2,543 research outputs found

    A yeast three-hybrid system that reconstitutes mammalian hypoxia inducible factor regulatory machinery

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    Background: Several human pathologies, including neoplasia and ischemic cardiovascular diseases, course with an unbalance between oxygen supply and demand ( hypoxia). Cells within hypoxic regions respond with the induction of a specific genetic program, under the control of the Hypoxia Inducible Factor (HIF), that mediates their adaptation to the lack of oxygen. The activity of HIF is mainly regulated by the EGL-nine homolog (EGLN) enzymes that hydroxylate the alpha subunit of this transcription factor in an oxygen-dependent reaction. Hydroxylated HIF is then recognized and ubiquitinilated by the product of the tumor suppressor gene, pVHL, leading to its proteosomal degradation. Under hypoxia, the hydroxylation of HIF by the EGLNs is compromised due to the lack of oxygen, which is a reaction cosubstrate. Thus, HIF escapes degradation and drives the transcription of its target genes. Since the progression of the aforementioned pathologies might be influenced by activation of HIF-target genes, development of small molecules with the ability to interfere with the HIF-regulatory machinery is of great interest.Results: Herein we describe a yeast three-hybrid system that reconstitutes mammalian HIF regulation by the EGLNs and VHL. In this system, yeast growth, under specific nutrient restrictions, is driven by the interaction between the beta domain of VHL and a hydroxyproline-containing HIF alpha peptide. In turn, this interaction is strictly dependent on EGLN activity that hydroxylates the HIFa peptide. Importantly, this system accurately preserves the specificity of the hydroxylation reaction toward specific substrates. We propose that this system, in combination with a matched control, can be used as a simple and inexpensive assay to identify molecules that specifically modulate EGLN activity. As a proof of principle we show that two known EGLN inhibitors, dimethyloxaloylglycine (DMOG) and 6-chlor-3-hydroxychinolin-2-carbonic acid-N-carboxymethylamide (S956711), have a profound and specific effect on the yeast HIF/EGLN/VHL system.Conclusion: The system described in this work accurately reconstitutes HIF regulation while preserving EGLN substrate specificity. Thus, it is a valuable tool to study HIF regulation, and particularly EGLN biochemistry, in a cellular context. In addition, we demonstrate that this system can be used to identify specific inhibitors of the EGLN enzymes

    Diseño térmico preliminar del Instrumento PHI de Solar Orbiter

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    En este trabajo se describe el subsistema de control térmico de PHI y se presentan las predicciones de temperaturas obtenidas para los distintos casos de carga. Debido a la naturaleza de la órbita seguida por el satélite en el cual PHI va embarcado (Solar Orbiter), el ambiente en el cual va a tener que operar PHI será muy exigente, convirtiendo el diseño térmico en un auténtico desafío. Los resultados obtenidos muestran la viabilidad de PHI desde el punto de vista térmico, aunque indiscutiblemente el instrumento va a operar en un entorno térmico muy hostil

    Thermal behaviour of Sunrise, a balloon-borne solar Telescope

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    Sunrise is a solar telescope, successfully flown in June 2009 with a long duration balloon from the Swedish Space Corporation Esrange launch site. The design of the thermal control of SUNRISE was quite critical because of the sensitivity to temperature of the optomechanical devices and the electronics. These problems got more complicated due the size and high power dissipation of the system. A detailed thermal mathematical model of SUNRISE was set up to predict temperatures. In this communication the thermal behaviour of SUNRISE during flight is presented. Flight temperatures of some devices are presented and analysed. The measured data have been compared with the predictions given by the thermal mathematical models. The main discrepancies between flight data and the temperatures predicted by the models have been identified. This allows thermal engineers to improve the knowledge of the thermal behaviour of the system for future missions

    Analysis of cosmic ray variations observed by the CARPET in association with solar flares in 2011-2012

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    The CARPET cosmic ray detector was installed on April 2006 at CASLEO (Complejo Astronmico El Leoncito) at the Argentinean Andes (31.8S, 69.3W, 2550 m, Rc=9.65 GV). This instrument was developed within an international cooperation between the Lebedev Physical Institute RAS (LPI; Russia), the Centro de Radio Astronomia e Astrofsica Mackenzie (CRAAM; Brazil) and the Complejo Astronmico el Leoncito (CASLEO; Argentina). In this paper we present results of analysis of cosmic ray variations recorded by the CARPET during increased solar flare activity in 2011-2012. Available solar and interplanetary medium observational data obtained onboard GOES, FERMI, ISS, as well as cosmic ray measurements by ground-based neutron monitor network were also used in the present analysis.Fil: Makhmutov, V.. Lebedev Physical Institute; Rusia. Universidade Presbiteriana Mackenzie; BrasilFil: Raulin, J. P.. Universidade Presbiteriana Mackenzie; BrasilFil: De Mendonca, R. R. S.. National Institute for Space Research; BrasilFil: Bazilevskaya, G. A.. Lebedev Physical Institute; RusiaFil: Correia, E.. Universidade Presbiteriana Mackenzie; Brasil. National Institute for Space Research; BrasilFil: Kaufmann, Pierre. Universidade Presbiteriana Mackenzie; BrasilFil: Marun, Adolfo Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Complejo Astronómico "El Leoncito". Universidad Nacional de Córdoba. Complejo Astronómico "El Leoncito". Universidad Nacional de la Plata. Complejo Astronómico "El Leoncito". Universidad Nacional de San Juan. Complejo Astronómico "El Leoncito"; ArgentinaFil: Fernandez, German Enzo Leonel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Complejo Astronómico "El Leoncito". Universidad Nacional de Córdoba. Complejo Astronómico "El Leoncito". Universidad Nacional de la Plata. Complejo Astronómico "El Leoncito". Universidad Nacional de San Juan. Complejo Astronómico "El Leoncito"; ArgentinaFil: Echer, E.. National Institute for Space Research; Brasi

    Decreased Expression of T-Cell Costimulatory Molecule CD28 on CD4 and CD8 T Cells of Mexican Patients with Pulmonary Tuberculosis

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    Patients with tuberculosis frequently develop anergy, a state of T-cell hyporesponsiveness in which defective T-cell costimulation could be a factor. To know if the expression of T-cell costimulatory molecules was altered in tuberculosis, we analyzed the peripheral blood T-cell phenotype of 23 Mexican patients with pulmonary tuberculosis. There was severe CD4 (P < .001) and CD8 (P < .01) lymphopenia and upregulation of costimulatory molecule CD30 on CD4 and CD8 T cells (P < .05); this increase was higher in relapsing tuberculosis. The main finding was severe downregulation of the major costimulatory molecule CD28 on both CD8 and CD4 T cells (P < .001). Depletion of the CD4/CD28 subset, a hitherto undescribed finding, is relevant because CD4 T cells constitute the main arm of the cell-mediated antimycobacterial immune response

    Polyorchidism: A rare cause of testicular torsion

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    Pacientes con PoliorquidismoBackground: Polyorchidism is a rare congenital anomaly of the urogenital tract. Usually, it requires conservative management; however, this varies according to each patient. This report summarizes the possible clinical presentation and the feasible management options depending on the patients and testicular characteristics. Case presentation: 23 years old young male presented to our outpatient clinic with intermittent left testicular pain associated with tenderness to palpation. On the physical exam, he had a palpable mass at the upper pole of the left testis. He was taken to an MRI, which showed a normal right testis with a left mass-dependent of the upper pole of the left testis. He was discharged after pain control was achieved; however, he presented again to the Emergency Room with acute left testicular pain one week later. The physical exam was suggestive of left testicular torsion. He was taken to surgery for scrotal exploration and bilateral testicular fixation. Polyorchidism was confirmed intraoperatively. Conclusions: Polyorchidism is a rare pathology of the male genitalia. When suspected, a thorough physical examination is always mandatory. It is essential to individualize the patients’ cases to decide whether conservative management is attainable, with radiologic studies support.https://orcid.org/0000-0002-0700-5686https://orcid.org/0000-0003-4297-6215https://orcid.org/0000-0002-3772-6177https://orcid.org/0000-0002-7495-5139https://orcid.org/0000-0002-9675-5963Revista Internacional - No indexadaN

    Picometer-Stable Hexagonal Optical Bench to Verify LISA Phase Extraction Linearity and Precision

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    The Laser Interferometer Space Antenna (LISA) and its metrology chain have to fulfill stringent performance requirements to enable the space-based detection of gravitational waves. This implies the necessity of performance verification methods. In particular, the extraction of the interferometric phase, implemented by a phasemeter, needs to be probed for linearity and phase noise contributions. This Letter reports on a hexagonal quasimonolithic optical bench implementing a three-signal test for this purpose. Its characterization as sufficiently stable down to picometer levels is presented as well as its usage for a benchmark phasemeter performance measurement under LISA conditions. These results make it a candidate for the core of a LISA metrology verification facility

    Prediction of regional agro-industrial wastes characteristics by thermogravimetric analysis to obtain bioenergy using thermal process

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    The use of energy from biomass is becoming more common worldwide. This energy source has several benefits that promote its acceptance; it is bio-renewable, non-toxic and biodegradable. To predict its behavior as a fuel during thermal treatment, its characterization is necessary. The experimental determination of ultimate analysis data requires special instrumentation, while proximate analysis data can be obtained easily by using common equipment but, the required time is high. In this work, a methodology is applied based on thermogravimetric analysis, curves deconvolution and empirical correlations for characterizing different regional agro-industrial wastes to determine the high heating value, the contents of moisture, volatiles matter, fixed carbon, ash, carbon, hydrogen, oxygen, lignin, cellulose and hemicellulose. The obtained results are similar to those using standard techniques, showing the accuracy of proposed method and its wide application range. This methodology allows to determine the main parameters required for industrial operation in only in one step, saving time.Fil: Saffe Pinto, María Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación y Desarrollo en Ingeniería de Procesos, Biotecnología y Energías Alternativas. Grupo Vinculado Instituto de Ingeniería Química | Universidad Nacional del Comahue. Instituto de Investigación y Desarrollo en Ingeniería de Procesos, Biotecnología y Energías Alternativas. Grupo Vinculado Instituto de Ingeniería Química; ArgentinaFil: Fernandez Brizuela, Anabel Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación y Desarrollo en Ingeniería de Procesos, Biotecnología y Energías Alternativas. Grupo Vinculado Instituto de Ingeniería Química | Universidad Nacional del Comahue. Instituto de Investigación y Desarrollo en Ingeniería de Procesos, Biotecnología y Energías Alternativas. Grupo Vinculado Instituto de Ingeniería Química; ArgentinaFil: Mazza, German Delfor. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación y Desarrollo en Ingeniería de Procesos, Biotecnología y Energías Alternativas. Universidad Nacional del Comahue. Instituto de Investigación y Desarrollo en Ingeniería de Procesos, Biotecnología y Energías Alternativas; ArgentinaFil: Rodriguez, Rosa Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación y Desarrollo en Ingeniería de Procesos, Biotecnología y Energías Alternativas. Grupo Vinculado Instituto de Ingeniería Química | Universidad Nacional del Comahue. Instituto de Investigación y Desarrollo en Ingeniería de Procesos, Biotecnología y Energías Alternativas. Grupo Vinculado Instituto de Ingeniería Química; Argentin
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