CD46-Mediated costimulation induces a Th1-biased response and enhances early TCR/CD3 signaling in human CD4+ T lymphocytes

10 páginas, 8 figuras -- PAGS nros. 2439-2448The role of membrane cofactor protein (MCP, CD46) on human T cell activation has been analyzed. Coligation of CD3 and CD46 in the presence of PMA or CD28 costimuli enhanced IL-2, IFN-γ, or IL-10 secretion by CD4+ T lymphocytes. The effect of CD46 on IL-10 secretion did not require additional costimuli like anti-CD28 antibodies or phorbol esters. CD46 also enhanced IL-2 or IFN-γ secretion by CD4+ blasts. In contrast, IL-5 secretion was inhibited upon CD46-CD3 coligation, in all the cells analyzed. These effects were independent of IL-12 and suggest that CD46 costimulation promotes a Th1-biased response in human CD4+ T lymphocytes. CD46 enhanced TCR/CD3-induced tyrosine phosphorylation of CD3ζ and ZAP-70, as well as the activation of the ERK, JNK, and p38, but did not modify intracellular calcium. The effect of specific inhibitors shows that enhanced ERK activation contributes to augmented IFN-γ and lower IL-5 secretion and, consequently, to the Th1 bias. Cross-linking CD46 alone induced weak tyrosine phosphorylation of CD3ζ and ZAP-70. However, CD46 cross-linking by itself did not induce cell proliferation or lymphokine secretion, and pretreatment of CD4+ T lymphocytes with anti-CD46 antibodies did not significantly alter TCR/CD3 activationThis work was supported by Grants FIS 98/0037-CO2–02 from “Fondo de Investigación Sanitaria” and ISCIII-01/30 (Ministerio de Sanidad y Consumo, Spain) and Grant BMC2001–2177 from Ministerio de Ciencia y Tecnología, Spain. A.S. was recipient of a Predoctoral Fellowship of Comunidad Autónoma de MadridPeer reviewe

Influence of special tool geometry in drilling woven CFRPs materials

Machining processes of Carbon Fiber Reinforced Polymer (CFRP) are commonly required in order to achieve final assembly specifications. Despite the good mechanical properties of this kind of materials, they are hard to be machined due to the presence of hard particles; delamination, fiber pull-out and matrix thermal degradation are usually observed during its machining. Drilling operations are required before mechanical joining of the CFRP components. The actual interest in reducing delamination rests in the fact that it is the most serious damage found during drilling. In this work, a comparative study of three special geometries under different cutting conditions is presented. Thrust force and torque were monitoring during drilling tests and delamination extension was quantified. Results showed that a good drill tip geometry and feed rate selection is fundamental to reduce delamination damages.The funding received from the Ministry of Economy and Competitiveness of Spain under the project DPI2011-25999 and FPI subprogram with the reference BES-2012-055162 is highly appreciated

Experimental and numerical analysis of step drill bit performance when drilling woven CFRPs

This paper focuses on the influence of the step drill bit geometry on the damage induced during drilling Carbon Fiber Reinforced Polymer materials (CFRPs). Step geometry designed with the aim of avoiding composite damage in CFRPs drilling, is compared to conventional twist configuration. Despite the reduction of thrust force and torque observed when using the step drill, the delamination was only reduced at low feed rates. A numerical model developed for the step geometry was validated with experimental data demonstrating its ability to predict thrust force and delamination for different values of feed rate and cutting speed. Numerical model allowed the development of a parametrical study. Finally, using a response surface methodology a mechanistic model and surface diagrams have been presented in order to help in the selection of optimum variables minimizing drilling induced damage.The authors acknowledge the financial support for this work from the Ministry of Economy and Competitiveness of Spain under the project DPI2011-25999, FEDER program, and the FPI subprogram associated to the project previously mentioned with the reference BES-2012-055162

Teaching R to Mathematical Students

Habiendo constatado la falta de formación en herramientas estadísticas en algunas titulaciones de matemáticas, así como la creciente importancia del software de programación R, se ha visto la necesidad de impartir un curso de Análisis de Datos con R. Éste se ha desarrollado dentro de la iniciativa “Compumates” de la Facultad de CC. Matemáticas, Universidad Complutense de Madrid, y ha constado de diferentes sesiones, que parten desde la instalación del software y uso de comandos básicos, hasta su aplicación en técnicas de análisis y predicción. Para ello se ha provisto a los alumnos de un manual de aprendizaje. En este trabajo se muestran los resultados que ha tenido la experiencia en el aprendizaje del alumno y la valoración que tiene éste sobre la misma.The lack of statistical tools in some bachelor’s degrees of Mathematics jointly with an increasing importance of the software R leads to the need of giving a course of Data Analysis with R. This course has been developed under the iniciative “Compumates” of the Faculty of Mathematics at Complutense University of Madrid. It consists on different sessions that go from the basic commands to their application to techniques of analysis and prediction. In this paper, it is shown the results obtained by the students and their opinion about the course.Depto. de Estadística e Investigación OperativaDepto. de Álgebra, Geometría y TopologíaFac. de Ciencias MatemáticasTRUEpu

Numerical analysis of the influence of tool wear and special cutting geometry when drilling woven CFRPs

CFRPs drilling is a common process in the aerospace industry carried out prior to components assembly. Machining induced damage leads to significant percentage of component rejection. Damage extension strongly depends on drilling geometry and cutting parameters. Fresh drill geometry changes with cutting time due to the wear progression and the risk for hole quality is enhanced as cutting progresses. The influence of wear on hole quality has been analyzed in the literature using mainly an experimental approach. Simulation of drilling process is an effective method that can be used to optimize drill geometry and process parameters in order to control hole quality and analyze the drill wear evolution. In this paper a finite element model for drilling woven CFRPs, reproducing both fresh and worn tools, is presented. Two different point angles considering fresh and honned edge were modeled. A progressive intra-laminar failure model based on the Chang and Chang model is considered. Cohesive elements allowed the analysis of inter-laminar damage (delamination). The model demonstrated its ability to predict thrust force and delamination for different values of feed rate and cutting speed. Model predictions show the influence of tool geometry (including variations induced due to wear) on delamination.This study has been developed under the financial support of the Ministry of Economy and Competitiveness of Spain under the projects DPI2011-25999 and DPI2013-41094-R, and the FPI subprogram associated to the project DPI2011-25999 with the reference BES-2012-055162

Enseñanza del Software Estadístico R a alumnos de Matemáticas

Habiendo constatado la falta de formación en herramientas estadísticas en algunas titulaciones de matemáticas, así como la creciente importancia del software de programación R, se ha visto la necesidad de impartir un curso de Análisis de Datos con R. Éste se ha desarrollado dentro de la iniciativa “Compumates” de la Facultad de CC. Matemáticas, Universidad Complutense de Madrid, y ha constado de diferentes sesiones, que parten desde la instalación del software y uso de comandos básicos, hasta su aplicación en técnicas de análisis y predicción. Para ello se ha provisto a los alumnos de un manual de aprendizaje. En este trabajo se muestran los resultados que ha tenido la experiencia en el aprendizaje del alumno y la valoración que tiene éste sobre la misma

Multivariate statistical techniques applied to the analysis and prediction of football matches in the main European leagues

El propósito de este estudio es analizar las estadísticas de juego en las principales ligas europeas y ver qué factores son más determinantes a la hora de predecir el resultado de un partido. Para ello usaremos técnicas de estadística multivariante incluyendo análisis de componentes principales y regresión logística. Las dos primeras componentes principales explican alrededor del 70 % de precisión obtenida cuando se predicen victorias fuera de casa tomando como variables predictivas las propias componentes. Este estudio también demuestra que en la liga inglesa los partidos son menos equilibrados.The purpose of this study is to analyse main game-related statistics differences between the main European leagues and which factors are more determinant when predicting a match score, by means of multivariate statistical techniques, including principal component analysis and logistic regression. The first two principal components explain around the 70 % of variance, and over a 70 % of accuracy is obtained when predicting away-team wins, with these two principal components as predictive variables. This study also shows that in English Premier League, games are less equilibrated.Depto. de Estadística e Investigación OperativaDepto. de Álgebra, Geometría y TopologíaFac. de Ciencias MatemáticasTRUEpu

Effects of a mesoporous bioactive glass on osteoblasts, osteoclasts and macrophages

A mesoporous bioactive glass (MBG) of molar composition 75SiO2-20CaO-5P2O5 (MBG-75S) has been synthetized as a potential bioceramic for bone regeneration purposes. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), nitrogen adsorption studies and transmission electron microscopy (TEM) demonstrated that MBG-75S possess a highly ordered mesoporous structure with high surface area and porosity, which would explain the high ionic exchange rate (mainly calcium and silicon soluble species) with the surrounded media. MBG-75S showed high biocompatibility in contact with Saos-2 osteoblast-like cells. Concentrations up to 1 mg/ml did not lead to significant alterations on either morphology or cell cycle. Regarding the effects on osteoclasts, MBG-75S allowed the differentiation of RAW264.7 macrophages into osteoclast-like cells but exhibiting a decreased resorptive activity. These results point out that MBG-75S does not inhibit osteoclastogenesis but reduces the osteoclast bone-resorbing capability. Finally, in vitro studies focused on the innate immune response, evidenced that MBG-75S allows the proliferation of macrophages without inducing their polarization towards the M1 pro-inflammatory phenotype. This in vitro behavior is indicative that MBG-75S would just induce the required innate immune response without further inflammatory complications under in vivo conditions. The overall behavior respect to osteoblasts, osteoclasts and macrophages, makes this MBG a very interesting candidate for bone grafting applications in osteoporotic patients

Nanocrystalline silicon substituted hydroxyapatite effects on osteoclast differentiation and resorptive activity

In the present study, the effects of nanocrystalline hydroxyapatite (nano-HA) and nanocrystalline Si-substituted hydroxyapatite (nano-SiHA) on osteoclast differentiation and resorptive activity have been evaluated in vitro using osteoclast-like cells. The action of these materials on proinflammatory and reparative macrophage populations was also studied. Nano-SiHA disks delayed the osteoclast differentiation and decreased the resorptive activity of these cells on their surface, as compared to nano-HA samples, without affecting cell viability. Powdered nano-SiHA also induced an increase of the reparative macrophage population. These results along with the beneficial effects on osteoblasts previously observed with powdered nano-SiHA suggest the potential of this biomaterial for modulating the fundamental processes of bone formation and turnover, preventing bone resorption and enhancing bone formation at implantation sites in treatment of osteoporotic bone and in bone repair and regeneration

Effects of immobilized VEGF on endothelial progenitor cells cultured on silicon substituted and nanocrystalline hydroxyapatites

Vascular endothelial growth factor (VEGF) plays an essential role in angiogenesis and vascular homeostasis. Endothelial progenitor cells (EPCs) are primitive bone marrow cells participating in neovascularization and revascularization processes, which also promote bone regeneration. Synthetic hydroxyapatite (HA) has been widely used in bone repair and implant coatings. In HA-based materials, small levels of ionic substitution by silicon (Si) have significant effects on osteoclastic and osteoblastic responses. Moreover, nanocrystalline hydroxyapatites (nano-HA) display enhanced bioreactivity and beneficial effects in bone formation. In this work, the angiogenic potential of VEGF-121 adsorbed on crystalline and nanocrystalline HAs with different Si proportion is evaluated with endothelial-like cells derived from EPCs cultured on nano-HA, nano-SiHA0.25, nano-SiHA0.4, HA, SiHA0.25 and SiHA0.4 disks. The Si amount incorporated for x ¼ 0.25 is enough to yield changes in the textural parameters and surface charge without decomposing the HA phase. Si substitution for x ¼ 0.4 does not result in pure Si-substituted apatites. Si probably remains at the grain boundaries as amorphous silica in nano-SiHA0.4 and SiHA0.4 is decomposed in a-TCP and HA after 1150 �C treatment. Immobilized VEGF on nano-HA, nano-SiHA0.25, nano-SiHA0.4, HA, SiHA0.25 and SiHA0.4 maintains its function exerting a local regulation of the cell response. The crystallite size and topography of nanocrystalline HAs could produce insufficient and weak contacts with endothelial-like cells triggering anoikis. Concerning Si proportion, the best results are obtained with SiHA0.25/VEGF and nano- SiHA0.25/VEGF disks. All these results suggest the potential utility of SiHA0.25/VEGF and nano-SiHA0.25/VEGF for bone repair and tissue engineering by promoting angiogenesis