790 research outputs found

    Contribuição de estirpes de rizóbio para o desenvolvimento e produtividade de grãos de feijão-caupi em Roraima.

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    O estudo objetivou avaliar a contribuição da fixação biológica de nitrogênio (FBN) promovida por estirpes de rizóbio para o desenvolvimento e rendimento de grãos do feijão-caupi em Roraima. Nos anos de 2005 e 2006 foram conduzidos experimentos em área de cerrado e mata alterada, onde foram testadas as estirpes INPA 03-11B, UFLA 3-84, BR3267 (recomendadas à cultura), a estirpe BR3299 e BR3262, duas doses de nitrogênio mineral (50 e 80 kg ha-1 de N) e um controle. As variáveis avaliadas foram: nodulação e produção de massa seca da parte aérea de plantas de feijão-caupi e, o rendimento de grãos na colheita. Na média geral, foi observado que a estirpe BR3262 proporcionou número e massa de nódulos significativamente maiores ao controle, ao passo que entre as estirpes recomendadas, isto só ocorreu de forma esporádica com INPA 03-11B e BR3267. Além disso, também foi observado que a população de rizóbio do solo foi determinante à nodulação das plantas dos experimentos. Comparativamente as demais estirpes, BR3262 juntamente com BR3267, proporcionaram maior efetividade na FBN à produção de massa seca da parte aérea. Em relação à produtividade de grãos, as estirpes BR3267 e INPA 03-11B apresentaram melhores resultadas comparadas a UFLA 3-84, entretanto, apenas a estirpe BR3262 proporcionou rendimento de grãos (na média geral cerca de 1700 kg ha-1) igual à dose de 50 kg ha-1 de N e superior ao controle em três dos quatro experimentos conduzidos, mostrando ser a mais indicada para a inoculação do feijão-caupi em Roraima

    Population pharmacokinetic study of benznidazole in pediatric chagas disease suggests efficacy despite lower plasma concentrations than in adults

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    Introduction: Chagas disease, caused by the parasite Trypanosoma cruzi, can lead to long term cardiac morbidity. Treatment of children with benznidazole is effective, but no pediatric pharmacokinetics data are available and clinical pharmacology information on the drug is scarce. Patients and Methods: Prospective population pharmacokinetic (PK) cohort study in children 2-12 years old with Chagas disease treated with oral benznidazole 5-8 mg/kg/day BID for 60 days. (clinicaltrials.gov #NCT00699387). Results: Forty children were enrolled in the study. Mean age was 7.3 years. A total of 117 samples were obtained from 38 patients for PK analysis. A one compartment model best fit the data. Weight-corrected clearance rate (CL/F) showed a good correlation with age, with younger patients having a significantly higher CL/F than older children and adults. Simulated median steady-state benznidazole concentrations, based on model parameters, were lower for children in our study than for adults and lowest for children under 7 years of age. Treatment was efficacious in the 37 patients who completed the treatment course, and well tolerated, with few, and mild, adverse drug reactions (ADRs). Discussion: Observed benznidazole plasma concentrations in children were markedly lower than those previously reported in adults (treated with comparable mg/kg doses), possibly due to a higher CL/F in smaller children. These lower blood concentrations were nevertheless associated to a high therapeutic response in our cohort. Unlike adults, children have few adverse reactions to the drug, suggesting that there may be a direct correlation between drug concentrations and incidence of ADRs. Our results suggest that studies with lower doses in adults may be warranted. Trial Registration: ClinicalTrails.gov NCT00699387.Facultad de Ciencias Exacta

    A locally quadratic Glimm functional and sharp convergence rate of the Glimm scheme for nonlinear hyperbolic systems

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    Consider the Cauchy problem for a strictly hyperbolic, N×NN\times N quasilinear system in one space dimension u_t+A(u) u_x=0,\qquad u(0,x)=\bar u(x), \eqno (1) where uA(u)u \mapsto A(u) is a smooth matrix-valued map, and the initial data u\overline u is assumed to have small total variation. We investigate the rate of convergence of approximate solutions of (1) constructed by the Glimm scheme, under the assumption that, letting λk(u)\lambda_k(u), rk(u)r_k(u) denote the kk-th eigenvalue and a corresponding eigenvector of A(u)A(u), respectively, for each kk-th characteristic family the linearly degenerate manifold Mk{uΩ:λk(u)rk(u)=0} \mathcal{M}_k \doteq \big\{u\in\Omega : \nabla\lambda_k(u)\cdot r_k(u)=0\big\} is either the whole space, or it is empty, or it consists of a finite number of smooth, N1N-1-dimensional, connected, manifolds that are transversal to the characteristic vector field rkr_k. We introduce a Glimm type functional which is the sum of the cubic interaction potential defined in \cite{sie}, and of a quadratic term that takes into account interactions of waves of the same family with strength smaller than some fixed threshold parameter. Relying on an adapted wave tracing method, and on the decrease amount of such a functional, we obtain the same type of error estimates valid for Glimm approximate solutions of hyperbolic systems satisfying the classical Lax assumptions of genuine nonlinearity or linear degeneracy of the characteristic families.Comment: To appear on Archive for Rational Mechanics and Analysi

    The CD28-Transmembrane Domain Mediates Chimeric Antigen Receptor Heterodimerization With CD28.

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    Anti-CD19 chimeric antigen receptor (CD19-CAR)-engineered T cells are approved therapeutics for malignancies. The impact of the hinge domain (HD) and the transmembrane domain (TMD) between the extracellular antigen-targeting CARs and the intracellular signaling modalities of CARs has not been systemically studied. In this study, a series of 19-CARs differing only by their HD (CD8, CD28, or IgG <sub>4</sub> ) and TMD (CD8 or CD28) was generated. CARs containing a CD28-TMD, but not a CD8-TMD, formed heterodimers with the endogenous CD28 in human T cells, as shown by co-immunoprecipitation and CAR-dependent proliferation of anti-CD28 stimulation. This dimerization was dependent on polar amino acids in the CD28-TMD and was more efficient with CARs containing CD28 or CD8 HD than IgG <sub>4</sub> -HD. The CD28-CAR heterodimers did not respond to CD80 and CD86 stimulation but had a significantly reduced CD28 cell-surface expression. These data unveiled a fundamental difference between CD28-TMD and CD8-TMD and indicated that CD28-TMD can modulate CAR T-cell activities by engaging endogenous partners

    An Overview of the 2014 ALMA Long Baseline Campaign

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    A major goal of the Atacama Large Millimeter/submillimeter Array (ALMA) is to make accurate images with resolutions of tens of milliarcseconds, which at submillimeter (submm) wavelengths requires baselines up to ~15 km. To develop and test this capability, a Long Baseline Campaign (LBC) was carried out from September to late November 2014, culminating in end-to-end observations, calibrations, and imaging of selected Science Verification (SV) targets. This paper presents an overview of the campaign and its main results, including an investigation of the short-term coherence properties and systematic phase errors over the long baselines at the ALMA site, a summary of the SV targets and observations, and recommendations for science observing strategies at long baselines. Deep ALMA images of the quasar 3C138 at 97 and 241 GHz are also compared to VLA 43 GHz results, demonstrating an agreement at a level of a few percent. As a result of the extensive program of LBC testing, the highly successful SV imaging at long baselines achieved angular resolutions as fine as 19 mas at ~350 GHz. Observing with ALMA on baselines of up to 15 km is now possible, and opens up new parameter space for submm astronomy.Comment: 11 pages, 7 figures, 2 tables; accepted for publication in the Astrophysical Journal Letters; this version with small changes to affiliation

    Features of mammalian microRNA promoters emerge from polymerase II chromatin immunoprecipitation data

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    Background: MicroRNAs (miRNAs) are short, non-coding RNA regulators of protein coding genes. miRNAs play a very important role in diverse biological processes and various diseases. Many algorithms are able to predict miRNA genes and their targets, but their transcription regulation is still under investigation. It is generally believed that intragenic miRNAs (located in introns or exons of protein coding genes) are co-transcribed with their host genes and most intergenic miRNAs transcribed from their own RNA polymerase II (Pol II) promoter. However, the length of the primary transcripts and promoter organization is currently unknown. Methodology: We performed Pol II chromatin immunoprecipitation (ChIP)-chip using a custom array surrounding regions of known miRNA genes. To identify the true core transcription start sites of the miRNA genes we developed a new tool (CPPP). We showed that miRNA genes can be transcribed from promoters located several kilobases away and that their promoters share the same general features as those of protein coding genes. Finally, we found evidence that as many as 26% of the intragenic miRNAs may be transcribed from their own unique promoters. Conclusion: miRNA promoters have similar features to those of protein coding genes, but miRNA transcript organization is more complex. © 2009 Corcoran et al

    miRNA Regulatory Circuits in ES Cells Differentiation: A Chemical Kinetics Modeling Approach

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    MicroRNAs (miRNAs) play an important role in gene regulation for Embryonic Stem cells (ES cells), where they either down-regulate target mRNA genes by degradation or repress protein expression of these mRNA genes by inhibiting translation. Well known tables TargetScan and miRanda may predict quite long lists of potential miRNAs inhibitors for each mRNA gene, and one of our goals was to strongly narrow down the list of mRNA targets potentially repressed by a known large list of 400 miRNAs. Our paper focuses on algorithmic analysis of ES cells microarray data to reliably detect repressive interactions between miRNAs and mRNAs. We model, by chemical kinetics equations, the interaction architectures implementing the two basic silencing processes of miRNAs, namely “direct degradation” or “translation inhibition” of targeted mRNAs. For each pair (M,G) of potentially interacting miRMA gene M and mRNA gene G, we parameterize our associated kinetic equations by optimizing their fit with microarray data. When this fit is high enough, we validate the pair (M,G) as a highly probable repressive interaction. This approach leads to the computation of a highly selective and drastically reduced list of repressive pairs (M,G) involved in ES cells differentiation

    Intramolecular additions of various π-nucleophiles to chemoselectively activated amides and application to the synthesis of (±)-tashiromine

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    Abstract: Vilsmeier-Haack type cyclizations proved to be particularly efficient for generating parts of the polycyclic cores of many alkaloids, although only monocyclizations have so far been reported. With the goal of rapidly and efficiently constructing polycyclic alkaloids, we decided to exploit the Vilsmeier-Haack reaction by utilizing iminium ions successively generated and trapped with tethered nucleophiles. To develop such a strategy, we had to set the first cyclization. This constitutes a great challenge in itself because amide activation conditions are usually not compatible with tethered nucleophiles, except for indoles and aromatic rings which have already been reported. This paper describes the comprehensive study of intramolecular addition of silyl enol ethers, allylsilanes, and enamines to chemoselectively activated formamides, aliphatic amides, and lactams. Good to excellent yields were obtained for the 5-exo, 6-exo, and 6-endo modes of cyclization. Moreover, we demonstrated that the species in solution after the cyclization are iminium ions. This is highly encouraging for the development of bis-cyclization strategies. An expeditious total synthesis of (()-tashiromine is also reported
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