999 resultados para Type IA topoisomerase
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In this dissertation, after a brief review on the Einstein s General Relativity Theory and its application to the Friedmann-Lemaitre-Robertson-Walker (FLRW) cosmological models, we present and discuss the alternative theories of gravity dubbed f(R) gravity. These theories come about when one substitute in the Einstein-Hilbert action the Ricci curvature R by some well behaved nonlinear function f(R). They provide an alternative way to explain the current cosmic acceleration with no need of invoking neither a dark energy component, nor the existence of extra spatial dimensions. In dealing with f(R) gravity, two different variational approaches may be followed, namely the metric and the Palatini formalisms, which lead to very different equations of motion. We briefly describe the metric formalism and then concentrate on the Palatini variational approach to the gravity action. We make a systematic and detailed derivation of the field equations for Palatini f(R) gravity, which generalize the Einsteins equations of General Relativity, and obtain also the generalized Friedmann equations, which can be used for cosmological tests. As an example, using recent compilations of type Ia Supernovae observations, we show how the f(R) = R − fi/Rn class of gravity theories explain the recent observed acceleration of the universe by placing reasonable constraints on the free parameters fi and n. We also examine the question as to whether Palatini f(R) gravity theories permit space-times in which causality, a fundamental issue in any physical theory [22], is violated. As is well known, in General Relativity there are solutions to the viii field equations that have causal anomalies in the form of closed time-like curves, the renowned Gödel model being the best known example of such a solution. Here we show that every perfect-fluid Gödel-type solution of Palatini f(R) gravity with density and pressure p that satisfy the weak energy condition + p 0 is necessarily isometric to the Gödel geometry, demonstrating, therefore, that these theories present causal anomalies in the form of closed time-like curves. This result extends a theorem on Gödel-type models to the framework of Palatini f(R) gravity theory. We derive an expression for a critical radius rc (beyond which causality is violated) for an arbitrary Palatini f(R) theory. The expression makes apparent that the violation of causality depends on the form of f(R) and on the matter content components. We concretely examine the Gödel-type perfect-fluid solutions in the f(R) = R−fi/Rn class of Palatini gravity theories, and show that for positive matter density and for fi and n in the range permitted by the observations, these theories do not admit the Gödel geometry as a perfect-fluid solution of its field equations. In this sense, f(R) gravity theory remedies the causal pathology in the form of closed timelike curves which is allowed in General Relativity. We also examine the violation of causality of Gödel-type by considering a single scalar field as the matter content. For this source, we show that Palatini f(R) gravity gives rise to a unique Gödeltype solution with no violation of causality. Finally, we show that by combining a perfect fluid plus a scalar field as sources of Gödel-type geometries, we obtain both solutions in the form of closed time-like curves, as well as solutions with no violation of causality
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Histamine release induced by plant lectins was studied with emphasis on the carbohydrate specificity, external calcium requirement, metal binding sites, and mast cell heterogeneity and on the importance of antibodies bound to the mast cell membrane to the lectin effect. Peritoneal mast cells were obtained by direct lavage of the rat peritoneal cavity and guinea pig intestine and hamster cheek pouch mast cells were obtained by dispersion with collagenase type IA. Histamine release was induced with concanavalin A (Con A), lectins from Canavalia brasiliensis, mannose-specific Cymbosema roseum, Maackia amurensis, Parkia platycephala, Triticum vulgaris (WGA), and demetallized Con A and C. brasiliensis, using 1-300 µg/ml lectin concentrations applied to Wistar rat peritoneal mast cells, peaking on 26.9, 21.0, 29.1, 24.9, 17.2, 10.7, 19.9, and 41.5%, respectively. This effect was inhibited in the absence of extracellular calcium. The lectins were also active on hamster cheek pouch mast cells (except demetallized Con A) and on Rowett nude rat (animal free of immunoglobulins) peritoneal mast cells (except for mannose-specific C. roseum, P. platycephala and WGA). No effect was observed in guinea pig intestine mast cells. Glucose-saturated Con A and C. brasiliensis also released histamine from Wistar rat peritoneal mast cells. These results suggest that histamine release induced by lectins is influenced by the heterogeneity of mast cells and depends on extracellular calcium. The results also suggest that this histamine release might occur by alternative mechanisms, because the usual mechanism of lectins is related to their binding properties to metals from which depend the binding to sugars, which would be their sites to bind to immunoglobulins. In the present study, we show that the histamine release by lectins was also induced by demetallized lectins and by sugar-saturated lectins (which would avoid their binding to other sugars). Additionally, the lectins also released histamine from Rowett nude mast cells that are free of immunoglobulins.
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Rate coefficients for radiative association of silicon and sulphur atoms to form silicon monosulphide (SiS) molecule are estimated. The radiative association is due mainly to approach in the E(1)Sigma(+) and A(1)Pi states of SiS. For temperatures ranging from similar to 1000 to similar to 14 000 K, the rate coefficients are found to vary from 8.43 x 10(-17) to 2.69 x 10(-16) cm(3) s(-1). Our calculated rate coefficient is higher than the values used in modelling the chemistry of Type Ia supernovae.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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The coumarin antibiotics are potent inhibitors of DNA replication whose target is the enzyme DNA gyrase, an ATP-dependent bacterial type II topoisomerase. The coumarin drugs inhibit gyrase action by competitive binding to the ATP-binding site of DNA gyrase B protein. The production of new biologically active products has stimulated additional studies on coumarin-gyrase interactions. In this regard, a 4.2 kDa peptide mimic of DNA gyrase B protein from Escherichia coli has been designed and synthesized. The peptide sequence includes the natural fragment 131-146 (coumarin resistance-determining region) and a segment containing the gyrase-DNA interaction region (positions 753-770). The peptide mimic binds to novobiocin (K-a = 1.4 +/- 0.3 x 10(5) m(-1)), plasmid (K-a = 1.6 +/- 0.5 x 10(6) m(-1)) and ATP (K-a = 1.9 f 0.4 x 10(3) m(-1)), results previously found with the intact B protein. on the other hand, the binding to novobiocin was reduced when a mutation of Arg-136 to Leu-136 was introduced, a change previously found in the DNA gyrase B protein from several coumarin-resistant clinical isolates of Escherichia coLi. In contrast, the binding to plasmid and to ATP was not altered. These results suggest that synthetic peptides designed in a similar way to that described here could be used as mimics of DNA gyrase in studies which seek a better understanding of the ATP, as well as coumarin, binding to the gyrase and also the mechanism of action of this class of antibacterial drugs. Copyright (C) 2004 European Peptide Society and John Wiley Sons, Ltd.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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We investigate theoretical and observational aspects of a time-dependent parameterization for the dark energy equation of state w(z), which is a well behaved function of the redshift z over the entire cosmological evolution, i.e., z is an element of [-1, infinity). By using a theoretical algorithm of constructing the quintes-sence potential directly from the w(z) function, we derive and discuss the general features of the resulting potential for the cases in which dark energy is separately conserved and when it is coupled to dark matter. Since the parameterization here discussed allows us to divide the parametric plane in defined regions associated to distinct classes of dark energy models, we use some of the most recent observations from type Ia supernovae, baryon acoustic oscillation peak and Cosmic Microwave Background shift parameter to check which class is observationally preferred. We show that the largest portion of the confidence contours lies into the region corresponding to a possible crossing of the so-called phantom divide line at some point of the cosmic evolution.
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CONTEXT: It is estimated that 3-30% of cases with isolated GH deficiency (IGHD) have a genetic etiology, with a number of mutations being reported in GH1 and GHRHR. The aim of our study was to genetically characterize a cohort of patients with congenital IGHD and analyze their characteristics. PATIENTS AND METHODS: A total of 224 patients (190 pedigrees) with IGHD and a eutopic posterior pituitary were screened for mutations in GH1 and GHRHR. To explore the possibility of an association of GH1 abnormalities with multiple pituitary hormone deficiencies, we have screened 62 patients with either multiple pituitary hormone deficiencies (42 pedigrees), or IGHD with an ectopic posterior pituitary (21 pedigrees). RESULTS: Mutations in GH1 and GHRHR were identified in 41 patients from 21 pedigrees (11.1%), with a higher prevalence in familial cases (38.6%). These included previously described and novel mutations in GH1 (C182X, G120V, R178H, IVS3+4nt, a>t) and GHRHR (W273S, R94L, R162W). Autosomal dominant, type II IGHD was the commonest form (52.4%), followed by type IB (42.8%) and type IA (4.8%). Patients with type II IGHD had highly variable phenotypes. There was no difference in the endocrinology or magnetic resonance imaging appearance between patients with and without mutations, although those with mutations presented with more significant growth failure (height, -4.7 +/- 1.6 SDS vs. -3.4 +/- 1.7 SDS) (P = 0.001). There was no apparent difference between patients with mutations in GH1 and GHRHR. CONCLUSIONS: IGHD patients with severe growth failure and a positive family history should be screened for genetic mutations; the evolving endocrinopathy observed in some of these patients suggests the need for long-term follow-up.
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OBJECTIVE To biomechanically test the properties of three different Universal Micro External Fixator (UMEX™) configurations with regard to their use in very small animals (<5kg) and compare the UMEX system to the widely used IMEX External Skeletal Fixation (SK™) system in terms of stiffness, space needed for pin placement and weight. METHODS Three different UMEX configurations (type Ia, type Ib, and type II modified) and one SK configuration type Ia were used to stabilize Delrin plastic rods in a 1 cm fracture gap model. These constructs were tested in axial compression, craniocaudal bending, mediolateral bending, and torsion. Testing was conducted within the elastic range and mean stiffness in each mode was determined from the slope of the linear portion of the load-deformation curve. A Kruskal Wallis one-way analysis of variance on ranks test was utilized to assess differences between constructs (p <0.05). RESULTS The UMEX type II modified configuration was significantly stiffer than the other UMEX configurations and the SK type Ia, except in craniocaudal bending, where the SK type Ia configuration was stiffer than all UMEX constructs. The UMEX type Ia configuration was significantly the weakest of those frames. The UMEX constructs were lighter and smaller than the SK, thus facilitating closer pin placement. CONCLUSIONS Results supported previous reports concerning the superiority of more complex constructs regarding stiffness. The UMEX system appears to be a valid alternative for the treatment of long-bone fractures in very small animals.
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Astronomical observations of luminosity distances derived from Type Ia supernovae, CMB spectrum and global matter distribution provide evidence of cosmic speed up of the Universe. Alternatively, cosmic acceleration might be due to an exotic fluid filling the Universe, known as dark energy. These have given rise to a collection of new cosmological evolutions, future singularites being the most perplexing ones (“big rip”, “sudden singularities”. . .).
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The GNAS1 gene encodes the α subunit of the guanine nucleotide-binding protein Gs, which couples signaling through peptide hormone receptors to cAMP generation. GNAS1 mutations underlie the hormone resistance syndrome pseudohypoparathyroidism type Ia (PHP-Ia), so the maternal inheritance displayed by PHP-Ia has raised suspicions that GNAS1 is imprinted. Despite this suggestion, in most tissues Gsα is biallelically encoded. In contrast, the large G protein XLαs, also encoded by GNAS1, is paternally derived. Because the inheritance of PHP-Ia predicts the existence of maternally, rather than paternally, expressed transcripts, we have investigated the allelic origin of other mRNAs derived from GNAS1. We find this gene to be remarkable in the complexity of its allele-specific regulation. Two upstream promoters, each associated with a large coding exon, lie only 11 kb apart, yet show opposite patterns of allele-specific methylation and monoallelic transcription. The more 5′ of these exons encodes the neuroendocrine secretory protein NESP55, which is expressed exclusively from the maternal allele. The NESP55 exon is 11 kb 5′ to the paternally expressed XLαs exon. The transcripts from these two promoters both splice onto GNAS1 exon 2, yet share no coding sequences. Despite their structural unrelatedness, the encoded proteins, of opposite allelic origin, both have been implicated in regulated secretion in neuroendocrine tissues. Remarkably, maternally (NESP55), paternally (XLαs), and biallelically (Gsα) derived proteins all are produced by different patterns of promoter use and alternative splicing of GNAS1, a gene showing simultaneous imprinting in both the paternal and maternal directions.
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Type Ia supernovae are thought to occur when a white dwarf made of carbon and oxygen accretes sufficient mass to trigger a thermonuclear explosion(1). The accretion could be slow, from an unevolved (main-sequence) or evolved (subgiant or giant) star(2,3) (the single-degenerate channel), or rapid, as the primary star breaks up a smaller orbiting white dwarf(3,4) (the double-degenerate channel). A companion star will survive the explosion only in the single-degenerate channel(5). Both channels might contribute to the production of type Ia supernovae(6,7), but the relative proportions of their contributions remain a fundamental puzzle in astronomy. Previous searches for remnant companions have revealed one possible case for SN 1572 (refs 8, 9), although that has been questioned(10). More recently, observations have restricted surviving companions to be small, main-sequence stars(11-13), ruling out giant companions but still allowing the single-degenerate channel. Here we report the results of a search for surviving companions of the progenitor of SN 1006 (ref. 14). None of the stars within 4 arc minutes of the apparent site of the explosion is associated with the supernova remnant, and we can firmly exclude all giant and subgiant stars from being companions of the progenitor. In combination with previous results, our findings indicate that fewer than 20 per cent of type Ia supernovae occur through the single-degenerate channel.