141 research outputs found

    Renormalization group study of one-dimensional systems with roughening transitions

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    A recently introduced real space renormalization group technique, developed for the analysis of processes in the Kardar-Parisi-Zhang universality class, is generalized and tested by applying it to a different family of surface growth processes. In particular, we consider a growth model exhibiting a rich phenomenology even in one dimension. It has four different phases and a directed percolation related roughening transition. The renormalization method reproduces extremely well all the phase diagram, the roughness exponents in all the phases and the separatrix among them. This proves the versatility of the method and elucidates interesting physical mechanisms.Comment: Submitted to Phys. Rev.

    Exact analysis of summary statistics for continuous-time discrete-state Markov processes on networks using graph-automorphism lumping

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    We propose a unified framework to represent a wide range of continuous-time discrete-state Markov processes on networks, and show how many network dynamics models in the literature can be represented in this unified framework. We show how a particular sub-set of these models, referred to here as single-vertex-transition (SVT) processes, lead to the analysis of quasi-birth-and-death (QBD) processes in the theory of continuous-time Markov chains. We illustrate how to analyse a number of summary statistics for these processes, such as absorption probabilities and first-passage times. We extend the graph-automorphism lumping approach [Kiss, Miller, Simon, Mathematics of Epidemics on Networks, 2017; Simon, Taylor, Kiss, J. Math. Bio. 62(4), 2011], by providing a matrix-oriented representation of this technique, and show how it can be applied to a very wide range of dynamical processes on networks. This approach can be used not only to solve the master equation of the system, but also to analyse the summary statistics of interest. We also show the interplay between the graph-automorphism lumping approach and the QBD structures when dealing with SVT processes. Finally, we illustrate our theoretical results with examples from the areas of opinion dynamics and mathematical epidemiology

    IL-7/IL-7R gene variants impact circulating IL-7/IL-7R homeostasis and ART-associated immune recovery status

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    Altres ajuts: This study would not have been possible without the collaboration of all the patients and medical and nursing staff who have taken part in the project. This work was supported by Gilead Fellowship Program GLD14/293 and GLD17/00299 and Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía (Proyecto de Investigación de Excelencia; CTS2593). YMP and ERM are supported by the Servicio Andaluz de Salud through Programa Nicolás Monardes (C-0013/17 and C-0032/17, respectively). We are also grateful to GESIDA for ''Premio para Jóvenes Investigadores 2019'' to AR. Authors greatly appreciate the comments and criticisms of the anonymous reviewers that greatly helped to improve the manuscript.A relationship between polymorphisms in genes encoding interleukin 7 (IL-7) and its cellular receptor (IL-7R) and antiretroviral therapy (ART)-associated immune recovery in HIV subjects has been previously reported. However, details of this relationship remain unclear, and the association of these polymorphisms with circulating IL-7/IL-7R levels is scarce. Here, we explored whether IL-7/IL-7R axis was associated with quantitative CD4 T-cell recovery in HIV-infected subjects. IL-7/IL-7R polymorphisms were assessed by genotyping, and multiple inheritance models were used to estimate both, their association with low pre-ART CD4 T-cell counts and incomplete immune recovery status after 48 weeks of suppressive ART. Integrated data from genetic variants association and soluble plasma IL-7/IL-7R quantification suggest that IL-7/IL-7R genotype expression could alter the homeostatic balance between soluble and membrane-bound receptors. The haplotype analyses indicates that allele combinations impacts pre-ART circulating CD4 T-cell counts, immune recovery status and the absolute increment of CD4 T-cell counts. The knowledge about how IL-7/IL-7R axis is related to quantitative CD4 T-cell recovery and immune recovery status after initiating ART could be useful regarding T-cell reservoirs investigations in HIV subjects

    A General Model of Dynamics on Networks with Graph Automorphism Lumping

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    In this paper we introduce a general Markov chain model of dynamical processes on networks. In this model, nodes in the network can adopt a finite number of states and transitions can occur that involve multiple nodes changing state at once. The rules that govern transitions only depend on measures related to the state and structure of the network and not on the particular nodes involved. We prove that symmetries of the network can be used to lump equivalent states in state-space. We illustrate how several examples of well-known dynamical processes on networks correspond to particular cases of our general model. This work connects a wide range of models specified in terms of node-based dynamical rules to their exact continuous-time Markov chain formulation

    Cognitive impairment induced by delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB1 and serotonin 5-HT2A receptors

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    Delta-9-tetrahydrocannabinol (THC), the main psychoactive compound of marijuana, induces numerous undesirable effects, including memory impairments, anxiety, and dependence. Conversely, THC also has potentially therapeutic effects, including analgesia, muscle relaxation, and neuroprotection. However, the mechanisms that dissociate these responses are still not known. Using mice lacking the serotonin receptor 5-HT2A, we revealed that the analgesic and amnesic effects of THC are independent of each other: while amnesia induced by THC disappears in the mutant mice, THC can still promote analgesia in these animals. In subsequent molecular studies, we showed that in specific brain regions involved in memory formation, the receptors for THC and the 5-HT2A receptors work together by physically interacting with each other. Experimentally interfering with this interaction prevented the memory deficits induced by THC, but not its analgesic properties. Our results highlight a novel mechanism by which the beneficial analgesic properties of THC can be dissociated from its cognitive side effects

    QUIJOTE Experiment: status of telescopes and instrumentation

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    The QUIJOTE Experiment (Q-U-I JOint TEnerife) is a combined operation of two telescopes and three instruments working in the microwave band to measure the polarization of the Cosmic Microwave Background (CMB) from the northern hemisphere, at medium and large angular scales. The experiment is located at the Teide Observatory in Tenerife, one of the seven Canary Islands (Spain). The project is a consortium maintained by several institutions: the Instituto de Astrofísica de Canarias (IAC), the Instituto de Física de Cantabria (IFCA), the Communications Engineering Department (DICOM) at Universidad de Cantabria, and the Universities of Manchester and Cambridge. The consortium is led by the IAC

    Análisis del switch guiado por farmacocinética de factores VIII de semivida estándar a factores de semivida extendida

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    CO-170 Introducción y objetivos: Los factores VIII (FVIII) de semivida extendida (EHL) han mostrado en los ensayos clínicos mejoras de al menos 1, 3 veces la semivida plasmática (t1/2) y 1, 25 veces el área bajo la curva (AUC) respecto a los FVIII estándar (SHL). Herramientas basadas en modelos farmacocinéticos (PK) poblacionales permiten estimar los parámetros PK individuales y ajustar la profilaxis. El objetivo de este estudio es analizar el switch PK-guiado de SHL a EHL en pacientes con hemofilia A (HA). Métodos: Estudio multicéntrico comparativo, cruzado, prospectivo que analiza las diferencias PK tras el cambio de factores SHL a EHL (Elocta® y Adynovi®) en pacientes con HA grave/moderada en profilaxis. Se ha empleado el PopPK WAPPS-Hemo® con 2-3 muestras para realizar un perfil PK individualizado de los valores de FVIII. Los parámetros PK analizados son: t1/2, AUC, nivel pico (NP), nivel valle a las 24, 48 y/o 72 h (NV24/NV48/NV72) y tiempo para alcanzar niveles de FVIII del 5%, 2% y 1% (T5%/T2%/T1%). También analizamos los ratios de t1/2 y AUC, el nº dosis semanales y la dosis/kg/semana. Para comparar los parámetros PK entre ambos periodos empleamos los test de Wilcoxon y Kruskal-Wallis (SPSS®). Los resultados se expresaron con la mediana y el rango o rango intercuartílico (RIC). Resultados: Se han analizado 64 pacientes procedentes de 8 hospitales españoles (48 switch a Elocta® y 16 a Adynovi®), 62 con HA grave y 2 con HA moderada, con una mediana de edad de 32 años (rango=5-64) y sin diferencias en el peso entre ambos periodo [71, 0 (rango=12-116) vs 72, 0 (16, 9- 116) kg; p=0, 156]. La dosis/kg/semana se redujo tras el switch a EHL [74, 5 (RIC:59, 2-108, 1) vs 69, 2 (RIC:46, 2-96, 7) UI/kg/semana; p<0, 0001], así como ..

    Modeling the adoption of innovations in the presence of geographic and media influences

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    While there has been much work examining the affects of social network structure on innovation adoption, models to date have lacked important features such as meta-populations reflecting real geography or influence from mass media forces. In this article, we show these are features crucial to producing more accurate predictions of a social contagion and technology adoption at the city level. Using data from the adoption of the popular micro-blogging platform, Twitter, we present a model of adoption on a network that places friendships in real geographic space and exposes individuals to mass media influence. We show that homopholy both amongst individuals with similar propensities to adopt a technology and geographic location are critical to reproduce features of real spatiotemporal adoption. Furthermore, we estimate that mass media was responsible for increasing Twitter's user base two to four fold. To reflect this strength, we extend traditional contagion models to include an endogenous mass media agent that responds to those adopting an innovation as well as influencing agents to adopt themselves

    Unraveling the effect of silent, intronic and missense mutations on VWF splicing: contribution of next generation sequencing in the study of mRNA

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    Large studies in von Willebrand disease patients, including Spanish and Portuguese registries, led to identification of >250 different mutations. It is a challenge to determine the pathogenic effect of potential splice site mutations on VWF mRNA. This study aimed to elucidate the true effects of 18 mutations on VWF mRNA processing, investigate the contribution of next-generation sequencing to in vivo mRNA study in von Willebrand disease, and compare the findings with in silico prediction. RNA extracted from patient platelets and leukocytes was amplified by RT-PCR and sequenced using Sanger and next generation sequencing techniques. Eight mutations affected VWF splicing: c.1533+1G>A, c.5664+2T>C and c.546G>A (p.=) prompted exon skipping; c.3223-7_3236dup and c.7082-2A>G resulted in activation of cryptic sites; c.3379+1G>A and c.7473G>A (p.=) demonstrated both molecular pathogenic mechanisms simultaneously; and the p.Cys370Tyr missense mutation generated two aberrant transcripts. Of note, the complete effect of 3 mutations was provided by next generation sequencing alone because of low expression of the aberrant transcripts. In the remaining 10 mutations, no effect was elucidated in the experiments. However, the differential findings obtained in platelets and leukocytes provided substantial evidence that 4 of these would have an effect on VWF levels. In this first report using next generation sequencing technology to unravel the effects of VWF mutations on splicing, the technique yielded valuable information. Our data bring to light the importance of studying the effect of synonymous and missense mutations on VWF splicing to improve the current knowledge of the molecular mechanisms behind von Willebrand disease.info:eu-repo/semantics/publishedVersio
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