965 resultados para p-Basis
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In this paper we present the results of the use of a methodology for multinodal load forecasting through an artificial neural network-type Multilayer Perceptron, making use of radial basis functions as activation function and the Backpropagation algorithm, as an algorithm to train the network. This methodology allows you to make the prediction at various points in power system, considering different types of consumers (residential, commercial, industrial) of the electric grid, is applied to the problem short-term electric load forecasting (24 hours ahead). We use a database (Centralised Dataset - CDS) provided by the Electricity Commission de New Zealand to this work.
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OBJETIVO: Avaliar os efeitos do ácido acetilsalicílico a 10% e 20% em linfonodos mesentéricos de coelhos para posterior embasamento e uso em metástases linfonodais. MÉTODOS: Um total de 20 linfonodos de 20 coelhos (divididos aleatoriamente em quatro grupos) foi avaliado. As soluções de aspirina a 10% (grupos A e C) e 20% (grupos B e D) foram injetadas em linfonodos mesentéricos de coelhos sadios e seus efeitos macroscópicos e histológicos foram avaliados em 24 horas (grupos A e B) e em sete dias (grupos C e D). RESULTADOS: Nos grupos avaliados em 24 horas (A e B) foi verificada intensa necrose e hemorragia, aumento importante de apoptose em todo o linfonodo, com alargamento dos seios medulares e aumento dos centros germinativos. Nos grupos avaliados em sete dias (C e D) também houve aumento da apoptose, com maior elevação de histiócitos e diminuição importante da necrose; a hemorragia foi ausente e aumento de células gigantes foi visualizado, conferindo processo inflamatório crônico do tipo corpo estranho. Não houve diferença entre as concentrações utilizadas (10 e 20%) em nenhuma das comparações. CONCLUSÕES: A injeção de aspirina em linfonodos causou necrose e um aumento de apoptose após 24 horas e após sete dias de tratamento, houve regeneração dos gânglios linfáticos, com diminuição intensa de necrose e grande aumento de apoptose. Uma vez que o aumento de apoptose é um dos pilares dos tratamentos antineoplásicos, estes resultados experimentais embasam eventual aplicação clínica da aspirina no tratamento de metástases linfonodais.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Five experiments were conducted on commercial farms in Brazil aiming to develop a fixed-time artificial insemination (TAI) protocol that achieved pregnancy rates between 40% and 55% in Bos indicus cows. These studies resulted in the development of the following protocol: insertion of all intravaginal device containing 1.9 g of progesterone (CIDR) plus 2.0 mg im estradiol benzoate on Day 0; 12.5 mg im dinoprost tromethamine on Day 7 in cycling cows or oil Day 9 in anestrous cows; CIDR withdrawal plus 0.5 mg im estradiol cypionate plus temporary calf removal on Day 9; TAI (48 h after CIDR withdrawal) plus reuniting of calves with their dams on Day 11. Reduced dose of prostaglandin F(2 alpha) (PGF(2 alpha): 12.5 mg im dinoprost tromethamine) effectively caused luteolysis. In cycling cows, fertility was greater when the treatment with PGF(2 alpha) was administered on Day 7 than oil Day 9, but in anestrous cows, no effects of time of the PGF(2 alpha) treatment were found. Estradiol cypionate effectively replaced estradiol benzoate or gonadotropin-releasing hormone as the ovulatory stimulus, reducing labor and cost. In this protocol, CIDR inserts were successfully used four times (9 d each use) with no detrimental effects on fertility. (C) 2009 Elsevier B.V. All rights reserved.
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Importin-alpha is the nuclear import receptor that recognizes cargo proteins carrying conventional basic monopartite and bipartite nuclear localization sequences (NLSs) and facilitates their transport into the nucleus. Bipartite NLSs contain two clusters of basic residues, connected by linkers of variable lengths. To determine the structural basis of the recognition of diverse bipartite NLSs by mammalian importin-alpha, we co-crystallized a non-autoinhibited mouse receptor protein with peptides corresponding to the NLSs from human retinoblastoma protein and Xenopus laevis phosphoprotein N1N2, containing diverse sequences and lengths of the linker. We show that the basic clusters interact analogously in both NLSs, but the linker sequences adopt different conformations, whereas both make specific contacts with the receptor. The available data allow us to draw general conclusions about the specificity of NLS binding by importin-alpha and facilitate an improved definition of the consensus sequence of a conventional basic/bipartite NLS (KRX10-12KRRK) that can be used to identify novel nuclear proteins.
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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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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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Crystallographic screening has been used to identify new inhibitors for potential target for drug development. Here, we describe the application of the crystallographic screening to assess the structural basis of specificity of ligands against a protein target. The method is efficient and results in detailed crystallographic information. The utility of the method is demonstrated in the study of the structural basis for specificity of ligands for human purine nucleoside phosphorylase (PNP). Purine nucleoside phosphorylase catalyzes the phosphorolysis of the N-ribosidic bonds of purine nucleosides and deoxynucleosides. This enzyme is a target for inhibitor development aiming at T-cell immune response modulation and has been submitted to extensive structure-based drug design. This methodology may help in the future development of a new generation of PNP inhibitors.
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Purine nucleoside phosphorylase (PNP) catalyzes the phosphorolysis of the N-ribosidic bonds of purine nucleosides and deoxynucleosides. PNP is a target for inhibitor development aiming at T-cell immune response modulation. This work reports on the crystallographic study of the complex of human PNP-immucillin-H (HsPNP-ImmH) solved at 2.6 Angstrom resolution using synchrotron radiation. Immucillin-H (ImmH) inhibits the growth of malignant T-cell lines in the presence of deoxyguanosine without affecting non-T-cell tumor lines. ImmH inhibits activated normal human T cells after antigenic stimulation in vitro. These biological effects of ImmH suggest that this agent may have utility in the treatment of certain human diseases characterized by abnormal T-cell growth or activation. This is the first structural report of human PNP complexed with immucillin-H. The comparison of the complex HsPNP-ImmH with recent crystallographic structures of human PNP explains the high specificity of immucillin-H for human PNP. (C) 2003 Elsevier B.V. All rights reserved.
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Sphingomyelinases D (SMases D) from Loxosceles spider venom are the principal toxins responsible for the manifestation of dermonecrosis, intravascular hemolysis, and acute renal failure, which can result in death. These enzymes catalyze the hydrolysis of sphingomyelin, resulting in the formation of ceramide 1-phosphate and choline or the hydrolysis of lysophosphatidyl choline, generating the lipid mediator lysophosphatidic acid. This report represents the first crystal structure of a member of the sphingomyelinase D family from Loxosceles laeta (SMase I), which has been determined at 1.75-angstrom resolution using the quick cryo-soaking technique and phases obtained from a single iodine derivative and data collected from a conventional rotating anode x-ray source. SMase I folds as an (alpha/beta)(8) barrel, the interfacial and catalytic sites encompass hydrophobic loops and a negatively charged surface. Substrate binding and/or the transition state are stabilized by a Mg2+ ion, which is coordinated by Glu(32), Asp(34), Asp(91), and solvent molecules. In the proposed acid base catalytic mechanism, His(12) and His(47) play key roles and are supported by a network of hydrogen bonds between Asp(34), Asp(52), Trp(230), Asp(233), and Asn(252).
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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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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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The pathogenesis of fibrosis and the functional features of pressure overload myocardial hypertrophy are still controversial. The objectives of the present study were to evaluate the function and morphology of the hypertrophied myocardium in renovascular hypertensive (RHT) rats. Male Wistar rats were sacrificed at week 4 (RHT4) and 8 (RHT8) after unilateral renal ischemia (Goldblatt II hypertension model). Normotensive rats were used as controls. Myocardial function was analyzed in isolated papillary muscle preparations, morphological features were defined by light microscopy, and myocardial hydroxyproline concentration (HOP) was determined by spectrophotometry. Renal artery clipping resulted in elevated systolic arterial pressure (RHT4: 178 ± 19 mmHg and RHT8: 194 ± 24 mmHg, P<0.05 vs control: 123 ± 7 mmHg). Myocardial hypertrophy was observed in both renovascular hypertensive groups. The myocardial HOP concentration was increased in the RHT8 group (control: 2.93 ± 0.38 µg/mg; RHT4: 3.02 ± 0.40 µg/mg; RHT8: 3.44 ± 0.45 µg/mg of dry tissue, P<0.05 vs control and RHT4 groups). The morphological study demonstrated myocyte necrosis, vascular damage and cellular inflammatory response throughout the experimental period. The increased cellularity was more intense in the adventitia of the arterioles. As a consequence of myocyte necrosis, there was an early, local, conjunctive stroma collapse with disarray and thickening of the argyrophilic interstitial fibers, followed by scarring. The functional data showed an increased passive myocardial stiffness in the RHT4 group. We conclude that renovascular hypertension induces myocyte and arteriole necrosis. Reparative fibrosis occurred as a consequence of the inflammatory response to necrosis. The mechanical behavior of the isolated papillary muscle was normal, except for an early increased myocardial passive stiffness