29 research outputs found

    Test-Driven Design of an Active Dual-Polarized Log-Periodic Antenna for the Square Kilometre Array

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    An active dual-polarized Log-Periodic antenna has been designed to meet the requirements of the low-frequency (50 - 350 MHz) radio telescope of the Square Kilometre Array (SKA). The integration of antenna and low noise amplifier has been conceived in order to achieve a high degree of testability. This aspect has been found to be crucial to obtain a smooth frequency response compatible with the SKA science cases. The design has also been driven by other factors such as the large-volume production (more than 130 000 antennas will be built) and the environmental conditions of the harsh Australian desert. A specific verification approach based on both wideband radiometric spectral and spatial measurements in relevant laboratory and in-situ conditions has been developed. Electromagnetic analyses and experimental results exhibit a very good agreement. In December 2019, this antenna was part of the reference solution for the System Critical Design Review of the SKA

    ASCs-exosomes recover coupling efficiency and mitochondrial membrane potential in an in vitro model of ALS

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    The amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by motoneurons death. Mutations in the superoxide dismutase 1 (SOD1) protein have been identified to be related to the disease. Beyond the different altered pathways, the mitochondrial dysfunction is one of the major features that leads to the selective death of motoneurons in ALS. The NSC-34 cell line, overexpressing human SOD1(G93A) mutant protein [NSC-34(G93A)], is considered an optimal in vitro model to study ALS. Here we investigated the energy metabolism in NSC-34(G93A) cells and in particular the effect of the mutated SOD1(G93A) protein on the mitochondrial respiratory capacity (complexes I-IV) by high resolution respirometry (HRR) and cytofluorimetry. We demonstrated that NSC-34(G93A) cells show a reduced mitochondrial oxidative capacity. In particular, we found significant impairment of the complex I-linked oxidative phosphorylation, reduced efficiency of the electron transfer system (ETS) associated with a higher rate of dissipative respiration, and a lower membrane potential. In order to rescue the effect of the mutated SOD1 gene on mitochondria impairment, we evaluated the efficacy of the exosomes, isolated from adipose-derived stem cells, administrated on the NSC-34(G93A) cells. These data show that ASCs-exosomes are able to restore complex I activity, coupling efficiency and mitochondrial membrane potential. Our results improve the knowledge about mitochondrial bioenergetic defects directly associated with the SOD1(G93A) mutation, and prove the efficacy of adipose-derived stem cells exosomes to rescue the function of mitochondria, indicating that these vesicles could represent a valuable approach to target mitochondrial dysfunction in ALS

    ASC-exosomes ameliorate the disease progression in SOD1(G93A) murine model underlining their potential therapeutic use in human ALS

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    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive degeneration of motoneurons. To date, there is no effective treatment available. Exosomes are extracellular vesicles that play important roles in intercellular communication, recapitulating the effect of origin cells. In this study, we tested the potential neuroprotective effect of exosomes isolated from adipose-derived stem cells (ASC-exosomes) on the in vivo model most widely used to study ALS, the human SOD1 gene with a G93A mutation (SOD1(G93A)) mouse. Moreover, we compared the effect of two different routes of exosomes administration, intravenous and intranasal. The effect of exosomes administration on disease progression was monitored by motor tests and analysis of lumbar motoneurons and glial cells, neuromuscular junction, and muscle. Our results demonstrated that repeated administration of ASC-exosomes improved the motor performance; protected lumbar motoneurons, the neuromuscular junction, and muscle; and decreased the glial cells activation in treated SOD1(G93A) mice. Moreover, exosomes have the ability to home to lesioned ALS regions of the animal brain. These data contribute by providing additional knowledge for the promising use of ASC-exosomes as a therapy in human ALS

    Test-Driven Design of an Active Dual-Polarized Log-Periodic Antenna for the Square Kilometre Array

    Get PDF
    An active dual-polarized Log-Periodic antenna has been designed to meet the requirements of the low-frequency (50-350 MHz) radio telescope of the Square Kilometre Array (SKA). The integration of antenna and low noise amplifier has been conceived in order to achieve a high degree of testability. This aspect has been found to be crucial to obtain a smooth frequency response compatible with the SKA science cases. The design has also been driven by other factors such as the large-volume production (more than 130 000 antennas will be built) and the environmental conditions of the harsh Australian desert. A specific verification approach based on both wideband radiometric spectral and spatial measurements in relevant laboratory and in-situ conditions has been developed. Electromagnetic analyses and experimental results exhibit a very good agreement. In December 2019, this antenna was part of the reference solution for the System Critical Design Review of the SKA

    LRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitus

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    Type 1 diabetes mellitus (T1DM) is due to the selective destruction of islet beta cells by immune cells. Current therapies focused on repressing the immune attack or stimulating beta cell regeneration still have limited clinical efficacy. Therefore, it is timely to identify innovative targets to dampen the immune process, while promoting beta cell survival and function. Liver receptor homologue-1 (LRH-1) is a nuclear receptor that represses inflammation in digestive organs, and protects pancreatic islets against apoptosis. Here, we show that BL001, a small LRH-1 agonist, impedes hyperglycemia progression and the immune-dependent inflammation of pancreas in murine models of T1DM, and beta cell apoptosis in islets of type 2 diabetic patients, while increasing beta cell mass and insulin secretion. Thus, we suggest that LRH-1 agonism favors a dialogue between immune and islet cells, which could be druggable to protect against diabetes mellitus.the Juvenile Diabetes Research Foundation (17-2013-372 to B.R.G.), the Consejeria de Salud, Fundacion Publica Andaluza Progreso y Salud, Junta de Andalucia (PI-0727-2010 to B.R.G. and P10CTS6505 to B.S.), Consejeria de Economia, Innovacion y Ciencia (P10.CTS.6359 to B.R.G.), the Ministerio de Economia y Competidividad cofunded by Fondos FEDER (PI10/00871, PI13/00593, and BFU2017-83588-P to B.R.G.; PI14/01015, RD12/0019/0028, and RD16/0011/0034 to B.S.; PI16/00259 to A. H.) and Deutsche Forschungsgemeinschaft (GRK-1789 麓CEMMA麓 and DFG SCHI-505/ 6-1 to R.S.). Special thanks to the families of the DiabetesCero Foundation that graciously supported this work (to B.R.G.). A.M.M. is a recipient of a Miguel Servet grant (CP14/ 00105) from the Instituto de Salud Carlos III co-funded by Fondos FEDER whereas E.F. M. is a recipient of a Juan de la Cierva Fellowship. I.G.H.G. is supported by a fellowship from Amarna Therapeutics. In some instances, human islets were procured through the European Consortium for Islet Transplantation funded by Juvenile Diabetes Research Foundation (3-RSC-2016-162-I-X)

    Los privilegios vecinales. Su aplicaci贸n en Chile en el siglo XVIII

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    Si nos remontamos en el tiempo, comprobamos que la obligaci贸n de premiar a los buenos servidores figura en el C贸digo de las Partidas y es "noci贸n capital en las monarqu铆as guerreras de la Reconquista". El mismo principio se sostuvo durante la colonizaci贸n espa帽ola en Indias, incorpor谩ndose a las Ordenanzas de Poblaci贸n de 1573 y a la Recopilaci贸n de Leyes de Indias de 1680. En los preceptos de ambos cuerpos legales se distingue a los primeros pobladores como una forma de destacar el sentido urbano de la colonizaci贸n

    Los privilegios vecinales. Su aplicaci贸n en Chile en el siglo XVIII

    No full text
    Si nos remontamos en el tiempo, comprobamos que la obligaci贸n de premiar a los buenos servidores figura en el C贸digo de las Partidas y es "noci贸n capital en las monarqu铆as guerreras de la Reconquista". El mismo principio se sostuvo durante la colonizaci贸n espa帽ola en Indias, incorpor谩ndose a las Ordenanzas de Poblaci贸n de 1573 y a la Recopilaci贸n de Leyes de Indias de 1680. En los preceptos de ambos cuerpos legales se distingue a los primeros pobladores como una forma de destacar el sentido urbano de la colonizaci贸n

    Intentos de redistribuci贸n de la propiedad de la tierra en Chile, en el siglo XVIII

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    Con la destrucci贸n de las ciudades del Sur despu茅s del desastre de Curalaba, la colonizaci贸n del pa铆s se reorient贸 a la regi贸n聽 ubicada al Norte del Biob铆o. Las p茅rdidas humanas, la disminuci贸n de la mano de obra y el abandono obligado de importantes lavaderos de oro, fueron determinantes para que de una econom铆a fundamentalmente aur铆fera, como la del siglo XVI, se pasase a una econom铆a pecuaria en el siglo XVII y a otra predominantemente cerealista a partir del siglo XVIII. Al centrarse en la ganader铆a y en la agricultura la actividad econ贸mica, la tierra se valoriz贸 y aument贸 la demanda de mercedes de tierras de parte de los colonos. Entre 1599 y 1602 la distribuci贸n de mercedes en el valle de Santiago Fue incre铆blemente r谩pida, tanto por motivos mercantiles como por la despoblaci贸n de las ciudades del Sur. El proceso de concesi贸n de mercedes de tierras se prolongar铆a en la Gobernaci贸n hasta 1718, tanto porque el Reino hab铆a quedado al margen de la pol铆tica inaugurada por la Corona en 1591, que convirti贸 "las tierras bald铆as en regal铆as de car谩cter fiscal. con el fin de enajenarlas o exigir el pago de una composici贸n pecuniaria, por defecto de t铆tulo",聽 cuanto porque los gobernadores siguieron otorgando ilegalmente concesiones de tierras, pese a que leyes de la Recopilaci贸n de 1680, las Rs. C茅dulas de 19 de mano de 1709, y 20 de marzo de 1710 las prohibieron

    Acetylation state of RelA modulated by epigenetic drugs prolongs survival and induces a neuroprotective effect on ALS murine model

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    Dysregulation in acetylation homeostasis has been implicated in the pathogenesis of the amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. It is known that the acetylation of transcriptional factors regulates their activity. The acetylation state of NF-kB RelA has been found to dictate the neuroprotective versus the neurotoxic effect of p50/RelA. Here we showed that the pro-apoptotic acetylation mode of RelA, involving a general lysine deacetylation of the subunit with the exclusion of the lysine 310, is evident in the lumbar spinal cord of SOD1(G93A) mice, a murine model of ALS. The administration of the HDAC inhibitor MS-275 and the AMPK/sirtuin 1 activator resveratrol restored the normal RelA acetylation in SOD1(G93A) mice. The SOD1(G93A) mice displayed a 3 weeks delay of the disease onset, associated with improvement of motor performance, and 2 weeks increase of lifespan. The epigenetic treatment rescued the lumbar motor neurons affected in SOD1(G93A) mice, accompanied by increased levels of protein products of NF-kB-target genes, Bcl-xL and brain-derived neurotrophic factor. In conclusion, we here demonstrate that MS-275 and resveratrol restore the acetylation state of RelA in the spinal cord, delaying the onset and increasing the lifespan of SOD1(G93A) mice
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