2,676 research outputs found

    Smart zero carbon city readiness level: sistema de indicadores para el diagnostico de las ciudades en su camino hacia la descarbonizacion y su aplicacion en el Pais Vasco

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    Nowadays urban environments concentrate more than half the world’s population, reaching up to 70% on 2050 according to forecasts. This concentration implies that most of future challenges will take place in cities as well as the opportunities coming from their potential solutions. Current technological innovation can provide support in facing one of main challenges society is facing: reducing carbon footprint from our cities. This ambitious transition, steered by the Smart Zero Carbon City (SZCC) concept, needs a flexible characterisation method, which can be adapted to different kinds of cities to evaluate the main features of each city, hence proposing and prioritising most suitable interventions. The aim of this study is focused on the characterisation of cities according to the SZCC concept through a set of indicators: the Smart Zero Carbon City Readiness Level (SZCC Readiness Level), able to analyse key aspects of cities according to SZCC concept (Characteristics of the city; City plans and strategies; Energy; Mobility; Infrastructures and ICT services; Citizen Engagement). This characterisation enlightens the development of SZCC concept in the city, identifying its strengths and weaknesses in order to ease the alternatives’ selection towards decarbonisation, being handy at a time for those small and medium-sized municipalities, so common in the European context, which usually hold less resources than big capitals to implement decision-making support diagnoses. In order to validate this set of indicators, SZCC Readiness Level has been implemented in 5 Basque cities, which represent different urban typologies, analysing its current situation regarding SZCC concept.Los autores quieren expresar su profundo agradecimiento a las administraciones de Donostia-San SebastiĂĄn, Eibar, IrĂșn, Sestao y Vitoria-Gasteiz por la estrecha colaboraciĂłn e involucraciĂłn de sus tĂ©cnicos en la tarea. Del mismo modo, agradecer al Departamento de Medio Ambiente, PlanificaciĂłn Territorial y Vivienda del Gobierno Vasco, mediante la convocatoria Eraikal, y a la ComisiĂłn Europea, a travĂ©s del proyecto SmartEnCity, por hacer posible este estudio

    Glioblastoma on a microfluidic chip: Generating pseudopalisades and enhancing aggressiveness through blood vessel obstruction events

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    Background: Glioblastoma (GBM) is one of the most lethal tumor types. Hypercellular regions, named pseudo- palisades, are characteristic in these tumors and have been hypothesized to be waves of migrating glioblastoma cells.These “waves” of cells are thought to be induced by oxygen and nutrient depletion caused by tumor-induced blood vessel occlusion. Although the universal presence of these structures in GBM tumors suggests that they may play an instrumental role in GBM’s spread and invasion, the recreation of these structures in vitro has remained challenging. Methods: Here we present a new microfluidic model of GBM that mimics the dynamics of pseudopalisade forma- tion.To do this, we embedded U-251 MG cells within a collagen hydrogel in a custom-designed microfluidic device. By controlling the medium flow through lateral microchannels, we can mimic and control blood-vessel obstruction events associated with this disease. Results: Through the use of this new system, we show that nutrient and oxygen starvation triggers a strong migratory process leading to pseudopalisade generation in vitro.These results validate the hypothesis of pseudo- palisade formation and show an excellent agreement with a systems-biology model based on a hypoxia-driven phenomenon. Conclusions: This paper shows the potential of microfluidic devices as advanced artificial systems capable of mod- eling in vivo nutrient and oxygen gradients during tumor evolution

    Analysis of TNFAIP3, a feedback inhibitor of nuclear factor-ÎșB and the neighbor intergenic 6q23 region in rheumatoid arthritis susceptibility

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    Introduction Genome-wide association studies of rheumatoid arthritis (RA) have identified an association of the disease with a 6q23 region devoid of genes. TNFAIP3, an RA candidate gene, flanks this region, and polymorphisms in both the TNFAIP3 gene and the intergenic region are associated with systemic lupus erythematosus. We hypothesized that there is a similar association with RA, including polymorphisms in TNFAIP3 and the intergenic region. Methods To test this hypothesis, we selected tag-single nucleotide polymorphisms (SNPs) in both loci. They were analyzed in 1,651 patients with RA and 1,619 control individuals of Spanish ancestry. Results Weak evidence of association was found both in the 6q23 intergenic region and in the TNFAIP3 locus. The rs582757 SNP and a common haplotype in the TNFAIP3 locus exhibited association with RA. In the intergenic region, two SNPs were associated, namely rs609438 and rs13207033. The latter was only associated in patients with anti-citrullinated peptide antibodies. Overall, statistical association was best explained by the interdependent contribution of SNPs from the two loci TNFAIP3 and the 6q23 intergenic region. Conclusions Our data are consistent with the hypothesis that several RA genetic factors exist in the 6q23 region, including polymorphisms in the TNFAIP3 gene, like that previously described for systemic lupus erythematosus

    Lack of replication of interactions between polymorphisms in rheumatoid arthritis susceptibility: case-control study

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    Introduction: Approximately 100 loci have been definitively associated with rheumatoid arthritis (RA) susceptibility. However, they explain only a fraction of RA heritability. Interactions between polymorphisms could explain part of the remaining heritability. Multiple interactions have been reported, but only the shared epitope (SE) × protein tyrosine phosphatase nonreceptor type 22 (PTPN22) interaction has been replicated convincingly. Two recent studies deserve attention because of their quality, including their replication in a second sample collection. In one of them, researchers identified interactions between PTPN22 and seven single-nucleotide polymorphisms (SNPs). The other showed interactions between the SE and the null genotype of glutathione S-transferase Mu 1 (GSTM1) in the anti-cyclic citrullinated peptide-positive (anti-CCP+) patients. In the present study, we aimed to replicate association with RA susceptibility of interactions described in these two high-quality studies. Methods: A total of 1,744 patients with RA and 1,650 healthy controls of Spanish ancestry were studied. Polymorphisms were genotyped by single-base extension. SE genotypes of 736 patients were available from previous studies. Interaction analysis was done using multiple methods, including those originally reported and the most powerful methods described. Results: Genotypes of one of the SNPs (rs4695888) failed quality control tests. The call rate for the other eight polymorphisms was 99.9%. The frequencies of the polymorphisms were similar in RA patients and controls, except for PTPN22 SNP. None of the interactions between PTPN22 SNPs and the six SNPs that met quality control tests was replicated as a significant interaction term the originally reported finding or with any of the other methods. Nor was the interaction between GSTM1 and the SE replicated as a departure from additivity in anti-CCP+ patients or with any of the other methods. Conclusions: None of the interactions tested were replicated in spite of sufficient power and assessment with different assays. These negative results indicate that whether interactions are significant contributors to RA susceptibility remains unknown and that strict standards need to be applied to claim that an interaction exists

    Infected Dendritic Cells Facilitate Systemic Dissemination and Transplacental Passage of the Obligate Intracellular Parasite Neospora caninum in Mice

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    The obligate intracellular parasite Neospora caninum disseminates across the placenta and the blood-brain barrier, to reach sites where it causes severe pathology or establishes chronic persistent infections. The mechanisms used by N. caninum to breach restrictive biological barriers remain elusive. To examine the cellular basis of these processes, migration of different N. caninum isolates (Nc-1, Nc-Liverpool, Nc-SweB1 and the Spanish isolates: Nc-Spain 3H, Nc-Spain 4H, Nc-Spain 6, Nc-Spain 7 and Nc-Spain 9) was studied in an in vitro model based on a placental trophoblast-derived BeWo cell line. Here, we describe that infection of dendritic cells (DC) by N. caninum tachyzoites potentiated translocation of parasites across polarized cellular monolayers. In addition, powered by the parasite's own gliding motility, extracellular N. caninum tachyzoites were able to transmigrate across cellular monolayers. Altogether, the presented data provides evidence of two putative complementary pathways utilized by N. caninum, in an isolate-specific fashion, for passage of restrictive cellular barriers. Interestingly, adoptive transfer of tachyzoite-infected DC in mice resulted in increased parasitic loads in various organs, e.g. the central nervous system, compared to infections with free parasites. Inoculation of pregnant mice with infected DC resulted in an accentuated vertical transmission to the offspring with increased parasitic loads and neonatal mortality. These findings reveal that N. caninum exploits the natural cell trafficking pathways in the host to cross cellular barriers and disseminate to deep tissues. The findings are indicative of conserved dissemination strategies among coccidian apicomplexan parasites

    The oncolytic virus Delta-24-RGD elicits an antitumor effect in pediatric glioma and DIPG mouse models

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    Pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors in desperate need of a curative treatment. Oncolytic virotherapy is emerging as a solid therapeutic approach. Delta-24-RGD is a replication competent adenovirus engineered to replicate in tumor cells with an aberrant RB pathway. This virus has proven to be safe and effective in adult gliomas. Here we report that the administration of Delta-24-RGD is safe in mice and results in a significant increase in survival in immunodeficient and immunocompetent models of pHGG and DIPGs. Our results show that the Delta-24-RGD antiglioma effect is mediated by the oncolytic effect and the immune response elicited against the tumor. Altogether, our data highlight the potential of this virus as treatment for patients with these tumors. Of clinical significance, these data have led to the start of a phase I/II clinical trial at our institution for newly diagnosed DIPG (NCT03178032)

    Life beyond 30: Probing the-20 < M (UV) <-17 Luminosity Function at 8 < z < 13 with the NIRCam Parallel Field of the MIRI Deep Survey

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    We present the ultraviolet luminosity function and an estimate of the cosmic star formation rate density at 8 8 galaxy candidates based on their dropout nature in the F115W and/or F150W filters, a high probability for their photometric redshifts, estimated with three different codes, being at z > 8, good fits based on χ 2 calculations, and predominant solutions compared to z < 8 alternatives. We find mild evolution in the luminosity function from z ∌ 13 to z ∌ 8, i.e., only a small increase in the average number density of ∌0.2 dex, while the faint-end slope and absolute magnitude of the knee remain approximately constant, with values α = − 2.2 ± 0.1, and M * = − 20.8 ± 0.2 mag. Comparing our results with the predictions of state-of-the-art galaxy evolution models, we find two main results: (1) a slower increase with time in the cosmic star formation rate density compared to a steeper rise predicted by models; (2) nearly a factor of 10 higher star formation activity concentrated in scales around 2 kpc in galaxies with stellar masses ∌108 M ⊙ during the first 350 Myr of the universe, z ∌ 12, with models matching better the luminosity density observational estimations ∌150 Myr later, by z ∌ 9

    Impact of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients: A nationwide study in Spain

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    Objective To assess the effect of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients in Spain. Settings The initial flood of COVID-19 patients overwhelmed an unprepared healthcare system. Different measures were taken to deal with this overburden. The effect of these measures on neurosurgical patients, as well as the effect of COVID-19 itself, has not been thoroughly studied. Participants This was a multicentre, nationwide, observational retrospective study of patients who underwent any neurosurgical operation from March to July 2020. Interventions An exploratory factorial analysis was performed to select the most relevant variables of the sample. Primary and secondary outcome measures Univariate and multivariate analyses were performed to identify independent predictors of mortality and postoperative SARS-CoV-2 infection. Results Sixteen hospitals registered 1677 operated patients. The overall mortality was 6.4%, and 2.9% (44 patients) suffered a perioperative SARS-CoV-2 infection. Of those infections, 24 were diagnosed postoperatively. Age (OR 1.05), perioperative SARS-CoV-2 infection (OR 4.7), community COVID-19 incidence (cases/10 5 people/week) (OR 1.006), postoperative neurological worsening (OR 5.9), postoperative need for airway support (OR 5.38), ASA grade =3 (OR 2.5) and preoperative GCS 3-8 (OR 2.82) were independently associated with mortality. For SARS-CoV-2 postoperative infection, screening swab test <72 hours preoperatively (OR 0.76), community COVID-19 incidence (cases/10 5 people/week) (OR 1.011), preoperative cognitive impairment (OR 2.784), postoperative sepsis (OR 3.807) and an absence of postoperative complications (OR 0.188) were independently associated. Conclusions Perioperative SARS-CoV-2 infection in neurosurgical patients was associated with an increase in mortality by almost fivefold. Community COVID-19 incidence (cases/10 5 people/week) was a statistically independent predictor of mortality. Trial registration number CEIM 20/217

    Calidad de las elecciones a titular del Ejecutivo en el Centro y Centro-occidente de MĂ©xico

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    Este libro, que tiene por objetivo analizar la calidad de las elecciones celebradas entre 2006 y 2011 para ocupar la titularidad del Poder Ejecutivo de las 14 entidades federativas de la RepĂșblica Mexicana que conforman las regiones Centro y Centro-occidente de este paĂ­s, ha sido elaborado por investigadores pertenecientes a la Red Nacional de InvestigaciĂłn sobre la Calidad de la Democracia en MĂ©xico (Renicadem), la cual cuenta con un equipo de investigaciĂłn en cada una de las entidades federativas del paĂ­s. A su vez, esta Red constituye una de las cuatro lĂ­neas temĂĄticas que componen la red temĂĄtica del Conacyt “Sociedad civil y calidad de la democracia”. Con todo, la presente obra puede considerarse, en dos sentidos, como el resultado parcial de estudios realizados por investigadores que conforman la mencionada Renicadem. Por un lado, trata sĂłlo de una de las varias dimensiones que esta Red ha establecido como necesarias para analizar la calidad de la democracia: la calidad electoral (otras dimensiones, que se encuentran en proceso de investigaciĂłn, son calidad de vida, rendiciĂłn de cuentas y Estado de derecho). TambiĂ©n es parcial porque no abarca la totalidad de la RepĂșblica Mexicana, sino Ășnicamente a las 14 entidades indicadas.UAE
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