Constitutively active mutants of the alpha 1B-adrenergic receptor: role of highly conserved polar amino acids in receptor activation.

Site-directed mutagenesis and molecular dynamics simulations of the alpha 1B-adrenergic receptor (AR) were combined to explore the potential molecular changes correlated with the transition from R (inactive state) to R (active state). Using molecular dynamics analysis we compared the structural/dynamic features of constitutively active mutants with those of the wild type and of an inactive alpha 1B-AR to build a theoretical model which defines the essential features of R and R. The results of site-directed mutagenesis were in striking agreement with the predictions of the model supporting the following hypothesis. (i) The equilibrium between R and R depends on the equilibrium between the deprotonated and protonated forms, respectively, of D142 of the DRY motif. In fact, replacement of D142 with alanine confers high constitutive activity to the alpha 1B-AR. (ii) The shift of R143 of the DRY sequence out of a conserved 'polar pocket' formed by N63, D91, N344 and Y348 is a feature common to all the active structures, suggesting that the role of R143 is fundamental for mediating receptor activation. Disruption of these intramolecular interactions by replacing N63 with alanine constitutively activates the alpha 1B-AR. Our findings might provide interesting generalities about the activation process of G protein-coupled receptors.

Entrepreneurship, organization and economic performance among Spanish firms, 1930-1975. The case of the motor industry

Before the Civil War (1936-1939), Spain had seen the emergence offirms of complex organizational forms. However, the conflict andthe postwar years changed this pattern. The argument put forwardin this paper is based on historical experience, the efforts willbe addressed to explain the development of Spanish entrepreneurshipduring the second half of the twentieth century. To illustrate thechange in entrepreneurship and organizational patterns among theSpanish firms during the Francoist regime we will turn to the caseof the motor vehicle industry.

Validation of the New Mix Design Process for Cold In-Place Rehabilitation Using Foamed Asphalt, 2007

Asphalt pavement recycling has grown dramatically over the last few years as a viable technology to rehabilitate existing asphalt pavements. Iowa's current Cold In-place Recycling (CIR) practice utilizes a generic recipe specification to define the characteristics of the CIR mixture. As CIR continues to evolve, the desire to place CIR mixture with specific engineering properties requires the use of a mix design process. A new mix design procedure was developed for Cold In-place Recycling using foamed asphalt (CIR-foam) in consideration of its predicted field performance. The new laboratory mix design process was validated against various Reclaimed Asphalt Pavement (RAP) materials to determine its consistency over a wide range of RAP materials available throughout Iowa. The performance tests, which include dynamic modulus test, dynamic creep test and raveling test, were conducted to evaluate the consistency of a new CIR-foam mix design process to ensure reliable mixture performance over a wide range of traffic and climatic conditions. The “lab designed” CIR will allow the pavement designer to take the properties of the CIR into account when determining the overlay thickness.

How to manage the left subclavian artery during endovascular stenting of the thoracic aorta.

We performed a systematic review of the literature to establish whether revascularisation of the left subclavian territory is necessary when this artery is covered by a stent. We retrieved data from 99 studies incorporating 4906 patients. Incidences of left-arm ischaemia (0.0% vs 9.2%, p=0.002) and stroke (4.7% vs 7.2%, p<0.001) were significantly less following revascularisation, although mortality (10.5% vs 3.4%, p=0.032) and endoleak incidence (25.8% vs 12.6%, p=0.008) were increased. No significant differences in spinal-cord ischaemia were seen. Revascularisation may reduce downstream ischaemic complications but can cause significant risk. Indications must be carefully considered on an individual patient basis.

The return of the wage Phillips curve

The standard New Keynesian model with staggered wage settingis shown to imply a simple dynamic relation between wage inflationand unemployment. Under some assumptions, that relation takes aform similar to that found in empirical wage equations-starting fromPhillips' (1958) original work-and may thus be viewed as providingsome theoretical foundations to the latter. The structural wage equation derived here is shown to account reasonably well for the comovement of wage inflation and the unemployment rate in the U.S. economy, even under the strong assumption of a constant natural rate ofunemployment.

On the term structure of Interbank interest rates: Jump-diffusion processes and option pricing

In this paper we study the dynamic behavior of the term structureof Interbank interest rates and the pricing of options on interest ratesensitive securities. We posit a generalized single factor model withjumps to take into account external influences in the market. Daily datais used to test for jump effects. Qualitative examination of the linkagebetween Monetary Authorities' interventions and jumps are studied. Pricingresults suggests a systematic underpricing in bonds and call options ifthe jumps component is not included. However, the pricing of put optionson bonds presents indeterminacies.

Review of the literature on reference pricing

This paper reviews the literature on reference pricing (RP) in pharmaceutical markets. The RP strategy for cost containment of expenditure on drugs is analyzed as part of the procurement mechanism. We review the existing literature and the state-of-the-art regarding RP by focusing on its economic effects. In particular, we consider: (1) the institutional context and problem-related factors which appear to underline the need to implement an RP strategy; i.e., its nature, characteristics and the sort of health care problems commonly addressed; (2) how RP operates in practice; that is, how third party-payers (the insurers/buyers) have established the RP systems existing on the international scene (i.e., information methods, monitoring procedures and legislative provisions); (3)the range of effects resulting from particular RP strategies (including effects on choice of appropriate pharmaceuticals, insurer savings, total drug expenditures, prices of referenced and non-referenced products and dynamic efficiency; (4) the market failures which an RP policy is supposed to address and the main advantages and drawbacks which emerge from an analysis of its effects. Results suggest that RP systems achieve better their postulated goals (1) if cost inflation in pharmaceuticals is due to high prices rather than to the excess of prescription rates, (2) when the larger is the existing difference in prices among equivalent drugs, and (3) more important is the actual market for generics.

Dynamic graphics of parametrically linked multivariate methods used in compositional data analysis

Many multivariate methods that are apparently distinct can be linked by introducing oneor more parameters in their definition. Methods that can be linked in this way arecorrespondence analysis, unweighted or weighted logratio analysis (the latter alsoknown as "spectral mapping"), nonsymmetric correspondence analysis, principalcomponent analysis (with and without logarithmic transformation of the data) andmultidimensional scaling. In this presentation I will show how several of thesemethods, which are frequently used in compositional data analysis, may be linkedthrough parametrizations such as power transformations, linear transformations andconvex linear combinations. Since the methods of interest here all lead to visual mapsof data, a "movie" can be made where where the linking parameter is allowed to vary insmall steps: the results are recalculated "frame by frame" and one can see the smoothchange from one method to another. Several of these "movies" will be shown, giving adeeper insight into the similarities and differences between these methods.

First description of reproductive behavior of the Amazonian damselfly Chalcopteryx rutilans (Rambur) (Odonata, Polythoridae)

Polythoridae comprise a widespread group of species in the New World tropics, but little is known about their behavior or life history. Here, we described the reproductive behavior of Amazonian Chalchopteryx rutilans, using mark-recapture techniques. Males were resident and territorial, though we found disputes (complex flight manoeuvres) to be rare. Trunks (rotting wood) were important to male persistence in sites, as these are the locations preferred by females for oviposition. The mating system of C. rutilans may be comparable to the resource limitation category, described by Conrad & Pritchard (1992), where males cannot control female access to oviposition sites. So, female choice becomes important and apparently, the observed displays (in which males flash the coppery coloration of their hind wings) may be related to attraction of females to territories, as in a lek system.

Track analysis of the Neotropical Entimini (Coleoptera: Curculionidae: Entiminae)

Track analysis of the Neotropical Entimini (Coleoptera, Curculionidae, Entiminae). Distributional patterns of the species belonging to the tribe Entimini from the Neotropical region were analyzed. Based on a track analysis of 22 species of Entimus, Rhigus, and Phaedropus, for which distributional data were available, two generalized tracks were found. One is located in northern Brazil, corresponding to the Amazonian subregion, and is determined by Phaedropus candidus and Rhigus speciosus. The other is located in southern Brazil, corresponding to the Parana subregion, and is determined by Entimus imperialis, E. excelsus, Phaedropus togatus, Rhigus dejeanii, R. faldermanni, R. horridus, R. lateritus, R. nigrosparsus, and R. tribuloides. The development of the Chacoan subregion is hypothesized to have been the dynamic vicariant event that fragmented the former Amazonian-Parana forest.

Insurance with frequent trading: A dynamic analysis of efficient insurance markets

This paper extends existing insurance results on the type of insurance contracts needed for insurance market efficiency toa dynamic setting. It introduces continuosly open markets that allow for more efficient asset allocation. It alsoeliminates the role of preferences and endowments in the classification of risks, which is done primarily in terms of the actuarial properties of the underlying riskprocess. The paper further extends insurability to include correlated and catstrophic events. Under these very general conditions the paper defines a condition that determines whether a small number of standard insurance contracts (together with aggregate assets) suffice to complete markets or one needs to introduce such assets as mutual insurance.

Metabolic labeling and protein linearization technology allow the study of proteins secreted by cultured cells in serum-containing media.

Supernatants from cell cultures (also called conditioned media, CMs) are commonly analyzed to study the pool of secreted proteins (secretome). To reduce the exogenous protein background, serum-free media are often used to obtain CMs. Serum deprivation, however, can severely affect cell viability and phenotype, including protein secretion. We present a strategy to analyze the proteins secreted by cells in fetal bovine serum-containing CMs, which combines the advantage of metabolic labeling and protein concentration linearization techniques. Incubation of CMs with a hexapeptide ligand library was used to reduce the dynamic range of the samples and led to the identification of 3 times more proteins than in untreated CM samples. Labeling with a deuterated amino acid was used to distinguish between cellular proteins and homologous bovine proteins contained in the medium. Application of the strategy to two breast cancer cell lines led to the identification of proteins secreted in different amounts and which could correlate with their varying degree of aggressiveness. Selected reaction monitoring (SRM)-based quantitation of three proteins of interest in the crude samples yielded data in good agreement with the results from concentration-equalized samples.

Mosquito community composition in dynamic landscapes from the Atlantic Forest biome (Diptera, Culicidae)

Mosquito community composition in dynamic landscapes from the Atlantic Forest biome (Diptera, Culicidae). Considering that some species of Culicidae are vectors of pathogens, both the knowledge of the diversity of the mosquito fauna and how some environment factors influence in it, are important subjects. In order to address the composition of Culicidae species in a forest reserve in southern Atlantic Forest, we compared biotic and abiotic environmental determinants and how they were associated with the occurrence of species between sunset and sunrise. The level of conservation of the area was also considered. The investigation was carried out at Reserva Natural do Morro da Mina, in Antonina, state of Paraná, Brazil. We performed sixteen mosquito collections employing Shannon traps at three-hour intervals, from July 2008 to June 2009. The characterization of the area was determined using ecological indices of diversity, evenness, dominance and similarity. We compared the frequency of specimens with abiotic variables, i.e., temperature, relative humidity and pluviosity. Seven thousand four hundred ten mosquito females were captured. They belong to 48 species of 12 genera. The most abundant genera were Anopheles, Culex, Coquillettidia, Aedes and Runchomyia. Among the species, the most abundant was Anopheles cruzii, the primary vector of Plasmodium spp. in the Atlantic Forest. Results of the analyses showed that the abiotic variables we tested did not influence the occurrence of species, although certain values suggested that there was an optimum range for the occurrence of culicid species. It was possible to detect the presence of species of Culicidae with different epidemiologic profiles and habitat preference.

GUINEA-BISSAU: The Role of Local and International NGOs in Environmental Preservation and Sustainability of the Bijagos Archipelago

Bijagos Archipelago in Guinea-Bissau is at present subject to numerous external impacts that affect its centuries old balance. Since 1975 Guinean society has been using its natural resources in an uncontrolled way over the territory and especially in the coastal area. The archipelago has been increasingly raising interest, most of which is incompatible with the guarantee for a long-term sustainable development. It has also displayed a general impoverishment as far as resource preservation is concerned, due to internal demographic pressure of a population that has doubled since 1981 and to external pressure related to neighboring migrations and consequent depletion of non-renewable resources. This article aims to analyze the actions of local and international NGOs in the preservation and sustainability of the Bijagos Archipelago. We seek through an interdisciplinary approach to analyze the phenomena that are configured within the strategies of NGOs, on the assumption that these issues are articulated in the field of geography and sociology, as well as in politics and international cooperation. It is proposed new challenges to environmental issues, especially in a current situation shaken by constant instability internal and external policies.

A dynamic analysis of human welfare in a warming planet

Climate science indicates that climate stabilization requires low GHG emissions. Is thisconsistent with nondecreasing human welfare?Our welfare or utility index emphasizes education, knowledge, and the environment. Weconstruct and calibrate a multigenerational model with intertemporal links provided by education,physical capital, knowledge and the environment.We reject discounted utilitarianism and adopt, first, the Pure Sustainability Optimization (orIntergenerational Maximin) criterion, and, second, the Sustainable Growth Optimization criterion,that maximizes the utility of the first generation subject to a given future rate of growth. We applythese criteria to our calibrated model via a novel algorithm inspired by the turnpike property.The computed paths yield levels of utility higher than the level at reference year 2000 for allgenerations. They require the doubling of the fraction of labor resources devoted to the creation ofknowledge relative to the reference level, whereas the fractions of labor allocated to consumptionand leisure are similar to the reference ones. On the other hand, higher growth rates requiresubstantial increases in the fraction of labor devoted to education, together with moderate increasesin the fractions of labor devoted to knowledge and the investment in physical capital.