83 research outputs found

    Variabilidad de los Parámetros de Salida del Modelado de Fluidodinámica Computacional de Incendios frente a Resultados Experimentales

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    Es conocido que las magnitudes físicas que caracterizan un fluido gaseoso cuando este es turbulento, varían bruscamente tanto espacial, como temporalmente[1, 2]. Esto es particularmente válido para los fluidos gaseosos que tienen lugar en los escenarios de incendios. No obstante, frecuentemente la variabilidad, sobre todo temporal, de los resultados obtenidos para estas magnitudes mediante algunos modelos de fluidodinámica computacional (CFD) parece ser exagerada y contradecir la natural inercia que los procesos termodinámicos y aerodinámicos suelen tener para las bajas velocidades de flujo que son comunes en estos escenarios. A efectos del trabajo de investigación fue empleado el modelo Fire Dynamics Simulator-FDS, donde esta intensa variabilidad se observa tanto en parámetros de salida locales como globales del programa. El propósito del trabajo fue analizar en que grado esta variabilidad se corresponde con la realidad o es artificialmente introducida por la simulación. Inicialmente, se procedió a estudiar la posible aleatoriedad de esta variabilidad, debido a la introducción de una cierta cantidad de ruido de forma aleatoria en algunas variables iniciales del modelo FDS a efectos de asegurar la resolución numérica. Para comprobar la afectación de este ruido aleatorio en los parámetros de salida, se realizaron simulaciones de escenarios idénticos en equipos diferentes para observar si esta aleatoriedad estaba presente en los resultados. Después de comprobar la no afectación de la aleatoriedad en los resultados mediante este análisis inicial, se procedió a comprobar que grado de la variabilidad presente en la simulación no se corresponde con los experimentos. Para ello se ha elaborado y aplicado un método basado en el análisis espectral de los resultados simulados y experimentales de estas variables

    The effect of orthodontic forces on calcitonin gene-related peptide (CGRP) expression in the human periodontal ligament and its relationship with the human dental pulp

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    The purpose of this study was to quantify the effect of moderate and severe orthodontic forces on Calcitonin gene-related peptide (CGRP) expression in the healthy human periodontal ligament (PDL) and its possible relationship with the human dental pulp

    Dynamics of Weyl Scale Invariant non-BPS p=3 Branes

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    In this paper a Weyl scale invariant p=3p=3 brane scenario is introduced, with the brane embedded in a higher dimensional bulk space with N=1,5DN=1, 5D Super--Weyl symmetry. Its action, which describes its long wave oscillation modes into the ambient superspace and breaks the target symmetry down to the lower dimensional Weyl W(1,3) symmetry, is constructed by the approach of coset method.Comment: 12 pages, modified versio

    Targeting IRE1 with small molecules counteracts progression of atherosclerosis

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    Metaflammation, an atypical, metabolically induced, chronic lowgrade inflammation, plays an important role in the development of obesity, diabetes, and atherosclerosis. An important primer for metaflammation is the persistent metabolic overloading of the endoplasmic reticulum (ER), leading to its functional impairment. Activation of the unfolded protein response (UPR), a homeostatic regulatory network that responds to ER stress, is a hallmark of all stages of atherosclerotic plaque formation. The most conserved ERresident UPR regulator, the kinase/endoribonuclease inositol-requiring enzyme 1 (IRE1), is activated in lipid-laden macrophages that infiltrate the atherosclerotic lesions. Using RNA sequencing in macrophages, we discovered that IRE1 regulates the expression of many proatherogenic genes, including several important cytokines and chemokines. We show that IRE1 inhibitors uncouple lipid-induced ER stress from inflammasome activation in both mouse and human macrophages. In vivo, these IRE1 inhibitors led to a significant decrease in hyperlipidemia-induced IL-1β and IL-18 production, lowered T-helper type-1 immune responses, and reduced atherosclerotic plaque size without altering the plasma lipid profiles in apolipoprotein E-deficient mice. These results show that pharmacologic modulation of IRE1 counteracts metaflammation and alleviates atherosclerosis

    Flying ad-hoc network application scenarios and mobility models

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    [EN] Flying ad-hoc networks are becoming a promising solution for different application scenarios involving unmanned aerial vehicles, like urban surveillance or search and rescue missions. However, such networks present various and very specific communication issues. As a consequence, there are several research studies focused on analyzing their performance via simulation. Correctly modeling mobility is crucial in this context and although many mobility models are already available to reproduce the behavior of mobile nodes in an ad-hoc network, most of these models cannot be used to reliably simulate the motion of unmanned aerial vehicles. In this article, we list the existing mobility models and provide guidance to understand whether they could be actually adopted depending on the specific flying ad-hoc network application scenarios, while discussing their advantages and disadvantages.Bujari, A.; Tavares De Araujo Cesariny Calafate, CM.; Cano, J.; Manzoni, P.; Palazzi, CE.; Ronzani, D. (2017). Flying ad-hoc network application scenarios and mobility models. International Journal of Distributed Sensor Networks. 13(10):1-17. doi:10.1177/1550147717738192S117131

    Genetic Variation of Promoter Sequence Modulates XBP1 Expression and Genetic Risk for Vitiligo

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    Our previous genome-wide linkage analysis identified a susceptibility locus for generalized vitiligo on 22q12. To search for susceptibility genes within the locus, we investigated a biological candidate gene, X-box binding protein 1(XBP1). First, we sequenced all the exons, exon-intron boundaries as well as some 5′ and 3′ flanking sequences of XBP1 in 319 cases and 294 controls of Chinese Hans. Of the 8 common variants identified, the significant association was observed at rs2269577 (p_trend = 0.007, OR = 1.36, 95% CI = 1.09–1.71), a putative regulatory polymorphism within the promoter region of XBP1. We then sequenced the variant in an additional 365 cases and 404 controls and found supporting evidence for the association (p_trend = 0.008, OR = 1.31, 95% CI = 1.07–1.59). To further validate the association, we genotyped the variant in another independent sample of 1,402 cases and 1,288 controls, including 94 parent-child trios, and confirmed the association by both case-control analysis (p_trend = 0.003, OR = 1.18, 95% CI = 1.06–1.32) and the family-based transmission disequilibrium test (TDT, p = 0.005, OR = 1.93, 95% CI = 1.21–3.07). The analysis of the combined 2,086 cases and 1,986 controls provided highly significant evidence for the association (p_trend = 2.94×10−6, OR = 1.23, 95% CI = 1.13–1.35). Furthermore, we also found suggestive epistatic effect between rs2269577 and HLA-DRB1*07 allele on the development of vitiligo (p = 0.033). Our subsequent functional study showed that the risk-associated C allele of rs2269577 had a stronger promoter activity than the non-risk G allele, and there was an elevated expression of XBP1 in the lesional skins of patients carrying the risk-associated C allele. Therefore, our study has demonstrated that the transcriptional modulation of XBP1 expression by a germ-line regulatory polymorphism has an impact on the development of vitiligo

    The ER-Bound RING Finger Protein 5 (RNF5/RMA1) Causes Degenerative Myopathy in Transgenic Mice and Is Deregulated in Inclusion Body Myositis

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    Growing evidence supports the importance of ubiquitin ligases in the pathogenesis of muscular disorders, although underlying mechanisms remain largely elusive. Here we show that the expression of RNF5 (aka RMA1), an ER-anchored RING finger E3 ligase implicated in muscle organization and in recognition and processing of malfolded proteins, is elevated and mislocalized to cytoplasmic aggregates in biopsies from patients suffering from sporadic-Inclusion Body Myositis (sIBM). Consistent with these findings, an animal model for hereditary IBM (hIBM), but not their control littermates, revealed deregulated expression of RNF5. Further studies for the role of RNF5 in the pathogenesis of s-IBM and more generally in muscle physiology were performed using RNF5 transgenic and KO animals. Transgenic mice carrying inducible expression of RNF5, under control of β-actin or muscle specific promoter, exhibit an early onset of muscle wasting, muscle degeneration and extensive fiber regeneration. Prolonged expression of RNF5 in the muscle also results in the formation of fibers containing congophilic material, blue-rimmed vacuoles and inclusion bodies. These phenotypes were associated with altered expression and activity of ER chaperones, characteristic of myodegenerative diseases such as s-IBM. Conversely, muscle regeneration and induction of ER stress markers were delayed in RNF5 KO mice subjected to cardiotoxin treatment. While supporting a role for RNF5 Tg mice as model for s-IBM, our study also establishes the importance of RNF5 in muscle physiology and its deregulation in ER stress associated muscular disorders

    Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

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    Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

    Regulation of proteasome assembly and activity in health and disease

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