Extensible Structural Analysis of Petri Net Product Lines

Petri nets are a popular formalism to represent concurrent systems. However, their standard form does not o er variability support to model and e ectively analyse large sets of variants of a given system. For this purpose, we propose a notion of product line of Petri nets to represent a set of similar concurrent systems. The formalization enriches Petri nets with a feature model characterizing the variability of the systems. Moreover, places, transitions and arcs can de ne presence conditions that determine the subset of system variants they belong to. To enable an e cient analysis of the set of all net variants, we have lifted several structural analysis methods for Petri nets, to the product line level. Currently, we support the lifted checking of the marked graph, state-machine, and (extended) free-choice properties, which avoids their analysis on each particular net of the product line in isolation. We demonstrate the feasibility of our proposal using examples in the domain of exible assembly lines, and introduce an extensible tool infrastructure. The tool is based on Eclipse and FeatureIDE, and permits adding new analysis methods externally. Moreover, we present an evaluation that shows the e ciency gains of our method with respect to an enumerative approach that analyses the properties on every net within the product line separately.Work funded by the Spanish Ministry of Science (RTI2018-095255-B-I00) and the R&D programme of Madrid (P2018/TCS-4314)

Lifted structural invariant analysis of Petri net product lines

Petri nets are commonly used to represent concurrent systems. However, they lack support for modelling and analysing system families, like variants of controllers, different variations of a process model, or the possible configurations of a flexible assembly line. To facilitate modelling potentially large collections of similar systems, in this paper, we enrich Petri nets with variability mechanisms based on product line engineering. Moreover, we present methods for the efficient analysis of the place and transition invariants in all defined versions of a Petri net. Efficiency is achieved by analysing the system family as a whole, instead of analysing each possible net variant separately. For this purpose, we lift the notion of incidence matrix to the product line level, and rely on constraint solving techniques. We present tool support and evaluate the benefits of our techniques on synthetic and realistic examples, achieving in some cases speed-ups of two orders of magnitude with respect to analysing each net variant separatelyThis work has been funded by the Spanish Ministry of Science (PID2021-122270OB-I00) and the R&D programme of Madrid (P2018/TCS-4314

Automated variability injection for graphical modelling languages

© ACM 2020. This is the author's version of the work. It is posted here for your personal use. Not for redistribution. The definitive Version of Record was published in International Conference on Generative Programming: Concepts and Experiences, https://doi.org/10.1145/3425898.3426957Model-based development approaches, such as Model-Driven Engineering (MDE), heavily rely on the use of modelling languages to achieve and automate software development tasks. To enable the definition of model variants (e.g., supporting the compact description of system families), one solution is to combine MDE with Software Product Lines. However, this is technically costly as it requires adapting many MDE artefacts associated to the modelling language -- especially the meta-models and graphical environments. To alleviate this situation, we propose a method for the automated injection of variability into graphical modelling languages. Given the meta-model and graphical environment of a particular language, our approach permits configuring the allowed model variability, and the graphical environment is automatically adapted to enable creating models with variability. Our solution is implemented atop the Eclipse Modeling Framework and Sirius, and synthesizes adapted graphical editors integrated with FeatureIDEWork funded by the R&D programme of Madrid (S2018/TCS4314), the Spanish Ministry of Science (RTI2018-095255-BI00), and the Austrian Science Fund (P 30525-N31

Insight into the biological pathways underlying fibromyalgia by a proteomic approach

Fibromyalgia (FM) is a form of non-articular rheumatism difficult to diagnose and treat because its etiology remains still elusive. Proteomics makes possible the systematic analysis of hundreds of proteins in clinical samples. Consequently, it has become a key tool for finding altered molecular pathways in different diseases. In this context, the present study analyzes changes in the plasma proteome of patients with FM by nanoscale liquid chromatography coupled to tandem mass spectrometry. Deregulated proteins were studied using Ingenuity Pathways Analysis (IPA) and Kyoto Encyclopedia of Genes and Genomes. Conventional analytical methods were used to validate selected proteins. We found a total of 33 proteins differentially expressed in patients with FM. Haptoglobin and fibrinogen showed the highest FM/control ratio. IPA analysis revealed that the top enriched canonical pathways were acute-phase response signaling, Liver-X Receptor/Retinoid-X Receptor activation, Farnesoid-X Receptor/Retinoid-X Receptor activation, and coagulation and complement systems. The importance of inflammation in FM was corroborated by the increase in erythrocyte sedimentation rate. In conclusion, our results support the existence of a plasma protein signature of FM that involves different biological pathways all of them related to inflammation, and point to haptoglobin and fibrinogen as plausible biomarkercandidates for future studies. Significance: The etiology of fibromyalgia (FM) remains elusive making its diagnosis and treatment difficult. The characterization of the proteome signature of this syndrome will improve its understanding. However, to date proteomic analyses in FM are scarce. The goal of the present work is to analyse, for the first time, changes in plasma protein profiles of patients with FM in comparison to control subjects, using label free relative protein quantification by nanoscale liquid chromatography coupled to tandem mass spectrometry. Our data demonstrate the existence of a common protein signature in the plasma of patients with FM that could explain some of the symptoms associated to this syndrome. The analysis of the 33 proteins differentially expressed corroborates the crucial role of inflammation in the pathogenesis of this syndrome. The interplay of the complement and coagulation cascades contributes to the inflammatory process, while the activation of Liver-X Receptor/Retinoid-X Receptor and Farnesoid-X Receptor/Retinoid-X Receptor could attempt to alleviate it. Finally, we have identified two proteins, haptoglobin and fibrinogen, as potential biomarker-candidates of FM for future studies

Manifestaciones digestivas en pacientes con enfermedad de Chagas-Mazza

In order to characterize the gastrointestinal manifestations in patients with American trypanosomiasis a descriptive cross-sectional study was conducted in a population consisting of 130 patients with positive IgG antibodies to Trypanosoma cruzi treated at the " Victoria South"Medical Center of integral diagnostic from José F. Ribas, municipality, Aragua State, Bolivarian Republic of Venezuela , from March 2012 to February 2013. The most affected age group was 61 years and over and not predominantly found in sex ; asymptomatic patients predominated , followed by those with digestive symptoms ; gingivostomatitis was the clinical finding was found , followed dyspeptic disorders and hepatomegaly , megacolon with chronic constipation, esophageal achalasia and megaesophagus . Hepatitis B was detected in four patients and C in two.Con el objetivo de caracterizar las manifestaciones digestivas en pacientes con tripanosomiasis americana se realizó un estudio descriptivo transversal en una población constituida por los 130 pacientes con anticuerpos IgG positivos para Trypanosoma cruzi atendidos en el Centro médico de diagnóstico integral “Victoria Sur”, del Municipio José F. Ribas, Estado de Aragua, República Bolivariana de Venezuela, desde marzo de 2012 a febrero de 2013. El grupo de edad más afectado fue el de 61 años y más y no se encontró predominio en cuanto al sexo; predominaron los pacientes asintomáticos, seguidos de los que padecen manifestaciones digestivas; la gingivoestomatitis fue el hallazgo clínico más encontrado, le siguen los trastornos dispépticos y la hepatomegalia, el megacolon con constipación crónica, la acalasia esofágica y el megaesófago. Se detectó hepatitis B en cuatro pacientes y C en dos

Usual Dietary Intake, Nutritional Adequacy and Food Sources of Calcium, Phosphorus, Magnesium and Vitamin D of Spanish Children Aged One to <10 Years. Findings from the EsNuPI Study †

The authors would like to thank IPN for its support and technical advice.Bone problems in the population begin to be establish in childhood. The present study aims to assess the usual calcium, phosphorus, magnesium, and vitamin D intakes, along with the food sources of these nutrients, in Spanish children participating in the EsNuPI (Estudio Nutricional en Población Infantil Española) study. Two 24 h dietary recalls were applied to 1448 children (1 to <10 years) divided into two sub-samples: one reference sample (RS) of the general population [n = 707] and another sample which exclusively included children consuming enriched or fortified milks, here called “adapted milks” (AMS) [n = 741]. Estimation of the usual intake shows that nutrient intake increased with age for all nutrients except vitamin D. Using as reference the Dietary Reference Values from the European Food Safety Authority (EFSA), calcium and magnesium intakes were found to be below the average requirement (AR) and adequate intake (AI), respectively, in a considerable percentage of children. Furthermore, phosphorus exceeded the AI in 100% of individuals and vitamin D was lower than the AI in almost all children studied. The results were very similar when considering only plausible reporters. When analyzing the food sources of the nutrients studied, milk and dairy products contributed the most to calcium, phosphorus, magnesium, and vitamin D. Other sources of calcium were cereals and vegetables; for phosphorus: meat, meat products, and cereals; for magnesium: cereals and fruits; and, for vitamin D: fish and eggs. These results highlight the desirability of improving the intake concerning these nutrients, which are involved in bone and metabolic health in children. The AMS group appeared to contribute better to the adequacy of those nutrients than the RS group, but both still need further improvement. Of special interest are the results of vitamin D intakes, which were significantly higher in the AMS group (although still below the AI), independent of age.Instituto Puleva de Nutricion (IPN

Cistatina C: Potencial antimicrobiano e inmunoregulador en la infección de macrófagos con Porphyromonas gingivalis

Introducción. Porphyromonas gingivalis es el principal patógeno asociado al desarrollo de periodontitis, una patología inflamatoria crónica caracterizada por la destrucción de tejido de soporte de los dientes. Los macrófagos, son reclutados en el infiltrado inflamatorio de pacientes con periodontitis y se polarizan hacia el fenotipo M1 por diversos factores de virulencia de P. gingivalis, lo cual promueve un microambiente inflamatorio caracterizado por la producción de citocinas y mediadores inflamatorios como óxido nítrico (ON) y especies reactivas de oxígeno (ROS). Además, estas células son utilizados por la P.gingivalis como sitio de mantenimiento intracelular transitorio, promoviendo a largo plazo la muerte celular del macrófago infectado. Cistatina C es un péptido antimicrobiano con actividad inmunoreguladora que participa en la disminución de la producción de citocinas como IL-1β y TNF-α e induce la polarización del macrófago hacia el fenotipo M2, lo cual favorece la producción de citocinas anti-inflammatorias como IL-10. Diseño. Los macrófagos fueron obtenidos de monocitos de sangre periférica. Las células fueron infectadas con P. gingivalis (MOI:1:100) durante 3 h y posteriormente fueron estimuladas con Cistatina C (2.5 µg/ml) durante 24 h. La localización intracelular de P. gingivalis y Cistatina C fue determinada por inmunofluorescencia e inmuno-oro por TEM. La actividad antimicrobiana intracelular de Cistatina C en macrófagos infectados fue evaluada por conteo de Unidades Formadoras de Colonias (CFU). La producción TNF-α, IL-1β, and IL-10 fue evaluada por ELISA. Para determinar la producción de ROS, las células fueron incubadas con 2′,7′- dichlorodihidrofluoresceina diacetato (H2DCFDA). La concentración de nitrito en sobrenadantes fue evaluada con reacción de Griess. La muerte celular fue analizada por ensayo de TUNEL, Anexina V, y caspasa 3. Resultados. Cistatina C es internalizada en macrófagos infectados y localizada en membrana plasmática y citoplasma. Además, Cistatina C reduce la carga bacteriana intracelular de P. gingivalis en macrófagos infectados. Así mismo, observamos una disminución en la producción de mediadores inflamatorios como TNF-α, e IL-1β, un incremento en la producción de IL-10 y producción de ROS. Al mismo tiempo se observó una regulación en la producción de ON. Sorprendentemente, Cistatina C disminuyó la muerte celular en macrófago infectados. Conclusiones. Cistatina C es internalizada por macrófagos infectados y ejerce actividad antimicrobiana e inmunoreguladora, debido a que inhibe la carga bacteriana intracelular de P. gingivalis y disminuye la respuesta inflamatoria y apoptosis celular en macrófagos infectados. Estos hallazgos, destacan la importancia de conocer las propiedades de Cistatina C y su posible aplicación en enfermedades orales infecciosas e inflamatorias

The Future We Want: a Learning Experience to Promote SDGs in Higher Education from the United Nations and University of Valencia

This article shares the strategy for mainstreaming the Sustainable Development Goals (SDGs) at the University of Valencia (UV), which, although limited in its scale, may compel other Higher Education Institutions to think in technological and social progress aligned with the 2030 Agenda. It explicates a process driven by the UV, on the occasion of the 75th anniversary of the United Nations (UN), and in collaboration with the Service for Geospatial, Information, and Telecommunications Technologies from the UN Support Base in Valencia (Spain) to prepare the online event: ¿The United Nations We Want¿. It was the culmination of a collaborative project between students and faculties from different scientific, technological, social, legal, humanistic, and health disciplines that structure the University of Valencia. The intention was that new generations experience the role they can have to shape the future we want, while the university community as a whole can become part of transformative institutional change that draws on both top-down and bottom-up strategies in pursuit of Education for Sustainable Development