Supervisió d'un procés industrial al palmell de la ma

L’objectiu principal del projecte és la monitorització i supervisió d’un sistema de control automatitzat que disposa d’un conjunt d’actuadors i sensors, més concretament s’ha desenvolupat el control d’un sistema complert el qual disposa de 5 PLCs de la marca OMRON amb connexió ethernet. Aquesta monitorització i supervisió inicialment volia realitzar-se amb aparells del tipus smartphones, però finalment s’ha creat una aplicació que pot monitoritzar el procés o conjunt de processos des de qualsevol dispositiu, d’aquesta manera l’aplicació té un major abast. L’aplicació desenvolupada permet manipular el procés via remota, des del smartphone, o connectats físicament a la mateixa xarxa, ja que amb qualsevol ordinador o dispositiu, tant si esta connectat a la xarxa per via ethernet com per wifi, es podrà monitoritzar i supervisar el procés de fabricació

uPAR-controlled oncolytic adenoviruses eliminate cancer stem cells in human pancreatic tumors

Abstract Pancreatic tumors contain cancer stem cells highly resistant to chemotherapy. The identification of therapies that can eliminate this population of cells might provide with more effective treatments. In the current work we evaluated the potential of oncolytic adenoviruses to act against pancreatic cancer stem cells (PCSC). PCSC from two patient-derived xenograft models were isolated from orthotopic pancreatic tumors treated with saline, or with the chemotherapeutic agent gemcitabine. An enrichment in the number of PCSC expressing the cell surface marker CD133 and a marked enhancement on tumorsphere formation was observed in gemcitabine treated tumors. No significant increase in the CD44, CD24, and epithelial-specific antigen (ESA) positive cells was observed. Neoplastic sphere-forming cells were susceptible to adenoviral infection and exposure to oncolytic adenoviruses resulted in elevated cytotoxicity with both Adwt and the tumor specific AduPARE1A adenovirus. In vivo, intravenous administration of a single dose of AduPARE1A in human-derived pancreatic xenografts led to a remarkable anti-tumor effect. In contrast to gemcitabine AduPARE1A treatment did not result in PCSC enrichment. No enrichment on tumorspheres neither on the CD133+ population was detected. Therefore our data provide evidences of the relevance of uPAR-controlled oncolytic adenoviruses for the elimination of pancreatic cancer stem cells

Intraductal Delivery Of Adenoviruses Targets Pancreatic Tumors In Transgenic Ela-myc Mice And Orthotopic Xenografts

Gene-based anticancer therapies delivered by adenoviruses are limited by the poor viral distribution into the tumor. In the current work we have explored the feasibility of targeting pancreatic tumors through a loco-regional route. We have taken advantage of the ductal network in the pancreas to retrogradelly inject adenoviruses through the common bile duct in two different mouse models of pancreatic carcinogenesis: The transgenic Ela-myc mice that develop mixed neoplasms displaying both acinar-like and duct-like neoplastic cells affecting the whole pancreas; and mice bearing PANC-1 and BxPC-3 orthotopic xenografts that constitute a model of localized human neoplastic tumors. We studied tumor targeting and the anticancer effects of newly thymidine kinase-engineered adenoviruses both in vitro and in vivo, and conducted comparative studies between intraductal or intravenous administration. Our data indicate that the intraductal delivery of adenovirus efficiently targets pancreatic tumors in the two mouse models. The in vivo application of AduPARTK(T) plus ganciclovir (GCV) treatment induced tumor regression in Ela-myc mice. Moreover, the intraductal injection of ICOVIR15-TKT oncolytic adenoviruses significantly improved mean survival of mice bearing PANC-1 and BxPC-3 pancreatic xenografts from 30 to 52 days and from 20 to 68 days respectively (p<0.0001) when combined with GCV. Of notice, both AduPARTK(T) and ICOVIR15-TKT antitumoral responses were stronger by ductal viral application than intravenously, in line with the 38-fold increase in pancreas transduction observed upon ductal administration. In summary our data show that cytotoxic adenoviruses retrogradelly injected to the pancreas can be a feasible approach to treat localized pancreatic tumors

Increased in vivo inhibition of gene expression by combining RNA interference and U1 inhibition

Inhibition of gene expression can be achieved with RNA interference (RNAi) or U1 small nuclear RNA—snRNA—interference (U1i). U1i is based on U1 inhibitors (U1in), U1 snRNA molecules modified to inhibit polyadenylation of a target pre-mRNA. In culture, we have shown that the combination of RNAi and U1i results in stronger inhibition of reporter or endogenous genes than that obtained using either of the techniques alone. We have now used these techniques to inhibit gene expression in mice. We show that U1ins can induce strong inhibition of the expression of target genes in vivo. Furthermore, combining U1i and RNAi results in synergistic inhibitions also in mice. This is shown for the inhibition of hepatitis B virus (HBV) sequences or endogenous Notch1. Surprisingly, inhibition obtained by combining a U1in and a RNAi mediator is higher than that obtained by combining two U1ins or two RNAi mediators. Our results suggest that RNAi and U1i cooperate by unknown mechanisms to result in synergistic inhibitions. Analysis of toxicity and specificity indicates that expression of U1i inhibitors is safe. Therefore, we believe that the combination of RNAi and U1i will be a good option to block damaging endogenous genes, HBV and other infectious agents in vivo

Comprehensive profiling of mammalian Tribbles interactomes implicates TRIB3 in gene repression

The three human Tribbles (TRIB) pseudokinases have been implicated in a plethora of signaling and metabolic processes linked to cancer initiation and progression and can potentially be used as biomarkers of disease and prognosis. While their modes of action reported so far center around protein–protein interactions, the comprehensive profiling of TRIB interactomes has not been reported yet. Here, we have developed a robust mass spectrometry (MS)-based proteomics approach to characterize Tribbles’ interactomes and report a comprehensive assessment and comparison of the TRIB1, -2 and -3 interactomes, as well as domain-specific interactions for TRIB3. Interestingly, TRIB3, which is predominantly localized in the nucleus, interacts with multiple transcriptional regulators, including proteins involved in gene repression. Indeed, we found that TRIB3 repressed gene transcription when tethered to DNA in breast cancer cells. Taken together, our comprehensive proteomic assessment reveals previously unknown interacting partners and functions of Tribbles proteins that expand our understanding of this family of proteins. In addition, our findings show that MS-based proteomics provides a powerful tool to unravel novel pseudokinase biology

Differential Ly-6C expression identifies the recruited macrophage phenotype, which orchestrates the regression of murine liver fibrosis

Although macrophages are widely recognized to have a profibrotic role in inflammation, we have used a highly tractable CCl(4)-induced model of reversible hepatic fibrosis to identify and characterize the macrophage phenotype responsible for tissue remodeling: the hitherto elusive restorative macrophage. This CD11B(hi) F4/80(int) Ly-6C(lo) macrophage subset was most abundant in livers during maximal fibrosis resolution and represented the principle matrix metalloproteinase (MMP) -expressing subset. Depletion of this population in CD11B promoter–diphtheria toxin receptor (CD11B-DTR) transgenic mice caused a failure of scar remodeling. Adoptive transfer and in situ labeling experiments showed that these restorative macrophages derive from recruited Ly-6C(hi) monocytes, a common origin with profibrotic Ly-6C(hi) macrophages, indicative of a phenotypic switch in vivo conferring proresolution properties. Microarray profiling of the Ly-6C(lo) subset, compared with Ly-6C(hi) macrophages, showed a phenotype outside the M1/M2 classification, with increased expression of MMPs, growth factors, and phagocytosis-related genes, including Mmp9, Mmp12, insulin-like growth factor 1 (Igf1), and Glycoprotein (transmembrane) nmb (Gpnmb). Confocal microscopy confirmed the postphagocytic nature of restorative macrophages. Furthermore, the restorative macrophage phenotype was recapitulated in vitro by the phagocytosis of cellular debris with associated activation of the ERK signaling cascade. Critically, induced phagocytic behavior in vivo, through administration of liposomes, increased restorative macrophage number and accelerated fibrosis resolution, offering a therapeutic strategy to this orphan pathological process

Propagación de grietas por fatiga en probetas CT de un acero AHSS soldado

En este proyecto se pretende estudiar cómo afecta un proceso de soldadura a un acero AHSS mediante probetas de tensión compacta C(T). Los aceros AHSS están siendo ampliamente utilizados en aplicaciones automotrices con la finalidad de reducir el peso de los vehículos debido a que son de muy alta resistencia, con lo cual se pueden reducir en gran medida los espesores de las chapas utilizadas. El uso de soldadura es inevitable para la realización de algunas juntas. Debido a que en dichas aplicaciones automotrices ocurre la actuación de cargas cíclicas, toma importancia el estudio del comportamiento de las grietas ante cargas de fatiga, con la finalidad de evitar el fallo catastrófico ya que las grietas por fatiga pueden iniciarse desde diferentes posiciones del material soldado debido a la complejidad de la situación de la fuerza automotriz. Específicamente el interés para el presente estudio es el conocimiento del comportamiento ante la presencia de grietas y la aplicación de cargas cíclicas en una unión soldada a tope de un acero AHSS. Para la realización de los ensayos se ha utilizado un acero microaleado STRENX 960®. Se han extraído de una placa de acero, de espesor 8 mm, 2 probetas de material base y 3 probetas de las zonas localizadas con soldadura con diferente orientación de entalla. Inicialmente se ha realizado un análisis microestructural de la sección transversal de la soldadura analizando la dureza de las distintas zonas de soldadura para la determinación de las zonas más críticas para el avance de la grieta. A continuación, para la determinación de la cinética de propagación de grietas por fatiga, se realizaron curvas de crecimiento de grietas para determinar las constantes de la Ecuación de Paris-Erdogan en la zona de crecimiento estable de grieta siguiendo las especificaciones de la norma ASTM E-647. Mediante este ensayo se ha observado que la soldadura afecta significativamente al avance de la grieta por fatiga, provocando un crecimiento discontinuo en lo que se refiere a velocidad de propagación de grietas por fatiga. Finalmente, para poder realizar una mejor valoración de la resistencia a la propagación de grietas, se ha procedido a la medición de la tenacidad de fractura para el material base y con soldadura siguiendo los lineamientos de la norma ASTM E-399

PLE como espacio de aprendizaje formal e informal en Educación Musical. Una investigación-acción en Educación Secundaria Obligatoria

En esta investigación se analiza la retroalimentación que se produce entre los entornos formal e informal de los PLE (Personal Learning Environments) de alumnos de 4º curso de Educación Secundaria en la materia de Educación Musical. Para ello, se realiza un estudio utilizando la metodología de Investigación Acción en tres cursos consecutivos (13-14, 14-15 y 15-16) con alumnos distintos, siendo el primero a modo de grupo piloto. Este estudio se desarrolla en tres fases en cada uno de los cursos. Una fase inicial en la que se analizan los PLE de los alumnos y se diseña un corpus de actividades basadas en ellos. Una segunda fase que ocupa el curso escolar y que permite obtener un registro de las interacciones entre alumnos en contextos presencial y virtuales a partir de un diseño didáctico plenamente curricular. Y una fase final que analiza las variaciones de sus PLE, mediante un instrumento que nos permite conocer la evolución de cada alumno en cada una de las seis categorías de análisis definidas previamente: Conocimientos musicales, Herramientas tecnológicas, Usos y estrategias, Motivaciones, Competencia digital y Competencia musical. Los resultados, una vez analizados los PLE a nivel individual y grupal, ponen de manifiesto que la creación de un contexto a modo de ecología de aprendizaje -mediado por tecnología y que parte de intereses y conocimientos de los alumnos- genera un entorno de aprendizaje que: (a) promueve la interacción entre alumnos y (b) facilita una sinergia de intercambio de conocimientos entre iguales, tanto en el contexto formal como en el informal. Se constata un flujo de intercambio, no solo de conocimientos, sino también de inquietudes, intereses y motivaciones que permiten a los alumnos aprender y tomar conciencia de sus conocimientos utilizando a sus compañeros como referencia y configurar una estructura de conocimiento compartido.The following research analyses the synergy between formal and informal environments of the PLE (Personal Learning Environments) in the field of Musical Education with students in the 4th year of Secondary Education. Action Research methodology was used for three consecutive courses (13-14, 14-15 and 15-16) with different students, the first being a pilot group. The investigation had three stages for each group. In the first stage students' PLEs were analyzed and personalized activities were designed. A second stage was developed throughout the school year and generated a record of interactions among students in both face-to-face and virtual contexts in a curricular based didactic design. In the final stage the variations of PLE were analyzed to trace the evolution of each student in each of the six previously defined analysis categories: Musical Knowledge, Technological Tools, Uses and Strategies, Motivations, Digital Competence and Musical Competence. The results show that the creation of a learning ecology context -mediated by technology and based on the interests and knowledge of students- generates a learning environment that: (a) promotes interaction among students and (b) generates synergy from knowledge sharing among equals, both in formal and informal contexts. There is an exchange flow, not only of knowledge, but also of concerns, interests and motivations that helps students to learn and become aware of their learning process, using their peers as a reference and configuring a shared knowledge structure

Supervisió d'un procés industrial al palmell de la ma

L’objectiu principal del projecte és la monitorització i supervisió d’un sistema de control automatitzat que disposa d’un conjunt d’actuadors i sensors, més concretament s’ha desenvolupat el control d’un sistema complert el qual disposa de 5 PLCs de la marca OMRON amb connexió ethernet. Aquesta monitorització i supervisió inicialment volia realitzar-se amb aparells del tipus smartphones, però finalment s’ha creat una aplicació que pot monitoritzar el procés o conjunt de processos des de qualsevol dispositiu, d’aquesta manera l’aplicació té un major abast. L’aplicació desenvolupada permet manipular el procés via remota, des del smartphone, o connectats físicament a la mateixa xarxa, ja que amb qualsevol ordinador o dispositiu, tant si esta connectat a la xarxa per via ethernet com per wifi, es podrà monitoritzar i supervisar el procés de fabricació