Mode of action of the positive modulator PNU-120596 on alpha7 nicotinic acetylcholine receptors.

We investigated the mode of action of PNU-120596, a type II positive allosteric modulator of the rat alpha7 nicotinic acetylcholine receptor expressed by GH4C1 cells, using patch-clamp and fast solution exchange. We made two important observations: first, while PNU-120596 rapidly associated to desensitized receptors, it had at least hundredfold lower affinity to resting conformation, therefore at 10 muM concentration it dissociated from resting receptors; and second, binding of PNU-120596 slowed down dissociation of choline molecules from the receptor radically. We propose that when agonist concentration is transiently elevated in the continuous presence of the modulator (as upon the neuronal release of acetylcholine in a modulator-treated animal) these two elements together cause occurrence of a cycle of events: Binding of the modulator is limited in the absence of the agonist. When the agonist is released, it binds to the receptor, and induces desensitization, thereby enabling modulator binding. Modulator binding in turn traps the agonist within its binding site for a prolonged period of time. Once the agonist finally dissociated, the modulator can also dissociate without re-binding, and the receptor assumes its original resting conformation. In kinetic simulations this "trapped agonist cycle" mechanism did not require that the orthosteric and allosteric ligands symmetrically modify each other's affinity, only the modulator must decrease agonist accessibility, and the agonist must induce a conformation that is accessible to the modulator. This mechanism effectively prolongs and amplifies the effect of the agonist

Configuration Methodology for Traffic-Responsive Plan Selection: A Global Perspective

Although several studies have shown the potential great benefits of traffic-responsive plan selection (TRPS) control, time-of-day operation continues to be the primary method used to select patterns for signal control applications. This practice could be largely attributed to the minimal guidelines available on the setup of the TRPS mode. An innovative framework for TRPS system setup is provided, and guidelines for implementing TRPS in a simplified manner are shown. The guidelines, developed at Texas Transportation Institute (TTI), use a comprehensive approach that incorporates a multiobjective evolutionary algorithm and a supervised discriminant analysis. Engineers can directly implement the guidelines presented as an initial design. Hardware-in-the-loop simulation is used to illustrate the performance of TTI’s TRPS configuration methodology

Alternatives to formulate laying hen diets beyond the traditional least-cost model

Owing to the high cost of feed for poultry, there is continuous pressure to formulate 'least-cost' diets that meet nutritional requirements. However, the main aim of any commercial enterprise is usually to maximize profits with the resources or inputs available, and the conventional or historic tool of least-cost ration formulation has limitations in a more demanding economic environment. The layer industry may experience particularly volatile changes in egg price, principally owing to changes in supply rather than demand, and in the past, it has been reported to possess less production and financial data reporting than other industries. Thus, increased flexibility during these uncertain times may give the layer industry greater opportunity and capacity to cope with market fluctuations. A practical example of how a laying hen operation may benefit from these approaches demonstrates that the maximum-profit solution does not always match the least-cost solution and that stochastic feed formulation may be used to accurately assign safety margins and define the level of certainty this safety margin will provide. Finally, as producers better understand how their hens respond to different dietary specifications, the opportunity arises to choose the set of specifications that result in maximum profits for their unique situations, rather than relying on least-cost diets formulated to nutrient requirements alone

Raw material nutrient variability has substantial impact on the potential profitability of chicken meat production

Feed accounts for more than 65% of live production costs of poultry production; thus, accurate feed formulation is vital to ensure poultry are receiving an optimal diet and nutrients are not in undersupply or oversupply. However, this is difficult when the nutrient compositions of feed ingredient batches are highly variable. To help reduce the variability in the specified finished feeds, appropriate sampling methodology is critical. Nevertheless, recommended methodology and depth of detail within technical articles varies greatly and does not always reflect the recommendations of the Association of Official Analytical Chemists, a nonprofit scientific association that publishes standardized analytical methods. It is often understood that increased variability in ingredients due to poor sampling technique is detrimental to industry, but the potential economic cost of poor sampling is often not appreciated. Thus, the extent that variation in protein in feed ingredients affects expected performance and profits for the poultry industry was modeled. It was demonstrated that it is possible to incur a 63% reduction in gross margin or a difference of up to $19,053 (USD) in gross margin from one cycle of 30,000 broilers by simply overestimating the nutrient content of feedstuffs. Assuming a poultry company may produce approximately 1,000 broiler cycles per year, this equates to a loss of up to$19 million (USD). Hence, it is clear that identifying the most accurate way to sample, and improving the understanding and implementation of proper sampling methodology, should be a priority

Don't tax me? : Determinants of individual attitudes toward progressive taxation

This contribution empirically analyses the individual determinants of tax rate preferences. For that purpose we make use of the representative German General Social Survey (ALLBUS) that offers data on the individual attitudes toward progressive, proportional, and regressive taxation. Our theoretical considerations suggest that beyond self-interest, information, fairness considerations, economic beliefs and several other individual factors drive individual preferences for tax rate structures. Our empirical results indicate that the self-interest view does not offer the sole explanation for the heterogeneity in attitudes toward progressive taxation. Rather, we show that the choice of the favoured tax rate is also driven by fairness considerations

Individual determinants of social fairness assessments : the case of Germany

In this contribution we study the determinants of how individuals assess the social fairness of a given income distribution. We propose an analytical framework distinguishing between potential impact factors related to the following fields: first fairness preferences, second beliefs on the sources of economic success and the functioning of democracy and third selfinterest. We test this framework on representative survey data for Germany for the years 1991, 2000 and 2004. Our results indicate that self-interest, beliefs and fairness preferences jointly shape fairness assessments. In addition, a number of personal characteristics are found to be important: Compared to their western fellow citizens, people born in GDR have a more critical view at social fairness. A particularly strong impact is related to the belief on the functioning of the democratic system. This points an important role of procedural fairness for the acceptance of a given distribution

The early bee catches the flower - circadian rhythmicity influences learning performance in honey bees, Apis mellifera

Circadian rhythmicity plays an important role for many aspects of honey bees’ lives. However, the question whether it also affects learning and memory remained unanswered. To address this question, we studied the effect of circadian timing on olfactory learning and memory in honey bees Apis mellifera using the olfactory conditioning of the proboscis extension reflex paradigm. Bees were differentially conditioned to odours and tested for their odour learning at four different “Zeitgeber” time points. We show that learning behaviour is influenced by circadian timing. Honey bees perform best in the morning compared to the other times of day. Additionally, we found influences of the light condition bees were trained at on the olfactory learning. This circadian-mediated learning is independent from feeding times bees were entrained to, indicating an inherited and not acquired mechanism. We hypothesise that a co-evolutionary mechanism between the honey bee as a pollinator and plants might be the driving force for the evolution of the time-dependent learning abilities of bees

Desempenho produtivo e qualidade da carne de frangos alimentados com ração contendo óleo de linhaça

O objetivo deste trabalho foi avaliar o efeito da utilização de óleo de linhaça, em substituição ao óleo de soja, sobre a produtividade e a qualidade da carne de frangos de corte de ambos os sexos. Foram utilizadas 320 aves, em um arranjo fatorial 4x2 - quatro combinações dos períodos de fornecimento de óleo de soja e óleo de linhaça e dois sexos - e quatro repetições. O desempenho produtivo foi avaliado por pesagens da ração e das aves com 1, 21, 42 dias e no momento do abate, aos 49 dias de idade. Após o abate, foi avaliado o rendimento de carcaça e sua composição: cortes, vísceras e gordura abdominal. Foram determinados os teores de lipídeos totais, umidade e colesterol da carne. A dieta contendo óleo de linhaça melhorou a qualidade nutricional da fração lipídica da carne de frango, mas prejudicou o desempenho produtivo das aves