972 resultados para Non-optimal Codon


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Human motion seems to be guided by some optimal principles. In general, it is assumed that human walking is generated with minimal energy consumption. However, in the presence of disturbances during gait, there is a trade-off between stability (avoiding a fall) and energy-consumption. This work analyses the obstacle-crossing with the leading foot. It was hypothesized that energy-saving mechanisms during obstacle-crossing are modulated by the requirement to avoid a fall using the available sensory information, particularly, by vision. A total of fourteen subjects, seven with no visual impairment and seven blind, walked along a 5 meter flat pathway with an obstacle of 0.26 m height located at 3 m from the starting point. The seven subjects with normal vision crossed the obstacle successfully 30 times in two conditions: blindfolded and with normal vision. The seven blind subjects did the same 30 times. The motion of the leading limb was recorded by video at 60 Hz. There were markers placed on the subject's hip, knee, ankle, rear foot, and forefoot. The motion data were filtered with a fourth order Butterworth filter with a cut-off frequency of 4 Hz. The following variables were calculated: horizontal distance between the leading foot and the obstacle at toe-off prior to (DHPO) and after (DHOP) crossing, minimal vertical height from the foot to the obstacle (DVPO), average step velocity (VELOm). The segmental energies were also calculated and the work consumed by the leading limb during the crossing obstacle was computed for each trial. A statistical analysis repeated-measures ANOVA was conducted on these dependent variables revealing significant differences between the vision and non-vision conditions in healthy subjects. In addition, there were no significant differences between the blind and people with vision blindfolded. These results indicate that vision is crucial to determine the optimal trade-off between energy consumption and avoiding a trip during obstacle crossing.

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An efficient heuristic algorithm is presented in this work in order to solve the optimal capacitor placement problem in radial distribution systems. The proposal uses the solution from the mathematical model after relaxing the integrality of the discrete variables as a strategy to identify the most attractive bus to add capacitors to each step of the heuristic algorithm. The relaxed mathematical model is a nonlinear programming problem and is solved using a specialized interior point method, The algorithm still incorporates an additional strategy of local search that enables the finding of a group of quality solutions after small alterations in the optimization strategy. Proposed solution methodology has been implemented and tested in known electric systems getting a satisfactory outcome compared with metaheuristic methods.The tests carried out in electric systems known in specialized literature reveal the satisfactory outcome of the proposed algorithm compared with metaheuristic methods. (C) 2009 Elsevier Ltd. All rights reserved.

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This work presents the application of a multiobjective evolutionary algorithm (MOEA) for optimal power flow (OPF) solution. The OPF is modeled as a constrained nonlinear optimization problem, non-convex of large-scale, with continuous and discrete variables. The violated inequality constraints are treated as objective function of the problem. This strategy allows attending the physical and operational restrictions without compromise the quality of the found solutions. The developed MOEA is based on the theory of Pareto and employs a diversity-preserving mechanism to overcome the premature convergence of algorithm and local optimal solutions. Fuzzy set theory is employed to extract the best compromises of the Pareto set. Results for the IEEE-30, RTS-96 and IEEE-354 test systems are presents to validate the efficiency of proposed model and solution technique.

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Squamous cell carcinoma of the upper aerodigestive tract (UADT) is associated with environmental factors, especially tobacco and alcohol consumption. Genetic factors, including cyclin D1 (CCND1) polymorphism have been suggested to play an important rote in tumorigenesis and progression of UADT cancer. To investigate the relationship between CCND1 polymorphism on susceptibility for UADT cancers, 147 cancer and 135 non-cancer subjects were included in this study. CCND1 genotype at codon 242(G870A) in exon 4 was undertaken using denaturing high performance liquid chromatography (DHPLC) and DNA sequencing. Significant odds ratio (OR) of the AA + GA genotypes [OR = 7.5 (95% Cl: 1.4-39.7)] was observed in non-drinkers but for non-smokers a non-significant [OR = 5.4 (95% Cl: 0.9-31.4)] was found in the adjusted model. These results suggest that allele A may be a risk factor for UADT cancer, especially in non-alcoholics. However, further epidemiological studies are needed to establish the exact role of CCND1 polymorphism and the development of UADT cancers. (C) 2004 Elsevier Ltd. All rights reserved.

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The effect of the presence of tartrate additive on the chemical stability of a Cu-Sn acid bath was evaluated. It was observed that this additive hinders decomposition of the Cu/Sn deposition bath with storage time, since the decrease in electrochemical efficiency was attenuated. In addition, it was observed that optimal galvanostatic deposition with or without tartrate occurs at approximately 11 mA cm(-2). However, in the presence of tartrate the deposition charge was lower, leading to lower energy consumption. SEM analysis showed that the tartrate added to the plating bath caused a marked change in the morphology of the Cu/Sn films obtained gal vanostatic ally. (C) 2002 Elsevier B.V. B.V. All rights reserved.

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This work concerns the application of the optimal control theory to Dengue epidemics. The dynamics of this insect-borne disease is modelled as a set of non-linear ordinary differential equations including the effect of educational campaigns organized to motivate the population to break the reproduction cycle of the mosquitoes by avoiding the accumulation of still water in open-air recipients. The cost functional is such that it reflects a compromise between actual financial spending (in insecticides and educational campaigns) and the population health (which can be objectively measured in terms of, for instance, treatment costs and loss of productivity). The optimal control problem is solved numerically using a multiple shooting method. However, the optimal control policy is difficult to implement by the health authorities because it is not practical to adjust the investment rate continuously in time. Therefore, a suboptimal control policy is computed assuming, as the admissible set, only those controls which are piecewise constant. The performance achieved by the optimal control and the sub-optimal control policies are compared with the cases of control using only insecticides when Breteau Index is greater or equal to 5 and the case of no-control. The results show that the sub-optimal policy yields a substantial reduction in the cost, in terms of the proposed functional, and is only slightly inferior to the optimal control policy. Copyright (C) 2001 John Wiley & Sons, Ltd.

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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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Canavan disease, an inherited leukodystrophy, is caused by mutations in the aspartoacylase (ASPA) gene. It is most common among children of Ashkenazi Jewish descent but has been diagnosed in many diverse ethnic groups. Two mutations comprise the majority of mutant alleles in Jewish patients, while mutations in the ASPA gene among non-Jewish patients are different and more diverse. In the present study, the ASPA gene was analysed in 22 unrelated non-Jewish patients with Canavan disease, and 24 different mutations were found. of these,14 are novel, including five missense mutations (E24G, D68A, D249V, C152W, H244R), two nonsense mutations (Q184X, E214X), three deletions (923delT, 33del13, 244delA), one insertion mutation (698insC), two sequence variations in one allele ([10T>G; 11insG]), an elimination of the stop codon (941A>G, TAG-->TGG, X314W), and one splice acceptor site mutation (IVS1 - 2A>T). The E24G mutation resulted in substitution of an invariable amino acid residue (Glu) in the first esterase catalytic domain consensus sequence. The IVS1 - 2A>T mutation caused the retention of 40 nucleotides of intron 1 upstream of exon 2. The results of transient expression of the mutant ASPA cDNA containing these mutations in COS-7 cells and assays for ASPA activity of patient fibroblasts indicated that these mutations were responsible for the enzyme deficiency. In addition, patients with the novel D249V mutation manifested clinically at birth and died early. Also, patients with certain other novel mutations, including C152W, E214X, X314W, and frameshift mutations in both alleles, developed clinical manifestations at an earlier age than in classical Canavan disease.

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The capacitor placement (replacement) problem for radial distribution networks determines capacitor types, sizes, locations and control schemes. Optimal capacitor placement is a hard combinatorial problem that can be formulated as a mixed integer nonlinear program. Since this is a NP complete problem (Non Polynomial time) the solution approach uses a combinatorial search algorithm. The paper proposes a hybrid method drawn upon the Tabu Search approach, extended with features taken from other combinatorial approaches such as genetic algorithms and simulated annealing, and from practical heuristic approaches. The proposed method has been tested in a range of networks available in the literature with superior results regarding both quality and cost of solutions.

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This paper proposes an approach of optimal sensitivity applied in the tertiary loop of the automatic generation control. The approach is based on the theorem of non-linear perturbation. From an optimal operation point obtained by an optimal power flow a new optimal operation point is directly determined after a perturbation, i.e., without the necessity of an iterative process. This new optimal operation point satisfies the constraints of the problem for small perturbation in the loads. The participation factors and the voltage set point of the automatic voltage regulators (AVR) of the generators are determined by the technique of optimal sensitivity, considering the effects of the active power losses minimization and the network constraints. The participation factors and voltage set point of the generators are supplied directly to a computational program of dynamic simulation of the automatic generation control, named by power sensitivity mode. Test results are presented to show the good performance of this approach. (C) 2008 Elsevier B.V. All rights reserved.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Skin cancers are the most common human malignant neoplasia and their incidence is growing, chiefly in tropical countries. There is evidence that ultraviolet (UV) radiation present in sunlight is important for genetic damage. Mutations due to such damage could be responsible for alterations in oncogenes and tumor suppressor genes. Recent studies have reported remarkable differences in mutation frequency of the RAS proto-oncogene in non-melanoma skin cancers. These findings may reflect differences in the molecular epidemiology of cutaneous tumors found in geographical areas with diverse sun exposure and ethnical origins of their populations. Our study proposed to perform molecular analyses of skin tumors on patients living in southeastern Brazil, in areas with high levels of sun exposure. DNA from eight solar keratose (SK), 26 basal cell carcinomas (BCC) and 19 squamous cell carcinomas (SCC) was submitted to PCR-SSCP analysis for codons 12, 13 and 61. Contradicting other authors, we found no mutations in codons 12,13 but detected two BCCs and one SCC with a mutation in codon 61. These findings suggest that the activation of KRAS oncogene may contribute to the pathogenicity of cutaneous lesions in southeastern Brazil.

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The crystal structures of five new non-electrophilic β-strand-templated thrombin active-site inhibitors have been determined bound to the enzyme. Four co-crystallize with hirugen and inhibitor isomorphously to produce thrombin-hirugen crystals (monoclinic, space group C2), while one co-crystallizes in the hexagonal system, space group P65. A 1,4-substituted cyclohexyl moiety is conserved at the P1 position of all the inhibitors, along with a fused hetero-bicyclic five- and six-membered ring that occupies the P2 site. Amino, amidino and aminoimidazole groups are attached to the cyclohexyl ring for recognition at the S1 specificity site, while benzylsulfonyl and diphenyl groups enhance the binding at the S3 subsite. The cyclohexyl groups at the P1 positions of three of the inhibitors appear to be in the energetically favored chair conformation, while the imidazole-substituted cyclohexyl rings are in a boat conformation. Somewhat unexpectedly, the two cyclohexyl-aminoimidazole groups bind differently in the specificity site; the unique binding of one is heretofore unreported. The other inhibitors generally mimic arginyl binding at S1. This group of inhibitors combines the nonelectrophilicity and selectivity of DAPA-like compounds and the more optimal binding features of the S1-S3 sites of thrombin for peptidic molecules, which results in highly potent (binding constants 12 nM-16 pM, one being 1.1 μM) and selective (ranging from 140 to 20 000 times more selective compared with trypsin) inhibitors of thrombin. The binding modes of these novel inhibitors are correlated with their binding constants, as is their selectivity, in order to provide further insight for the design of therapeutic antithrombotic agents that inhibit thrombin directly at the active site.

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In this paper we present a weak maximum principle for optimal control problems involving mixed constraints and pointwise set control constraints. Notably such result holds for problems with possibly nonsmooth mixed constraints. Although the setback of such result resides on a convexity assumption on the extended velocity set, we show that if the number of mixed constraints is one, such convexity assumption may be removed when an interiority assumption holds. © 2008 IEEE.