3,169 research outputs found

    Bismuth incorporation and the role of ordering in GaAsBi/GaAs structures

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    The structure and composition of single GaAsBi/GaAs epilayers grown by molecular beam epitaxy were investigated by optical and transmission electron microscopy techniques. Firstly, the GaAsBi layers exhibit two distinct regions and a varying Bi composition profile in the growth direction. In the lower (25 nm) region, the Bi content decays exponentially from an initial maximum value, while the upper region comprises an almost constant Bi content until the end of the layer. Secondly, despite the relatively low Bi content, CuPtB-type ordering was observed both in electron diffraction patterns and in fast Fourier transform reconstructions from high-resolution transmission electron microscopy images. The estimation of the long-range ordering parameter and the development of ordering maps by using geometrical phase algorithms indicate a direct connection between the solubility of Bi and the amount of ordering. The occurrence of both phase separation and atomic ordering has a significant effect on the optical properties of these layers

    Systematic identification of phenotypically enriched loci using a patient network of genomic disorders

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    Background Network medicine is a promising new discipline that combines systems biology approaches and network science to understand the complexity of pathological phenotypes. Given the growing availability of personalized genomic and phenotypic profiles, network models offer a robust integrative framework for the analysis of "omics" data, allowing the characterization of the molecular aetiology of pathological processes underpinning genetic diseases. Methods Here we make use of patient genomic data to exploit different network-based analyses to study genetic and phenotypic relationships between individuals. For this method, we analyzed a dataset of structural variants and phenotypes for 6,564 patients from the DECIPHER database, which encompasses one of the most comprehensive collections of pathogenic Copy Number Variations (CNVs) and their associated ontology-controlled phenotypes. We developed a computational strategy that identifies clusters of patients in a synthetic patient network according to their genetic overlap and phenotype enrichments. Results Many of these clusters of patients represent new genotype-phenotype associations, suggesting the identification of newly discovered phenotypically enriched loci (indicative of potential novel syndromes) that are currently absent from reference genomic disorder databases such as ClinVar, OMIM or DECIPHER itself. Conclusions We provide a high-resolution map of pathogenic phenotypes associated with their respective significant genomic regions and a new powerful tool for diagnosis of currently uncharacterized mutations leading to deleterious phenotypes and syndromes

    Evaluación de la severidad de la incontinencia urinaria de esfuerzo con estudios urodinámicos: un estudio comparativo para detectar deficiencia intrínseca del esfínter uretral externo

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    ResumenObjetivoDeterminar la sensibilidad y especificidad del punto de presión de fuga abdominal (ALPP), para evaluar la presencia de deficiencia intrínseca del esfínter (DIE) comparativamente con la presión máxima de cierre uretral (MUCP, por sus siglas en inglés), estableciendo la correlación clínico-urodinámica correspondiente.ResultadosFueron evaluadas 34 pacientes con incontinencia urinaria de esfuerzo (IUE); 17 paciente (50%) fueron diagnosticadas urodinámicamente con DIE por punto de ALPP; 9 tuvieron IUE severa mientras que sólo 2 (5.8%) lo fueron por MUCP, de las cuales una tuvo IUE severa y otra, IUE moderada. Dieciocho pacientes fueron catalogadas clínicamente como IUE severa, de las cuales 17 tuvieron DIE por ALPP entre severa y moderada (94%).ConclusionesLa evaluación urodinámica de la IUE permite establecer de manera clara la fisiopatología de una disfunción del tracto urinario inferior concomitante, con la posibilidad de objetivar la presencia de IUE con el ALPP en al menos 85% de los casos, con una sensibilidad y especificidad para diagnosticar DIE muy superior a la MUCP.AbstractAimsTo determine the sensitivity and specificity of the abdominal leak point pressure (ALPP) in order to comparatively evalúate the presence of intrinsic sphincter deficiency (ISD) with máximum urethral closure pressure (MUCP) and establish the corresponding clinical and urodynamic correlation.ResultsThirty-four patients with stress urinary incontinence (SUI) were evaluated. Seventeen of those patients (50%) were urodynamically diagnosed with ISD through ALPP and 9 of them had severe SUI. Only 2 patients were diagnosed with ISD through MUCP; one of them had severe SUI and the other presented with modérate SUI. Eighteen patients were clinically classified with severe SUI, 17 of whom had moderate to severe ISD diagnosed through ALPP (94%).ConclusionsUrodynamic evaluation of SUI made it possible to clearly establish the pathophysiology of concomitant lower urinary tract dysfunction and to objectify the presence of SUI through ALPP in at least 85% of the cases. ALPP had a much higher sensitivity and specificity for diagnosing ISD than MUCP

    Anticipated Discrimination, Choices, and Performance: Experimental Evidence

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    This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.This paper studies experimentally whether potential perceived discrimination affects decisions in a labor-market setting with different stereotypes. Participants are assigned to a seven-person group and randomly allocated a role as a firm or worker. In each group, there are five workers and two firms. The only information firms have about each worker is a self-selected avatar (male, female or neutral) representing a worker's gender. Each firm then decides which worker to hire. Female workers react to potential discrimination when they know the task is math-related, but not otherwise. Men choose similar avatar patterns regardless of the task. Men do perform at much higher levels in the math-related task, but there is no difference in performance in the emotion-recognition task, where there is a strong female stereotype.American University of SharjahUniversity of Exete

    Phenotype-loci associations in networks of patients with rare disorders: application to assist in the diagnosis of novel clinical cases

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    Copy number variations (CNVs) are genomic structural variations (deletions, duplications, or translocations) that represent the 4.8–9.5% of human genome variation in healthy individuals. In some cases, CNVs can also lead to disease, being the etiology of many known rare genetic/genomic disorders. Despite the last advances in genomic sequencing and diagnosis, the pathological effects of many rare genetic variations remain unresolved, largely due to the low number of patients available for these cases, making it difficult to identify consistent patterns of genotype–phenotype relationships. We aimed to improve the identification of statistically consistent genotype–phenotype relationships by integrating all the genetic and clinical data of thousands of patients with rare genomic disorders (obtained from the DECIPHER database) into a phenotype–patient–genotype tripartite network. Then we assessed how our network approach could help in the characterization and diagnosis of novel cases in clinical genetics. The systematic approach implemented in this work is able to better define the relationships between phenotypes and specific loci, by exploiting large-scale association networks of phenotypes and genotypes in thousands of rare disease patients. The application of the described methodology facilitated the diagnosis of novel clinical cases, ranking phenotypes by locus specificity and reporting putative new clinical features that may suggest additional clinical follow-ups. In this work, the proof of concept developed over a set of novel clinical cases demonstrates that this network-based methodology might help improve the precision of patient clinical records and the characterization of rare syndromes

    Are seed mass and seedling size and shape related to altitude? Evidence in Gymnocalycium monvillei (Cactaceae)

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    "Several studies reported a negative relationship between altitude and seed mass. In cactus species, seed mass has been also related to seedling morphology (size and shape). Here we studied Gymnocalycium monvillei (Lem.) Pfeiff. ex Britton & Rose, a cactus species with a wide altitudinal distribution, with the main aim of analyzing how altitude affects seed mass and seedling size (height and width) and shape (globose or columnar). We collected seeds from five sites along the entire altitudinal distribution of the species in the Córdoba Mountains (sites were located between 878 and 2230 m a.s.l.), encompassing a marked climatic gradient (6 °C of mean annual temperature difference between the extreme sites). Seed mass and seedling traits were measured in the laboratory. Seedling height increased with altitude, whereas seed mass was not related to this parameter. Seedlings became more globose (reduced surface/volume ratio) with decreasing altitude. Variation in seedling shape along the altitudinal gradient may be related to the contrasting climatic conditions to which seedlings are exposed, and could account for the wide altitudinal distribution of G. monvillei. Our results highlight the importance of seedling traits in the species’ response to climatic change.

    Effect of annealing in the Sb and In distribution of type II GaAsSb-capped InAs quantum dots

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    Type II emission optoelectronic devices using GaAsSb strain reduction layers (SRL) over InAs quantum dots (QDs) have aroused great interest. Recent studies have demonstrated an extraordinary increase in photoluminescence (PL) intensity maintaining type II emission after a rapid thermal anneal (RTA), but with an undesirable blueshift. In this work, we have characterized the effect of RTA on InAs/GaAs QDs embedded in a SRL of GaAsSb by transmission electron microscopy (TEM) and finite element simulations. We find that annealing alters both the distribution of Sb in the SRL as well as the exchange of cations (In and Ga) between the QDs and the SRL. First, annealing causes modifications in the capping layer, reducing its thickness but maintaining the maximum Sb content and improving its homogeneity. In addition, the formation of Sb-rich clusters with loop dislocations is noticed, which seems not to be an impediment for an increased PL intensity. Second, RTA produces flatter QDs with larger base diameter and induces a more homogeneous QD height distribution. The Sb is accumulated over the QDs and the RTA enlarges the Sb-rich region, but the Sb contents are very similar. This fact leaves the type II alignment without major changes. Atomic-scale strain analysis of the nanostructures reveal a strong intermixing of In/Ga between the QDs and the capping layer, which is the main responsible mechanism of the PL blueshift. The improvement of the crystalline quality of the capping layer together with higher homogeneity QD sizes could be the origin of the enhancement of the PL emission

    Green Alga Ulva spp. Hydrolysates and Their Peptide Fractions Regulate Cytokine Production in Splenic Macrophages and Lymphocytes Involving the TLR4-NFkB/MAPK Pathways

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    Hydrolysates of food protein sources have immunomodulatory effects, which are of interest for use as functional foods. In this study, we have characterized the immune regulatory effect on rat splenocytes, macrophages and T lymphocytes of Ulva spp. hydrolysates and their peptide fractions with or without in vitro gastrointestinal digestion and/or ultrafiltration. IL-10 was induced in almost all conditions and cell types obtained from wild type animals. The induction was in general increased by ultrafiltration and in vitro gastrointestinal digestion. TNF was also induced in basal conditions. In turn, TNF and IFN- production was attenuated by the hydrolysate products in lipopolysaccharide or concanavalin A immune stimulated cells. Inhibitors for the activation of NF B, MAPK p38 and JNK inhibited IL-10 induction in rat splenocytes. The response was dramatically attenuated in TLR4-/- cells, and only modestly in TLR2-/- cells. Food peptides from Ulva spp. genus exert anti-inflammatory effects in immune cells mediated by TLR4 and NF B. Similarity with the immunomodulatory profile of protein hydrolysates from other sources suggests a common mechanism.This work was supported by funds from the Ministry of Economy and Competitivity, partly with Fondo Europeo de Desarrollo Regional FEDER funds [SAF2017-88457-R, AGL2017-85270-R, BFU2014-57736-P, AGL2014-58883-R] and by Junta de Andalucía [CTS235, CTS164]. C.H.-C. and R.G.-B. were supported by the University of Granada (Contrato Puente Program—Plan Propio) and the Ministry of Education [Spain], respectively. CIBERehd is funded by Instituto de Salud Carlos III

    Experimental and theoretical assessment of native oxide in the superconducting TaN

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    In this manuscript, we show through an experimental-computational proof of concept the native oxide formation into superconducting TaN films. First, TaN was synthesized at an ultra-high vacuum system by reactive pulsed laser deposition and characterized in situ by X-ray photoelectron spectroscopy. The material was also characterized ex situ by X-ray diffraction, transmission electron microscopy, and the four-point probe method. It was detected that TaN contained considerable oxygen impurities (up to 26 %O) even though it was grown in an ultra-high vacuum chamber. Furthermore, the impurified TaN evidence a face-centered cubic crystalline structure only and exhibits superconductivity at 2.99 K. To understand the feasibility of the native oxide in TaN, we study the effect of incorporating different amounts of O atoms in TaN using ab-initio calculations. A thermodynamic stability analysis shows that a TaOxN1-x model increases its stability as oxygen is added, demonstrating that oxygen may always be present in TaN, even when obtained at ultra-high vacuum conditions. All analyzed models exhibit metallic behavior. Charge density difference maps reveal that N and O atoms have a higher charge density redistribution than Ta atoms. The electron localization function maps and line profiles indicate that Ta-O and Ta-N bonds are mainly ionic. As expected, stronger ionic behavior is observed in the Ta-O bonds due to the electronegativity difference between O and N atoms. Recent evidence points to superconductivity in bulk TaO, confirming the asseverations of superconductivity in our samples. The results discussed here highlight the importance of considering native oxide when reporting superconductivity in TaN films since the TaO regions formed in the compound may be key to understanding the different critical temperatures reported in the literature.Comment: 23 pages, 7 figure

    Cannabidiol skews biased agonism at cannabinoid CB1 and CB2 receptors with smaller effect in CB1-CB2 heteroreceptor complexes

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    Currently, biased agonism is at the center stage of drug development approaches. We analyzed effects of a battery of cannabinoids plus/minus cannabidiol (CBD) in four functional parameters (cAMP levels, phosphorylation of extracellular signal–regulated kinases (ERK1/2), β-arrestin recruitment and label-free/DMR) in HEK-293T cells expressing cannabinoid receptors, CB or CB, or CB-CB heteroreceptor complexes. In all cases two natural agonists plus two selective synthetic agonists were used. Furthermore, the effect of cannabidiol, at a dose (100 nM) that does not allow significant binding to the orthosteric center of either receptor, was measured. From the huge amount of generated data, we would like to highlight that the two psychotropic molecules (Δ-tetrahydrocannabinol/THC and CP-55940) showed similar bias in CBR and that the bias of THC was particularly relevant toward MAPK pathway. Furthermore, THC did not activate the G protein coupled to CBR. Interestingly, the biased agonism was reduced when assays were performed in cells expressing the two receptors, thus suggesting that the heteromer allows less functional selectivity. In terms of cannabidiol action, the phytocannabinoid altered the functional responses, likely by allosteric means, and modified potency, agonist IC/EC values and biased agonism in qualitative and/or quantitative different ways depending on the agonist. The effect of cannabidiol on anandamide actions on both cannabinoid receptors was particularly noteworthy as was significantly different from that of other compounds. Results are a compendium of data on biased agonism on cannabinoid receptors in the absence and presence of cannabidiol. In addition, for the first time, GPCR biased agonism is characterized in an heteromeric context.This work was partially supported by grants from the Spanish Ministry of Economy and Competitiveness (Ref. no. BFU2015-64405-R and SAF2017-84117-R; they may include FEDER funds) and by grant 201413-30 from: Fundació la Marató de TV3Peer Reviewe
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