Showing papers by "Miquel Nofrarías published in 2012"
TL;DR: Fusion of the extracellular domain of the ASFV Hemagglutinin to p54 and p30, two immunodominant structural viral antigens, exponentially improved both the humoral and the cellular responses induced in pigs after DNA immunization.
Abstract: The lack of available vaccines against African swine fever virus (ASFV) means that the evaluation of new immunization strategies is required. Here we show that fusion of the extracellular domain of the ASFV Hemagglutinin (sHA) to p54 and p30, two immunodominant structural viral antigens, exponentially improved both the humoral and the cellular responses induced in pigs after DNA immunization. However, immunization with the resulting plasmid (pCMV-sHAPQ) did not confer protection against lethal challenge with the virulent E75 ASFV-strain. Due to the fact that CD8+ T-cell responses are emerging as key components for ASFV protection, we designed a new plasmid construct, pCMV-UbsHAPQ, encoding the three viral determinants above mentioned (sHA, p54 and p30) fused to ubiquitin, aiming to improve Class I antigen presentation and to enhance the CTL responses induced. As expected, immunization with pCMV-UbsHAPQ induced specific T-cell responses in the absence of antibodies and, more important, protected a proportion of immunized-pigs from lethal challenge with ASFV. In contrast with control pigs, survivor animals showed a peak of CD8+ T-cells at day 3 post-infection, coinciding with the absence of viremia at this time point. Finally, an in silico prediction of CTL peptides has allowed the identification of two SLA I-restricted 9-mer peptides within the hemagglutinin of the virus, capable of in vitro stimulating the specific secretion of IFNγ when using PBMCs from survivor pigs. Our results confirm the relevance of T-cell responses in protection against ASF and open new expectations for the future development of more efficient recombinant vaccines against this disease.
130 citations
University of Trento1, European Space Agency2, Max Planck Society3, Paris Diderot University4, Dornier Flugzeugwerke5, Spanish National Research Council6, Autonomous University of Barcelona7, University of Birmingham8, University of Hertfordshire9, University of Glasgow10, ETH Zurich11, European Space Operations Centre12, Imperial College London13, University of Zurich14, Polytechnic University of Catalonia15, University of Florida16
TL;DR: The current status of the LISA Pathfinder mission is described, a precursor mission aimed at demonstrating key technologies for future space-based gravitational wave detectors, like LISA, and performance measurements and analysis of these flight components lead to an expected performance of theLISA Pathfinder which is a significant improvement over the mission requirements.
Abstract: In this paper, we describe the current status of the LISA Pathfinder mission, a precursor mission aimed at demonstrating key technologies for future space-based gravitational wave detectors, like LISA. Since much of the flight hardware has already been constructed and tested, we will show that performance measurements and analysis of these flight components lead to an expected performance of the LISA Pathfinder which is a significant improvement over the mission requirements, and which actually reaches the LISA requirements over the entire LISA Pathfinder measurement band.
74 citations
TL;DR: The vaccine product was able to reduce clinical signs, PCV2 viral load in sera and faeces, and overall mortality in nurseries and fattening units, and average daily gain was significantly higher in vaccinated versus non-vaccinated piglets during the trial period.
63 citations
TL;DR: PCV2 vaccination was able to overcome this interference in piglet humoral response development since the ADWG was improved in both groups of vaccinated piglets, independently of the sow treatment, being the highest ones obtained in the double vaccination group.
52 citations
TL;DR: There were significant reductions in bacterial load in both groups of vaccinated goats, but the reduction was more pronounced in prime-boosted animals, and Antigen-specific gamma interferon (IFN-γ and humoral responses were identified as prognostic biomarkers of vaccination outcome depending on their correlation with pathological and bacteriological results.
Abstract: This is the first efficacy study using the experimental goat model, a natural host of tuberculosis (TB), to evaluate the efficacy of heterologous Mycobacterium bovis bacillus Calmette-Guerin (BCG) prime followed by boosting with a replication-deficient adenovirus expressing the antigen Ag85A (AdAg85A). Three experimental groups of 11 goat kids each were used: BCG vaccinated, BCG vaccinated and AdAg85A boosted, and nonvaccinated. Twenty-two goat kids were vaccinated with ∼5 × 105 CFU of BCG (week 0), and 11 of them were boosted at week 8 with 109 PFU of AdAg85A. At week 14, all goats were challenged by the endobronchial route with ∼1.5 × 103 CFU of Mycobacterium caprae. The animals were euthanized at week 28. Cellular and humoral immunity induced by vaccination and M. caprae infection was measured throughout the study. After challenge BCG-AdAg85A-vaccinated animals exhibited reduced pathology compared to BCG-vaccinated animals in lungs and in pulmonary lymph nodes. There were significant reductions in bacterial load in both groups of vaccinated goats, but the reduction was more pronounced in prime-boosted animals. Antigen-specific gamma interferon (IFN-γ) and humoral responses were identified as prognostic biomarkers of vaccination outcome depending on their correlation with pathological and bacteriological results. As far as we know, this is the first report using multidetector computed tomography (MDCT) to measure vaccine efficacy against pulmonary TB in an animal model. The use in vaccine trials of animals that are natural hosts of TB may improve research into human TB vaccines.
47 citations
TL;DR: Clove at doses of 100–200 mg/kg seem to improve feed efficiency and interesting changes in intestinal microbiota and epithelium were observed but further studies are required to clarify the mode of action of clove in broiler chickens.
36 citations
TL;DR: A degree of interference of PTB vaccination with current TB diagnostics that can be fully mitigated when using new DIVA reagents is suggested.
Abstract: Most countries carrying out campaigns of bovine tuberculosis (TB) eradication impose a ban on the use of mycobacterial vaccines in cattle. However, vaccination against paratuberculosis (PTB) in goats is often allowed even when its effect on TB diagnosis has not been fully evaluated. To address this issue, goat kids previously vaccinated against PTB were experimentally infected with TB. Evaluation of interferon-γ (IFN-γ) secretion induced by avian and bovine tuberculins (PPD) showed a predominant avian PPD-biased response in the vaccinated group from week 4 post-vaccination onward. Although 60% of the animals were bovine reactors at week 14, avian PPD-biased responses returned at week 16. After challenge with M. caprae, the IFN-γ responses radically changed to show predominant bovine PPD-biased responses from week 18 onward. In addition, cross-reactions with bovine PPD that had been observed in the vaccinated group at week 14 were reduced when using the M. tuberculosis complex-specific antigens ESAT-6/CFP-10 and Rv3615c as new DIVA (differentiation of infected and vaccinated animals) reagents, which further maintained sensitivity post-challenge. Ninety percent of the animals reacted positively to the tuberculin cervical comparative intradermal test performed at 12 weeks post-infection. Furthermore, post-mortem analysis showed reductions in tuberculous lesions and bacterial burden in some vaccinated animals, particularly expressed in terms of the degree of extrapulmonary dissemination of TB infection. Our results suggest a degree of interference of PTB vaccination with current TB diagnostics that can be fully mitigated when using new DIVA reagents. A partial protective effect associated with vaccination was also observed in some vaccinated animals.
30 citations
TL;DR: Concurrent inoculation of porcine circovirus type 2 and Mycoplasma hyopneumoniae into conventional, seropositive 6-week-old piglets did not result in potentiation of clinical signs and lesions attributed to either infection.
23 citations
TL;DR: The results confirm the relevant role of the B-cell epitope in residues 694-712 of the glycoprotein E2 for protection against CSFV, as well as the appropriateness of the newly used NS3 peptide as a specific T-cell peptide in domestic pigs.
22 citations
TL;DR: Assessment of the potential relationship between Mycoplasma hyopneumoniae infection and seroconversion dynamics and climatological conditions in four groups of pigs from the same farm born in different seasons of the year found animals born in autumn, entering finishing units in winter, and reaching slaughter in spring had the highest probability of being infected by M. hyop pneumoniae.
Abstract: The objective of the present work was to elucidate the potential relationship between Mycoplasma hyopneumoniae infection and seroconversion dynamics and climatological conditions in four groups of pigs from the same farm born in different seasons of the year. Nasal swabs and blood samples were taken from 184 pigs at 1, 3, 6, 9, 12, 15, 18, 22 and 25 (slaughter age) weeks of age. Outside climatologic parameters, including temperature (°C), relative humidity (%), precipitation (l/m2) and wind speed (m/s) were recorded weekly from January 2003 to June 2004. Percentage of nPCR detection of M. hyopneumoniae in nasal swabs was associated significantly with the weekly precipitation rate [P = 0.0018, OR = 1.31 (IC = 1.11–1.55)]; the higher the precipitation rate, the higher the probability of being M. hyopneumoniae nPCR-positive. On the other hand, the percentage of seropositive pigs had a significant association with mean weekly temperature rate [P = 0.0012, OR = 0.89 [IC = 0.84–0.95]); the lower the temperature, the higher the probability of being M. hyopneumoniae seropositive. Animals born in autumn (when higher precipitations rates were recorded), entering finishing units in winter (when lower temperatures were recorded), and reaching slaughter in spring, had the highest probability of being infected by M. hyopneumoniae and the highest probability of being M. hyopneumoniae seropositive.
18 citations
13 Jan 2012
TL;DR: The Yellow Book as mentioned in this paper contains the results of ESA's assessment study (phase 0/A) of the candidate L-class Cosmic Vision mission NGO, which results from the reformulation of the LISA mission into a European-led mission.
Abstract: The NGO (New Gravitational wave Observatory) concept results from the reformulation of the LISA mission into a European-led mission. This report, the so-called Yellow Book, contains the results of ESA's assessment study (Phase 0/A) of the candidate L-class Cosmic Vision mission NGO.
TL;DR: Cellular immunity to Porcine circovirus type 2 (PCV2) Cap and Rep proteins in pigs vaccinated with a commercial PCV2 genotype a (PCv2a) based sub-unit vaccine is investigated before and after a heterologous challenge with a PCV 2b isolate.
TL;DR: The present study reflects the complex interaction among different pathogens and their effects in order to trigger PMWS in PCV2 infected pigs.
TL;DR: In this article, the design, implementation and characterization of fully digital control loops for laser frequency stabilization, differential phase-locking and performance optimization of the optical metrology system on-board the LISA Pathfinder space mission is described.
Abstract: We report on the design, implementation and characterization of fully digital control loops for laser frequency stabilization, differential phase-locking and performance optimization of the optical metrology system on-board the LISA Pathfinder space mission. The optical metrology system consists of a laser with modulator, four Mach-Zehnder interferometers, a phase-meter and a digital processing unit for data analysis. The digital loop design has the advantage of easy and flexible controller implementation and loop calibration, automated and flexible locking and resetting, and improved performance over analogue circuitry. Using the practical ability of our system to modulate the laser frequency allows us to accurately determine the open loop transfer function and other system properties. Various noise sources and their impact on system performance are investigated in detail.
01 Jun 2012
TL;DR: In this article, the authors used a low noise/low temperature coefficient current source to supply the sensor's bridge to enhance the thermal performance of the sensors at the lower end of the LISA bandwidth.
Abstract: Previous research with Anisotropic Magnetoresistive sensors (AMR) have shown significant improvements for weak magnetic field applications using dedicated noise reduction techniques in the signal conditioning circuit. However, an important source of error that must be addressed is the thermal dependence of the sensor system, more significant in the AMR sensitivity. The external temperature fluctuations affect the output of the sensors due to the temperature coefficient of the magnetoresistors, which may cause an increase of the estimation of the noise spectral density at low frequencies. Ongoing research using a low noise/low temperature coefficient current source to supply the sensor's bridge enhances the thermal performance of the sensors at the lower end of the LISA bandwidth. Preliminary results are shown in this paper.
Journal Article•
TL;DR: Clinical efficacy was investigated by comparing the synergistic or antagonistic effects of ASA administered with an antibiotic versus use of the antibiotic alone to reduce fever or clinical signs or both.
Abstract: Materials and methods: The animals were divided into two groups. The experimental group received doxycycline hyclate and ASA in the drinking water for 5 consecutive days at doses of 10 mg per kg and 100 mg per kg of body weight, respectively, whereas the control group received only doxycycline hyclate (10 mg per kg). Clinical efficacy was investigated by comparing the synergistic or antagonistic effects of ASA administered with an antibiotic versus use of the antibiotic alone to reduce fever or clinical signs or both.
01 Jun 2012
TL;DR: In this paper, the design of the Radiation Monitor in the LISA Technology Package on board LISA Pathnder is based on two silicon PIN diodes, placed parallel to each other in a telescopic configuration.
Abstract: The design of the Radiation Monitor in the LISA Technology Package on board LISA Pathnder is based on two silicon PIN diodes, placed parallel to each other in a telescopic configuration. One of them is able to record spectral information of the particle hitting the diode. A test campaign for the flight model Radiation Monitor was done in the Paul Scherrer Institute Proton Irradiation Facility in September 2010. Its purpose was to check correct functionality of the Radiation Monitor under real high energy proton fluxes. Here we present the results of the experiments done and their assessment by means of a simulated flight model geometry using GEANT4 toolkit. No deviation from nominal RM performance was detected, which means the instrument is fully ready for flight.
TL;DR: A maximum likelihood parameter estimation technique in time domain being devised for this calibration of the key system parameters is presented and its robustness to non-standard scenarios possibly arising during the real-life mission, as well as its independence to the initial guess and non-gaussianities are discussed.
Abstract: LISA is the upcoming space-based gravitational-wave detector. LISA Pathfinder, to be launched in the coming years, will be the in-flight test of the LISA arm, with a hardware (control scheme, sensors, and actuators) identical in design to LISA. LISA Pathfinder will collect a picture of all noise disturbances possibly affecting LISA, achieving the unprecedented pureness of geodesic motion of test masses necessary for the detection of gravitational waves. The first steps of both missions will crucially depend on a very precise calibration of the key system parameters. Moreover, robust parameters estimation has a fundamental importance in the correct assessment of the residual acceleration noise between the test masses, an essential part of the data preprocessing for LISA. In this paper, we present a maximum likelihood parameter estimation technique in time domain employed for system identification, being devised for this calibration, and show its proficiency on simulated data and validation through Monte Carlo realizations of independent noise runs. We discuss its robustness to nonstandard scenarios possibly arising during the real mission. Furthermore, we apply the same technique to data produced in missionlike fashion during operational exercises with a realistic simulator provided by European Space Agency. The result of the investigation is that parameter estimation is mandatory to avoid systematic errors in the estimated differential acceleration noise.
01 Jun 2012
TL;DR: In this paper, the authors report on the modelling of these simulated experiments, including the parametrisation of different thermal effects (radiation pressure effect, radiometer effect) that will appear in the Inertial Sensor environment of the LTP (LISA Technology Package).
Abstract: The OSE (Offline Simulations Environment) simulator of the LPF (LISA Pathfinder) mission is intended to simulate the different experiments to be carried out in flight. Amongst these, the thermal diagnostics experiments are intended to relate thermal disturbances and interferometer readouts, thereby allowing the subtraction of thermally induced interferences from the interferometer channels. In this paper we report on the modelling of these simulated experiments, including the parametrisation of different thermal effects (radiation pressure effect, radiometer effect) that will appear in the Inertial Sensor environment of the LTP (LISA Technology Package). We report as well how these experiments are going to be implemented in the LTPDA toolbox, which is a dedicated tool for LPF data analysis that will allow full traceability and reproducibility of the analysis thanks to complete recording of the processes.
01 Jun 2012
TL;DR: The results obtained with three different parameter estimation methods during one of these operational exercises, a detailed LISA Pathfinder non-linear simulator that will serve as a reference simulator during mission operations are reported.
Abstract: The LISA Pathfinder data analysis team has been developing in the last years the infrastructure and methods required to run the mission during flight operations. These are gathered in the LTPDA toolbox, an object oriented MATLAB toolbox that allows all the data analysis functionalities for the mission, while storing the history of all operations performed to the data, thus easing traceability and reproducibility of the analysis. The parameter estimation methods in the toolbox have been applied recently to data sets generated with the OSE (Off-line Simulations Environment), a detailed LISA Pathfinder non-linear simulator that will serve as a reference simulator during mission operations. These simulations, so called operational exercises, are the last verification step before translating these experiments into tele-command sequences for the spacecraft, producing therefore very relevant datasets to test our data analysis methods. In this contribution we report the results obtained with three different parameter estimation methods during one of these operational exercises.
01 Jun 2012
TL;DR: The Data Analysis team has developed algorithms for parameter estimation of the LISA Pathfinder system and one of them is the Markov Chain Monte Carlo, which will lead to creating a robust and reliable tool for parameters estimation during the LPF mission.
Abstract: The LISA Pathfinder mission (LPF) aims to test key technologies for the future LISA mission. The LISA Technology Package (LTP) on-board LPF will consist of an exhaustive suite of experiments and its outcome will be crucial for the future detection of gravitational waves. In order to achieve maximum sensitivity, we need to have an understanding of every instrument on-board and parametrize the properties of the underlying noise models. The Data Analysis team has developed algorithms for parameter estimation of the system. A very promising one implemented for LISA Pathfinder data analysis is the Markov Chain Monte Carlo. A series of experiments are going to take place during flight operations and each experiment is going to provide us with essential information for the next in the sequence. Therefore, it is a priority to optimize and improve our tools available for data analysis during the mission. Using a Bayesian framework analysis allows us to apply prior knowledge for each experiment, which means that we can efficiently use our prior estimates for the parameters, making the method more accurate and significantly faster. This, together with other algorithm improvements, will lead us to our main goal, which is no other than creating a robust and reliable tool for parameter estimation during the LPF mission.
TL;DR: In this article, the authors report on the modelling of these simulated experiments, including the parametrisation of different thermal effects (radiation pressure effect, radiometer effect) that will appear in the Inertial Sensor environment of the LTP (LISA Technology Package).
Abstract: The OSE (Offline Simulations Environment) simulator of the LPF (LISA Pathfinder) mission is intended to simulate the different experiments to be carried out in flight. Amongst these, the thermal diagnostics experiments are intended to relate thermal disturbances and interferometer readouts, thereby allowing the subtraction of thermally induced interferences from the interferometer channels. In this paper we report on the modelling of these simulated experiments, including the parametrisation of different thermal effects (radiation pressure effect, radiometer effect) that will appear in the Inertial Sensor environment of the LTP (LISA Technology Package). We report as well how these experiments are going to be implemented in the LTPDA toolbox, which is a dedicated tool for LPF data analysis that will allow full traceability and reproducibility of the analysis thanks to complete recording of the processes.