208 research outputs found
Tecnología constructiva y cultura ambiental Edificio Enrico Tedeschi caso de estudio sobre construcción sustentable
CIES2020 - XVII Congresso Ibérico e XIII Congresso Ibero-americano de Energia SolarRESUMEN: El trabajo expone cómo los criterios formales de la instancia constructiva material son determinante para la ecuación arquitectura / sustentabilidad. El Edificio FAUD / Enrico Tedeschi de 1960, es fuente de referencia para la investigación. Se destacan criterios materiales y formales respecto de la tecnología y la materialización para el desarrollo progresivo de un tipo arquitectónico referente para un cambio en la cultura material generacional. La estricta racionalidad constructiva y la lógica de la tecnicidad, son las principales razones para proporcionar una guía de validación relativa a los procedimientos constructivos sustentables. Basado en la metodología del redibujo y de monitoreo ambiental, se presenta una controversia entre la capacidad tectónica estructural y la racionalidad ambiental. La falta de aislamiento y estanqueidad del cerramiento requiere que los parámetros térmico interior estén supeditados al acondicionamiento mecánico adicional. Se simula la posibilidad de una adecuación de eficiencia energética siguiendo los patrones propios de la materialización en diálogo entre la compatibilidad tectónica y la racionalidad ambiental.ABSTRACT: The work exposes how the formal criteria of the material constructive instance are decisive for the architecture / sustainability equation. The FAUD / Enrico Tedeschi Building from 1960 is a reference source for research. Material and formal criteria are highlighted regarding technology and materialization for the progressive development of an architectural type of reference for a change in generational material culture. Constructive rationality and the logic of technicality are the main reasons for providing a validation guide regarding sustainable construction procedures.
Based on the redrawing and environmental monitoring methodology, there is a controversy between structural tectonic capacity and environmental rationality. Little insulation and airtightness of the enclosure requires that the interior thermal parameters be subject to additional mechanical conditioning. The possibility of an energy efficiency adaptation is simulated following the patterns of the materialization in dialogue between tectonic compatibility and environmental rationality.info:eu-repo/semantics/publishedVersio
Modulation of vaccine-induced immune responses to hepatitis C virus in rhesus macaques by altering priming before adenovirus boosting
BACKGROUND:
Preventive and therapeutic vaccine strategies aimed at controlling hepatitis C virus (HCV) infection should mimic the immune responses observed in patients who control or clear HCV, specifically T helper (Th) type 1 and CD8+ cell responses to multiple antigens, including nonstructural protein (NS) 3. Given the experience with human immunodeficiency virus, the best candidates for this are based on DNA prime, pox, or adenovirus boost regimens.
METHODS:
In rhesus macaques, we compared NS3-expressing DNA prime and adenovirus boost strategy with 2 alternative priming approaches aimed at modifying Th1 and CD8+ responses: DNA adjuvanted with interleukin (IL)-2- and -12-encoding plasmids or Semliki Forest virus (SFV).
RESULTS:
All prime-boost regimens elicited NS3-specific B and T cell responses in rhesus macaques, including CD8+ responses. SFV priming induced higher lymphoproliferation and longer Th1 memory responses. The use of IL-2- and IL-12-expressing vectors resulted in reduced Th2 and antibody responses, which led to increased Th1 skewing but not to an increase in the magnitude of the IFN- gamma and CD8+ responses.
CONCLUSIONS:
All strategies induced Th1 cellular responses to HCV NS3, with fine modulations depending on the different priming approaches. When they are developed for more HCV antigens, these strategies could be beneficial in therapeutic vaccine approaches
A strategy to characterize the LISA-Pathfinder cold gas thruster system
The cold gas micro-propulsion system that will be used during the LISA-Pathfinder mission will be one of the most important component used to ensure the "free-fall" of the enclosed test masses. In this paper we present a possible strategy to characterize the effective direction and amplitude gain of each of the 6 thrusters of this system
Free-flight experiments in LISA Pathfinder
The LISA Pathfinder mission will demonstrate the technology of drag-free test
masses for use as inertial references in future space-based gravitational wave
detectors. To accomplish this, the Pathfinder spacecraft will perform drag-free
flight about a test mass while measuring the acceleration of this primary test
mass relative to a second reference test mass. Because the reference test mass
is contained within the same spacecraft, it is necessary to apply forces on it
to maintain its position and attitude relative to the spacecraft. These forces
are a potential source of acceleration noise in the LISA Pathfinder system that
are not present in the full LISA configuration. While LISA Pathfinder has been
designed to meet it's primary mission requirements in the presence of this
noise, recent estimates suggest that the on-orbit performance may be limited by
this `suspension noise'. The drift-mode or free-flight experiments provide an
opportunity to mitigate this noise source and further characterize the
underlying disturbances that are of interest to the designers of LISA-like
instruments. This article provides a high-level overview of these experiments
and the methods under development to analyze the resulting data.Comment: 13 pages, 5 figures. Accepted to Journal Of Physics, Conference
Series. Presented at 10th International LISA Symposium, May 2014,
Gainesville, FL, US
T- and B-cell responses to multivalent prime-boost DNA and viral vectored vaccine combinations against hepatitis C virus in non-human primates.
Immune responses against multiple epitopes are required for the prevention of hepatitis C virus (HCV) infection, and the progression to phase I trials of candidates may be guided by comparative immunogenicity studies in non-human primates. Four vectors, DNA, SFV, human serotype 5 adenovirus (HuAd5) and Modified Vaccinia Ankara (MVA) poxvirus, all expressing hepatitis C virus Core, E1, E2 and NS3, were combined in three prime-boost regimen, and their ability to elicit immune responses against HCV antigens in rhesus macaques was explored and compared. All combinations induced specific T-cell immune responses, including high IFN-γ production. The group immunized with the SFV+MVA regimen elicited higher E2-specific responses as compared with the two other modalities, while animals receiving HuAd5 injections elicited lower IL-4 responses as compared with those receiving MVA. The IFN-γ responses to NS3 were remarkably similar between groups. Only the adenovirus induced envelope-specific antibody responses, but these failed to show neutralizing activity. Therefore, the two novel regimens failed to induce superior responses as compared with already existing HCV vaccine candidates. Differences were found in response to envelope proteins, but the relevance of these remain uncertain given the surprisingly poor correlation with immunogenicity data in chimpanzees, underlining the difficulty to predict efficacy from immunology studies.This work was supported by European Union contract QLK2-CT-1999-
00356, by the Biomedical Primate Research Centre, The Netherlands, and by the Swedish
Research Council. We are grateful to Alexander van den Berg for technical assistance with the
ICS, to our colleagues from Animal Science Department for technical assistance and expert care
of the macaques, to the participants of the European HCVacc Cluster who provided help and
support, and to Thomas Darton (Oxford Vaccine Group, UK) for input and advice on the
manuscript. Christine Rollier is an Oxford Martin fellow and a Jenner Insitute Investigator.This is the author accepted manuscript. The final version is available from Nature Publishing Group at https://doi.org/10.1038/gt.2016.55
Measuring the Galactic Cosmic Ray Flux with the LISA Pathfinder Radiation Monitor
Test mass charging caused by cosmic rays will be a significant source of acceleration noise for space-based gravitational wave detectors like LISA. Operating between December 2015 and July 2017, the technology demonstration mission LISA Pathfinder included a bespoke monitor to help characterise the relationship between test mass charging and the local radiation environment. The radiation monitor made in situ measurements of the cosmic ray flux while also providing information about its energy spectrum. We describe the monitor and present measurements which show a gradual 40% increase in count rate coinciding with the declining phase of the solar cycle. Modulations of up to 10% were also observed with periods of 13 and 26 days that are associated with co-rotating interaction regions and heliospheric current sheet crossings. These variations in the flux above the monitor detection threshold (approximately 70 MeV) are shown to be coherent with measurements made by the IREM monitor on-board the Earth orbiting INTEGRAL spacecraft. Finally we use the measured deposited energy spectra, in combination with a GEANT4 model, to estimate the galactic cosmic ray differential energy spectrum over the course of the mission
“Negative Vaccination” by Specific CD4+ T Cell Tolerisation Enhances Virus-Specific Protective Antibody Responses
Genetic variability of hepatitis C virus before and after combined therapy of interferon plus ribavirin
We present an analysis of the selective forces acting on two hepatitis C virus genome regions previously postulated to be involved in the viral response to combined antiviral therapy. One includes the three hypervariable regions in the envelope E2 glycoprotein, and the other encompasses the PKR binding domain and the V3 domain in the NS5A region. We used a cohort of 22 non-responder patients to combined therapy (interferon alpha-2a plus ribavirin) for which samples were obtained before initiation of therapy and after 6 or/and 12 months of treatment. A range of 25-100 clones per patient, genome region and time sample were sequenced. These were used to detect general patterns of adaptation, to identify particular adaptation mechanisms and to analyze the patterns of evolutionary change in both genome regions. These analyses failed to detect a common adaptive mechanism for the lack of response to antiviral treatment in these patients. On the contrary, a wide range of situations were observed, from patients showing no positively selected sites to others with many, and with completely different topologies in the reconstructed phylogenetic trees. Altogether, these results suggest that viral strategies to evade selection pressure from the immune system and antiviral therapies do not result from a single mechanism and they are likely based on a range of different alternatives, in which several different changes, or their combination, along the HCV genome confer viruses the ability to overcome strong selective [email protected]; [email protected]; [email protected]; [email protected]; [email protected]; [email protected]; [email protected]; [email protected]
DNA Vaccines against Dengue Virus Type 2 Based on Truncate Envelope Protein or Its Domain III
Two DNA vaccines were constructed encoding the ectodomain (domains I, II and III) of the DENV2 envelope protein (pE1D2) or only its domain III (pE2D2), fused to the human tissue plasminogen activator signal peptide (t-PA). The expression and secretion of recombinant proteins was confirmed in vitro in BHK cells transfected with the two plasmids, detected by immunofluorescence or immunoprecipitation of metabolically labeled gene products, using polyclonal and monoclonal antibodies against DENV2. Besides, results reveal that the ectodomain of the E protein can be efficiently expressed in vivo, in a mammalian system, without the prM protein that is hypothesized to act as a chaperonin during dengue infection. Balb/c mice were immunized with the DNA vaccines and challenged with a lethal dose of DENV2. All pE1D2-vaccinated mice survived challenge, while 45% of animals immunized with the pE2D2 died after infection. Furthermore, only 10% of pE1D2-immunized mice presented some clinical signs of infection after challenge, whereas most of animals inoculated with the pE2D2 showed effects of the disease with high morbidity degrees. Levels of neutralizing antibodies were significantly higher in pE1D2-vaccinated mice than in pE2D2-immunized animals, also suggesting that the pE1D2 vaccine was more protective than the pE2D2
The mechanism of functional up-regulation of P2X3 receptors of trigeminal sensory neurons in a genetic mouse model of Familial Hemiplegic Migraine type 1 (FHM-1)
A knock-in (KI) mouse model of FHM-1 expressing the R192Q missense mutation of the Cacna1a gene coding for the \u3b11 subunit of CaV2.1 channels shows, at the level of the trigeminal ganglion, selective functional up-regulation of ATP -gated P2X3 receptors of sensory neurons that convey nociceptive signals to the brainstem. Why P2X3 receptors are constitutively more responsive, however, remains unclear as their membrane expression and TRPV1 nociceptor activity are the same as in wildtype (WT) neurons. Using primary cultures of WT or KI trigeminal ganglia, we investigated whether soluble compounds that may contribute to initiating (or maintaining) migraine attacks, such as TNF\u3b1, CGRP, and BDNF, might be responsible for increasing P2X3 receptor responses. Exogenous application of TNF\u3b1 potentiated P2X3 receptor-mediated currents of WT but not of KI neurons, most of which expressed both the P2X3 receptor and the TNF\u3b1 receptor TNFR2. However, sustained TNF\u3b1 neutralization failed to change WT or KI P2X3 receptor currents. This suggests that endogenous TNF\u3b1 does not regulate P2X3 receptor responses. Nonetheless, on cultures made from both genotypes, exogenous TNF\u3b1 enhanced TRPV1 receptor-mediated currents expressed by a few neurons, suggesting transient amplification of TRPV1 nociceptor responses. CGRP increased P2X3 receptor currents only in WT cultures, although prolonged CGRP receptor antagonism or BDNF neutralization reduced KI currents to WT levels. Our data suggest that, in KI trigeminal ganglion cultures, constitutive up-regulation of P2X3 receptors probably is already maximal and is apparently contributed by basal CGRP and BDNF levels, thereby rendering these neurons more responsive to extracellular ATP. \ua9 2013 Hullugundi et al
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