Mechanisms of inverse agonist action at D-2 dopamine receptors

1 Mechanisms of inverse agonist action at the D-2(short) dopamine receptor have been examined. 2 Discrimination of G-protein-coupled and -uncoupled forms of the receptor by inverse agonists was examined in competition ligand-binding studies versus the agonist [H-3]NPA at a concentration labelling both G-protein-coupled and -uncoupled receptors. 3 Competition of inverse agonists versus [H-3] NPA gave data that were fitted best by a two-binding site model in the absence of GTP but by a one-binding site model in the presence of GTP. K-i values were derived from the competition data for binding of the inverse agonists to G-protein-uncoupled and -coupled receptors. K-coupled and K-uncoupled were statistically different for the set of compounds tested ( ANOVA) but the individual values were different in a post hoc test only for (+)-butaclamol. 4 These observations were supported by simulations of these competition experiments according to the extended ternary complex model. 5 Inverse agonist efficacy of the ligands was assessed from their ability to reduce agonist-independent [S-35]GTPγ S binding to varying degrees in concentration-response curves. Inverse agonism by (+)-butaclamol and spiperone occurred at higher potency when GDP was added to assays, whereas the potency of (-)-sulpiride was unaffected. 6 These data show that some inverse agonists ((+)-butaclamol, spiperone) achieve inverse agonism by stabilising the uncoupled form of the receptor at the expense of the coupled form. For other compounds tested, we were unable to define the mechanism.

The land assembly problem revisited

As in the standard land assembly problem, a developer wants to buy two adjacent blocks of land belonging to two di¤erent owners. The value of the two blocks of land to the developer is greater than the sum of the individual values of the blocks for each owner. Unlike the land assembly literature, however, our focus is on the incentive that each lot owner has to delay the start of negotiations, rather than on the public goods nature of the problem. An incentive for delay exists, for example, when owners perceive that being last to sell will allow them to capture a larger share of the joint surplus from the development. We show that competition at point of sale can cause equilibrium delay, and that cooperation at point of sale will eliminate delay.

Utilização de soluções business-to-business (B2B) no segmento downstream da cadeia de suprimentos de uma distribuidora de combustíveis

The pursuit of competitive advantage is lobbying organizations to strategically plan the use of their material, human, technological and financial resources, so that it s possible to add value to the product, even when it is considered a commodity. The scenario for this planning should not be limited to the company in question, but cover an entire supply chain, which is composed of several organizations which have common goals of growth and sustainability of the market. They should form trade links, integrating the chains of individual values, in a perspective of value system. In this supply chain there is a flow of services, payments and information, as products well as. The training of these links can be supported by the adoption of a set of information technology, here called solutions business-to-business (B2B), which will be responsible for the production, storage and distribution of relevant information to business transactions between the companies involved. On this view, this thesis aims to describe the B2B solutions adopted in the downstream segment of the supply chain of a distributor of fuel and the nature of these technologies as well as their impact on the creation of value for business and optimization of the relationship between companies. This is a case study on a national distributor of fuels, from a model of research produced under the influence of theories of integrated logistics system and value of Michael Porter. The analyses came to the conclusion that information technology is perceived as an essential tool to the operation of all activities carried out by the company. Among them, at was also brought the key activities of integrated logistics: administration of applications, inventory management, management transport and customer services, which were highlighted in this study. It was also noticed that even these activities are, in principle, purely operational; they all had in the adoption of strategies for leadership in cost or differentiation, supported by B2B solutions identified, making it more conducive to business and direct customer, the clinic reseller of fuel, to obtain value and benefits of this market segment as competitive

Máxima fase estável de lactato sanguíneo e potência crítica em ciclistas bem treinados

O principal objetivo deste estudo foi comparar a intensidade correspondente à máxima fase estável de lactato (MLSS) e a potência crítica (PC) durante o ciclismo em indivíduos bem treinados. Seis ciclistas do sexo masculino (25,5 ± 4,4 anos, 68,8 ± 3,0kg, 173,0 ± 4,0cm) realizaram em diferentes dias os seguintes testes: exercício incremental até a exaustão para a determinação do pico de consumo de oxigênio (VO2pico) e sua respectiva intensidade (IVO2pico); cinco a sete testes de carga constante para a determinação da MLSS e da PC; e um exercício até a exaustão na PC. A MLSS foi considerada com a maior intensidade de exercício onde a concentração de lactato não aumentou mais do que 1mM entre o 10º e o 30º min de exercício. Os valores individuais de potência (95, 100 e 110% IVO2pico) e seu respectivo tempo máximo de exercício (Tlim) foram ajustados a partir do modelo hiperbólico de dois parâmetros para a determinação da PC. Embora altamente correlacionadas (r = 0,99; p = 0,0001), a PC (313,5 ± 32,3W) foi significantemente maior do que a MLLS (287,0 ± 37,8W) (p = 0,0002). A diferença percentual da PC em relação à MLSS foi de 9,5 ± 3,1%. No exercício realizado na PC, embora tenha existido componente lento do VO2 (CL = 400,8 ± 267,0 ml.min-1), o VO2pico não foi alcançado (91,1 ± 3,3 %). Com base nesses resultados pode-se concluir que a PC e a MLSS identificam diferentes intensidades de exercício, mesmo em atletas com elevada aptidão aeróbia. Entretanto, o percentual da diferença entre a MLLS e PC (9%) indica que relação entre esses dois índices pode depender da aptidão aeróbia. Durante o exercício realizado até a exaustão na PC, o CL que é desenvolvido não permite que o VO2pico seja alcançado.

Estimativa do custo energético e contribuição das diferentes vias metabólicas na canoagem de velocidade

O desempenho na canoagem de velocidade depende da capacidade de o organismo regenerar ATP em grandes quantidades e a altas taxas, a partir das diferentes vias metabólicas. Assim, o objetivo do presente estudo foi combinar dois modelos bioenergéticos, um genérico denominado de potência crítica e outro específico para a canoagem, proposto por Zamparo et al. (1999), na tentativa de produzir estimativas de aptidão aeróbia e anaeróbia para essa modalidade, bem como estabelecer estimativas não-invasivas da contribuição dos sistemas aeróbio e anaeróbio para diferentes distâncias percorridas. Para tanto, 11 atletas de canoagem (16,0 ± 1,2 anos; 174,0 ± 2,4cm; 65,2 ± 4,4kg), do sexo masculino, percorreram diferentes distâncias (500, 1.000 e 1.790m), na máxima velocidade possível, em embarcações do tipo K-1, em um lago com águas calmas. As informações obtidas foram inicialmente convertidas em quantidades geradas de trabalho (kJ) e potência interna (W). Posteriormente, os valores individuais estimados foram aplicados às três equações preditivas da potência crítica (PCrit) e capacidade de trabalho anaeróbio (CTAnaer). Por fim, os valores produzidos foram transformados em unidades de equivalentes de oxigênio para a estimativa da contribuição aeróbia (equivalente de O2 para a PCrit x tempo para a distância) e anaeróbia (equivalente de O2 para a CTAnaer x tempo para a distância), nas diferentes distâncias. A contribuição aeróbia relativa encontrada para as diferentes distâncias analisadas (500, 1.000 e 1.790m) foi de 60,6, 78,6 e 89,4%, respectivamente. Os resultados encontrados confirmaram as informações produzidas anteriormente por outras investigações, o que sugere que os procedimentos adotados neste estudo podem fornecer estimativas confiáveis sobre a participação das vias energéticas no desempenho de canoagem.

Seven years of external control of fluoride levels in the public water supply in Bauru, São Paulo, Brazil

luoridation of the public water supplies is recognized as among the top ten public health achievements of the twentieth century. However, the positive aspects of this measure depend on the maintenance of fluoride concentrations within adequate levels. Objective: To report the results of seven years of external control of the fluoride (F) concentrations in the public water supply in Bauru, SP, Brazil in an attempt to verify, on the basis of risk/ benefit balance, whether the levels are appropriate. Material and Methods: From March 2004 to February 2011, 60 samples were collected every month from the 19 supply sectors of the city, totaling 4,641 samples. F concentrations in water samples were determined in duplicate, using an ion-speciflc electrode (Orion 9609) coupled to a potentiometer after buffering with TISAB II. After the analysis, the samples were classified according to the best risk-benefit adjustment. Results: Means (±standard deviation) of F concentrations ranged between 0.73±0.06 and 0.81±0.10 mg/L for the different sectors during the seven years. The individual values ranged between 0.03 and 2.63 mg/L. The percentages of the samples considered low risk for dental fluorosis development and of maximum benefit for dental caries prevention (0.55-0.84 mg F/L) in the first, second, third, fourth, fifth, sixth, and seventh years of the study were 82.0, 58.5, 37.4, 61.0, 89.9, 77.3, and 72.4%, respectively, and 69.0% for the entire period. Conclusions: Fluctuations of F levels were found in the public water supply in Bauru during the seven years of evaluation. These results suggest that external monitoring of water fluoridation by an independent assessor should be implemented in cities where there is adjusted fluoridation. This measure should be continued in order to verify that fluoride levels are suitable and, if not, to provide support for the appropriate adjustments.

Estimadores da resistência mecânica característica da madeira

Pós-graduação em Agronomia (Energia na Agricultura) - FCA

Efeito do nível do treinamento aeróbio na determinação do limite superior do domínio pesado no ciclismo

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação da resistência adesiva entre um cimento resinoso e ligas para metalo-cerâmica submetidas a dois diferentes condicionamentos de supefície

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Ferramentas da qualidade na colheita mecanizada de cana-de-açúcar

Pós-graduação em Agronomia (Produção Vegetal) - FCAV

Comportamento do cálcio e fósforo plasmáticos, em pacientes com hipoparatireoidismo, após administração de carbonato de cálcio em diferentes formas de ingestão

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Cartas de controle para gerenciamento de operações agrícolas mecanizadas

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Influence of dental materials used for sealing caries lesions on laser fluorescence measurements

The aim of this study was to determine the influence of thickness and aging on the intrinsic fluorescence of sealing materials and their ability to block fluorescence from the underlying surface as assessed using a laser fluorescence device. Cavities of 0.5 mm and 1 mm depth were drilled into acrylic boards which were placed over two surfaces with different fluorescence properties: a low-fluorescence surface, to assess the intrinsic fluorescence of the sealing materials, and a high-fluorescence surface, to assess the fluorescence-blocking ability of the sealing materials. Ten cavities of each depth were filled with different sealing materials: Adper Scotchbond Multi-Purpose, Adper Single Bond 2, FluroShield, Conseal f and UltraSeal XT Plus. Fluorescence was measured with a DIAGNOdent pen at five different time points: empty cavity, after polymerization, and 1 day, 1 week and 1 month after filling. The individual values after polymerization, as well as the area under the curve for the different periods were submitted to ANOVA and the Tukey test (p < 0.05). At 0.5 mm, Scotchbond, FluroShield and UltraSeal showed insignificant changes in intrinsic fluorescence with aging and lower fluorescence after polymerization than Single Bond and Conseal. At 1 mm, Scotchbond and FluroShield showed the lowest intrinsic fluorescence, but only Scotchbond showed no chagnes in fluorescence with aging. At both depths, Scotchbond blocked significantly less fluorescence. All sealing materials blocked more fluorescence when applied to a depth of 1 mm. At 0.5 mm, fissure sealants blocked more fluorescence than adhesives, and did not show significant changes with aging. Scotchbond had the least affect on the fluorescence from the underlying surface and would probably have the least affect on the monitoring of sealed dental caries by laser fluorescence.

Seven years of external control of fluoride levels in the public water supply in Bauru, São Paulo, Brazil

Fluoridation of the public water supplies is recognized as among the top ten public health achievements of the twentieth century. However, the positive aspects of this measure depend on the maintenance of fluoride concentrations within adequate levels. To report the results of seven years of external control of the fluoride (F) concentrations in the public water supply in Bauru, SP, Brazil in an attempt to verify, on the basis of risk/benefit balance, whether the levels are appropriate. From March 2004 to February 2011, 60 samples were collected every month from the 19 supply sectors of the city, totaling 4,641 samples. F concentrations in water samples were determined in duplicate, using an ion-specific electrode (Orion 9609) coupled to a potentiometer after buffering with TISAB II. After the analysis, the samples were classified according to the best risk-benefit adjustment. Means (±standard deviation) of F concentrations ranged between 0.73±0.06 and 0.81±0.10 mg/L for the different sectors during the seven years. The individual values ranged between 0.03 and 2.63 mg/L. The percentages of the samples considered “low risk” for dental fluorosis development and of “maximum benefit” for dental caries prevention (0.55-0.84 mg F/L) in the first, second, third, fourth, fifth, sixth, and seventh years of the study were 82.0, 58.5, 37.4, 61.0, 89.9, 77.3, and 72.4%, respectively, and 69.0% for the entire period. Fluctuations of F levels were found in the public water supply in Bauru during the seven years of evaluation. These results suggest that external monitoring of water fluoridation by an independent assessor should be implemented in cities where there is adjusted fluoridation. This measure should be continued in order to verify that fluoride levels are suitable and, if not, to provide support for the appropriate adjustments

Calibrazione di modelli idrologici con algoritmi multiobiettivo

Traditional procedures for rainfall-runoff model calibration are generally based on the fit of the individual values of simulated and observed hydrographs. It is used here an alternative option that is carried out by matching, in the optimisation process, a set of statistics of the river flow. Such approach has the additional, significant advantage to allow also a straightforward regional calibration of the model parameters, based on the regionalisation of the selected statistics. The minimisation of the set of objective functions is carried out by using the AMALGAM algorithm, leading to the identification of behavioural parameter sets. The procedure is applied to a set of river basins located in central Italy: the basins are treated alternatively as gauged and ungauged and, as a term of comparison, the results obtained with a traditional time-domain calibration is also presented. The results show that a suitable choice of the statistics to be optimised leads to interesting results in real world case studies as far as the reproduction of the different flow regimes is concerned.