981 resultados para kappa statistic
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Pós-graduação em Engenharia Elétrica - FEIS
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
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Caseins are the major milk proteins associated with lactation performance, milk composition and cheese yield efficiency, representing around 80% of the total amount of proteins found in milk. Among the caseins, kappa-casein is the protein that stabilizes micelle structure during milk coagulation process and being used during the cheese production. The kappa-casein gene (CSN3) has been previously mapped to buffalo chromosome 7 using a radiation hybrid panel and a comparative map was established using the sequence from bovine chromosome 6. The molecular structure of this gene has also been established in river buffalo, with a total length of 13,191 bp (GenBank: AM900443.1) and containing five exons. In this study we searched for single nucleotide variations in specific regions of the CSN3 gene in three animals representing the Murrah breed. Sequencing reactions were performed using ABI3730xl sequencer. The primer walking method was used to span the 5'-UTR and intron 2 regions of the gene, for which ten primer pairs were designed using Oligo 6 software. BLAST tool was used to verify the primers specificity. DNA sequences assemblies from all three animals were performed with Sequencher (R) software 4.1, while multiple alignments were performed using Clustal W software to identify single nucleotide variations. The sequencing revealed a total of 19 single nucleotide variations with 13 located in the upstream regulatory region of the gene (5'-UTR) and six on intron 2. These variations can be validated using commercial populations segregating specific economic traits.
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We present an implementation of the F-statistic to carry out the first search in data from the Virgo laser interferometric gravitational wave detector for periodic gravitational waves from a priori unknown, isolated rotating neutron stars. We searched a frequency f(0) range from 100 Hz to 1 kHz and the frequency dependent spindown f(1) range from -1.6(f(0)/100 Hz) x 10(-9) Hz s(-1) to zero. A large part of this frequency-spindown space was unexplored by any of the all-sky searches published so far. Our method consisted of a coherent search over two-day periods using the F-statistic, followed by a search for coincidences among the candidates from the two-day segments. We have introduced a number of novel techniques and algorithms that allow the use of the fast Fourier transform (FFT) algorithm in the coherent part of the search resulting in a fifty-fold speed-up in computation of the F-statistic with respect to the algorithm used in the other pipelines. No significant gravitational wave signal was found. The sensitivity of the search was estimated by injecting signals into the data. In the most sensitive parts of the detector band more than 90% of signals would have been detected with dimensionless gravitational-wave amplitude greater than 5 x 10(-24).
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The new market, focused on sustainability and other environmental concerns, refers to innovations that seek alternative forms of production. In pulp and paper bleaching alternative reagents are studied, for example, hydrogen peroxide, in partial substitution of chlorine dioxide in order to reduce the formation of organochlorines. In this context, this study examined the burden of hydrogen peroxide (H2O2) on alkaline extraction stage (stage Ep) required for the bleaching of pulp with eucalyptus kraft pulp, pre-oxygen delignified to obtain equivalent brightness at 90 ± 0.5% ISO, as well as its effect on quality of pulp produced. The pulp was bleached by the sequence D(Ep)DP, with the application of factor kappa of 0.14 and varying the concentration of hydrogen peroxide in Ep stage three, five, seven and nine kilograms of reagent per ton of pulp absolutely drought. The final P stage was optimized with the use of six, nine and twelve pounds of hydrogen peroxide per ton of absolutely dry pulp to achieve the required brightness. The quality of the pulp produced was analyzed based on the kappa number, the brightness and the viscosity. The methods were performed according to standards set by the standard TAPPI (Technical Association of the Pulp and Paper Industry). The best result was obtained using the following D0Ep(7)D1P(6), which showed a viscosity of 19.9 cP, 89.6% ISO brightness, consumption of 94.9 kg / t of reagents and reagent costs of US$ 28.15, because it showed better pulp quality for a lower cost compared to the others. It was found that the greater the amount of hydrogen peroxide in alkaline extraction, the lower the kappa number and increased the amount of residual hydrogen peroxide. The higher the charge of hydrogen peroxide in Ep stage, the lower the need for hydrogen peroxide in the final P stage, reducing the cost of bleaching
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Osteosarcoma (OS) is the most common primary malignant bone tumor, usually developing in children and adolescents, and is highly invasive and metastatic, potentially developing chemoresistance. Thus, novel effective treatment regimens are urgently needed. This study was the first to investigate the anticancer effects of dehydroxymethylepoxyquinomicin (DHMEQ), a highly specific nuclear factor-kappa B (NF-kappa B) inhibitor, on the OS cell lines HOS and MG-63. We demonstrate that NF-kappa B blockade by DHMEQ inhibits proliferation, decreases the mitotic index, and triggers apoptosis of OS cells. We examined the effects of combination treatment with DHMEQ and cisplatin, doxorubicin, or methotrexate, drugs commonly used in OS treatment. Using the median effect method of Chou and Talalay, we evaluated the combination indices for simultaneous and sequential treatment schedules. In all cases, combination with a chemotherapeutic drug produced a synergistic effect, even at low single-agent cytotoxic levels. When cells were treated with DHMEQ and cisplatin, a more synergistic effect was obtained using simultaneous treatment. For the doxorubicin and methotrexate combination, a more synergistic effect was achieved with sequential treatment using DHMEQ before chemotherapy. These synergistic effects were accompanied by enhancement of chemoinduced apoptosis. Interestingly, the highest apoptotic effect was reached with sequential exposure in both cell lines, independent of the chemotherapeutic agent used. Likewise, DHMEQ decreased cell invasion and migration, crucial steps for tumor progression. Our data suggest that combining DHMEQ with chemotherapeutic drugs might be useful for planning new therapeutic strategies for OS treatment, mainly in resistant and metastatic cases. Anti-Cancer Drugs 23:638-650 (C) 2012 Wolters Kluwer Health broken vertical bar Lippincott Williams & Wilkins.
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It has been shown that ouabain (OUA) can activate the Na,K-ATPase complex and mediate intracellular signaling in the central nervous system (CNS). Inflammatory stimulus increases glutamatergic transmission, especially at N-methyl-D-aspartate (NMDA) receptors, which are usually coupled to the activation of nitric oxide synthase (NOS). Nuclear factor-kappa B (NF-kappa B) activation modulates the expression of genes involved in development, plasticity, and inflammation. The present work investigated the effects of OUA on NF-kappa B binding activity in rat hippocampus and the influence of this OUA-Na,K-ATPase signaling cascade in NMDA-mediated NF-kappa B activation. The findings presented here are the first report indicating that intrahippocampal administration of OUA, in a concentration that did not alter Na,K-ATPase or NOS activity, induced an activation of NF-kappa B, leading to increases in brain-derived neurotrophic factor (Bdnf), inducible NOS (iNos), tumor necrosis factor-alpha (Tnf-alpha), and B-cell leukemia/lymphoma 2 (Bcl2) mRNA levels. This response was not linked to any significant signs of neurodegeneration as showed via Fluoro-Jade B and Nissl stain. Intrahippocampal administration of NMDA induced NF alpha B activation and increased NOS and alpha 2/3-Na,K-ATPase activities. NMDA treatment further increased OUA-induced NF-kappa B activation, which was partially blocked by MK-801, an antagonist of NMDA receptor. These results suggest that OUA-induced NF-kappa B activation is at least in part dependent on Na,K-ATPase modulatory action of NMDA receptor in hippocampus. The interaction of these signaling pathways could be associated with biological mechanisms that may underlie the basal homeostatic state linked to the inflammatory signaling cascade in the brain. (c) 2011 Wiley Periodicals, Inc.
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Background: In addition to their central effects, opioids cause peripheral analgesia. There is evidence showing that peripheral activation of kappa opioid receptors (KORs) inhibits inflammatory pain. Moreover, peripheral mu-opioid receptor (MOR) activation are able to direct block PGE(2)-induced ongoing hyperalgesia However, this effect was not tested for KOR selective activation. In the present study, the effect of the peripheral activation of KORs on PGE(2)-induced ongoing hyperalgesia was investigated. The mechanisms involved were also evaluated. Results: Local (paw) administration of U50488 (a selective KOR agonist) directly blocked, PGE(2)-induced mechanical hyperalgesia in both rats and mice. This effect was reversed by treating animals with L-NMMA or N-propyl-L-arginine (a selective inhibitor of neuronal nitric oxide synthase, nNOS), suggesting involvement of the nNOS/NO pathway. U50488 peripheral effect was also dependent on stimulation of PI3K gamma/AKT because inhibitors of these kinases also reduced peripheral antinociception induced by U50488. Furthermore, U50488 lost its peripheral analgesic effect in PI3K gamma null mice. Observations made in vivo were confirmed after incubation of dorsal root ganglion cultured neurons with U50488 produced an increase in the activation of AKT as evaluated by western blot analyses of its phosphorylated form. Finally, immunofluorescence of DRG neurons revealed that KOR-expressing neurons also express PI3K gamma (congruent to 43%). Conclusions: The present study indicates that activation of peripheral KORs directly blocks inflammatory hyperalgesia through stimulation of the nNOS/NO signaling pathway which is probably stimulated by PI3K gamma/AKT signaling. This study extends a previously study of our group suggesting that PI3K gamma/AKT/nNOS/NO is an important analgesic pathway in primary nociceptive neurons.
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We evaluated how the mild stress-induced increase in endogenous corticosterone affected the pineal gland in Syrian hamsters (Mesocricetus auratus). The animals were maintained under constant light for 1 day, instead of a cycle of 14:10-h, to increase the circulating corticosterone levels during the daytime. The nuclear translocation of nuclear factor kappa B (NFKB), which is the pivotal transcription factor for stress and injury, presented a daily rhythm in normal animals. NFKB nuclear content increased linearly from the onset of light [Zeitgeber Time 0 (ZT0)] until ZT11 and decreased after ZT12 when the plasma corticosterone peak was detected in normal animals. However, the 24-h profiles of the two curves were different, and they did not clearly support an exclusive relationship between corticosterone levels and NFKB content. Therefore, we tested the effect of increased endogenous corticosterone through inducing mild stress by maintaining daytime illumination for one night. This stressful condition, which increased daytime corticosterone levels, resulted in a daytime decrease in NFKB nuclear content, and this was inhibited by mifepristone. Overall, this study shows that NFKB has a daily rhythm in Syrian hamster pineal glands and, by increasing endogenous corticosterone with a stressful condition, NFKB activity is regulated. Therefore, this study suggests that the pineal gland in the Syrian hamster is a sensor of stressful conditions.
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Background. Nuclear factor kappa B (NF kappa B) plays a potential role in tolerance by orchestrating onset and resolution of inflammation and regulatory T cell differentiation through subunit c-Rel. We characterized cellular infiltrates and expression of NF kappa B1, c-Rel and its upstream regulators phosphatidylinositol 3-kinase/RAC-alpha serine/threonine kinase, in allograft biopsies from patients with spontaneous clinical operational tolerance (COT). Methods. Paraffin-fixed kidney allograft biopsies from 40 patients with COT (n=4), interstitial rejection (IR; n=12), borderline changes (BC; n=12), and long-term allograft function without rejection (NR; n=12) were used in the study. Cellular infiltrates and immunohistochemical expression of key proteins of the NF kappa B pathway were evaluated in the cortical tubulointerstitium and in cellular infiltrates using digital image analysis software. Results were given as mean +/- SEM. Results. Biopsies from patients with COT exhibited a comparable amount of cellular infiltrate to IR, BC, and NR (COT, 191 +/- 81; IR, 291 +/- 62; BC, 178 +/- 45; and NR, 210 +/- 42 cells/mm(2)) but a significantly higher proportion of forkhead box P3-positive cells (COT, 11%+/- 1.7%; IR, 3.5%+/- 0.70%; BC, 3.4%+/- 0.57%; and NR, 3.7%+/- 0.78% of infiltrating cells; P=0.02). c-Rel expression in cellular infiltrates was significantly elevated in IR, BC, and NR when analyzing the number of positive cells per mm(2) (P=0.02) and positive cells per infiltrating cells (P=0.04). In contrast, tubular PI3K and c-Rel expression were significantly higher in IR and BC but not in NR compared with COT (P=0.03 and P=0.006, respectively). With RAC-alpha serine-threonine kinase, similar tendencies were observed (P=0.2). Conclusions. Allografts from COT patients show significant cellular infiltrates but a distinct expression of proteins involved in the NF kappa B pathway and a higher proportion of forkhead box P3-positive cells.
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de Souza ACCP, Volpini RA, Shimizu MH, Sanches TR, Camara NOS, Semedo P, Rodrigues CE, Seguro AC, Andrade L. Erythropoietin prevents sepsis-related acute kidney injury in rats by inhibiting nuclear factor-kappa B and upregulating endothelial nitric oxide synthase. Am J Physiol Renal Physiol 302: F1045-F1054, 2012. First published January 11, 2012; doi:10.1152/ajprenal.00148.2011.-The pathophysiology of sepsis involves complex cytokine and inflammatory mediator networks, a mechanism to which NF-kappa B activation is central. Downregulation of endothelial nitric oxide synthase (eNOS) contributes to sepsis-induced endothelial dysfunction. Erythropoietin (EPO) has emerged as a major tissue-protective cytokine in the setting of stress. We investigated the role of EPO in sepsis-related acute kidney injury using a cecal ligation and puncture (CLP) model. Wistar rats were divided into three primary groups: control (sham-operated); CLP; and CLP + EPO. EPO (4,000 IU/kg body wt ip) was administered 24 and 1 h before CLP. Another group of rats received N-nitro-L-arginine methyl ester (L-NAME) simultaneously with EPO administration (CLP + EPO + L-NAME). A fifth group (CLP + EPOtreat) received EPO at 1 and 4 h after CLP. At 48 h postprocedure, CLP + EPO rats presented significantly higher inulin clearance than did CLP and CLP + EPO + L-NAME rats; hematocrit levels, mean arterial pressure, and metabolic balance remained unchanged in the CLP + EPO rats; and inulin clearance was significantly higher in CLP + EPOtreat rats than in CLP rats. At 48 h after CLP, creatinine clearance was significantly higher in the CLP + EPO rats than in the CLP rats. In renal tissue, pre-CLP EPO administration prevented the sepsis-induced increase in macrophage infiltration, as well as preserving eNOS expression, EPO receptor (EpoR) expression, IKK-alpha activation, NF-kappa B activation, and inflammatory cytokine levels, thereby increasing survival. We conclude that this protection, which appears to be dependent on EpoR activation and on eNOS expression, is attributable, in part, to inhibition of the inflammatory response via NF-kappa B downregulation.
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Ocular enucleation produces significant morphological and physiological changes in central visual areas. However, our knowledge of the molecular events resulting from eye enucleation in visual brain areas remains elusive. We characterized here the transcription nuclear factor kappa-B (NF-kappa B) activation induced by ocular enucleation in the rat superior colliculus (SC). We also tested the effectiveness of the synthetic glucocorticoid dexamethasone in inhibiting its activation. Electrophoretic mobility shift assays to detect NF-kappa B indicated that this transcription factor is activated in the SC from 1 h to day 15 postlesion. The expression of p65 and p50 proteins in the nuclear extracts was also increased. Dexamethasone treatment was able to significantly inhibit NF-kappa B activation. These findings suggest that this transcriptional factor is importantly involved in the visual system short-term processes that ensue after retinal lesions in the adult brain. (C) 2012 Elsevier Ireland Ltd. All rights reserved.