2015). The proportion of LTBI was computed using both tests. Logistic regression models assessed risk factors for a positive test and for discordant results between tests. The adjusted odds ratio (OR) and respective 95% confidence interval (95% CI) were obtained. Out of 367 patients included in the analysis, 79.8% had a positive TST and 46.0% of them had a positive IGRA. In comparison with contacts of active TB cases, healthcare workers and inmates presented higher odds of TST positivity (OR 4.38, 95% CI 1.59–12.09 and OR 4.74, 95% CI 1.45–15.49, respectively), but immunocompromised people presented lower odds of TST positivity (OR 0.14; 95% CI 0.06–0.31). Instead, healthcare workers (OR 0.44, 95% CI 0.24–0.80) and immunocompromised people (OR 0.24, 95% CI 0.10–0.56) presented lower odds of a positive IGRA. There were 42.0% concordant positive results, 16.1% concordant negative results, and 41.9% discordant results, with healthcare workers presenting higher odds of discordant results (OR 3.34, 95% CI 1.84–6.05). The proportion of LTBI estimated by TST and IGRA among people advised for screening in our setting is high, highlighting the need of preventive strategies. Among healthcare workers, TST results should be read with caution as the higher proportion of discordant results with a positive TST suggests the impact of the booster reaction in this group.info:eu-repo/semantics/publishedVersio

    Contributions of IFN-gamma and granulysin to the clearance of Plasmodium yoelii blood stage

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    P. vivax-infected Retics (iRetics) express human leukocyte antigen class I (HLA-I), are recognized by CD8+ T cells and killed by granulysin (GNLY) and granzymes. However, how Plasmodium infection induces MHC-I expression on Retics is unknown. In addition, whether GNLY helps control Plasmodium infection in vivo has not been studied. Here, we examine these questions using rodent infection with the P. yoelii 17XNL strain, which has tropism for Retics. Infection with P. yoelii caused extramedullary erythropoiesis, reticulocytosis and expansion of CD8+CD44+CD62L- IFN-gamma-producing T cells that form immune synapses with iRetics. We now provide evidence that MHC-I expression by iRetic is dependent on IFN-gamma-induced transcription of IRF-1, MHC-I and beta2-microglobulin (beta2-m) in erythroblasts. Consistently, CTLs from infected wild type (WT) mice formed immune synapses with iRetics in an IFN-gamma- and MHC-I-dependent manner. When challenged with P. yoelii 17XNL, WT mice cleared parasitemia and survived, while IFN-gamma KO mice remained parasitemic and all died. beta2-m KO mice that do not express MHC-I and have virtually no CD8+ T cells had prolonged parasitemia, and 80% survived. Because mice do not express GNLY, GNLY-transgenic mice can be used to assess the in vivo importance of GNLY. Parasite clearance was accelerated in GNLY-transgenic mice and depletion of CD8+ T cells ablated the GNLY-mediated resistance to P. yoelii. Altogether, our results indicate that in addition to previously described mechanisms, IFN-gamma promotes host resistance to the Retic-tropic P. yoelii 17XNL strain by promoting MHC-I expression on iRetics that become targets for CD8+ cytotoxic T lymphocytes and GNLY
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