Targeted-pig trial on safety and immunogenicity of serum-derived extracellular vesicles enriched fractions obtained from Porcine Respiratory and Reproductive virus infections

The Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is the etiological agent of one of the most important swine diseases with a significant economic burden worldwide. Unfortunately, available vaccines are partially effective highlighting the need of novel approaches. Previously, antigenic viral proteins were described in serum-derived extracellular vesicles (EVs) from pigs previously infected with PRRSV. Here, a targeted-pig trial was designed to determine the safety and immunogenicity of such extracellular vesicles enriched fractions. Our results showed that immunizations with EV-enriched fractions from convalescence animals in combination with montanide is safe and free of virus as immunizations with up-to two milligrams of EV-enriched fractions did not induce clinical symptoms, adverse effects and detectable viral replication. In addition, this vaccine formulation was able to elicit specific humoral IgG immune response in vaccinated animals, albeit variably. Noticeably, sera from vaccinated animals was diagnosed negative when tested for PRRSV using a commercial ELISA test; thus, indicating that this new approach differentiates vaccinated from infected animals. Lastly, after priming animals with EV-enriched fractions from sera of convalescence animals and boosting them with synthetic viral peptides identified by mass spectrometry, a distinctive high and specific IFN-γ response was elicited. Altogether, our data strongly suggest the use of serum EV-enriched fractions as a novel vaccine strategy against PRRSV.Anti-CD9, Anti-CD63 and anti-CD81 antibodies were kindly donated by Francisco Sánchez-Madrid and Maria Yañez-Mo, Hospital de la Princesa, Madrid, Spain. The authors wish to particularly thank Glòria Abella for her collaboration in conducting the field study and to Marta Alcobé, Miriam Moron Font and Paula Crego Mendez for technical assistance. This study received support from Innovex Therapeutics S.L., Pinsos del Segre SA, Granja Casanyé, Grup de Sanejament Porci (GSP, Lleida, Spain) and the FEDER project (COMRDI16-1-0035-03). Sergio Montanter-Tarbes is an industrial doctorate awarded by the Government of Catalonia, Spain (No. 2014 DI 044). ISGlobal and IGTP are members of the CERCA Programme, Generalitat de Catalunya

A parametric model for analysing atherosclerotic arteries: On the FSI coupling

There are many evidences that coronary plaque is not only dependent on the formation and progression of atherosclerosis, but also on the vascular remodelling response. If the local wall shear stress is low, a proliferative plaque may develop. Local inflammatory response will stimulate the formation of a plaque prone to rupture with superimposed thrombus formation (vulnerable plaque). Furthermore, the role of the wall shear stress in the genesis and the development of atherosclerotic diseases has been recently intensively investigated, examining its relationship with the presence of lesions and the intima media thickness. Due to the important role of pulsating blood flow, pressure and hemodynamics factors in atheroma growth, a Fluid Structure Interaction (FSI) parametric study of a 3D atherosclerotic artery has been carried out, with aim of studying the main geometrical risk factors in terms of plaque vulnerability

Serum-derived exosomes from non-viremic animals previously exposed to the porcine respiratory and reproductive virus contain antigenic viral proteins

PRRSV is the etiological agent of one of the most important swine diseases with a significant economic burden worldwide and limitations in vaccinology. Exosomes are 30–100 nm vesicles of endocytic origin. Remarkably, immunizations with exosomes containing antigens from tumors or pathogens are capable of eliciting protective immune responses, albeit variably, in cancer and infectious diseases. Here we describe the isolation, molecular composition and immunogenicity of serum-derived exosomes from naïve animals, from PRRSV viremic animals and from animals previously PRRSV infected but already free of viruses (non viremic). Exosomes were isolated through size exclusion chromatography and characterized by different methodologies. Exosome-enriched fractions from naïve and natural infected animals contained classical tetraspanin exosomal markers (CD63 and CD81) and high concentrations of particles in the size-range of exosomes as detected by nanoparticle tracking analysis and cryo-TEM. NanoLC-MS/MS was used to identify viral antigens associated to exosomes. PRRSV-proteins were detected in serum samples from only viremic animals and from animals previously infected already free of viruses (non-viremic), but not in controls. Moreover, immune sera from pigs previously exposed to PRRSV specifically reacted against exosomes purified from non-viremic pig sera in a dose-dependent manner, a reactivity not detected when naïve sera was used in the assay. To facilitate future studies, a scaling-up process was implemented. To the best of our knowledge, this is the first molecular characterization of serum-derived exosomes from naïve pigs and pigs actively or previously infected with PRRSV. The presence of antigenic viral proteins in serum-derived exosomes free of virus, suggest their use as a novel vaccine approach against PRRSV.Anti‑ CD63 and anti‑ CD81 antibodies were kindly donated by Francisco Sánchez‑Madrid and Maria Yañez‑Mo, Hospital de la Princesa, Madrid, Spain. We thank Miriam Morón Font for technical assistance and Inés Lozano and Marta Monguió ‑Tortajada for valuable scientific discussions. SMT is supported by an Industrial PhD Fellowship from the government of Catalonia (AGAUR) as part of a collaborative agreement between INNOVEX THERAPEUTICS SL and the University of Lleida (Id No 2014 DI 044

Study of idfferential protein expression in healthy human skeletal muscles using electrophoresis bidimentional

Comunicaciones a congreso

Double quantum dot with tunable coupling in an enhancement-mode silicon metal-oxide semiconductor device with lateral geometry

We present transport measurements of a tunable silicon metal-oxide-semiconductor double quantum dot device with lateral geometry. Experimentally extracted gate-to-dot capacitances show that the device is largely symmetric under the gate voltages applied. Intriguingly, these gate voltages themselves are not symmetric. Comparison with numerical simulations indicates that the applied gate voltages serve to offset an intrinsic asymmetry in the physical device. We also show a transition from a large single dot to two well isolated coupled dots, where the central gate of the device is used to controllably tune the interdot coupling.Comment: 4 pages, 3 figures, to be published in Applied Physics Letter

Magnetic exchange interaction in a pair of orbitally degenerate ions: Magnetic anisotropy of [Ti2Cl9]−3

The theory of the kinetic exchange in a pair of orbitally degenerate ions developed by the authors [J. Phys. Chem. A 102, 200 (1998)] is applied to the case of face-shared bioctahedral dimer (overall D3h-symmetry). The effective kinetic exchange Hamiltonian is found for a 2T2–2T2 system taking into account all relevant transfer pathways and charge-transfer crystal field states. The influence of different transfer integrals involved in the kinetic exchange on the energy pattern and magnetic properties of the system is examined. The role of other related interactions (trigonal crystal field, spin–orbit coupling) is also discussed in detail. Using the pseudoangular momentum representation and the technique of the irreducible tensor operators of R3-group we give a general outlook on the nontrivial symmetry properties of the effective Hamiltonian for the D3h-pair, and on the magnetic anisotropy arising from the orbital interactions specific for the case of orbital degeneracy. The magnetic properties of the binuclear unit [Ti2Cl9]−3 in Cs3Ti2Cl9 are discussed with a special emphasis on the magnetic anisotropy experimentally observed in this system. The existing exchange models for [Ti2Cl9]−3 and the concept of the effective Hamiltonian are discussed in the context of the present [email protected] ; [email protected] ; [email protected] ; [email protected]

Adaptación transcultural de un cuestionario para medir la calidad de vida de los pacientes con anticoagulación oral

ObjetivoAdaptar a la cultura y el idioma españoles un cuestionario desarrollado para evaluar la calidad de vida de los pacientes con tratamiento anticoagulante oral (TAO) y medir su validezDiseñoEstudio observacional, descriptivo, de validación de un instrumento de medida de calidad de vida relacionada con la salud. Emplazamiento. Atención primaria y atención especializadaParticipantesUn total de 225 pacientes que incluía a todos los pacientes de nuestro centro que utilizan TAO y una muestra consecutiva de pacientes con TAO del servicio de hematología del hospital de referenciaMediciones principalesTraducción directa,traducción inversa y prueba de validez. Análisis factorial y agrupación por dimensiones de los ítems, análisis de la consistencia interna y análisis de correlación ítem-total de la versión definitiva del cuestionario en españolResultadosLa edad media de los pacientes fue de 65 ± 13 años, el 51,1% era mujer y el 45,8% era controlado en atención primaria. En el estudio de validez se realizó un análisis factorial con la extracción de 5 factores que explican el 41,62% del valor total de la varianza y la obtención de una agrupación diferente de la original, con unvalor de alfa de Cronbach global de 0,82 y de 0,56–0,74 en las diferentes dimensiones y análisis de correlación ítem-total con valores estadísticamente significativos, excepto en la pregunta número 29ConclusionesTras realizar la adaptación a la cultura y el idioma españoles de un cuestionario desarrollado para evaluar la calidad de vida de los pacientes con TAO, se ha obtenido un instrumento útil y válido para nuestro entornoObjectiveTo adapt to Spanish culture and language a questionnaire developed to evaluate the quality of life of patients taking oral anticoagulation treatment (OAT) and to measure its validityDesignA descriptive observation study to validate an instrument to measure health-related quality of lifeSettingPrimary and specialist careParticipants225 patients, all the patients at our centre who were on OAT and a consecutive sample of patients on OAT from the referral hospital's haemotology serviceMain measurementsDirect translation, back- translation, and pilot study. Factor analysis and item-dimension grouping, internal consistency analysis and analysis of the item- total correlation of the definitive version of the questionnaire in SpanishResultsMean age was 65 (SD=13 years); 51% were women; 45.8% were monitored in PC. Validity study: factor analysis extracted 5 factors that explained 41.62% of total variance value and obtained a grouping different from the original; Cronbach's alpha was .82 overall and ran from .56 to .74 in the various dimensions; and item-total correlation analysis had statistically significant values,except for question 29ConclusionsAfter adaptation to Spanish culture and language of a questionnaire developed to evaluate the quality of life of patients taking OAT, it was found to be a useful instrument, valid for use in our milie

Development of a gas chromatography - mass spectrometry method for the determination of carbon disulfide in the atmosphere

[EN] Carbon disulfide (CS2), a relevant reduced sulfur compound in air, is well-known for its malodor and its significant effect on global atmospheric chemistry. Therefore, a reliable method for determining CS2 in atmospheric samples has been developed based on solid-phase sampling and gas chromatography-mass spectrometry (GC-MS). Two types of solid-phase sampling supports (Orbo-32 and SKC) and the elution with organic solvents - hexane and toluene - were evaluated for low-volume outdoor sampling. Recovery studies and the standard addition method were carried out to demonstrate the proper determination of CS2 in the absence of the influence of interferences such as ozone, hydrogen sulfide or water - important atmospheric pollutants. The proposed methodology was validated by performing experiments in a high-volume smog chamber and by comparison with two reference optical methods, Fourier Transform Infrared (FTIR) and Differential Optical Absorption Spectroscopy (DOAS) installed in these facilities. Satisfactory analytical parameters were reported: fast analysis, a correct repeatability of 6±1% and reproducibility of 14±3%, and low detection limits of 0.3-0.9pgm-3. Finally, the method was successfully applied to industrial samples near a pulp factory area, where a high correlation between industrial emissions and reported carbon disulfide concentrations were observed. © 2011 Elsevier B.V.The research leading to these results received funding from the Centro de Investigacion del Medio Ambiente (CIMA), Consejeria de Medio Ambiente, Gobierno de Cantabria. The Instituto Universitario CEAM-UMH is partly supported by Generalitat Valenciana, Fundacion Bancaja, and the projects GRACCIE (Consolider-Ingenio 2010) and FEEDBACKS (Prometeo - Generalitat Valenciana). We also acknowledged the European Community's Seventh Framework Program under the grant agreement no. 228335 (Eurochamp2), the Spanish Ministry of Science and Innovation, through INNPLANTA project: PCT-440000-2010-003 and the EUPHORE staff for their support in the chamber experiments. The authors also thank J.T.B. for his contribution.Borrás García, EM.; Ródenas, M.; Dieguez, J.; Pérez-García, M.; Lomba, R.; Lavin, J.; Tortajada-Genaro, LA. (2012). Development of a gas chromatography - mass spectrometry method for the determination of carbon disulfide in the atmosphere. Microchemical Journal. 101:37-42. https://doi.org/10.1016/j.microc.2011.10.002S374210

Experimental data on SOA formation from mixtures of anthropogenic and biogenic organic compounds

AbstractSecondary organic aerosols (SOA) constitute a significant fraction of the atmospheric particulate matter. Theses particles are formed as a consequence of the oxidation reaction of certain organic gases that leads to the formation of low-volatility compounds. As for other pollutants, air quality models allow the simulation of particle levels and thus models constitute a powerful tool in air quality management. Nevertheless, the accepted use of models must be based on the validation of its capacity to reproduce observed concentrations. Air monitoring sites provide measured information of a large variety of ambient pollutants. Unfortunately, measurements on SOA are not normally available, as current monitoring networks do not include instrumentation to distinguish primary from secondary sources of organic carbonaceous aerosol. This paper presents a set of photooxidation experiments performed in the European Photorreactor (EUPHORE) smog chamber (CEAM, Spain) under different experimental conditions to investigate SOA formation. The use of chambers allows the isolation of atmospheric chemistry and aerosol formation processes. Thus, although these measurements were obtained at initial precursor concentrations higher than those in atmospheric conditions, they constitute a valuable set of information for SOA model evaluation purposes

Way Combination for an Adaptive and Scalable Coherence Directory

© 2019 IEEE. Personal use of this material is permitted. Permissíon from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertisíng or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.[EN] This manuscript opens the way to a new class of coherence directory structures that are based on the brand-new concept of way combining. A Way-Combining Directory (WC-dir) builds on a typical sparse directory but allows to take advantage of several ways in the same set to codify the sharing information of each memory block. The result is a sparse directory with variable effective associativity per set and variable length entries, thus being able to dynamically adapt the directory structure to the particular requirements of each application. In particular, our proposal uses just enough bits per entry to store a single pointer, which is optimal for the common case of having just one sharer. For those addresses that have more than one sharer, we have observed that in the majority of cases extra bits could be taken from other empty ways in the same set. All in all, our proposal minimizes the storage overheads without losing the flexibility to adapt to several sharing degrees and without the complexities of other previously proposed techniques. Detailed simulations of a 128-core multicore architecture running benchmarks from PARSEC-3.0 and SPLASH-3 demonstrate that WC-dir can closely approach the performance of a non-scalable bit vector sparse directory, beating the state-of-the-art Scalable Coherence Directory (SCD) and Pool directory proposals.This work has been supported by the Spanish MCIU and AEI, as well as European Commission FEDER funds, under grant "RTI2018-098156-B-C53".Titos-Gil, R.; Flores, A.; Fernández-Pascual, R.; Ros, A.; Petit Martí, SV.; Sahuquillo Borrás, J.; Acacio, ME. (2019). Way Combination for an Adaptive and Scalable Coherence Directory. IEEE Transactions on Parallel and Distributed Systems. 30(11):2608-2623. https://doi.org/10.1109/TPDS.2019.2917185S26082623301