Propuesta metodológica para la implementación de una arquitectura orientada a servicios en entornos de Sistemas de Fabricación Distribuida

Los Sistemas de Fabricación de Siguiente Generación, concebidos por la organización IMS (Intelligent Manufacturing Systems), cubrirán la demanda de un mercado cada vez más cambiante y exigente, reuniendo de forma dinámica las funciones de múltiples sistemas internos y externos a la propia empresa de fabricación en lo que conocemos por una empresa extendida. Sin embargo, resulta difícil estructurar estos sistemas para conseguir la flexibilidad deseada y la interoperabilidad con los de las demás organizaciones. Además, un defecto en el sistema tendría un fuerte impacto: afectaría no sólo a la empresa propietaria del sistema, sino también a sus colaboradores. Por estas razones, creemos que una buena decisión sería emplear una arquitectura orientada a servicios diseñada siguiendo una metodología que adopte los servicios como concepto central, en vez de como un detalle de implementación. Para que la arquitectura sea fiable en su conjunto, tendrá que ayudar a localizar errores antes de que sucedan en un entorno de producción. En este artículo proponemos el uso de técnicas de pruebas específicas para este tipo de sistemas, realizamos una comparación de las metodologías existentes para el desarrollo de arquitecturas orientadas a servicios y esbozamos una serie de extensiones sobre una de las existentes para integrar técnicas de prueba.As envisioned by the IMS (Intelligent Manufacturing Systems), Next Generation Manufacturing Systems will satisfy the needs of an increasingly fast-paced and demanding market by dynamically integrating systems from inside and outside the manufacturing firm itself into a so-called extended enterprise. However, organizing these systems to ensure the maximum flexibility and interoperability with those from other organizations is difficult. Additionally, a defect in the system would have a great impact: it would affect not only its owner, but also its partners. For these reasons, we argue that a service-oriented architecture (SOA) would be a good candidate. It should be designed following a methodology where services play a central role, instead of being an implementation detail. In order for the architecture to be reliable enough as a whole, the methodology will need to help find errors before they arise in a production environment. In this paper we propose using SOA-specific testing techniques, compare some of the existing SOA methodologies and outline several extensions upon one of them to integrate testing techniques

Conocimientos y factores de riesgo relacionados con la enfermedad de Chagas en dos comunidades panameñas donde Rhodnius pallescens es el vector principal

Introduction: The implementation of surveillance, control and prevention measures for Chagas’ disease requires an integrated approach. The sustainability of programs depends on community participation supported on a basic understanding of the problem.Objective: To evaluate the knowledge of people interviewed which facilitates or limits the surveillance, prevention and control of Chagas’ disease in two endemic Panamanian communities where Rhodnius pallescens is the main vector.Materials and methods: A questionnaire assessed the knowledge and risk factors related to Chagas’ disease in 201 people over 10 years of age from the endemic communities of Las Pavas and Lagartera Grande located on the western shore of Panama Canal. Additionally, with the help of the residents, the presence of triatomine bugs in 93 dwellings was evaluated during a year.Results: Of those interviewed, 69.2% (139/201) had poor or very poor knowledge about Chagas’ disease. Nearly 93% (187/201) was exposed to moderate or high risk factors. Triatomine bugs were collected in 20.4% (19/93) of the evaluated homes; 80% (66/76) of them were R. pallescens. Significant association was found between the presence of triatomines inside the houses and precarious housing (p<0.01).Conclusion: Despite having been exposed to health education-related programs, it is necessary to strengthen the basic knowledge about Chagas’ disease in the two communities before establishing prevention and surveillance measures which involve active participation of its inhabitants.Introducción. La implementación de los programas de vigilancia, prevención y control de la enfermedad de Chagas requiere una aproximación integral. La sostenibilidad de los programas depende de la participación comunitaria amparada en un conocimiento básico del problema.Objetivo. Evaluar los conocimientos de los entrevistados que facilitan o limitan la vigilancia, prevención y control de la enfermedad de Chagas en dos comunidades endémicas de Panamá donde Rhodnius pallescens es el vector principal.Materiales y métodos. Mediante un cuestionario se evaluaron los conocimientos y los factores de riesgo relacionados con la enfermedad de Chagas en 201 personas mayores de 10 años de las comunidades endémicas de Las Pavas y Lagartera Grande, ubicadas en la ribera oeste del Canal de Panamá. Con ayuda de los moradores también se evaluó la presencia de chinches triatominos en 93 viviendas a lo largo de un año.Resultados. De las personas entrevistadas, 69,2 % (139/201) tenía pocos o muy pocos conocimientos sobre la enfermedad de Chagas y 93 % (187/201) estaba expuesto a factores de riesgo moderados o altos. Se capturaron chinches triatominos en 20,4 % (19/93) de las viviendas evaluadas, de los cuales, el 86,8 % (66/76) era R. pallescens. Se encontró asociación significativa entre la presencia de chinches dentro de las viviendas y las viviendas catalogadas como precarias (p<0,01).Conclusión. A pesar de que en estas dos comunidades se han desarrollado programas de educación sanitaria, es necesario reforzar los conocimientos básicos sobre la enfermedad de Chagas antes de establecer medidas de prevención y vigilancia que involucren la participación activa de sus habitantes

Relationship Between Sonic Hedgehog Protein, Brain-Derived Neurotrophic Factor and Oxidative Stress in Autism Spectrum Disorders

The etiology of autism spectrum disorders (ASD) is not well known but oxidative stress has been suggested to play a pathological role. We report here that the serum levels of Sonic hedgehog (SHH) protein and brain-derived neurotrophic factor (BDNF) might be linked to oxidative stress in ASD. By using the whole blood or polymorphonuclear leukocytes, we demonstrated that autistic children produced a significantly higher level of oxygen free radicals (OFR). In addition, we found significantly higher levels of serum SHH protein in children with mild as well as severe form of autism. We also found that the serum level of BDNF was significantly reduced in autistic children with mild form of the disorder but not with severe form of the disorder. Our findings are the first to report a correlation between SHH, BDNF and OFR in autistic children, suggesting a pathological role of oxidative stress and SHH in autism spectrum disorders

Survival of infants born with esophageal atresia among 24 international birth defects surveillance programs

Background: Esophageal atresia (EA) affects around 2.3–2.6 per 10,000 births world-wide. Infants born with this condition require surgical correction soon after birth. Most survival studies of infants with EA are locally or regionally based. We aimed to describe survival across multiple world regions. Methods: We included infants diagnosed with EA between 1980 and 2015 from 24 birth defects surveillance programs that are members of the International Clearinghouse for Birth Defects Surveillance and Research. We calculated survival as the proportion of liveborn infants alive at 1 month, 1- and 5-years, among all infants with EA, those with isolated EA, those with EA and additional anomalies or EA and a chromosomal anomaly or genetic syndrome. We also investigated trends in survival over the decades, 1980s–2010s. Results: We included 6,466 liveborn infants with EA. Survival was 89.4% (95% CI 88.1–90.5) at 1-month, 84.5% (95% CI 83.0–85.9) at 1-year and 82.7% (95% CI 81.2–84.2) at 5-years. One-month survival for infants with isolated EA (97.1%) was higher than for infants with additional anomalies (89.7%) or infants with chromosomal or genetic syndrome diagnoses (57.3%) with little change at 1- and 5-years. Survival at 1 month improved from the 1980s to the 2010s, by 6.5% for infants with isolated EA and by 21.5% for infants with EA and additional anomalies. Conclusions: Almost all infants with isolated EA survived to 5 years. Mortality was higher for infants with EA and an additional anomaly, including chromosomal or genetic syndromes. Survival improved from the 1980s, particularly for those with additional anomalies

Zebrafish Mutants calamity and catastrophe Define Critical Pathways of Gene–Nutrient Interactions in Developmental Copper Metabolism

Nutrient availability is an important environmental variable during development that has significant effects on the metabolism, health, and viability of an organism. To understand these interactions for the nutrient copper, we used a chemical genetic screen for zebrafish mutants sensitive to developmental copper deficiency. In this screen, we isolated two mutants that define subtleties of copper metabolism. The first contains a viable hypomorphic allele of atp7a and results in a loss of pigmentation when exposed to mild nutritional copper deficiency. This mutant displays incompletely penetrant skeletal defects affected by developmental copper availability. The second carries an inactivating mutation in the vacuolar ATPase that causes punctate melanocytes and embryonic lethality. This mutant, catastrophe, is sensitive to copper deprivation revealing overlap between ion metabolic pathways. Together, the two mutants illustrate the utility of chemical genetic screens in zebrafish to elucidate the interaction of nutrient availability and genetic polymorphisms in cellular metabolism

Receptor Sorting within Endosomal Trafficking Pathway Is Facilitated by Dynamic Actin Filaments

Early endosomes (EEs) are known to be a sorting station for internalized molecules destined for degradation, recycling, or other intracellular organelles. Segregation is an essential step in such sorting, but the molecular mechanism of this process remains to be elucidated. Here, we show that actin is required for efficient recycling and endosomal maturation by producing a motile force. Perturbation of actin dynamics by drugs induced a few enlarged EEs containing several degradative vacuoles and also interfered with their transporting ability. Actin repolymerization induced by washout of the drug caused the vacuoles to dissociate and individually translocate toward the perinuclear region. We further elucidated that cortactin, an actin-nucleating factor, was required for transporting contents from within EEs. Actin filaments regulated by cortactin may provide a motile force for efficient sorting within early endosomes. These data suggest that actin filaments coordinate with microtubules to mediate segregation in EEs

Fission of Tubular Endosomes Triggers Endosomal Acidification and Movement

The early endosome acts as a sorting station for internalized molecules destined for recycling or degradation. While recycled molecules are sorted and delivered to tubular endosomes, residual compartments containing molecules to be degraded undergo “maturation” before final degradation in the lysosome. This maturation involves acidification, microtubule-dependent motility, and perinuclear localization. It is currently unknown how sorting and the processes of maturation cooperate with each other. Here, we show that fission of a tubular endosome triggers the maturation of the residual endosome, leading to degradation. Use of the dynamin inhibitor dynasore to block tubular endosome fission inhibited acidification, endosomal motility along microtubules, perinuclear localization, and degradation. However, tubular endosome fission was not affected by inhibiting endosomal acidification or by depolymerizing the microtubules. These results demonstrate that the fission of recycling tubules is the first important step in endosomal maturation and degradation in the lysosome. We believe this to be the first evidence of a cascade from sorting to degradation

Omeprazole Inhibits Proliferation and Modulates Autophagy in Pancreatic Cancer Cells

BACKGROUND: Omeprazole has recently been described as a modulator of tumour chemoresistance, although its underlying molecular mechanisms remain controversial. Since pancreatic tumours are highly chemoresistant, a logical step would be to investigate the pharmacodynamic, morphological and biochemical effects of omeprazole on pancreatic cancer cell lines. METHODOLOGY/PRINCIPAL FINDINGS: Dose-effect curves of omeprazole, pantoprazole, gemcitabine, 5-fluorouracil and the combinations of omeprazole and 5-fluorouracil or gemcitabine were generated for the pancreatic cancer cell lines MiaPaCa-2, ASPC-1, Colo357, PancTu-1, Panc1 and Panc89. They revealed that omeprazole inhibited proliferation at probably non-toxic concentrations and reversed the hormesis phenomena of 5-fluorouracil. Electron microscopy showed that omeprazole led to accumulation of phagophores and early autophagosomes in ASPC-1 and MiaPaCa-2 cells. Signal changes indicating inhibited proliferation and programmed cell death were found by proton NMR spectroscopy of both cell lines when treated with omeprazole which was identified intracellularly. Omeprazole modulates the lysosomal transport pathway as shown by Western blot analysis of the expression of LAMP-1, Cathepsin-D and β-COP in lysosome- and Golgi complex containing cell fractions. Acridine orange staining revealed that the pump function of the vATPase was not specifically inhibited by omeprazole. Gene expression of the autophagy-related LC3 gene as well as of Bad, Mdr-1, Atg12 and the vATPase was analysed after treatment of cells with 5-fluorouracil and omeprazole and confirmed the above mentioned results. CONCLUSIONS: We hypothesise that omeprazole interacts with the regulatory functions of the vATPase without inhibiting its pump function. A modulation of the lysosomal transport pathway and autophagy is caused in pancreatic cancer cells leading to programmed cell death. This may circumvent common resistance mechanisms of pancreatic cancer. Since omeprazole use has already been established in clinical practice these results could lead to new clinical applications