BlueState: un entorno para el aprendizaje de máquinas de estados de UML

El modelo de máquinas de estados es el más complejo de los que integran el lenguaje UML, base actual de la docencia en la mayoría de las asignaturas de Ingeniería del Software. La complejidad (y la consiguiente dificultad de aprendizaje) del modelo viene dada tanto por el elevado número de componentes que lo integran como por el nivel de abstracción propio del modelo. Para solventar estas dificultades se ha desarrollado BlueState, una herramienta que permite al alumno ejecutar una simulación de la ejecución de cualquier máquina de estados, acompañada de un seguimiento gráfico. BlueState también aporta un módulo de generación de código, que permite al alumno aprender a implementar el comportamiento de un sistema empleando una metodología dirigida por modelos

Oral Methylthioadenosine Administration Attenuates Fibrosis and Chronic Liver Disease Progression in Mdr2−/− Mice

BACKGROUND: Inflammation and fibrogenesis are directly related to chronic liver disease progression, including hepatocellular carcinoma (HCC) development. Currently there are few therapeutic options available to inhibit liver fibrosis. We have evaluated the hepatoprotective and anti-fibrotic potential of orally-administered 5'-methylthioadenosine (MTA) in Mdr2(-/-) mice, a clinically relevant model of sclerosing cholangitis and spontaneous biliary fibrosis, followed at later stages by HCC development. METHODOLOGY: MTA was administered daily by gavage to wild type and Mdr2(-/-) mice for three weeks. MTA anti-inflammatory and anti-fibrotic effects and potential mechanisms of action were examined in the liver of Mdr2(-/-) mice with ongoing fibrogenesis and in cultured liver fibrogenic cells (myofibroblasts). PRINCIPAL FINDINGS: MTA treatment reduced hepatomegaly and liver injury. α-Smooth muscle actin immunoreactivity and collagen deposition were also significantly decreased. Inflammatory infiltrate, the expression of the cytokines IL6 and Mcp-1, pro-fibrogenic factors like TGFβ2 and tenascin-C, as well as pro-fibrogenic intracellular signalling pathways were reduced by MTA in vivo. MTA inhibited the activation and proliferation of isolated myofibroblasts and down-regulated cyclin D1 gene expression at the transcriptional level. The expression of JunD, a key transcription factor in liver fibrogenesis, was also reduced by MTA in activated myofibroblasts. CONCLUSIONS/SIGNIFICANCE: Oral MTA administration was well tolerated and proved its efficacy in reducing liver inflammation and fibrosis. MTA may have multiple molecular and cellular targets. These include the inhibition of inflammatory and pro-fibrogenic cytokines, as well as the attenuation of myofibroblast activation and proliferation. Downregulation of JunD and cyclin D1 expression in myofibroblasts may be important regarding the mechanism of action of MTA. This compound could be a good candidate to be tested for the treatment of (biliary) liver fibrosis

Maresin 1 activates brown adipose tissue and promotes browning of white adipose tissue in mice

Objective Maresin 1 (MaR1) is a docosahexaenoic acid-derived proresolving lipid mediator with insulin-sensitizing and anti-steatosis properties. Here, we aim to unravel MaR1 actions on brown adipose tissue (BAT) activation and white adipose tissue (WAT) browning. Methods MaR1 actions were tested in cultured murine brown adipocytes and in human mesenchymal stem cells (hMSC)-derived adipocytes. In vivo effects of MaR1 were tested in diet-induced obese (DIO) mice and lean WT and Il6 knockout (Il6−/−) mice. Results In cultured differentiated murine brown adipocytes, MaR1 reduces the expression of inflammatory genes, while stimulates glucose uptake, fatty acid utilization and oxygen consumption rate, along with the upregulation of mitochondrial mass and genes involved in mitochondrial biogenesis and function and the thermogenic program. In Leucine Rich Repeat Containing G Protein-Coupled Receptor 6 (LGR6)-depleted brown adipocytes using siRNA, the stimulatory effect of MaR1 on thermogenic genes was abrogated. In DIO mice, MaR1 promotes BAT remodeling, characterized by higher expression of genes encoding for master regulators of mitochondrial biogenesis and function and iBAT thermogenic activation, together with increased M2 macrophage markers. In addition, MaR1-treated DIO mice exhibit a better response to cold-induced BAT activation. Moreover, MaR1 induces a beige adipocyte signature in inguinal WAT of DIO mice and in hMSC-derived adipocytes. MaR1 potentiates Il6 expression in brown adipocytes and BAT of cold exposed lean WT mice. Interestingly, the thermogenic properties of MaR1 were abrogated in Il6−/− mice. Conclusions These data reveal MaR1 as a novel agent that promotes BAT activation and WAT browning by regulating thermogenic program in adipocytes and M2 polarization of macrophages. Moreover, our data suggest that LGR6 receptor is mediating MaR1 actions on brown adipocytes, and that IL-6 is required for the thermogenic effects of MaR1

La investigación científica en el queso Idiazabal

Desde hace unos 15 años el queso Idiazabal ha sido objeto de una extensa investigación científica. Se describen algunos de los principales factores que inciden directamente en su calidad sensorial e higiénico-sanitaria, tanto durante el proceso de elaboración como durante los meses que dura la maduración. Entre estos factores destacamos el cuajo artesanal en pasta y la alimentación de las ovejas.Idiazabal gaztari buruzko zientzia-azterketa ugari egin izan dute azken 15 urteotan. Azterketa horiek agerian utzi dituzte gaztaren kalitatea eragiten duten eragileak, bai zentzumen-ezaugarrien aldetik baita higienearen eta osasunaren ikuspegitik ere, gazta egiteko prozesuan zein gazta heltzeko hilabeteetan zehar. Eragile horien artean, artisautza-gatzagia eta ardien elikadura azpimarratu ditzakegu.Depuis 15 ans, le fromage Idiazabal fait l'objet d'un vaste travail de recherche scientifique. Il comprend la description des principaux facteurs qui influent directement sur sa qualité sensorielle et hygièno-sanitaire, aussi bien durant le processus d'élaboration que pendant la période de maturation. Des facteurs tels que, notamment, la présure artisanale en pâte et l'alimentation des brebis.Idiazabal cheese has been extensively studied from a scientific perspective for the last 15 years. The present article describes some of the main factors that directly influence its sensory and hygienic quality, both during the fabrication process and during the ripening period. Among these factors the artisanally-prepared rennet and the role of grazing are considered

El neurodesarrollo a los dos años de vida de neonatos tratados en una unidad de cuidados intensivos neonatales

El objetivo principal de este estudio fue evaluar de forma prospectiva, a los 2 años de vida, el desarrollo de un grupo de neonatos tratados en la unidad de cuidados intensivos neonatales (UCIN) del Instituto Nacional de Perinatología de México. Se estudió desde el punto de vista neurológico, psicológico, auditivo, lingüístico, motor y neuromuscular a todos los neonatos nacidos entre el 1 de enero de 1992 y el 31 de diciembre de 1993 que hubieran ingresado a la UCIN y permanecido en ella 3 días o más. Se incluyó a 134 pacientes con una edad gestacional promedio de 32 semanas y un peso promedio al nacer de 1 677 g. De ellos, 75% habían sido sometidos a ventilación mecánica, con una estancia hospitalaria promedio de 51 días. En el examen efectuado a los 2 años, 66,5% de los niños fueron normales y 8,2% tuvieron alteraciones graves. Se encontraron asociaciones significativas entre el estado neurológico y los días de ventilación artificial (P < 0,0001), los días de estancia en la UCIN (P < 0,000004) y la edad gestacional en semanas (P < 0,03). No hubo ninguna asociación entre el sexo y el resultado de las valoraciones. En conclusión, los resultados obtenidos en este trabajo muestran una disminución de las alteraciones del neurodesarrollo en comparación con los resultados obtenidos en estudios similares hace 10 años

Prospective longitudinal study: use of faecal gluten immunogenic peptides to monitor children diagnosed with coeliac disease during transition to a gluten-free diet.

Treatment for coeliac disease is a lifelong strict gluten-free diet. Although guidelines recommend regular follow-up with dietary interviews and coeliac serology, these methods may be inaccurate. To evaluate the usefulness of faecal gluten immunogenic peptides to support the diagnosis and to determine the adherence to the gluten-free diet in coeliac children. Multicentre prospective observational study including 64 coeliac children. Faecal gluten peptides, and tissue transglutaminase and deamidated gliadin peptide antibodies were analyzed at diagnosis, and 6, 12 and 24 months thereafter. Gluten consumption was estimated from gluten peptide levels. Most children (97%) had detectable gluten peptides at diagnosis. On a gluten-free diet, the rate of gluten peptides increased from 13% at 6 months to 25% at 24 months. Mean estimated gluten exposure dropped from 5543 mg/d at diagnosis to 144 mg/d at 6 months, then increased to 606 mg/d by 24 months. In contrast, deamidated gliadin peptide antibodies normalised and only 20% had elevated tissue transglutaminase antibody by 24 months. The elevation of tissue transglutaminase antibody was more prolonged in patients with detectable gluten peptides (P  0.1). Dietitian assessment was only moderately correlated with gluten peptide detection (κ = 0.5). Faecal gluten peptides testing may guide treatment of coeliac disease prior to diagnosis and during the assessment diet adherence. Further studies could determine if early identification of gluten exposure reduces the need for expensive/invasive investigations for non-responsive coeliac disease. ClinicalTrials.gov Number: NCT02711397