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En la búsqueda de una alternativa a las fuentes de alimentación tradicionales aparecen los energy harvester con el objetivo de aprovechar la energía que se genera en el ambiente o con la propia actividad humana para el uso de dispositivos biomédicos como puede ser una bomba de insulina. Se realiza un análisis de la situación actual de estos dispositivos y más concretamente de los generadores piezoeléctricos, termoeléctricos y solares. Posteriormente se realizan simulaciones para comprobar su funcionalidad., In the search for an alternative to traditional power sources, energy harvesters appear with the aim of taking advantage of the energy generated in the environment or with human activity itself for the use of biomedical devices such as an insulin pump. An analysis of the current situation of these devices and more specifically of piezoelectric, thermoelectric, and solar generators is conducted. Subsequently, simulations are conducted to verify its functionality

In the last years, the Radio Frequency Integrated Circuit (RFIC) market has grown significantly, being part of an RFIC Innovation Cycle. Due to the two main application drivers of communication and sensing, the market is pushing to have circuits operating at higher and higher frequencies, making the role of millimeter wave (mmWave) devices more and more important. In this band, many applications such as mmWave 5G, automotive radars and imaging unfold. However, circuit design at such high frequencies brings new challenges that must be faced. One of the main challenges is the design for power amplifier (PA) stability. The need of high gain in operating frequencies together with the fact that PA designs are becoming more integrated, with higher density, more potential feedback loops, easier resonances due to smaller wavelengths and less accessibility after fabrication, results in an increased risk of instability. On top of that, very often, designs that appear to be stable in simulations are not in measurements. This thesis aims to study the stability of mmWave PAs, providing a set of techniques that can be used by PA designers during design and layout to analyze and improve the stability of the design. With that goal, an extensive review of literature covering the main stability verification techniques is presented, showing their advantages and drawbacks and outlining the use of pole-zero identification together with loop gain as the most rigorous and insightful techniques. A stability analysis framework based on MATLAB and combined with Keysight ADS is described. The framework includes parametric and multiple nodes simulation, identification of critical nodes, improvements in selection of order of transfer function and modifications for computational efficiency. The framework is tested with three different designs, showing the expected results. The framework, together with complementary techniques, is applied to the use case of a 28-GHz Gallium Nitride (GaN) multista

Background and Purpose Liver fibrosis induced by chronic hepatic injury remains a major cause of morbidity and mortality worldwide. Identification of susceptibility/prognosis factors and new therapeutic tools for treating hepatic fibrotic disorders are urgent medical needs. Cortistatin is a neuropeptide with potent anti-inflammatory and anti-fibrotic activities in lung that binds to receptors that are expressed in liver fibroblasts and hepatic stellate cells. We evaluated the capacity of cortistatin to regulate liver fibrosis. Experimental Approach We experimentally induced liver fibrosis in mice by chronic CCl4 exposure and bile duct ligation and evaluated the histopathological signs and fibrotic markers. Key Results Hepatic expression of cortistatin inversely correlated with liver fibrosis grade in mice and humans with hepatic disorders. Cortistatin-deficient mice showed exacerbated signs of liver damage and fibrosis and increased mortality rates when challenged by hepatotoxic and cholestatic injury. Compared with wild-type mice, non-parenchymal liver cells isolated from cortistatin-deficient mice showed increased presence of cells with activated myofibroblast phenotypes and a differential genetic signature that is indicative of activated hepatic stellate cells and periportal fibroblasts and of myofibroblasts with active contractile apparatus. Cortistatin treatment reversed in vivo and in vitro these exaggerated fibrogenic phenotypes and protected from progression to severe liver fibrosis in response to hepatic injury. Conclusion and Implications: We identify cortistatin as an endogenous molecular brake on liver fibrosis and its deficiency as a potential poor-prognosis marker for chronic hepatic disorders that link with fibrosis. Cortistatin-based therapies emerge as attractive strategies for ameliorating severe hepatic fibrosis of various aetiologies.

Mesenchymal stromal stem/cells (MSC) therapies are clinically used in a wide range of disorders based on their robust HLA-independent immunosuppressive and anti-inflammatory properties. However, the mechanisms underlying MSC therapeutic activity remain elusive as demonstrated by the unpredictable therapeutic efficacy of MSC infusions reported in multiple clinical trials. A seminal recent study showed that infused MSCs are actively induced to undergo apoptosis by recipient cytotoxic T cells, a mechanism that triggers in vivo recipient-induced immunomodulation by such apoptotic MSCs, and the need for such recipient cytotoxic cell activity could be replaced by the administration of ex vivo-generated apoptotic MSCs. Moreover, the use of MSC-derived extracellular vesicles (MSC-EVs) is being actively explored as a cell-free therapeutic alternative over the parental MSCs. We hypothesized that the introduction of a "suicide gene" switch into MSCs may offer on-demand in vivo apoptosis of transplanted MSCs. Here, we prompted to investigate the utility of the iCasp9/AP1903 suicide gene system in inducing apoptosis of MSCs. iCasp9/AP1903-induced apoptotic MSCs (MSCiCasp9+) were tested in vitro and in in vivo models of acute colitis. Our data show a very similar and robust immunosuppressive and anti-inflammatory properties of both "parental" alive MSCGFP+ cells and apoptotic MSCiCasp9+ cells in vitro and in vivo regardless of whether apoptosis was induced in vivo or in vitro before administering MSCiCasp9+ lysates. This development of an efficient iCasp9 switch may potentiate the safety of MSC-based therapies in the case of an adverse event and, will also circumvent current logistic technical limitations and biological uncertainties associated to MSC-EVs.

Neurological disorders, including neurodegenerative diseases, are often characterized by neuroinflammation, which is largely driven by microglia, the resident immune cells of the central nervous system (CNS). Under these conditions, microglia are able to secrete neurotoxic substances, provoking neuronal cell death. However, microglia in the healthy brain carry out CNS-supporting functions. This is due to the ability of microglia to acquire different phenotypes that can play a neuroprotective role under physiological conditions or a pro-inflammatory, damaging one during disease. Therefore, therapeutic strategies focus on the downregulation of these neuroinflammatory processes and try to re-activate the neuroprotective features of microglia. Mesenchymal stem cells (MSC) of different origins have been shown to exert such effects, due to their immunomodulatory properties. In recent years, MSC derived from adipose tissue have been made the center of attention because of their easy availability and extraction methods. These cells induce a neuroprotective phenotype in microglia and downregulate neuroinflammation, resulting in an improvement of clinical symptoms in a variety of animal models for neurological pathologies, e.g., Alzheimer¿s disease, traumatic brain injury and ischemic stroke. In this review, we will discuss the application of adipose tissue-derived MSC and their conditioned medium, including extracellular vesicles, in neurological disorders, their beneficial effect on microglia and the signaling pathways involved.

El Consejo Superior de Investigaciones Científicas (CSIC) lanza 14 Temáticas estratégicas para coordinar equipos de investigación punteros y multidisciplinares que amplíen las fronteras del conocimiento en áreas como el origen de la vida, la composición de la materia, la exploración del espacio, el funcionamiento del cerebro, la transición energética, la sociedad global y el impacto del cambio global, entre otros. Estas temáticas funcionarán como grandes equipos de investigación para potenciar la sinergia entre áreas del conocimiento que logren objetivos a largo plazo. Las nuevas Temáticas estratégicas han sido impulsadas desde la Vicepresidencia de Investigación Científica y Técnica del CSIC, con la colaboración de las Comisiones de Áreas globales, y durante el último año ha supuesto un gran esfuerzo colaborativo de más de 1.100 investigadores pertenecientes a 112 centros del CSIC, así como colaboradores externos de otros Organismos Públicos de Investigación y Universidades, que han contribuido activamente a identificar estos retos para los próximos años, así como su evolución en el horizonte 2030.

El Libro Blanco Desafíos Científicos CSIC 2030 presenta la reflexión planteada desde el CSIC en torno a 14 Temáticas estratégicas elegidas por su impacto científico e importancia social. Se analizan cuestiones fundamentales que incluyen la futura exploración del universo, la inteligencia artificial, la investigación de los océanos, el desarrollo de una energía limpia, segura y eficiente o la comprensión de cómo funciona el cerebro. El documento aborda retos complejos en áreas como la salud y las ciencias sociales y las temáticas estratégicas seleccionadas cubren tanto cuestiones básicas, como potenciales aplicaciones del conocimiento. “Los 14 Libros Blancos, diseñados como referencia para la elaboración de la estrategia científica de la institución, permiten conocer la investigación que se realiza hoy en día en los centros del CSIC, y a la vez proporcionan una visión global de lo que serán las prioridades científicas a lo largo de la próxima década”, explica Victoria Moreno-Arribas, vicepresidenta adjunta de Áreas Científico-Técnicas del CSIC. En cada uno de los desafíos se identifican, además, las líneas de trabajo que, a través de la colaboración de varios equipos del CSIC altamente complementarios y otros grupos asociados, ampliarán las fronteras del conocimiento y plantearán soluciones a grandes desafíos globales.

Natural phenolic compounds found in food have demonstrated interesting preventive and therapeutic effects on a large variety of pathologies. Indeed, some of them, such as resveratrol (RES), have been examined in clinical trials. Nevertheless, their success has been scarce mainly due to their low bioavailability. In this study, we found serendipitously that O-silyl RES derivatives exerted a better neuroprotective activity than resveratrol itself and decided to explore them as potential drugs for neurodegenerative and neurological diseases. We have also designed and prepared a series of O-silyl RES prodrugs to improve their bioavailability. We found that di-triethylsilyl and di-triisopropylsilyl RES derivatives were better in vitro neuroprotective and anti-inflammatory agents than RES. Among these derivatives and their corresponding acyl-, glycosyl- and carbamoyl-prodrugs, 3,5-triethylsilyl-4’-(6″-octanoylglucopyranosyl) resveratrol 26 showed the best profile on toxicity and neuroprotective activity in zebra fish embryo. Compound 26 was also capable of reducing the loss of motor coordination in a 3-nitropropionic acid mice model of Huntington's disease, in a similar way to RES. However, 26 diminished pro-inflammatory cytokine IL-6 to a higher extent than RES and improved the latency to fall in the rotarod test by 10% with respect to RES. Finally, we investigated 26 and RES as potential treatments on an experimental autoimmune encephalomyelitis (EAE) multiple sclerosis mice model. We observed that, in a therapeutic regimen, 26 significantly diminished the progression of EAE severity and reduced the percentage of animals with moderate to severe clinical score, whereas RES showed no improvement.