92 research outputs found

    Analysis and Evaluation of a Wired/Wireless Hybrid Architecture for Distributed Control Systems With Mobility Requirements

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    Wireless communications offer significant benefits over wired communications, which has increased their popularity in industrial applications. Nevertheless, the existing wireless standard technologies do not satisfy the requirements demanded by the most critical industrial applications and thus, wired communications cannot be directly replaced by wireless solutions. Moreover, the inclusion of movable nodes in the network brings new challenges, such as the handover mechanism. In this paper, a hybrid wired/wireless architecture designed for industrial control applications is proposed. To control the wired network, a time-sensitive network (TSN) is used and to control the wireless network a medium access control (MAC) protocol is designed. In order to communicate both networks, a bridge that acts as a deterministic access point (AP) with real-time features is also proposed. One of the fundamental parts of the proposed architecture is that it can be used in applications with mobility requirements. Hence, a soft-handover algorithm is designed which guarantees uninterrupted communication during its execution without the need for a second radio interface and with reduced growth in network overhead. The proposed architecture is evaluated in order to assess its performance. This paper extends our previous work, including both a theoretical analysis to determine the delay bounds of the proposed architecture and a comparison between the performances of the proposed handover algorithm with other algorithms proposed in the literature. The evaluation has been carried out through OMNeT++ simulations. The results demonstrate the superiority of the proposed handover algorithm compared with other state-of-the-art solutions

    Self-calibration technique for on-machine spindle-mounted vision systems

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    On-machine measuring (OMM) systems are being more and more applied in machine tools in order to measure workpieces on the machine itself. Many of these systems are directly mounted in the machine spindle, so the measuring uncertainty is affected by clamping positioning and orientation variations, especially when integrating optical systems based on machine vision. This paper presents a self-calibration technique for vision systems by using redundant information of on machine measurements, avoiding extra mechanical anchoring or calibration means. It has been applied to a vision system with the angular placement uncertainty of a tool holder coupling being the main uncertainty contributor. A milling machine pilot case has been selected for demonstration, showing an effective self-calibration capability both in laboratory and industrial conditions

    Mutual modulation of gut microbiota and the immune system in type 1 diabetes models

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    Immunological disorders; Metabolic disorders; Molecular biologyTrastorns immunològics; Trastorns metabòlics; Biologia molecularTrastornos inmunológicos; Trastornos metabólicos; Biología MolecularThe transgenic 116C-NOD mouse strain exhibits a prevalent Th17 phenotype, and reduced type 1 diabetes (T1D) compared to non-obese diabetic (NOD) mice. A cohousing experiment between both models revealed lower T1D incidence in NOD mice cohoused with 116C-NOD, associated with gut microbiota changes, reduced intestinal permeability, shifts in T and B cell subsets, and a transition from Th1 to Th17 responses. Distinct gut bacterial signatures were linked to T1D in each group. Using a RAG-2−/− genetic background, we found that T cell alterations promoted segmented filamentous bacteria proliferation in young NOD and 116C-NOD, as well as in immunodeficient NOD.RAG-2−/− and 116C-NOD.RAG-2−/− mice across all ages. Bifidobacterium colonization depended on lymphocytes and thrived in a non-diabetogenic environment. Additionally, 116C-NOD B cells in 116C-NOD.RAG-2−/− mice enriched the gut microbiota in Adlercreutzia and reduced intestinal permeability. Collectively, these results indicate reciprocal modulation between gut microbiota and the immune system in rodent T1D models.This work was supported by the Plan Nacional de I + D + i of the Spanish Ministry of Science and Innovation (PID2019-109302RB-I00), the DiabetesCERO Foundation (Becas Impulso Talento Joven 2022), and CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM) that is an initiative from Instituto de Salud Carlos III (Spain). E.R.-M. was supported by predoctoral fellowships from the Generalitat de Catalunya (AGAUR FI-DGR, grant number: 2013FI_B 00585), the Spanish Government (FPU, grant number: FPU13/02045) and the IRBLleida. M.C.-P., B.A., and L.E.-M. were supported by UdL and IRBLleida predoctoral fellowships. F. Y. was supported by a predoctoral fellowship from the Chilean Government (ANID, grant number: 72190278). G.S.-G. was supported by a predoctoral fellowship from VHIR

    Desarrollo de un proceso de alineación de piezas en bruto basado en fotogrametría para el mecanizado de componenetes de grandes dimensiones

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    Esta tesis se enmarca dentro del ámbito de la fotogrametría con marcadores ópticos retro-reflectantes aplicada a la metrología dimensional de alto rango. Se propone el desarrollo de un proceso de alineación de pieza en bruto basado en fotogrametría, dirigido a incrementar la sencillez y eficiencia de este proceso industrial, limitante crítico de la productividad alcanzable en la fabricación de componentes de grandes dimensiones, compuesto por dos sistemas de medida: (1) fotogrametría portable con cámaras digitales de consumo y bajo coste para el control dimensional de pieza en bruto fuera de máquina, y (2) estéreo-fotogrametría portable e integrable en cabezal de máquina-herramienta fresadora para la medición automatizada de la posición y orientación de pieza durante su alineación en máquina. Partiendo del potencial ofrecido por la fotogrametría para disponer de información redundante en las imágenes del mismo proceso de medida, la principal propuesta de conocimiento del presente trabajo consta del desarrollo de técnicas de auto-calibración en proceso computacionalmente eficientes, demostrando su validez para la compensación eficaz de fuentes de error de medida relevantes en cada uno de los medidores fotogramétricos, evitando la necesidad de adoptar procesos de calibración específicos para su compensación. La solución propuesta se evalúa en escenarios tanto de laboratorio como industriales, demostrando su validez para el control dimensional de tolerancias de sobrematerial de ± 1 mm en piezas con un volumen superior a 100 m3.<br /

    Inhibition of BCR signaling using the Syk inhibitor TAK-659 prevents stroma-mediated signaling in chronic lymphocytic leukemia cells

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    Altres ajuts: This work was cofinanced by the European Regional Development Fund (ERDF) and Asociación Española Contra el Cáncer (AECC, M.C). N.P. is a recipient of a PhD fellowship granted by Institut de Recerca Vall d'Hebron. C.C. is supported by a grant from Sociedad Española de Hematología y Hemoterapia (SEHH).Proliferation and survival of chronic lymphocytic leukemia (CLL) cells depend on microenvironmental signals coming from lymphoid organs. One of the key players involved in the crosstalk between CLL cells and the microenvironment is the B-cell receptor (BCR). Syk protein, a tyrosine kinase essential for BCR signaling, is therefore a rational candidate for targeted therapy in CLL. Against this background, we tested the efficacy of the highly specific Syk inhibitor TAK-659 in suppressing the favorable signaling derived from the microenvironment. To ex vivo mimic the microenvironment found in the proliferation centers, we co-cultured primary CLL cells with BM stromal cells (BMSC), CD40L and CpG ODN along with BCR stimulation. In this setting, TAK-659 inhibited the microenvironment-induced activation of Syk and downstream signaling molecules, without inhibiting the protein homologue ZAP-70 in T cells. Importantly, the pro-survival, proliferative, chemoresistant and activation effects promoted by the microenvironment were abrogated by TAK-659, which furthermore blocked CLL cell migration toward BMSC, CXCL12, and CXCL13. Combination of TAK-659 with other BCR inhibitors showed synergistic effect in inducing apoptosis, and the sequential addition of TAK-659 in ibrutinib-treated CLL cells induced significantly higher cytotoxicity. These findings provide a strong rationale for the clinical development of TAK-659 in CLL

    B-Lymphocyte Phenotype Determines T-Lymphocyte Subset Differentiation in Autoimmune Diabetes.

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    Previous studies indicate that B-lymphocytes play a key role activating diabetogenic T-lymphocytes during the development of autoimmune diabetes. Recently, two transgenic NOD mouse models were generated: the NOD-PerIg and the 116C-NOD mice. In NOD-PerIg mice, B-lymphocytes acquire an activated proliferative phenotype and support accelerated autoimmune diabetes development. In contrast, in 116C-NOD mice, B-lymphocytes display an anergic-like phenotype delaying autoimmune diabetes onset and decreasing disease incidence. The present study further evaluates the T- and B-lymphocyte phenotype in both models. In islet-infiltrating B-lymphocytes (IIBLs) from 116C-NOD mice, the expression of H2-Kd and H2-Ag7 is decreased, whereas that of BAFF, BAFF-R, and TACI is increased. In contrast, IIBLs from NOD-PerIg show an increase in CD86 and FAS expression. In addition, islet-infiltrating T-lymphocytes (IITLs) from NOD-PerIg mice exhibit an increase in PD-1 expression. Moreover, proliferation assays indicate a high capacity of B-lymphocytes from NOD-PerIg mice to secrete high amounts of cytokines and induce T-lymphocyte activation compared to 116C B-lymphocytes. This functional variability between 116C and PerIg B-lymphocytes ultimately results in differences in the ability to shape T-lymphocyte phenotype. These results support the role of B-lymphocytes as key regulators of T-lymphocytes in autoimmune diabetes and provide essential information on the phenotypic characteristics of the T- and B-lymphocytes involved in the autoimmune response in autoimmune diabetes

    Hypoxia Reduces Cell Attachment of SARS-CoV-2 Spike Protein by Modulating the Expression of ACE2, Neuropilin-1, Syndecan-1 and Cellular Heparan Sulfate

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    A main clinical parameter of COVID-19 pathophysiology is hypoxia. Here we show that hypoxia decreases the attachment of the receptor-binding domain (RBD) and the S1 subunit (S1) of the spike protein of SARS-CoV-2 to epithelial cells. In Vero E6 cells, hypoxia reduces the protein levels of ACE2 and neuropilin-1 (NRP1), which might in part explain the observed reduction of the infection rate. In addition, hypoxia inhibits the binding of the spike to NCI-H460 human lung epithelial cells by decreasing the cell surface levels of heparan sulfate (HS), a known attachment receptor of SARS-CoV-2. This interaction is also reduced by lactoferrin, a glycoprotein that blocks HS moieties on the cell surface. The expression of syndecan-1, an HS-containing proteoglycan expressed in lung, is inhibited by hypoxia on a HIF-1αdependent manner. Hypoxia or deletion of syndecan-1 results in reduced binding of the RBD to host cells. Our study indicates that hypoxia acts to prevent SARS-CoV-2 infection, suggesting that the hypoxia signalling pathway might offer therapeutic opportunities for the treatment of COVID-19.This research was supported by the SPRI I+D COVID-19 fund (Basque Government, bG-COVID-19), the European Research Council (ERC) (grant numbers: ERC-2018-StG 804236-NEXTGEN-IO to A.P and ERC-2017-AdG 788143-RECGLYCANMR to J.J-B.), the Severo Ochoa Excellence Accreditation from MCIU (SEV-2016-0644) and the FERO Foundation. Personal fellowships: E.P. (Juan de la Cierva-Formación, FJC2018-035449-I), L.V. (Juan de la Cierva-Formación, FJCI-2017-34099), A.B. (AECC Bizkaia Scientific Foundation, PRDVZ19003BOSC), A.G. (Programa Bikaintek from the Basque Government, 48-AF-W1-2019-00012), A.A (La Caixa Inphinit, LCF/BQ/DR20/11790022), B.J. (Basque Government, PRE_2019_1_0320), L.M. (Juan de la Cierva-Formación, FJC2019-039983-I), E.B. (MINECO, BFU2016-76872-R; Excellence Networks, SAF2017-90794-REDT) and A.P. (Ramón y Cajal, RYC2018-024183-I; Proyectos I+D+I, PID2019-107956RA-I00; and Ikerbasque Research Associate)

    Sensitive detection of SARS-CoV-2 seroconversion by flow cytometry reveals the presence of nucleoprotein-reactive antibodies in unexposed individuals

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    There is an ongoing need of developing sensitive and specific methods for the determination of SARS-CoV-2 seroconversion. For this purpose, we have developed a multiplexed flow cytometric bead array (C19BA) that allows the identification of IgG and IgM antibodies against three immunogenic proteins simultaneously: the spike receptor-binding domain (RBD), the spike protein subunit 1 (S1) and the nucleoprotein (N). Using different cohorts of samples collected before and after the pandemic, we show that this assay is more sensitive than ELISAs performed in our laboratory. The combination of three viral antigens allows for the interrogation of full seroconversion. Importantly, we have detected N-reactive antibodies in COVID-19-negative individuals. Here we present an immunoassay that can be easily implemented and has superior potential to detect low antibody titers compared to current gold standard serology methods.Acknowledgements: We thank Petros Tyrakis and Iván Martínez-Forero for critical reading and editing of the manuscript. Support was provided by the Severo Ochoa Excellence Accreditation from MCIU (SEV-2016-0644) and the SPRI I+D COVID-19 fund (Gobierno Vasco). Personal fellowships: A.A.-V. (La Caixa Inphinit LCF/BQ/DR20/11790022), A.B. (AECC Bizkaia), A.G.d.R (Bikaintek), A.P. (Ramón y Cajal), B.J.-L. (Gob. Vasco), and E.P.-F. (Juan de la Cierva-Formación). M.L.M.-C. acknowledges RTC2019-007125-1, DTS20/00138, SAF2017-87301-R, and BBVA UMBRELLA project. M.L.-H. acknowledges the ISCIII for grant COV20-0170 and the Government of Cantabria for grant 2020UIC22-PUB-0019. O.M., J.-M.M., and N.G.A.A. acknowledge the Agencia Estatal de Investigación (Spain) for grants CTQ2015-68756-R, RTI2018-101269-BI00, and RTI2018-095700-B-I00, respectively. A.P. has received grant funding from the European Research Council (ERC), grant agreement number 804236 (Horizon 2020), and the FERO Foundation
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