967 resultados para Pearson, Emma Maria, d. 1893.
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Inclui bibliografia.
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Inclui notas explicativas e bibliografia
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Inclui notas explicativas e bibliografia
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O conteúdo essencial na doutrina de Smend -- O conteúdo essencial na teoria de Düring -- Conteúdo essencial na teoria de Häbert -- A relativização dos direitos fundamentais
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Despite considerable concerns with pharmacological stimulation of fetal hemoglobin (Hb F) as a therapeutic option for the β-globin disorders, the molecular basis of action of Hb F-inducing agents remains unclear. Here we show that an intracellular pathway including soluble guanylate cyclase (sGC) and cGMP-dependent protein kinase (PKG) plays a role in induced expression of the γ-globin gene. sGC, an obligate heterodimer of α- and β-subunits, participates in a variety of physiological processes by converting GTP to cGMP. Northern blot analyses with erythroid cell lines expressing different β-like globin genes showed that, whereas the β-subunit is expressed at similar levels, high-level expression of the α-subunit is preferentially observed in erythroid cells expressing γ-globin but not those expressing β-globin. Also, the levels of expression of the γ-globin gene correlate to those of the α-subunit. sGC activators or cGMP analogs increased expression of the γ-globin gene in erythroleukemic cells as well as in primary erythroblasts from normal subjects and patients with β-thalassemia. Nuclear run-off assays showed that the sGC activator protoporphyrin IX stimulates transcription of the γ-globin gene. Furthermore, increased expression of the γ-globin gene by well known Hb F-inducers such as hemin and butyrate was abolished by inhibiting sGC or PKG activity. Taken together, these results strongly suggest that the sGC–PKG pathway constitutes a mechanism that regulates expression of the γ-globin gene. Further characterization of this pathway should permit us to develop new therapeutics for the β-globin disorders.
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Operon structure is an important organization feature of bacterial genomes. Many sets of genes occur in the same order on multiple genomes; these conserved gene groupings represent candidate operons. This study describes a computational method to estimate the likelihood that such conserved gene sets form operons. The method was used to analyze 34 bacterial and archaeal genomes, and yielded more than 7600 pairs of genes that are highly likely (P ≥ 0.98) to belong to the same operon. The sensitivity of our method is 30–50% for the Escherichia coli genome. The predicted gene pairs are available from our World Wide Web site http://www.tigr.org/tigr-scripts/operons/operons.cgi.
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Bacterial artificial chromosomes (BACs) and P1 artificial chromosomes (PACs), which contain large fragments of genomic DNA, have been successfully used as transgenes to create mouse models of dose-dependent diseases. They are also potentially valuable as transgenes for dominant diseases given that point mutations and/or small rearrangements can be accurately introduced. Here, we describe a new method to introduce small alterations in BACs, which results in the generation of point mutations with high frequency. The method involves homologous recombination between the original BAC and a shuttle vector providing the mutation. Each recombination step is monitored using positive and negative selection markers, which are the Kanamycin-resistance gene, the sacB gene and temperature-sensitive replication, all conferred by the shuttle plasmid. We have used this method to introduce four different point mutations and the insertion of the β-galactosidase gene in a BAC, which has subsequently been used for transgenic animal production.
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The discovery almost three decades ago of non-nuclear, point-like X-ray sources with X-ray luminosities LX ≥ 3 × 1039 erg s−1 revolutionized the physics of black hole accretion. If of stellar origin, such Ultraluminous X-ray sources (ULXs) would have to accrete at super-Eddington rates in order to reach the observed high X-ray luminosities. Alternatively, ULXs could host sub-Eddington accreting intermediate-mass black holes, which are the long-time sought missing link between stellar and supermassive black holes and the possible seeds of the supermassive black holes that formed in the early Universe. The nature of ULXs can be better investigated in those cases for which a radio counterpart is detected. Radio observations of ULXs have revealed a wide variety of morphologies and source types, from compact and extended jets to radio nebulae and transient behaviours, providing the best observational evidence for the presence of an intermediate-mass black hole in some of them. The high sensitivity of the SKA will allow us to study the faintest ULX radio counterparts in the Local Universe as well as to detect new sources at much larger distances. It will thus perform a leap step in understanding ULXs, their accretion physics, and their possible role as seed black holes in supermassive black hole and galaxy growth.
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Mode of access: Internet.
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Includes index.
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Vol. 1-4 pub. by J. S. Valenzuela; v. 5 by R. Jover.
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Edited by Amélie (Cyvoct) Lenormant.
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Originally published, Oberlin, 1847.
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Facsimile reproduction of the 1st ed. published by Pictorial Bureau of the Press, 1888