Sistema gráfico de visualización del motor de reglas CLIPS de un simulador empresarial

El objetivo principal de este proyecto es la obtención de una representación gráfica del sistema de módulos, cálculos, reglas y atributos que componen el programa en CLIPS, de forma que se pueda entender a través de grafos la relación entre todas las partes que conforman el motor de simulación. Para ello hay que realizar un análisis profundo, en el que se estudien bien las partes en las que se divide la implementación en CLIPS, diferenciando que características tienen las reglas, para poder extraer de ellas la información que interesa desglosar, y luego así catalogarla en una serie de módulos. El formato escogido donde plasmar toda esta información desglosada, es en forma de grafo, que se entiende como una “serie de nodos relacionados entre si”. Llevado a este proyecto, los nodos serían la representación de las reglas y atributos, que estarían unidos mediante flechas en función de la influencia de unos sobre otros. A lo largo de la presente memoria se irán desglosando las diferentes partes, que de una forma u otra, han influido en el desarrollo del sistema gráfico. Por ello, a continuación se va a hacer un breve resumen de lo que se va a ver en los próximos apartados de este proyecto fin de carrera. En primer lugar, se van a describir las tecnologías con las que se ha tenido que trabajar. En este caso han sido dos, el lenguaje CLIPS en el que está desarrollado el motor de reglas y que es la fuente de información de este proyecto, y el lenguaje JAVA, que es con el que se ha implementado el sistema gráfico. Tras tecnologías, se va a describir todo el proceso de creación del sistema gráfico, que se divide en 3 apartados. El primero de ellos será la fase de análisis, a la que pertenecen las tareas de recopilación de la información necesaria para el desarrollo del sistema gráfico, mediante el estudio del programa en CLIPS. Después se pasará a la fase de diseño donde se explica todo lo referente a la elaboración de la “forma” que se quiere del sistema gráfico. Y en tercer lugar dentro de la fase de creación se tendría la fase de evaluación, donde se realizan una serie de pruebas de “buen funcionamiento” de las partes críticas de la aplicación desarrollada. Tras el apartado de pruebas, llegará la parte de conclusiones y trabajos futuros, donde se hace una valoración de todo el trabajo realizado, y de las posibilidades que se abren tras la consecución del mismo. La parte final de la memoria está destinada para la documentación extra acerca del proyecto realizado, que en este caso serán los referentes a ejemplos del simulador, al diseño detallado, el manual de usuario y la gestión de proyecto.Ingeniería Técnica en Informática de Gestió

RESHAPING THE ROLE OF TUTORS IN THE FOREIGN LANGUAGE LEARNING PROCESS: NON-DIRECTIVE E-LEARNING AND THE NET OF TUTORS IN PARKUR

Foreign language learning and teaching have been object of study for many decades and from many different approaches to which we could devote an entire volume. Changes and evolution in the field of education and learning have always meant adaptations, and this evolving, constantly-changing situation is what makes educators, teachers, researches and professionals of the field to look for innovative, adapted approaches. Some of these changes include: the way learners can access content and knowledge, which has been immensely affected by the evolution of information technologies and the Internet; the relationship between the two parts in the learning process (learner and teacher/tutor), which is now much more learner-centered and in a non-directive atmosphere where the former has a very active role while the latter acts more like a facilitator and guide who does not impose but accompanies instead; and the learning objectives and goals, which are now more practice-oriented, since many learners start learning a foreign language for practical reasons and want it to be useful and applicable in a globalized, multicultural and constantly moving working environment. In view of these changing factors, the European project DELCYME is developing an online language learning platform named PARKUR, which offers access to five European languages (Spanish, French, Italian, German and Polish) with the particularity of its design and approach to the learning process: each learner goes through an individualized content path and accesses linguistic, cultural and practical content depending on their learning goals. Another particularity presented here is the double figure of tutors created by this platform, having what has been coined as tutor coaches and tutor islands, having not only different responsibilities but also different trainings and abilities, which are nonetheless combined for the sake of offering the most reliable attention and the best learning outcome possible. The object of this paper is therefore to present and justify this pioneer learning platform and its net of tutors.   Rimodellare il ruolo dei tutor nel processo di apprendimento delle lingue straniere: l'e-learning non direttivo e la rete di tutor in PARKUR  L’apprendimento e l’insegnamento delle lingue straniere sono stati oggetto di studio per molti decenni e molti sono gli approcci ai quali potremmo dedicare un intero volume. I cambiamenti e l’evoluzione nel campo dell’educazione e dell’apprendimento hanno sempre portato ad adattamenti, e questa situazione in costante evoluzione e cambiamento è ciò che rende gli educatori, gli insegnanti, i ricercatori e i professionisti del settore alla ricerca di approcci innovativi. Alcuni di questi cambiamenti riguardano: il modo in cui i discenti possono accedere ai contenuti e alla conoscenza, modo che è stato immensamente influenzato dall’evoluzione delle tecnologie dell’informazione e di Internet; il rapporto tra i due attori del processo di apprendimento/insegnamento (discente e insegnante/tutor), che è ora molto più centrato sul discente e in un’atmosfera non direttiva in cui il primo ha un ruolo molto attivo mentre il secondo agisce più come facilitatore e guida che non impone ma accompagna; e gli obiettivi e le finalità di apprendimento, che ora sono più orientati alla pratica poiché molti studenti iniziano ad imparare una lingua straniera per motivi pratici e vogliono che sia utile e applicabile in un ambiente di lavoro globalizzato, multiculturale e in continuo movimento. Alla luce di questi fattori di cambiamento, il progetto europeo DELCYME sta sviluppando una piattaforma di apprendimento linguistico online denominata PARKUR, che offre l’accesso a cinque lingue europee (spagnolo, francese, italiano, tedesco e polacco) con uno specifico e particolare design e approccio al processo di apprendimento: ogni studente passa attraverso un percorso di contenuti individualizzati e accede a contenuti linguistici, culturali e pratici a seconda dei suoi obiettivi di apprendimento. Un’altra particolarità è la doppia figura di tutor creati per questa piattaforma, il tutor coach e il tutor island, che hanno non solo responsabilità diverse ma anche formazione e abilità diverse che sono comunque combinate per offrire la più affidabile attenzione e il miglior risultato di apprendimento possibile. L’obiettivo di questo contributo è quindi quello di presentare questa piattaforma di apprendimento pionieristica e la sua rete di tutor

MKP1 mediates chemosensitizer effects of E1a in response to cisplatin in non-small cell lung carcinoma cells

The adenoviral gene E1a is known to enhance the antitumor effect of cisplatin, one of the cornerstones of the current cancer chemotherapy. Here we study the molecular basis of E1a mediated sensitivity to cisplatin in an experimental model of Non-small cell lung cancer. Our data show how E1a blocks the induction of autophagy triggered by cisplatin and promotes the apoptotic response in resistant cells. Interestingly, at the molecular level, we present evidences showing how the phosphatase MKP1 is a major determinant of cisplatin sensitivity and its upregulation is strictly required for the induction of chemosensitivity mediated by E1a. Indeed, E1a is almost unable to promote sensitivity in H460, in which the high expression of MKP1 remains unaffected by E1a. However, in resistant cell as H1299, H23 or H661, which display low levels of MKP1, E1a expression promotes a dramatic increase in the amount of MKP1 correlating with cisplatin sensitivity. Furthermore, effective knock down of MKP1 in H1299 E1a expressing cells restores resistance to a similar extent than parental cells. stores resistance to a similar extent than parental cells. In summary, the present work reinforce the critical role of MKP1 in the cellular response to cisplatin highlighting the importance of this phosphatase in future gene therapy approach based on E1a gene

Exploiting the potential of autophagy in cisplatin therapy: a new strategy to overcome resistance

Resistance to cisplatin is a major challenge in the current cancer therapy. In order to explore new therapeutic strategies to cisplatin resistance, we evaluated, in a model of lung cancer (H1299 and H460 cell lines), the nature of the pathways leading to cell death. We observed that H1299 displayed a natural resistance to cisplatin due to an inability to trigger an apoptotic response that correlates with the induction of autophagy. However, pharmacological and genetic approaches showed how autophagy was a mechanism associated to cell death rather than to resistance. Indeed, pro-autophagic stimuli such as mTOR or Akt inhibition mediate cell death in both cell lines to a similar extent. We next evaluated the response to a novel platinum compound, monoplatin, able to promote cell death in an exclusive autophagy-dependent manner. In this case, no differences were observed between both cell lines. Furthermore, in response to monoplatin, two molecular hallmarks of cisplatin response (p53 and MAPKs) were not implicated, indicating the ability of this pro-autophagic compound to overcome cisplatin resistance. In summary, our data highlight how induction of autophagy could be used in cisplatin resistant tumours and an alternative treatment for p53 mutated patient in a synthetic lethally approach

Exploiting the potential of autophagy in cisplatin therapy: A new strategy to overcome resistance

Resistance to cisplatin is a major challenge in the current cancer therapy. In order to explore new therapeutic strategies to cisplatin resistance, we evaluated, in a model of lung cancer (H1299 and H460 cell lines), the nature of the pathways leading to cell death. We observed that H1299 displayed a natural resistance to cisplatin due to an inability to trigger an apoptotic response that correlates with the induction of autophagy. However, pharmacological and genetic approaches showed how autophagy was a mechanism associated to cell death rather than to resistance. Indeed, pro-autophagic stimuli such as mTOR or Akt inhibition mediate cell death in both cell lines to a similar extent. We next evaluated the response to a novel platinum compound, monoplatin, able to promote cell death in an exclusive autophagy-dependent manner. In this case, no differences were observed between both cell lines. Furthermore, in response to monoplatin, two molecular hallmarks of cisplatin response (p53 and MAPKs) were not implicated, indicating the ability of this pro-autophagic compound to overcome cisplatin resistance. In summary, our data highlight how induction of autophagy could be used in cisplatin resistant tumours and an alternative treatment for p53 mutated patient in a synthetic lethally approach.This work was supported by grants from Fundación Leticia Castillejo Castillo and Ministerio de Economía y Competitividad (grant SAF2012-30862 to RSP and grant CTQ2011-24434 to FAJ). RSP Research Institute, and the work carried out in his laboratory receive support from the European Community through the regional development funding program (FEDER). JGC received funding from the Regional Ministry of Education and Science of Castilla–La Mancha (FPI-JCCM) and from Fundación Leticia Castillejo Castillo. MCC and RSP have a contract from the INCRECYT progra

Tyrphostin AG126 exerts neuroprotection in CNS inflammation by a dual mechanism

© 2015 Wiley Periodicals, Inc. Acknowledgement Grant sponsor: State of Lower Saxony-Israel Research Cooperation; Grant number: ZN2035; Grant sponsor:German Research Council; Grant number: SFB/TRR43 and FOR1336; Grant sponsor: Parkinson UK; Grant number: K-1001; Grant sponsor: ProFutura Program (University of Gottingen); Grant sponsor: Else Kroner Fresenius Stiftung;Grant number: A69/2010; Grant sponsor: DFG; Grant number: WE 3547/4–1; Grant sponsor: US National Multiple Sclerosis Society; Grant numbers: NMSS; PP 1660. The authors thank Elke Pralle, Susanne Kiecke and Caroline Jaß (University of Gottingen) for excellent technical assistance.Peer reviewedPostprin

Blockage of autophagic ux is associated with lymphocytosis and higher percentage of tumoral cells in chronic lymphocytic leukemia of B-cells

Póster presentado al 42nd Congress of the Spanish Society of Biochemistry and Molecular Biology (SEBBM), celebrado en Madrid del 16 al 19 de julio de 2019.[Objective] Autophagy has lately emerged as an important biological process with implications in several hematological pathologies. Recently, a growing body of evidence supports a putative role of autophagy in chronic lymphocytic leukemia, however no definitive clue has been established so far. To elucidate this issue, we have developed a pilot study to measure autophagic flux in peripheral blood mononuclear cells from chronic lymphocytic leukemia patients, and explored its correlation with classical clinical/analytical parameters. [Methods/Patients] Thirty-three chronic lymphocytic leukemia patients participated in the study. Autophagic flux in peripheral blood mononuclear cells was determined by western blot measuring the levels of the proteins p62 and lipidated LC3. Moreover, p62 mRNA levels were studied by RT-qPCR. [Results] Lymphocytosis and the percentage of tumoral lymphocytes in chronic lymphocityc leukemia patients statistically correlates with a blocked autophagic flux. [Conclusion] Alterations in autophagic flux could play an important role in the physiopathology of chronic lymphocytic leukemia.Fundación Leticia Castillejo Castillo, Ministerio de Economía y Competitividad. Sociedad Castellano Manchega de Hematología y Hemoterapia. RSP and MJRH Research Institutes, and the work carried out in their laboratories received support from the European Community through the Regional Development Funding Program (FEDER).Peer reviewe

In Vitro and In Vivo High-Throughput Assays for the Testing of Anti-Trypanosoma cruzi Compounds

The treatment of Trypanosoma cruzi infection (the cause of human Chagas disease) remains a significant challenge. Only two drugs, both with substantial toxicity, are available and the efficacy of these dugs is often questioned – in many cases due to the limitations of the methods for assessing efficacy rather than to true lack of efficacy. For these reasons relatively few individuals infected with T. cruzi actually have their infections treated. In this study, we report on innovative methods that will facilitate the discovery of new compounds for the treatment of T. cruzi infection and Chagas disease. Utilizing fluorescent and bioluminescent parasite lines, we have developed in vitro tests that are reproducible and facile and can be scaled for high-throughput screening of large compound libraries. We also validate an in vivo screening test that monitors parasite replication at the site of infection and determines the effectiveness of drug treatment in less than two weeks. More importantly, results in this rapid in vivo test show strong correlations with those obtained in long-term (e.g. 40 day or more) treatment assays. The results of this study remove one of the obstacles for identification of effective and safe compounds to treat Chagas disease