906 resultados para Keyed One-Way Functions
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Os projetos são atualmente parte indispensável das organizações. O campo de gerenciamento de projetos vem ganhando importância e as organizações buscam meios de garantir que seus projetos sejam mais eficazes e eficientes gerando retorno. Dentro deste contexto, o escritório de projetos surge como um meio de alavancar a gestão de projetos dentro das organizações. Na administração pública os escritórios ainda são vistos como um caminho para fazer a transição de um modelo de gestão voltado para processos para outro voltado para resultados. A literatura destaca suas inúmeras qualidades, entretanto estudos mostram que as pessoas ainda não tem clareza do valor gerado pelos escritórios. Desta forma, esta pesquisa buscou verificar quais são os benefícios percebidos de escritórios de gerenciamento de projetos da administração pública e também qual a sua aceitação dentro da organização. A pesquisa foi conduzida através de um estudo de casos múltiplos onde as entrevistas realizadas foram tratadas por meio de uma análise de conteúdo estruturalista que resultou numa estrutura que relaciona os benefícios dos escritórios de projetos a sua aceitação. A estrutura mostra como fatores organizacionais levam a uma resistência e baixa aceitação ao escritório de projetos e as suas funções. Ao mesmo tempo, as funções geram os benefícios que são responsáveis por legitimar os escritórios e aumentar a sua aceitação. O cenário colocado é fundamental para compreender o tempo necessário para que o escritório possa agregar valor à organização.
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Objective: the objectives were to analyze the cardiac effects of exposure to tobacco smoke (ETS), for a period of 30 days, alone and in combination with beta-carotene supplementation (BC). Research methods and procedures: Rats were allocated into: Air (control, n = 13); Air + BC (n = 11); ETS (n = 11); and BC + ETS (n = 9). In Air + BC and BC + ETS, 500 mg of BC were added to the diet. After three months of randomization, cardiac structure and function were assessed by echocardiogram. After that, animals were euthanized and morphological data were analyzed post-morten. One-way and two-way ANOVA were used to assess the effects of ETS, BC and the interaction between ETS and BC on the variables. Results: ETS presented smaller cardiac output (0.087 +/- 0.001 vs. 0.105 +/- 0.004 l/min; p = 0.007), higher left ventricular diastolic diameter (19.6 +/- 0.5 vs. 18.0 +/- 0.5 mm/kg; p = 0.024), higher left ventricular (2.02 +/- 0.05 vs. 1.70 +/- 0.03 g/kg; p < 0.001) and atrium (0.24 +/- 0.01 vs. 0.19 +/- 0.01 g/kg; p = 0.003) weight, adjusted to body weight of animals, and higher values of hepatic lipid hydroperoxide (5.32 +/- 0.1 vs. 4.84 +/- 0.1 nmol/g tissue; p = 0.031) than Air. However, considering those variables, there were no differences between Air and BC + ETS (0.099 +/- 0.004 l/min; 19.0 +/- 0.5 mm/kg; 1.83 +/- 0.04 g/kg; 0.19 +/- 0.01 g/kg; 4.88 +/- 0.1 nmol/g tissue, respectively; p > 0.05). Ultrastructural alterations were found in ETS: disorganization or loss of myofilaments, plasmatic membrane infolding, sarcoplasm reticulum dilatation, polymorphic mitochondria with swelling and decreased cristae. In BC + ETS, most fibers showed normal morphological aspects. Conclusion: One-month tobacco-smoke exposure induces functional and morphological cardiac alterations and BC supplementation attenuates this ventricular remodeling process.
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Aim: Based on the hypothesis the application of a low-viscosity hydrophobic resin coating improves the bond of all-in-one adhesive, the purpose of the study was to evaluate the bond strength of four adhesive systems to bovine root dentin using the push-out test method. Methods and Materials: The root canals of 32 bovine roots (16 mm) were prepared to a length of 12 mm using a FRC Postec Plus preparation drill. The specimens were allocated into four groups according to the adhesive system used: (Group 1) All-in-one Xeno III; (Group 2) All-in-one Xeno III+ScotchBond Multi-Purpose Plus Adhesive; (Group 3) Simplified Etch & Rinse One Step Plus; and (Group 4) Multi-Bottle Etch & Rinse All-Bond 2. A fiber-reinforced composite retention post was reproduced using an additional silicon impression and fabricated with DuoLink resin cement. The root specimens were treated with the selected adhesive systems, and the resin posts were luted in the canals with DuoLink resin cement. Each root specimen was cross sectioned into four samples (±1.8 mm in thickness), and the post sections were pushed-out to determine the bond strength to dentin. Results: Group 2 (2.9±1.2) was statistically higher than Group 1 (1.1±0.5) and Group 3 (1.1±0.5). Groups 1 and 3 showed no statistically significant difference while Group 4 (2.0±0.7) presented similar values (p>0.05) to Groups 1, 2, and 3 [(one-way analysis of variance (ANOVA)] and Tukey test, α=0.05). Conclusion: The hypothesis was accepted since the application of the additional layer of a low-viscosity bonding resin improved the bond of the all-in-one adhesive. Further studies must be conducted to evaluate the long-term bond.
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Low-grade chronic systemic inflammation is often associated with chronic non-communicable diseases, and its most frequently used marker, the C-reactive protein (CRP), has become an identifier of such diseases as well as an independent predictor for cardiovascular disorders and mortality. CRP is produced in response to pro-inflammatory signaling and to individual and behavioral factors, leading to pathological states. The aim of this study was to rank the predicting factors of high CRP concentrations in free-living adults from a community-based sample. We evaluated 522 adults (40-84 years old; 381 women) for anthropometric characteristics, dietary intake, clinical and physical tests, and blood analysis. Subjects were assigned to groups, according to CRP concentrations, as normal CRP (G1;<3.0 mg/L; n = 269), high CRP (G2; 3.0-6.0 mg/L; n = 139), and very high CRP (G3; >6.0 mg/dL; n = 116). Statistical comparison between groups used one-way ANOVA or Kruskal-Wallis tests, and prediction of altered values in increasing CRP was evaluated by proportional hazard models (odds ratio). CRP distribution was influenced by gender, body mass index, body and abdominal fatness, blood leukocytes, and neutrophil counts. The higher CRP group was discriminated by the above variables in addition to lower VO2max, serum metabolic syndrome components (triglycerides, glucose, and HDL cholesterol), higher insulin, homeostasis assessment of insulin resistance, uric acid, gamma-GT, and homocysteine. After adjustments, only fatness, blood leukocytes, and hyperglycemia remained as independent predictors for increased serum CRP concentrations. Intervention procedures to treat low-grade chronic inflammation in overweight women would mainly focus on restoring muscle mass and functions in addition to an antioxidant-rich diet. © 2012 Springer Science+Business Media, LLC.
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Brain insulin has had widespread metabolic, neurotrophic, and neuromodulatory functions and has been involved in the central regulation of food intake and body weight, learning and memory, neuronal development, and neuronal apoptosis. Purpose: The present study investigated the role of swimming training on cerebral metabolism on insulin concentrations in cerebellum and the body balance performance of diabetic rats. Methods: Forty Male Wistar rats were divided in four groups: sedentary control (SC), trained control (TC), sedentary diabetic (SD), and trained diabetic (TD). Diabetes was induced by alloxan (32 mg kg b.w.), single dose injection. The mean blood glucose of diabetic groups was 367 ± 40 mg/dl. Training program consisted in swimming 5 days/week, 1 h/day, 8 weeks, supporting a workload corresponding to 90% of maximal lactate steady state (MLSS). For the body balance testing rats were trained to traverse for 5 min daily for 5-7 days. All dependent variables were analyzed by one-way analysis of variance (ANOVA) and a significance level of p < 0.05 was used for all comparisons. Results: The body balance testing scores were different between groups. Insulin concentrations in cerebellum were not different between groups. Conclusion: It was concluded that in diabetic rats, aerobic training does not induce alterations on cerebellum insulin but induces important metabolic, hormonal and behavioral alterations which are associated with an improvement in glucose homeostasis, serum insulin concentrations and body balance. © 2013 Elsevier Inc.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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Background: A current challenge in gene annotation is to define the gene function in the context of the network of relationships instead of using single genes. The inference of gene networks (GNs) has emerged as an approach to better understand the biology of the system and to study how several components of this network interact with each other and keep their functions stable. However, in general there is no sufficient data to accurately recover the GNs from their expression levels leading to the curse of dimensionality, in which the number of variables is higher than samples. One way to mitigate this problem is to integrate biological data instead of using only the expression profiles in the inference process. Nowadays, the use of several biological information in inference methods had a significant increase in order to better recover the connections between genes and reduce the false positives. What makes this strategy so interesting is the possibility of confirming the known connections through the included biological data, and the possibility of discovering new relationships between genes when observed the expression data. Although several works in data integration have increased the performance of the network inference methods, the real contribution of adding each type of biological information in the obtained improvement is not clear. Methods: We propose a methodology to include biological information into an inference algorithm in order to assess its prediction gain by using biological information and expression profile together. We also evaluated and compared the gain of adding four types of biological information: (a) protein-protein interaction, (b) Rosetta stone fusion proteins, (c) KEGG and (d) KEGG+GO. Results and conclusions: This work presents a first comparison of the gain in the use of prior biological information in the inference of GNs by considering the eukaryote (P. falciparum) organism. Our results indicates that information based on direct interaction can produce a higher improvement in the gain than data about a less specific relationship as GO or KEGG. Also, as expected, the results show that the use of biological information is a very important approach for the improvement of the inference. We also compared the gain in the inference of the global network and only the hubs. The results indicates that the use of biological information can improve the identification of the most connected proteins.
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Brain functions, such as learning, orchestrating locomotion, memory recall, and processing information, all require glucose as a source of energy. During these functions, the glucose concentration decreases as the glucose is being consumed by brain cells. By measuring this drop in concentration, it is possible to determine which parts of the brain are used during specific functions and consequently, how much energy the brain requires to complete the function. One way to measure in vivo brain glucose levels is with a microdialysis probe. The drawback of this analytical procedure, as with many steadystate fluid flow systems, is that the probe fluid will not reach equilibrium with the brain fluid. Therefore, brain concentration is inferred by taking samples at multiple inlet glucose concentrations and finding a point of convergence. The goal of this thesis is to create a three-dimensional, time-dependent, finite element representation of the brainprobe system in COMSOL 4.2 that describes the diffusion and convection of glucose. Once validated with experimental results, this model can then be used to test parameters that experiments cannot access. When simulations were run using published values for physical constants (i.e. diffusivities, density and viscosity), the resulting glucose model concentrations were within the error of the experimental data. This verifies that the model is an accurate representation of the physical system. In addition to accurately describing the experimental brain-probe system, the model I created is able to show the validity of zero-net-flux for a given experiment. A useful discovery is that the slope of the zero-net-flux line is dependent on perfusate flow rate and diffusion coefficients, but it is independent of brain glucose concentrations. The model was simplified with the realization that the perfusate is at thermal equilibrium with the brain throughout the active region of the probe. This allowed for the assumption that all model parameters are temperature independent. The time to steady-state for the probe is approximately one minute. However, the signal degrades in the exit tubing due to Taylor dispersion, on the order of two minutes for two meters of tubing. Given an analytical instrument requiring a five μL aliquot, the smallest brain process measurable for this system is 13 minutes.
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The development of the brain and its underlying circuitry is dependent on the formation of trillions of chemical synapses, which are highly specialized contacts that regulate the flow of information from one neuron to the next. It is through these synaptic connections that neurons wire together into networks capable of performing specific tasks, and activity-dependent changes in their structural and physiological state is one way that the brain is thought to adapt and store information. At the ultrastructural level, developmental and activity-dependent changes in the size and shape of dendritic spines have been well documented, and it is widely believed that structural changes in spines are a hallmark sign of synapse maturation and alteration of synaptic physiology. While changes in spine structure have been studied extensively, changes in one of its most prominent components, the postsynaptic density (PSD), have largely evaded observation. The PSD is a protein-rich organelle on the cytoplasmic side of the postsynaptic membrane, where it sits in direct opposition to the presynaptic terminal. The PSD functions both to cluster neurotransmitter receptors at the cell surface as well as organize the intracellular signaling molecules responsible for transducing extracellular signals to the postsynaptic cell. Much is known about the chemical composition of the PSD, but the structural arrangement of its molecular components is not well documented. Adding to the difficulty of understanding such a complex mass of protein machinery is the fact that its protein composition is known to change in response to synaptic activity, meaning that its structure is plastic and no two PSDs are identical. Here, immuno-gold labeling and electron tomography of PSDs isolated throughout development was used to track changes in both the structure and molecular composition of the PSD. State-of-the-art cryo-electron tomography was used to study the fine structure of the PSD during development, and provides an unprecedented glimpse into its molecular architecture in an un-fixed, unstained and hydrated state. Through this analysis, large structural and compositional changes are apparent and suggest a model by which the PSD is first assembled as a mesh-like lattice of proteins that function as support for the later recruitment of various PSD components. Spatial analysis of the recruitment of proteins into the PSD demonstrated that its assembly has an underlying order.
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The rates of childhood and adolescent obesity in the United States have been increasing steadily. American youth continue to eat more (increase energy intake) and reduce physical activity (decrease energy expenditure) resulting in increased body weight and body fatness. One way to help reduce body weight in children is to increase physical activity. The purpose of this study was to determine if an age appropriate before-school physical activity intervention would be successful in increasing energy expenditure, intensity of activity, and behavioral approaches in overweight girls. The subjects were recruited from Parker Memorial School in Tolland, Connecticut, and two testing periods occurred over an eight week period. Video recordings of each physical activity session were analyzed to determine energy expenditure, exercise intensity, and behaviors during exercise. Data was evaluated for normal distribution, and paired t-tests were used to determine statistical significance. This study showed that the age appropriate before school physical activity intervention was able to increase energy expenditure and exercise intensity and have a positive effect on behavioral approaches in overweight girls.
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The corepressor complex Tup1-Ssn6 regulates many classes of genes in yeast including cell type specific, glucose repressible, and DNA damage inducible. Tup1 and Ssn6 are recruited to target promoters through their interactions with specific DNA binding proteins such as α2, Mig1, and Crt1. Most promoters that are repressed by this corepressor complex exhibit a high degree of nucleosomal organization. This chromatin domain occludes transcription factor access to the promoter element resulting in gene repression. Previous work indicated that Tup1 interacts with underacetylated isoforms of H3 and H4, and that mutation of these histones synergistically compromises repression. These studies predict that Tup1-hypoacetyalted histone interaction is important to the repression mechanism, and in vivo hyperacetylation might compromise the corepressors ability to repress target genes. ^ One way to alter histone acetylation levels in vivo is to alter the balance between histone acetyltransferases and histone deacetylases. To date five histone deacetylases (HDACs) have been identified in yeast Rpd3, Hos1, Hos2, Hos3 and Hda1. Deletion of single or double HDAC genes had little to no effect on Tup1-Ssn6 repression, but simultaneous deletion of three specific activities Rpd3, Hos1, and Hos2 abolished repression in vivo. Promoter regions of Tup1-Ssn6 target genes in these triple deacetylase mutant cells are dramatically hyperacetylated in both H3 and H4. Examination of bulk histone acetylation levels showed that this specific HDAC triple mutant combination (rpd3 hos1 hos2) caused a dramatic and concomitant hyperacetylation of both H3 and H4. The loss of repression in the rpd3 hos1 hos2 cells, but not in other mutants, is consistent with previous observations, which indicate that histones provide redundant functions in the repression mechanism and that high levels of acetylation are required to prevent Tup1 binding. Investigation into a potential direct interaction between the Tup1-Ssn6 corepressor complex and one or more HDAC activities showed that both Rpd3 and Hos2 interact with the corepressor complex in vivo. These findings indicate that Tup1-Ssn6 repression involves the recruitment of histone deacetylase activities to target promoters, where they locally deacetylate histone residues promoting Tup1-histone tail interaction to initiate and/or maintain the repressed state. ^
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The cytochrome P450 4F subfamily comprises a group of enzymes that metabolize derivatives of arachidonic acid such as prostaglandins, lipoxins leukotrienes and hydroxyeicosatetraenoic acids, which are important mediators involved in the inflammatory response. Therefore, we speculate that CYP4Fs might be able to modulate the extent of the inflammation by controlling of the tissue levels of these inflammatory mediators, especially, leukotriene B4. One way to provide support for this hypothesis is to test whether the expression of CYP4Fs changes under inflammatory conditions, since these changes are required to adjust the levels of inflammatory mediators. ^ A lipopolysacchride (LPS) induced rat inflammation model was used to analyze the expressions of rat CYP4F4 and CYP4F5 in liver and kidney. LPS administration did not change the constitutive expression level of CYP4F4 and CYP4F5. In liver, the expressions of CYP4F4 and CYP4F5 decreased to 50–60% of the untreated level. The same effect of LPS on CYP4F4 and CYP4F5 expression can be mimicked in hepatocyte primary cultures treated with LPS, indicating a direct of effect of LPS on hepatocytes. LPS treatment also decreased the activity of liver microsomes towards chlorpromazine, however, antibody inhibition study revealed that liver CYP4Fs are not the only players in metabolizing chlorpromazine. To study further the underlying mechanism, CYP4F5 gene was isolated, characterized, and the promoter region was defined. ^ Accumulating evidence showed that peroxisome proliferator-activated receptors (PPARs) play an active role in inflammation. To investigate the possible role of PPARα in regulating CYP4F expression by inflammation or by clofibrate treatment, the expressions of two new mouse 4F isoforms were analyzed in PPARα knockout mice upon LPS or clofibrate challenge. A novel induction of CYP4F15 by LPS and clofibrate was observed in kidney, and this effect is totally dependent on the presence of PPARα. Renal CYP4F16 expression was not affected by LPS or clofibrate in both (+/+) and (−/−) mice. In contrast, hepatic expressions of CYP4F15 and CYP4F16 were reduced significantly in (+/+) mice, but much less in (−/−) mice, suggesting that PPARα is partially responsible for this down-regulation. Clofibrate treatment reduced the expression of CYP4F16 in liver, but has no effect on CYP4F15 and PPARα does not have a role in hepatic CYP4F expression regulated by clofibrate. In general, CYP4Fs are regulated in an isoform-, tissue- and species-specific manner. ^ A human CYP4F isoform, CYP4F11, was isolated. The genomic structure was also solved by using database mining and bioinformatics tools. Localization of CYP4F11 to chromosome 19, 16 kb upstream of CYP4F2, suggests that human CYP4F genes may form a cluster on chromosome 19. This novel human 4F is highly expressed in liver, as well as in kidney, heart and skeletal muscle. Further study of the activity and gene regulation on CYP4F11 will provide us more insights into the physiological functions of CYP4F subfamily. ^
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One way developing embryos regulate the expression of their genes is by localizing mRNAs to specific subcellular regions. In the oocyte of the frog, Xenopus laevis, many RNAs are localized specifically to the animal or the vegetal halves of the oocyte. The localization of these RNAs contributes to the primary polarity of the oocyte, the asymmetry that is the basis for patterning and lineage specification in the embryo. I have screened a cDNA library for clones containing the Xlsirt repeat, an element known to target RNAs to the vegetal cortex of the oocyte. I have identified seventeen cDNA clones that contain this element. One of these cDNAs encodes the RNA binding protein Hermes. The Hermes mRNA is localized to the vegetal cortex of the oocyte. Additionally, Hermes protein is also vegetally localized in the oocyte and is found in subcellular structures known to contain localized mRNAs. This suggests that Hermes might interact with localized RNAs. While Hermes protein is present in oocytes, it disappears at germinal vesicle breakdown during maturation. We therefore believe that the time period during which Hermes functions is during oogenesis or maturation prior to the time of Hermes degradation. To determine Hermes function, an antisense depletion strategy was used that involved injecting morpholino oligos (HE-MO) into oocytes. Injection of these morpholinos causes the level of Hennes protein to drop prematurely during maturation. Embryos produced from these oocytes exhibit cleavage defects that are most prevalent in the vegetal blastomeres. The phenotype can be partially rescued by injection of a heterologous Hermes mRNA and is therefore specific to Hermes. The Hermes expression and depletion results are consistent with a model in which Hermes interacts with one or more vegetally localized mRNAs in the oocyte and during the early stages of maturation. The interaction is required for cleavage of the vegetal blastomeres. Therefore, it is likely that at least one mRNA that interacts with Hermes is a cell cycle regulator. ^