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Rodriguez D.,CSIC - National Center for Biotechnology | Gonzalez-Aseguinolaza G.,CIMA | Rodriguez J.R.,CSIC - National Center for Biotechnology | Vijayan A.,CSIC - National Center for Biotechnology | And 4 more authors.
PLoS ONE | Year: 2012

With the aim to develop an efficient and cost-effective approach to control malaria, we have generated porcine parvovirus-like particles (PPV-VLPs) carrying the CD8+ T cell epitope (SYVPSAEQI) of the circumsporozoite (CS) protein from Plasmodium yoelii fused to the PPV VP2 capsid protein (PPV-PYCS), and tested in prime/boost protocols with poxvirus vectors for efficacy in a rodent malaria model. As a proof-of concept, we have characterized the anti-CS CD8+ T cell response elicited by these hybrid PPV-VLPs in BALB/c mice after immunizations with the protein PPV-PYCS administered alone or in combination with recombinant vaccinia virus (VACV) vectors from the Western Reserve (WR) and modified virus Ankara (MVA) strains expressing the entire P. yoelii CS protein. The results of different immunization protocols showed that the combination of PPV-PYCS prime/poxvirus boost was highly immunogenic, inducing specific CD8+ T cell responses to CS resulting in 95% reduction in liver stage parasites two days following sporozoite challenge. In contrast, neither the administration of PPV-PYCS alone nor the immunization with the vectors given in the order poxvirus/VLPs was as effective. The immune profile induced by VLPs/MVA boost was associated with polyfunctional and effector memory CD8+ T cell responses. These findings highlight the use of recombinant parvovirus PPV-PYCS particles as priming agents and poxvirus vectors, like MVA, as booster to enhance specific CD8+ T cell responses to Plasmodium antigens and to control infection. These observations are relevant in the design of T cell-inducing vaccines against malaria. © 2012 Rodríguez et al.

Valleron W.,University Paul Sabatier | Laprevotte E.,University Paul Sabatier | Gautier E.-F.,University Paul Sabatier | Quelen C.,University Paul Sabatier | And 9 more authors.
Leukemia | Year: 2012

Apart from microRNAs, little is known about the regulation of expression of non-coding RNAs in cancer. We investigated whether small nucleolar RNAs (snoRNAs) accumulation displayed specific signatures in acute myeloblastic and acute lymphoblastic leukemias. Using microarrays and high-throughput quantitative PCR (qPCR), we demonstrate here that snoRNA expression patterns are negatively altered in leukemic cells compared with controls. Interestingly, a specific signature was found in acute promyelocytic leukemia (APL) with ectopic expression of SNORD112-114 snoRNAs located at the DLK1-DIO3 locus. In vitro experiments carried out on APL blasts demonstrate that transcription of these snoRNAs was lost under all-trans retinoic acid-mediated differentiation and induced by enforced expression of the PML-RARalpha fusion protein in negative leukemic cell lines. Further experiments revealed that the SNORD114-1 (14q(II-1)) variant promoted cell growth through cell cycle modulation; its expression was implicated in the G0/G1 to S phase transition mediated by the Rb/p16 pathways. This study thus reports three important observations: (1) snoRNA regulation is different in normal cells compared with cancer cells; (2) a relationship exists between a chromosomal translocation and expression of snoRNA loci; and (3) snoRNA expression can affect Rb/p16 cell cycle regulation. Taken together, these data strongly suggest that snoRNAs have a role in cancer development. © 2012 Macmillan Publishers Limited All rights reserved.

Hadayeghi A.,CIMA | Shalaby A.S.,University of Toronto | Persaud B.N.,Ryerson University
Accident Analysis and Prevention | Year: 2010

A common technique used for the calibration of collision prediction models is the Generalized Linear Modeling (GLM) procedure with the assumption of Negative Binomial or Poisson error distribution. In this technique, fixed coefficients that represent the average relationship between the dependent variable and each explanatory variable are estimated. However, the stationary relationship assumed may hide some important spatial factors of the number of collisions at a particular traffic analysis zone. Consequently, the accuracy of such models for explaining the relationship between the dependent variable and the explanatory variables may be suspected since collision frequency is likely influenced by many spatially defined factors such as land use, demographic characteristics, and traffic volume patterns. The primary objective of this study is to investigate the spatial variations in the relationship between the number of zonal collisions and potential transportation planning predictors, using the Geographically Weighted Poisson Regression modeling technique. The secondary objective is to build on knowledge comparing the accuracy of Geographically Weighted Poisson Regression models to that of Generalized Linear Models. The results show that the Geographically Weighted Poisson Regression models are useful for capturing spatially dependent relationships and generally perform better than the conventional Generalized Linear Models. © 2009 Elsevier Ltd. All rights reserved.

Carvalho A.,University of Aveiro | Monteiro A.,University of Aveiro | Flannigan M.,University of Alberta | Solman S.,CIMA | And 2 more authors.
Atmospheric Environment | Year: 2011

In a future climate scenario forest fire activity over Portugal will substantially increase and consequently area burned and forest fire emissions to the atmosphere are also expected to increase. This study investigated the impact of future forest fire emissions on air quality over Portugal under the IPCC SRES A2 scenario. Reference and future climate change scenarios were simulated using the MM5/CHIMERE air quality modelling system, which was applied over Europe and over Portugal, using nesting capabilities. The initial and boundary conditions were provided by the HadAM3P model simulations for the reference and the future climate. The forest fire emissions were estimated using a methodology, which included the selection of emission factors for each pollutant, burning efficiency, fuel loads and the predicted area burned. These emissions were added to the simulation grid using specific parameterizations for their vertical distribution. Modelling results for Portugal pointed out that future forest fire activity will increase the O3 concentrations of almost 23 μg m-3 by 2100 but a decrease of approximately 6 μg m-3 is detected close to the main forest fire locations. Future forest fire emissions will also impact the PM10 concentrations over Portugal with increases reaching 20 μg m-3 along the Northern coastal region in July. The highest increases are estimated over the north and centre of Portugal where the area burned projections in future climate are higher. © 2011 Elsevier Ltd.

Carvalho A.,University of Aveiro | Monteiro A.,University of Aveiro | Solman S.,CIMA | Miranda A.I.,University of Aveiro | Borrego C.,University of Aveiro
Environmental Science and Policy | Year: 2010

Climate change alone may deeply impact air quality levels in the atmosphere because the changes in the meteorological conditions will induce changes on the transport, dispersion and transformation of air pollutants. The aim of this work was to evaluate the impact of climate change on the air quality over Europe and Portugal, using a reference year (year 1990) and a IPCC SRES A2 year (year 2100). The Hadley Centre global atmospheric circulation model (HadAM3P) was used to provide results for these two climatic scenarios, which were then used as synoptic forcing for the MM5-CHIMERE air quality modelling system. In order to assess the contribution of future climate change on O3 and PM concentrations, no changes in regional emissions were assumed and only climate change forcing was considered. The modelling results suggest that the O3 monthly mean levels in the atmosphere may increase almost 50μgm-3 across Europe in July under the IPCC SRES A2 scenario. In Portugal, this increase may reach 20μgm-3. The changes of PM10 monthly average values over Europe will depend on the region. The increase in PM10 concentrations during specific months could be explained by the average reduction of the boundary layer height and wind speed. © 2010 Elsevier Ltd.

Godat A.,University of Québec | Legeron F.,Université de Sherbrooke | Bazonga D.,CIMA
Thin-Walled Structures | Year: 2012

This paper presents experimental tests conducted to investigate the local buckling behavior of thin-walled tubular polygon steel columns. The experimental program consists of six stub columns with three different cross-sections, octagonal (eight-sided), dodecagonal (twelve-sided) and hexdecagonal (sixteen-sided), tested under concentric compression. For each cross-section, two values of the plate slenderness ratio (plate width-to-thickness ratio) are considered. Accurate measurements of geometrical imperfections are taken prior to the test. The experimental results show that the local buckling mode of failure depends on the type of the cross-section. Moreover, the plate slenderness ratio is the main factor controlling the local buckling capacity. Design equations provided in the ASCE 48-05, the EC3 and Migita and Fukumoto to predict the local buckling capacity of tubular polygons are evaluated against experimental results of 22 polygons tested under concentric compression available in the literature. Based on drawbacks observed in the design equations, the Loovs equation developed on basis of the ultimate stress concept is adjusted with new fitting parameters to fit for tubular polygon columns. The accuracy of the new equation is evaluated through a comparison with the experimental results. © 2011 Elsevier Ltd. All rights reserved.

Zmigrodzki S.,CIMA
Large Structures and Infrastructures for Environmentally Constrained and Urbanised Areas | Year: 2010

The existing open air aquatic complex on Sainte-Hélène Island was chosen to host 2005 Aquatic Sports World Championships. The old concrete pools built in 1953 had to be replaced by new structures and fit in the existing site. In the new layout, the swimming pool was relocated which led to problems due to soil conditions. The soil was sensitive and heterogeneous so settlements and resulting lateral displacements had to be considered in the design in order to respect dimensional criteria for Olympic pools. To guarantee the quality of works within a tight schedule, the upper section of the walls was made of prefabricated steel panels. As result, the rigid "box" formed by the concrete corridor around the pool was lost. Consequently, a combination of soil consolidation, interaction of soil-structure and phasing of construction-backfilling became part of design.

Labiano S.,CIMA | Palazon A.,University of Cambridge | Melero I.,CIMA
Seminars in Oncology | Year: 2015

Lymphocytes and myeloid cells sense hypoxia by the hypoxia-inducible factor (HIF) transcriptional system and via other molecular mechanisms. Low O2 availability is a hallmark of most solid tumors in which infiltrating leukocytes experience severe hypoxia once away from nurturing blood vessels. HIF controls migration, differentiation, and effector functions on immune cells. Importantly, in the tumor microenvironment the hypoxia response modulates the expression levels for important molecular targets in immunotherapy such as CD137, OX-40, FOXP3, and PD-L1. Modulation by hypoxia of tumor-associated macrophages, myeloid-derived suppressor cells, and dendritic cells ought to play an important underexplored role in modulating tumor immunity. Overall, low O2 seems to invigorate some anti-tumor effector T-cell functions while conflictingly favoring T-regulatory cells (Tregs) in terms of their differentiation, suppressive functions, and recruitment. Hypoxia also has been shown to uphold myeloid cell-mediated tumor-promoting inflammation and the immunosuppressive functions of tumor-associated macrophages. Detailed research of this intricate and poorly understood balance is warranted to improve the outcome of cancer immunotherapy. © 2015 Elsevier Inc.

Martinez E.,University of Oviedo | Navarro A.,University of Oviedo | Ordoez C.,CIMA | Del Valle E.,University of Oviedo | Tolivia J.,University of Oviedo
Journal of Alzheimer's Disease | Year: 2012

Apolipoprotein D (ApoD) is a secreted glycoprotein that is markedly induced in several pathological and stressful conditions in the nervous system. In the central nervous system, ApoD expression is upregulated during aging, after traumatic brain injury, and in several human neuropathologies such as Alzheimer's disease (AD), where it is found associated with amyloid-β (Aβ) plaques. Recent studies have indicated that ApoD has an important function as a neuroprotective and antioxidant protein. The aim of this work is to study the effect of the peptide fragment Aβ 25-35, which is believed to play a major role in the neurodegenerative process of AD, in ApoD expression in a mouse hippocampal cell line. In addition, we studied whether direct addition of exogenous human recombinant ApoD protein has neuroprotective effect against Aβ 25-35 treatment on neuronal cells. Our results demonstrate that Aβ 25-35 induces ApoD expression in hippocampal cells in response to stress-induced growth arrest. This observed relationship between Aβ and ApoD expression could explain the elevated levels of ApoD found in AD brain, where it may be a neuroprotective molecule in the course of AD, probably related to its lipid transport function or a direct antioxidant property. However, the addition of exogenous human recombinant ApoD does not exert any protective effect, most likely due to its major structural modifications. © 2012-IOS Press and the authors. All rights reserved.

Zmigrodzki S.,CIMA
Proceedings of the Institution of Civil Engineers: Forensic Engineering | Year: 2011

This paper discusses a complex, multi-parameter approach to questioning the capacity of the roof of an industrial facility in the Montreal area. The failure of a portion of the roof in March 2008 under heavier than usual snow loads triggered an investigation process that continues to this day. The roof was immediately repaired in order to allow the facility to continue its commercial activities. After the repair, an investigation of the snow loads on the roof was first conducted; this was followed by an assessment of the capacity of the roof joists and beams as designed and as built. An evaluation of the snow loads surrounding mechanical units on the roof was conducted. The building was erected in the 1960s and a significant number of changes took place following an expansion of the facility, including an addition with a roof higher than that of the existing building. The new elevated roof reduced the wind effects and created significant snow accumulation not only around the higher roof but also surrounding the mechanical units present almost everywhere. In the assessment of the joists, particular attention was paid to the welds between the web and the chords; these welds were at the origin of the failure of the roof as a whole. An evaluation of the mechanical equipment suspended from the joists was also carried out. An overall assessment of the structural system for earthquake resistance ultimately led to a seismic evaluation of the building, which is currently underway.

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