5 research outputs found

    Caracterización de válvulas de admisión y expulsión de aire comerciales

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    El objetivo del trabajo es estudiar en detalle el comportamiento real de diferentes ventosas (válvulas de admisión y expulsión de aire). La primera parte del trabajo describe las diferentes técnicas experimentales de caracterización de ventosas. En la segunda parte se utiliza el banco de pruebas de válvulas de aire construido por Bermad CS en su fábrica de Evron, Israel, para realizar los ensayos de caracterización estática a diferentes ventosas comerciales. Finalmente se realiza un estudio comparativo del comportamiento de los diferentes modelos analizados, analizando los coeficientes más adecuados para la caracterización matemática de estos elementos

    Functional and structural characterization of mouse mono-clonal antibodies against human C5a

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    1 p.Background: The signaling pathways mediated by the ana-phylatoxins complement component 3a and 5a (C3a and C5a) are potent proinflammatory cytokines (Guo and Ward, 2005). While in the context of infection biology, C5a-mediated neutrophil chemo-taxis is seen as an integral part of the immune system defense against pathogens, there are other scenarios where chronic C5a overstimulation can have dire consequences (Wood et al., 2018).Examples include immune complex disease, ischemia-reperfusion injury, and allergic asthma and bronchoconstriction. Anti-C5a anti-bodies have been proposed as a viable therapeutic option to control C5a-mediated inflammatory conditions. Here, we present our ongoing efforts to develop and characterize a set of anti-C5a antibodies for the pharmaceutical immunomodulation of anaphy-latoxin signaling pathways.Methods: Anti-C5a antibodies were raised in mouse using recombinant human C5a. Purification of the anti-C5a antibodies was accomplished with Protein G affinity chromatography. Human C5a was generated by zymosan activation of human plasma sam-ples. The effect of anti-C5a antibodies on neutrophil migration down C5a chemical gradients was assessed with a transwell assay.Migrating neutrophils were quantified by flow cytometry. Binding constants were measured by surface plasmon resonance (SPR). The structure and dynamics of a mAb-C5a complex were interrogatedwith small-angle X-ray scattering (SAXS).Results: We have characterized antibodies that recognize recombinant and authentic human and mouse C5a, inhibit C5a induced chemotactic responses in neutrophils and macrophages and show nM affinity and adequate kinetic dissociation parameters. We have tested the properties of several anti-C5a antibodies using human granulocytes purified from EDTA venous blood sam-ples. As expected, treatment of the C5a-containing samples with the anti-C5a antibodies efficiently depleted C5a and, therefore, lowered the number of migrating neutrophils. SAXS shape restoration of a mAb-C5a complex reveals a tight complex with substantial flexibility around the IgG hinge region.Conclusions: A set of mouse anti-C5a mAbs with high affinity for C5a and the capacity to inhibit C5a mediated neutrophil migration have been characterized biochemically, biophysically,functionally using in vitro neutrophil-migration assays and struc-turally by SAXS.Peer reviewe

    Neuroblastoma in Spain : Linking the national clinical database and epidemiological registries - A study by the Joint Action on Rare Cancers

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    Altres ajuts: Ministerio de Sanidad; Universitat de València; Sociedad Española de Oncología Pediátrica; Fundación de Oncología Infantil Enriqueta Villavecchia.Purpose: Linkage between clinical databases and population-based cancer registries may serve to evaluate European Reference Networks' (ERNs) activity, by monitoring the proportion of patients benefiting from these and their impact on survival at a population level. To test this, a study targeting neuroblastoma (Nb) was conducted in Spain by the European Joint Action on Rare Cancers. Material and methods: Subjects: Nb cases, incident 1999-2017, aged < 15 years. Linkage included: Spanish Neuroblastoma Clinical Database (NbCDB) (1217 cases); Spanish Registry of Childhood Tumours (RETI) (1514 cases); and 10 regional population-based registries (RPBCRs) which cover 33% of the childhood population (332 cases). Linkage was semiautomatic. We estimated completeness, incidence, contribution, deficit, and 5-year survival in the databases and specific subsets. Results: National completeness estimates for RETI and NbCDB were 91% and 72% respectively, using the Spanish RPBCRs on International Incidence of Childhood Cancer (https://iicc.iarc.fr/) as reference. RPBCRs' specific contribution was 1.6%. Linkage required manual crossover in 54% of the semiautomatic matches. Five-year survival was 74% (0-14 years) and 90% (0-18 months). Conclusions: All three databases were incomplete as regards Spain as a whole and should therefore be combined to achieve full childhood cancer registration. A unique personal patient identifier could facilitate such linkage. Most children have access to Nb clinical trials. Consolidated interconnections between the national registry and clinical registries (including ERNs and paediatric oncology clinical groups) should be established to evaluate outcomes

    Combined dark matter searches towards dwarf spheroidal galaxies with Fermi-LAT, HAWC, H.E.S.S., MAGIC, and VERITAS

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    Cosmological and astrophysical observations suggest that 85\% of the total matter of the Universe is made of Dark Matter (DM). However, its nature remains one of the most challenging and fundamental open questions of particle physics. Assuming particle DM, this exotic form of matter cannot consist of Standard Model (SM) particles. Many models have been developed to attempt unraveling the nature of DM such as Weakly Interacting Massive Particles (WIMPs), the most favored particle candidates. WIMP annihilations and decay could produce SM particles which in turn hadronize and decay to give SM secondaries such as high energy γ\gamma rays. In the framework of indirect DM search, observations of promising targets are used to search for signatures of DM annihilation. Among these, the dwarf spheroidal galaxies (dSphs) are commonly favored owing to their expected high DM content and negligible astrophysical background. In this work, we present the very first combination of 20 dSph observations, performed by the Fermi-LAT, HAWC, H.E.S.S., MAGIC, and VERITAS collaborations in order to maximize the sensitivity of DM searches and improve the current results. We use a joint maximum likelihood approach combining each experiment's individual analysis to derive more constraining upper limits on the WIMP DM self-annihilation cross-section as a function of DM particle mass. We present new DM constraints over the widest mass range ever reported, extending from 5 GeV to 100 TeV thanks to the combination of these five different γ\gamma-ray instruments
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