61 research outputs found

    Understanding Flash Sintering of Semiconductor Oxide Materials at the Nano- Atomic Scale

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    Small and long regulatory RNAs in the immune system and immune diseases

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    Cellular differentiation is regulated on the level of gene expression and it is known that dysregulation of gene expression can lead to deficiencies in differentiation that contribute to a variety of diseases, particularly of the immune system. Until recently, it was thought that the dysregulation was governed by changes in the binding or activity of a class of proteins called transcription factors. However, the discovery of micro-RNAs and recent descriptions of long noncoding RNAs have given enormous momentum to a whole new field of biology: the regulatory RNAs. In this review, we describe these two classes of regulatory RNAs and summarize what is known about how they regulate aspects of the adaptive and innate immune systems. Finally, we describe what is known about the involvement of micro-RNAs and long noncoding RNAs in three different autoimmune diseases (celiac disease, inflammatory bowel disease, and multiple sclerosis)

    Concordancia entre ecoscopia realizada por médicos no cardiológos y ecocardiografía convencional

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    Introduction: Focused cardiac ultrasound has been proposed as a useful approach for improving clinical decision making, as well as to be able to rapidly identify the ultrasound signs of a specific list of potential diagnoses. Objective: To evaluate a training program for physicians with no experience in cardiac ultrasound with the aim performing focused cardiac ultrasound using a portable device (echoscopy). Materials and methods: The results obtained from echoscopy performed by the physicians that received training were compared with those obtained with conventional cardiac ultrasound carried out by expert cardiologists. A total of 5 non-cardiologist doctors, including 1 medical student, 2 Internal Medicine residents, and 2 from Intensive Medicine, took part in a four-week training course given by a Level III Cardiology specialist. The course included: First week: Theory and basis of cardiac ultrasound (3 hours daily) Second week: Theory of acquiring images. Normal and abnormal findings (50 studies). Third week: handling of the echoscope (50 studies). Fourth week: Data collection. The study included patients scheduled for conventional cardiac ultrasound in the Non-Invasive Methods Laboratory. Two examinations were carried out on each patient. The first consisted of an echoscopy performed by a doctor that had received the training, and the second consisted of a cardiac ultrasound carried out by an expert cardiologist. The ultrasound parameters evaluated were: left ventricular ejection fraction, right ventricular dysfunction, left atrial enlargement, pulmonary hypertension, cardiac valve disease, and pericardial effusion. The results found in echoscopy versus cardiac ultrasound were compared using concordance analysis (Kappa Index). Results: The following results were obtained on the 221 studies performed: moderate agreement in left ventricular ejection fraction (? = 0.541, p less than .000), right ventricular function (? = 0.403, p less than .001), left atrial enlargement (? = 0.413, p less than .001), mitral valve and tricuspid valve disease (? = 0.437, p less than .001 and (? = 0.466, P less than .001, respectively). There was weak agreement with aortic valve disease. Pericardiac effusion and the presence of pulmonary hypertension had a poor and week agreement, respectively. Conclusions: With a limited training period, the participants with no previous experience in ultrasound techniques and using echoscopy achieved a moderate agreement in the majority of measurements when compared with conventional cardiac ultrasound performed by experts in the technique. A study with a larger number of participants is required in order to determine the ideal training period to obtain results comparable with cardiac ultrasound. © 201

    Systematic Prioritization of Candidate Genes in Disease Loci Identifies TRAFD1 as a Master Regulator of IFN gamma Signaling in Celiac Disease

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    Celiac disease (CeD) is a complex T cell-mediated enteropathy induced by gluten. Although genome-wide association studies have identified numerous genomic regions associated with CeD, it is difficult to accurately pinpoint which genes in these loci are most likely to cause CeD. We used four different in silico approaches-Mendelian randomization inverse variance weighting, COLOC, LD overlap, and DEPICT-to integrate information gathered from a large transcriptomics dataset. This identified 118 prioritized genes across 50 CeD-associated regions. Co-expression and pathway analysis of these genes indicated an association with adaptive and innate cytokine signaling and T cell activation pathways. Fifty-one of these genes are targets of known drug compounds or likely druggable genes, suggesting that our methods can be used to pinpoint potential therapeutic targets. In addition, we detected 172 gene combinations that were affected by our CeD-prioritized genes in trans. Notably, 41 of these trans-mediated genes appear to be under control of one master regulator, TRAF-type zinc finger domain containing 1 (TRAFD1), and were found to be involved in interferon (IFN)gamma signaling and MHC I antigen processing/presentation. Finally, we performed in vitro experiments in a human monocytic cell line that validated the role of TRAFD1 as an immune regulator acting in trans. Our strategy confirmed the role of adaptive immunity in CeD and revealed a genetic link between CeD and IFN gamma signaling as well as with MHC I antigen processing, both major players of immune activation and CeD pathogenesis

    pSESYNTH project: Community mobilization for a multi-disciplinary paleo database of the Global South

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    How to enhance paleoscientific research, collaboration and application in the Global South? The INQUA-funded multi-year pSESYNTH project envisions the first multi-disciplinary Holocene paleo database through a collaborative vision for past human-environmental systems in the Global South, and their future sustainability

    Refined mapping of autoimmune disease associated genetic variants with gene expression suggests an important role for non-coding RNAs

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    Genome-wide association and fine-mapping studies in 14 autoimmune diseases (AID) have implicated more than 250 loci in one or more of these diseases. As more than 90% of AID-associated SNPs are intergenic or intronic, pinpointing the causal genes is challenging. We performed a systematic analysis to link 460 SNPs that are associated with 14 AID to causal genes using transcriptomic data from 629 blood samples. We were able to link 71 (39%) of the AID-SNPs to two or more nearby genes, providing evidence that for part of the AID loci multiple causal genes exist. While 54 of the AID loci are shared by one or more AID, 17% of them do not share candidate causal genes. In addition to finding novel genes such as ULK3, we also implicate novel disease mechanisms and pathways like autophagy in celiac disease pathogenesis. Furthermore, 42 of the AID SNPs specifically affected the expression of 53 non-coding RNA genes. To further understand how the non-coding genome contributes to AID, the SNPs were linked to functional regulatory elements, which suggest a model where AID genes are regulated by network of chromatin looping/non-coding RNAs interactions. The looping model also explains how a causal candidate gene is not necessarily the gene closest to the AID SNP, which was the case in nearly 50% of cases

    Deconvolution of bulk blood eQTL effects into immune cell subpopulations

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    BACKGROUND: Expression quantitative trait loci (eQTL) studies are used to interpret the function of disease-associated genetic risk factors. To date, most eQTL analyses have been conducted in bulk tissues, such as whole blood and tissue biopsies, which are likely to mask the cell type-context of the eQTL regulatory effects. Although this context can be investigated by generating transcriptional profiles from purified cell subpopulations, current methods to do this are labor-intensive and expensive. We introduce a new method, Decon2, as a framework for estimating cell proportions using expression profiles from bulk blood samples (Decon-cell) followed by deconvolution of cell type eQTLs (Decon-eQTL). RESULTS: The estimated cell proportions from Decon-cell agree with experimental measurements across cohorts (R ≥ 0.77). Using Decon-cell, we could predict the proportions of 34 circulating cell types for 3194 samples from a population-based cohort. Next, we identified 16,362 whole-blood eQTLs and deconvoluted cell type interaction (CTi) eQTLs using the predicted cell proportions from Decon-cell. CTi eQTLs show excellent allelic directional concordance with eQTL (≥ 96-100%) and chromatin mark QTL (≥87-92%) studies that used either purified cell subpopulations or single-cell RNA-seq, outperforming the conventional interaction effect. CONCLUSIONS: Decon2 provides a method to detect cell type interaction effects from bulk blood eQTLs that is useful for pinpointing the most relevant cell type for a given complex disease. Decon2 is available as an R package and Java application (https://github.com/molgenis/systemsgenetics/tree/master/Decon2) and as a web tool (www.molgenis.org/deconvolution)

    Estudio de factibilidad para el escalamiento de core local de SDH a DWDM para Movistar Colombia

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    Los estudios de factibilidad en telecomunicaciones pretenden identiicar, entre otros asuntos, los beneicios que se obtendrían al migrar una tecnología de red hacia nuevas o novedosas tecnologías. La empresa telefónica de móviles Movistar no es la excepción. Actualmente, el Core local (Bogotá) de transmisión se encuentra soportado sobre tecnología SDH. La cantidad de tráico que se transporta indica una saturación del canal, lo que ha implicado utilizar carriers externos que no garantizan iabilidad en la prestación del servicio. Este artículo describe el estudio de la proyección en el Core local, migrando a tecnología DWDM. La metodología se basa en estudios de tráico, escalabilidad del Core, escalabilidad a nivel comercial. Se compara el comportamiento de la red actual con el que tendría si se realizara la implementación, teniendo en cuenta diversas variables, como la disponibilidad y los parámetros de QoS

    Análisis de la absorción de microondas en el compuesto superconductor YBa2Cu3O7

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    En este trabajo se estudia teóricamente la respuesta de una muestra superconductora de YBaCuO sometida a ondas electromagnéticas en la frecuencia de las microondas; evaluada mediante el modelo de absorción de microondas en un campo magnético barrido, en el cual al menos una componente de la resistencia superficial esta asociada a la densidad de flujo. Los resultados de los modelos ajustan con el comportamiento observado experimentalmente en el YBaCuO y reportado en la literatura
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