147 research outputs found

    Investigation of inertia response and rate of change of frequency in low rotational inertial scenario of synchronous dominated system

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    The shift to a sustainable energy future is becoming more reliant on large-scale deployment of renewable and distributed energy resources raising concerns about frequency stability. Rate of Change of Frequency (RoCoF) is necessary as a system inertia metric in order for network operators to perform control steps to preserve system operation. This paper presents in a straightforward and illustrative way several relevant aspects of the inertia response and RoCoF calculation that could help to understand and explain the implementation and results of inertial response controllers on power converter-based technologies. Qualitative explanations based on illustrative numerical experiments are used to cover the effects on the system frequency response of reduced rotational inertia in synchronous dominated power systems. One main contribution of this paper is making evident the importance of the governor action to avoid the synchronous machine taking active power from the system during the recovering period of kinetic energy in an under frequency event

    Protein kinase B (AKT) upregulation and Thy-1-α<sub>v</sub>β<sub>3</sub> integrin-induced phosphorylation of Connexin43 by activated AKT in astrogliosis.

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    In response to brain injury or inflammation, astrocytes undergo hypertrophy, proliferate, and migrate to the damaged zone. These changes, collectively known as "astrogliosis", initially protect the brain; however, astrogliosis can also cause neuronal dysfunction. Additionally, these astrocytes undergo intracellular changes involving alterations in the expression and localization of many proteins, including α &lt;sub&gt;v&lt;/sub&gt; β &lt;sub&gt;3&lt;/sub&gt; integrin. Our previous reports indicate that Thy-1, a neuronal glycoprotein, binds to this integrin inducing Connexin43 (Cx43) hemichannel (HC) opening, ATP release, and astrocyte migration. Despite such insight, important links and molecular events leading to astrogliosis remain to be defined. Using bioinformatics approaches, we analyzed different Gene Expression Omnibus datasets to identify changes occurring in reactive astrocytes as compared to astrocytes from the normal mouse brain. In silico analysis was validated by both qRT-PCR and immunoblotting using reactive astrocyte cultures from the normal rat brain treated with TNF and from the brain of a hSOD1 &lt;sup&gt;G93A&lt;/sup&gt; transgenic mouse model. We evaluated the phosphorylation of Cx43 serine residue 373 (S373) by AKT and ATP release as a functional assay for HC opening. In vivo experiments were also performed with an AKT inhibitor (AKTi). The bioinformatics analysis revealed that genes of the PI3K/AKT signaling pathway were among the most significantly altered in reactive astrocytes. mRNA and protein levels of PI3K, AKT, as well as Cx43, were elevated in reactive astrocytes from normal rats and from hSOD1 &lt;sup&gt;G93A&lt;/sup&gt; transgenic mice, as compared to controls. In vitro, reactive astrocytes stimulated with Thy-1 responded by activating AKT, which phosphorylated S373Cx43. Increased pS373Cx43 augmented the release of ATP to the extracellular medium and AKTi inhibited these Thy-1-induced responses. Furthermore, in an in vivo model of inflammation (brain damage), AKTi decreased the levels of astrocyte reactivity markers and S373Cx43 phosphorylation. Here, we identify changes in the PI3K/AKT molecular signaling network and show how they participate in astrogliosis by regulating the HC protein Cx43. Moreover, because HC opening and ATP release are important in astrocyte reactivity, the phosphorylation of Cx43 by AKT and the associated increase in ATP release identify a potential therapeutic window of opportunity to limit the adverse effects of astrogliosis

    Motivación y burnout en profesores de educación física: incidencia de la frustración de las necesidades psicológicas básicas

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    A través del presente trabajo se pretende valorar la importanciade las necesidades psicológicas básicas para explicar y predecir el tipo demotivación y los niveles de burnout en profesores de educación física. Paraello, la muestra estuvo formada por 357 docentes de género masculino yfemenino, pertenecientes a diferentes centros educativos públicos y privadosde España. Se realizó un análisis de regresión lineal por cada variabledependiente, que indicaron cómo la frustración de la necesidad de competenciapredecía positivamente la desmotivación, el agotamiento emocionaly el cinismo, y negativamente la motivación intrínseca y la eficacia profesional;la frustración de autonomía predecía positivamente el agotamientosemocional y negativamente la eficacia profesional; y la frustración de relacionessociales predecía positivamente la eficacia profesional. Estos resultadosestán en la línea de la Teoría de la Autodeterminación (Deci y Ryan,2000; Ryan y Deci, 2000), destacando la importancia que adquieren lasatisfacción de autonomía, competencia y relaciones sociales para optimizarla motivación y el bienestar de los profesores de educación física

    Detection and validation of circular DNA fragments using nanopore sequencing

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    Occurrence of extra-chromosomal circular DNA is a phenomenon frequently observed in tumor cells, and the presence of such DNA has been recognized as a marker of adverse outcome across cancer types. We here describe a computational workflow for identification of DNA circles from long-read sequencing data. The workflow is implemented based on the Snakemake workflow management system. Its key step uses a graph-theoretic approach to identify putative circular fragments validated on simulated reads. We then demonstrate robustness of our approach using nanopore sequencing of selectively enriched circular DNA by highly sensitive and specific recovery of plasmids and the mitochondrial genome, which is the only circular DNA in normal human cells. Finally, we show that the workflow facilitates detection of larger circular DNA fragments containing extrachromosomal copies of the MYCN oncogene and the respective breakpoints, which is a potentially useful application in disease monitoring of several cancer types

    Partner-independent fusion gene detection by multiplexed CRISPR/Cas9 enrichment and long-read Nanopore sequencing

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    Fusion genes are hallmarks of various cancer types and important determinants for diagnosis, prognosis and treatment possibilities. The promiscuity of fusion genes with respect to partner choice and exact breakpoint-positions restricts their detection in the diagnostic setting, even for known and recurrent fusion gene configurations. To accurately identify these gene fusions in an unbiased manner, we developed FUDGE: a FUsion gene Detection assay from Gene Enrichment. FUDGE couples target-selected and strand-specific CRISPR/Cas9 activity for enrichment and detection of fusion gene drivers (e.g. BRAF, EWSR1, KMT2A/MLL) - without prior knowledge of fusion partner or breakpoint-location - to long-read Nanopore sequencing. FUDGE encompasses a dedicated bioinformatics approach (NanoFG) to detect fusion genes from Nanopore sequencing data. Our strategy is flexible with respect to target choice and enables multiplexed enrichment for simultaneous analysis of several genes in multiple samples in a single sequencing run. We observe on average a 508 fold on-target enrichment and identify fusion breakpoints at nucleotide resolution - all within two days. We demonstrate that FUDGE effectively identifies fusion genes in cancer cell lines, tumor samples and on whole genome amplified DNA irrespective of partner gene or breakpoint-position in 100% of cases. Furthermore, we show that FUDGE is superior to routine diagnostic methods for fusion gene detection. In summary, we have developed a rapid and versatile fusion gene detection assay, providing an unparalleled opportunity for pan-cancer detection of fusion genes in routine diagnostics

    Relativistic Static Thin Disks with Radial Stress Suport

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    New solutions for static non-rotating thin disks of finite radius with nonzero radial stress are studied. A method to introduce either radial pressure or radial tension is presented. The method is based on the use of conformal transformations.Comment: 19 pages, LaTeX, 7 figures, submitted to Class. Quan. Gra

    Exact General Relativistic Disks with Magnetic Fields

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    The well-known ``displace, cut, and reflect'' method used to generate cold disks from given solutions of Einstein equations is extended to solutions of Einstein-Maxwell equations. Four exact solutions of the these last equations are used to construct models of hot disks with surface density, azimuthal pressure, and azimuthal current. The solutions are closely related to Kerr, Taub-NUT, Lynden-Bell-Pinault and to a one-soliton solution. We find that the presence of the magnetic field can change in a nontrivial way the different properties of the disks. In particular, the pure general relativistic instability studied by Bicak, Lynden-Bell and Katz [Phys. Rev. D47, 4334, 1993] can be enhanced or cured by different distributions of currents inside the disk. These currents, outside the disk, generate a variety of axial symmetric magnetic fields. As far as we know these are the first models of hot disks studied in the context of general relativity.Comment: 21 pages, 11 figures, uses package graphics, accepted in PR

    Partner independent fusion gene detection by multiplexed CRISPR-Cas9 enrichment and long read nanopore sequencing

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    Fusion genes are hallmarks of various cancer types and important determinants for diagnosis, prognosis and treatment. Fusion gene partner choice and breakpoint-position promiscuity restricts diagnostic detection, even for known and recurrent configurations. Here, we develop FUDGE (FUsion Detection from Gene Enrichment) to accurately and impartially identify fusions. FUDGE couples target-selected and strand-specific CRISPR-Cas9 activity for fusion gene driver enrichment - without prior knowledge of fusion partner or breakpoint-location - to long read nanopore sequencing with the bioinformatics pipeline NanoFG. FUDGE has flexible target-loci choices and enables multiplexed enrichment for simultaneous analysis of several genes in multiple samples in one sequencing run. We observe on-average 665 fold breakpoint-site enrichment and identify nucleotide resolution fusion breakpoints within 2 days. The assay identifies cancer cell line and tumor sample fusions irrespective of partner gene or breakpoint-position. FUDGE is a rapid and versatile fusion detection assay for diagnostic pan-cancer fusion detection
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