155 research outputs found

    Combining analytical models and LES data to determine the transfer function from swirled premixed flames

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    A methodology is developed where the acoustic response of a swirl stabilized flame is obtained from a reduced set of simulations. Building upon previous analytical flame transfer functions, a parametriza- tion of the flame response is first proposed, based on six independent physical parameters: a Strouhal number, the mean flame angle with respect to the main flow direction, the vortical structures convection speed, a swirl intensity parameter, a time delay between acoustic and vortical perturbations, as well as a phase shift between bulk and local velocity signals. It is then shown how these parameters can be de- duced from steady and unsteady simulations. The methodology is applied to a laboratory scale premixed swirl stabilized flame exhibiting features representative of real aero-engines. In this matter, cold and re- active flow Large Eddy Simulations are first validated by comparing results with reference data from experiments. The high fidelity simulations are seen to be able to capture the flame structure and velocity profiles at different locations while forced flame dynamics for the frequency range of interest also match the experimental data. From the same analytical transfer function model, three methodologies of increas- ing complexity are presented for the determination of the model parameters, depending on the available data or computational resources. A first estimation of the flame acoustic response is obtained by evalu- ating parameters from a single stationary flame simulation in conjunction with analytical estimations for the acoustic-convective time delay. Flame dynamics and swirl related parameters can then be determined from a series of robust treatments on pulsed simulations data to improve the model accuracy. It is shown that good qualitative agreement for the flame transfer function can be obtained from a single non-forced simulation while quantitative agreement over the frequency range of interest can be obtained using ad- ditional reactive or non-reactive pulsed simulations at one single forcing frequency corresponding to a local gain minimum. The method also naturally handles different perturbation levels

    Nighttime chlorine monoxide observations by the Odin satellite and implications for the ClO/Cl2O2 equilibrium

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    We use measurements of chlorine monoxide (ClO) by the SMR instrument onboard the Odin satellite to study the nighttime thermal equilibrium between ClO and its dimer Cl2O2. Observations performed in the polar vortex during the 2002–2003 Arctic winter showed enhanced amounts of nighttime ClO over a wide range of stratospheric temperatures (185 < T < 225 K). Odin/SMR measurements are here compared to three-dimensional model calculations using various published estimations of the Keq equilibrium constant between ClO and Cl2O2. Our results show that the value of Keq currently recommended by JPL (Sander et al., 2003) leads to a large underestimation of the observed nighttime ClO amounts, and that a realistic estimation of Keq must lie between the values determined by Cox and Hayman (1988) and Von Hobe et al. (2005)

    LILAC pilot study : effects of metformin on mTOR activation and HIV reservoir persistence during antiretroviral therapy

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    Background: Chronic inflammation and residual HIV transcription persist in people living with HIV (PLWH) receiving antiretroviral therapy (ART), thus increasing the risk of developing non-AIDS co-morbidities. The mechanistic target of rapamycin (mTOR) is a key regulator of cellular metabolism and HIV transcription, and therefore represents an interesting novel therapeutic target. Methods: The LILAC pilot clinical trial, performed on non-diabetic ART-treated PLWH with CD4+ /CD8+ T-cell ratios <0.8, evaluated the effects of metformin (12 weeks oral administration; 500-850 mg twice daily), an indirect mTOR inhibitor, on the dynamics of immunological/virological markers and changes in mTOR activation/phosphorylation in blood collected at Baseline, Week 12, and 12 weeks after metformin discontinuation (Week 24) and sigmoid colon biopsies (SCB) collected at Baseline and Week 12. Findings: CD4+ T-cell counts, CD4+ /CD8+ T-cell ratios, plasma markers of inflammation/gut damage, as well as levels of cell-associated integrated HIV-DNA and HIV-RNA, and transcriptionally-inducible HIV reservoirs, underwent minor variations in the blood in response to metformin. The highest levels of mTOR activation/ phosphorylation were observed in SCB at Baseline. Consistently, metformin significantly decreased CD4+ Tcell infiltration in the colon, as well as mTOR activation/phosphorylation, especially in CD4+ T-cells expressing the Th17 marker CCR6. Also, metformin decreased the HIV-RNA/HIV-DNA ratios, a surrogate marker of viral transcription, in colon-infiltrating CD4+ T-cells of 8/13 participants

    Ewing sarcoma from molecular biology to the clinic

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    In Europe, with an incidence of 7.5 cases per million, Ewing sarcoma (ES) is the second most common primary malignant bone tumor in children, adolescents and young adults, after osteosarcoma. Since the 1980s, conventional treatment has been based on the use of neoadjuvant and adjuvant chemotherapeutic agents combined with surgical resection of the tumor when possible. These treatments have increased the patient survival rate to 70% for localized forms, which drops drastically to less than 30% when patients are resistant to chemotherapy or when pulmonary metastases are present at diagnosis. However, the lack of improvement in these survival rates over the last decades points to the urgent need for new therapies. Genetically, ES is characterized by a chromosomal translocation between a member of the FET family and a member of the ETS family. In 85% of cases, the chromosomal translocation found is (11; 22) (q24; q12), between the EWS RNA-binding protein and the FLI1 transcription factor, leading to the EWS-FLI1 fusion protein. This chimeric protein acts as an oncogenic factor playing a crucial role in the development of ES. This review provides a non-exhaustive overview of ES from a clinical and biological point of view, describing its main clinical, cellular and molecular aspects

    CXCL13 as a Biomarker of Immune Activation During Early and Chronic HIV Infection

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    Background: CXCL13 is preferentially secreted by Follicular Helper T cells (TFH) to attract B cells to germinal centers. Plasma levels of CXCL13 have been reported to be elevated during chronic HIV-infection, however there is limited data on such elevation during early phases of infection and on the effect of ART. Moreover, the contribution of CXCL13 to disease progression and systemic immune activation have been partially defined. Herein, we assessed the relationship between plasma levels of CXCL13 and systemic immune activation.Methods: Study samples were collected in 114 people living with HIV (PLWH) who were in early (EHI) or chronic (CHI) HIV infection and 35 elite controllers (EC) compared to 17 uninfected controls (UC). A subgroup of 11 EHI who initiated ART and 14 who did not were followed prospectively. Plasma levels of CXCL13 were correlated with CD4 T cell count, CD4/CD8 ratio, plasma viral load (VL), markers of microbial translocation [LPS, sCD14, and (1→3)-β-D-Glucan], markers of B cell activation (total IgG, IgM, IgA, and IgG1-4), and inflammatory/activation markers like IL-6, IL-8, IL-1β, TNF-α, IDO-1 activity, and frequency of CD38+HLA-DR+ T cells on CD4+ and CD8+ T cells.Results: Plasma levels of CXCL13 were elevated in EHI (127.9 ± 64.9 pg/mL) and CHI (229.4 ± 28.5 pg/mL) compared to EC (71.3 ± 20.11 pg/mL), and UC (33.4 ± 14.9 pg/mL). Longitudinal analysis demonstrated that CXCL13 remains significantly elevated after 14 months without ART (p &lt; 0.001) and was reduced without normalization after 24 months on ART (p = 0.002). Correlations were observed with VL, CD4 T cell count, CD4/CD8 ratio, LPS, sCD14, (1→3)-β-D-Glucan, total IgG, TNF-α, Kynurenine/Tryptophan ratio, and frequency of CD38+HLA-DR+ CD4 and CD8 T cells. In addition, CMV+ PLWH presented with higher levels of plasma CXCL13 than CMV- PLWH (p = 0.005).Conclusion: Plasma CXCL13 levels increased with HIV disease progression. Early initiation of ART reduces plasma CXCL13 and B cell activation without normalization. CXCL13 represents a novel marker of systemic immune activation during early and chronic HIV infection and may be used to predict the development of non-AIDS events

    Producción ovina agroecológica en áreas periurbanas con regulaciones ambientales. ¿Una opción productiva y económicamente factible?

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    En Argentina, la intensificación de los sistemas agrícolas y las consecuencias sociales y ambientales derivadas del proceso, han generado cuestionamientos respecto del modelo productivo imperante. Esta situación se ha traducido en la sanción de normas que regulan el uso de agroquímicos en las zonas urbanas, periurbanas que se convierten en restricciones como la ley provincial N° 3288, que establece zonas de resguardo ambiental. Esta nueva situación de las zonas de transición urbano-rural genera una necesaria evolución hacia sistemas con bases agroecológicas. La Facultad de Ciencias Veterinarias de la Universidad Nacional de la Pampa gestiona un Campo Escuela en inmediaciones de la Ciudad de General Pico que se encuentra alcanzado por la citada ley, lo que implica un importante desafío de gestión lograr en forma exitosa este proceso de transición. En este contexto, surgen una serie de medidas y estudios, entre otros la creación de la Unidad Demostrativa Ganadera de Producción Pastoril Agroecológica (UDGPPA) en el Campo Escuela UDEP “Dr. Hugo Roberto Álvarez” y el proyecto de investigación “Análisis de la rentabilidad económica de un sistema de producción ovina agroecológica en el periurbano de la ciudad de General Pico”. El proyecto citado tiene como objetivos: a) Evaluar la factibilidad económica del sistema de producción ovina de la UDGPPA, de la Facultad de Ciencias Veterinarias de la UNLPam. b) Determinar la escala de un sistema mínimo rentable que permita mantener una familia tipo por encima de la línea de pobreza. Básicamente, intenta contribuir al fortalecimiento de la transición de los sistemas pecuarios periurbanos hacia prácticas sostenibles, en línea con las metas propuestas por los ODS con un enfoque de escala local. El documento expone el marco conceptual desarrollado por el equipo de investigació

    Thèse médecine

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