Current drug discovery strategies against arenavirus infections.

Arenaviruses are a large group of emerging viruses including several causative agents of severe hemorrhagic fevers with high mortality in man. Considering the number of people affected and the currently limited therapeutic options, novel efficacious therapeutics against arenaviruses are urgently needed. Over the past decade, significant advances in knowledge about the basic virology of arenaviruses have been accompanied by the development of novel therapeutics targeting different steps of the arenaviral life cycle. High-throughput, small-molecule screens identified potent and broadly active inhibitors of arenavirus entry that were instrumental for the dissection of unique features of arenavirus fusion. Novel inhibitors of arenavirus replication have been successfully tested in animal models and hold promise for application in humans. Late in the arenavirus life cycle, the proteolytic processing of the arenavirus envelope glycoprotein precursor and cellular factors critically involved virion assembly and budding provide further promising 'druggable' targets for novel therapeutics to combat human arenavirus infection.

Little effect of seasonal constraints on population genetic structure in eusocial paper wasps.

Climate has long been suggested to affect population genetic structures of eusocial insect societies. For instance, Hamilton [Journal of Theoretical Biology7 (1964) 17] discusses whether temperate and tropical eusocial insects may show differences in population-level genetic structure and viscosity, and how this might relate to differences in the degree of synchrony in their life cycles or modes of nest founding. Despite the importance of Hamilton's 1964 papers, this specific idea has not been tested in actual populations of wasps, probably due to the paucity of studies on tropical species. Here, we compare colony and population genetic structures in two species of primitively eusocial paper wasps with contrasting ecologies: the tropical species Polistes canadensis and the temperate species P. dominulus. Our results provide important clarifications of Hamilton's discussion. Specifically, we show that the genetic structures of the temperate and tropical species were very similar, indicating that seasonality does not greatly affect population viscosity or inbreeding. For both species, the high genetic differentiation between nests suggests strong selection at the nest level to live with relatives, whereas low population viscosity and low genetic differentiation between nest aggregations might reflect balancing selection to disperse, avoiding competition with relatives. Overall, our study suggests no prevalence of seasonal constraints of the life cycle in affecting the population genetic structure of eusocial paper wasps. These conclusions are likely to apply also to other primitively eusocial insects, such as halictine bees. They also highlight how selection for a kin structure that promotes altruism can override potential effects of ecology in eusocial insects.

Superantigens of mouse mammary tumor virus.

Superantigens (SAgs) are proteins of microbial origin that bind to major histocompatibility complex (MHC) class II molecules and stimulate T cells via interaction with the V beta domain of the T cell receptor (TCR). Mouse mammary tumor virus (MMTV) is a milk-transmitted type B retrovirus that encodes a SAg in its 3' long terminal repeat. Upon MMTV infection, B cells present SAg to the appropriate T cell subset, which leads to a strong "cognate" T-B interaction. This immune reaction results in preferential clonal expansion of infected B cells and differentiation of some of these cells into long-lived memory cells. In this way a stable MMTV infection is achieved that ultimately results in infection of the mammary gland and virus transmission via milk. Thus, in contrast to many microorganisms that attempt to evade the host immune system (reviewed in 1), MMTV depends upon a strong SAg-induced immune response for its survival. Because of their ability to stimulate very strong T cell responses in MHC-identical mice, minor lymphocyte stimulatory (Mls) antigens, discovered more than 20 years ago, are now known to be SAgs encoded by endogenous MMTV proviruses that have randomly integrated into germ cells. The aim of this review is to combine the extensive biology of Mls SAgs with our current understanding of the life cycle of MMTV.

Executive Order Number Thirty Seven, July 1980

Create the Governor's Life Cycle Purchasing Advisory Committee.

Evaluation of a Bridge Constructed using High Performance Steel, May 2006

Of the approximately 25,000 bridges in Iowa, 28% are classified as structurally deficient, functionally obsolete, or both. Because many Iowa bridges require repair or replacement with a relatively limited funding base, there is a need to develop new bridge materials that may lead to longer life spans and reduced life-cycle costs. In addition, new and effective methods for determining the condition of structures are needed to identify when the useful life has expired or other maintenance is needed. Due to its unique alloy blend, high-performance steel (HPS) has been shown to have improved weldability, weathering capabilities, and fracture toughness than conventional structural steels. Since the development of HPS in the mid-1990s, numerous bridges using HPS girders have been constructed, and many have been economically built. The East 12th Street Bridge, which replaced a deteriorated box girder bridge, is Iowa’s first bridge constructed using HPS girders. The new structure is a two-span bridge that crosses I-235 in Des Moines, Iowa, providing one lane of traffic in each direction. A remote, continuous, fiber-optic based structural health monitoring (SHM) system for the bridge was developed using off-the-shelf technologies. In the system, sensors strategically located on the bridge collect raw strain data and then transfer the data via wireless communication to a gateway system at a nearby secure facility. The data are integrated and converted to text files before being uploaded automatically to a website that provides live strain data and a live video stream. A data storage/processing system at the Bridge Engineering Center in Ames, Iowa, permanently stores and processes the data files. Several processes are performed to check the overall system’s operation, eliminate temperature effects from the complete strain record, compute the global behavior of the bridge, and count strain cycles at the various sensor locations.

Social spending and demographics: The role of public policies in the intergenerational redistribution of income. Empirical evidence from Spain and Catalonia

The demographic shift underway in Southern Europe requires a revision of some of the fundamental principles of the traditional welfare state. We analyze the evolution of several aspects of welfare and social expenditure over the last two decades. We find that in the context of the present demographic changes and real estate boom current social and pension policy leads to a new distribution of benefits and burdens which is highly intergenerationally unequal. We argue for a revised definition of public policy based on Musgrave's proposition as a possible rule for an intergenerationally fair distribution.

Employment Protection, International Specialization, and Innovation

We develop a model to analyse the implications of firing costs on incentives for R&D and international specialization. The Key idea is paying the firing cost, the country with a rigid labor market will tend to produce relatively secure goods, at a late stage of their product life cycle. Under international trade, an international product cycle emerges where, roughly, new goods are first produced in the low firing cost country will specialize in 'secondary innovations', that is, improvements in existing goods, while the low firing cost country will more specialize in 'primary innovation', that is, invention of new goods.

Biologia de Neotrioza tavaresi Crawford, 1925 (Hemiptera, Psyllidae), galhador da folha do araçazeiro (Psidium cattleianum)

Biology of the leaf gall inducer Neotrioza tavaresi Crawford, 1925 (Hemiptera, Psyllidae) on strawberry guava tree (Psidium cattleianum). A field study was conducted in Curitiba region, State of Paraná, southern Brazil, to describe the life cycle of Neotrioza tavaresi Crawford, 1925, a leaf galling insect in strawberry guava trees (Psidium cattleianum). Three cycles were observed (1997, 1998, 1999) during regular field trips and the insects were observed in Piraquara municipality, where 15 samples with 50 infested leaves were sampled in the 1997-98 cycle. Galls were dissected for detailed studies. Neotrioza tavaresi has a univoltine cycle in which adult individuals were found inside the galls from August onwards. The sexually mature insects with sex ratio 1, emerged from the galls after their dehiscence caused by feeding of the adult insects on the gall walls. Adult emergence started in early October and ended by early December, with its peak in November. Copulation took place as soon as adults exit the gall and egg laying started the next day. Females had more than 100 ovarioles containing 218.7±44.7 (n=50) fully formed eggs. This indicated the short sexual adult life-span (aprox. 5-7 days) of the species, also characterized by a concentrated oviposition. Adult individuals fed and laid their eggs on younger shoots of the plant. The bottoms of the yellowish eggs were inserted into the leaf tissue, mainly on its adaxial edge (78.1%). The nymphs hatched and, as they fed on the adaxial side of expanding leaves, modified the cell growth pattern and the round-shape galls developed on the adaxial side with one insect inside. The gall wall showed distinct layers, with the inner one suppliyng the food to the insects, and the outer layer supplying gall protection. Nymphs went through five instars and the exuviae remained stuck on a ball of wax inside the gall. All parasitoids found were Hymenoptera belonging to Chalcidoidea: Eulophidae (1 sp), Pteromalidae (2 spp) and Encyrtidae (3 spp). The findings suggest that leaf gall inducer and parasitoids insects and plant life cycles are closely connected and both leaf sprouting and gall opening seem to be triggered by the same environmental and plant conditions. The high abundance of shoots may favor insect performance as adult individuals can easily find an ideal place for feeding, copulating and laying eggs.

The effects of employment uncertainty and wealth shocks on the labor supply and claiming behavior of older American workers

Unemployment rates in developed countries have recently reached levels not seenin a generation, and workers of all ages are facing increasing probabilities of losingtheir jobs and considerable losses in accumulated assets. These events likely increasethe reliance that most older workers will have on public social insurance programs,exactly at a time that public finances are suffering from a large drop in contributions.Our paper explicitly accounts for employment uncertainty and unexpectedwealth shocks, something that has been relatively overlooked in the literature, butthat has grown in importance in recent years. Using administrative and householdlevel data we empirically characterize a life-cycle model of retirement and claimingdecisions in terms of the employment, wage, health, and mortality uncertainty facedby individuals. Our benchmark model explains with great accuracy the strikinglyhigh proportion of individuals who claim benefits exactly at the Early RetirementAge, while still explaining the increased claiming hazard at the Normal RetirementAge. We also discuss some policy experiments and their interplay with employmentuncertainty. Additionally, we analyze the effects of negative wealth shocks on thelabor supply and claiming decisions of older Americans. Our results can explainwhy early claiming has remained very high in the last years even as the early retirementpenalties have increased substantially compared with previous periods, andwhy labor force participation has remained quite high for older workers even in themidst of the worse employment crisis in decades.

Aspectos biológicos de Zabrotes subfasciatus (Bohemann, 1833) (Coleoptera, Bruchidae) em Phaseolus vulgaris L., cv. Carioca (Fabaceae), sob condições de laboratório

Zabrotes subfasciatus is a serious pest of common beans, P. vulgaris L.. In Brazil there are several studies dealing with resistance of bean genotypes to this insect, while other studies have emphasized the utilization of oils and powders from plants to repel their attack. In this paper, fecundity, fertility, pattern of oviposition, life cycle and longevity were evaluated for a Brazilian stock from the Goiás State on P. vulgaris cv. Carioca, at 30ºC and 70% R.H. The mean fecundity was 38 eggs per female and 73% of viability. Egg laying showed an aggregated pattern. Males and females lived an average of 13 and 9 days, respectively. The total life cycle lasted for about 28 days.

Evolutionary genetics of arbuscular mycorrhizal fungi - causes and consequences of multiple genomes in Glomus intraradices

Résumé Les champignons endomycorhiziens arbusculaires (CEA) forment des symbioses avec la plupart des plantes terrestres. Les CEA influencent la croissance des plantes et la biodiversité. Ils sont supposés avoir évolué de manière asexuée pendant au moins 400 millions d'années et aucune diversification morphologique majeure n'a été constatée. Pour ces raisons, les CEA sont considérés comme d'anciens asexués. Très peu d'espèces sont connues actuellement. Les individus de ces champignons contiennent des noyaux génétiquement différents dans un cytoplasme continu. La signification évolutive, la variabilité et la maintenance des génomes multiples au sein des individus sont inconnues. Ce travail a démontré qu'une population du CEA Glomus intraradices est génétiquement très variable. Nous avons conclu que les plantes hôtes plutôt que la différenciation géographique devraient être responsables de cette grande diversité. Puis nous avons cherché l'existence de recombinaison entre génotypes dans une population. Nous avons détecté un groupe recombinant au sein de la population, ce qui met en doute l'état d'anciens asexués des CEA. Nous avons également détecté l'occurrence de fusions d'hyphes et l'échange de noyaux entre isolats génétiquement différents. La descendance hybride issue de cet échange était viable et distincte phénotypiquement des isolats parentaux. En résumé, ce travail identifie des événements cruciaux dans le cycle de vie des CEA qui ont le potentiel d'influencer l'évolution de génomes multiples. L'étude des conséquences de ces événements sur les interactions avec les plantes hôtes pourrait éclaircir significativement la compréhension de la symbiose entre plantes et CEA. Abstract Arbuscular mycorrhizal fungi (AMF) are important symbionts of most land plants. AMF influence plant growth and biodiversity. Very few extant species are described. AMF are thought to have evolved asexually for at least 400 million years and no major morphological diversification has occurred. Due to these reasons, they were termed `ancient asexuals'. Fungal individuals harbour genetically different nuclei in a continuous cytoplasm. The variability, maintenance and evolutionary significance of multiple genomes within individuals are unknown. This work showed that a population of the AMF Glomus intraradices harbours very high genetic diversity. We concluded that host plants rather than geographic differentiation were responsible for this diversity. Furthermore, we investigated whether recombination occurred among genotypes of a G. intraradices population. The identification of a core group of recombining genotypes in the population refutes the assumption of ancient asexuality in AMF. We found that genetically different isolates can form hyphal fusions and exchange nuclei. The hybrid progeny produced by the exchange was viable and phenotypically distinct from the parental isolates. Taken together, this work provided evidence for key events in the AMF life cycle, that influence the evolution of multiple genomes. Studying the consequences of these events on the interaction with host plants may significantly further the understanding of the AMF-plant symbiosis.

Three essays on organizations and their external environment

Abstract: The literature on the various links between organizations and their external environment is very extensive and fragmented. This thesis is comprised of three separate essays, each examining specific research questions related to these links. The first essay deals with the notion of industry life cycle and how the geographical concentration of an industry is linked to the particular life cycle stage in which the industry finds itself. The aim of this first essay is firstly to verify if the evolution of the Swiss hotel industry fits some of the stylized facts of the industry life cycle. The second aim is to verify if there is evidence of geographical clustering of the hotel industry, and by extension of tourism. The third aim is to verify a hypothesis that industry decline manifests itself mainly by company closures in decentralized locations. The importance for organizational survival and performance of adapting and reacting to environmental changes has long been ascertained. This adaptation requires managers, under conditions of uncertainty, to identify relevant changes in their external environment and to interpret the possible effects of those changes on their organization. Furthermore, it requires finding and adopting organizational responses in reaction to the environmental changes. The second essay explores how managers perceive their environment by reporting the results of two workshops held with managers from the European hotel industry. In the third essay we examine in more detail the role of uncertainty in the interpretation by executives of environmental changes. We integrate existing theories of interpretation and uncertainty into one framework, which we then test using national survey data from the hotel industry. In all three essays we are able to provide some evidence to support our main hypotheses, but.also make suggestions far further research into the topics examined.

Testing demographic models of effective population size.

Due to practical difficulties in obtaining direct genetic estimates of effective sizes, conservation biologists have to rely on so-called 'demographic models' which combine life-history and mating-system parameters with F-statistics in order to produce indirect estimates of effective sizes. However, for the same practical reasons that prevent direct genetic estimates, the accuracy of demographic models is difficult to evaluate. Here we use individual-based, genetically explicit computer simulations in order to investigate the accuracy of two such demographic models aimed at investigating the hierarchical structure of populations. We show that, by and large, these models provide good estimates under a wide range of mating systems and dispersal patterns. However, one of the models should be avoided whenever the focal species' breeding system approaches monogamy with no sex bias in dispersal or when a substructure within social groups is suspected because effective sizes may then be strongly overestimated. The timing during the life cycle at which F-statistics are evaluated is also of crucial importance and attention should be paid to it when designing field sampling since different demographic models assume different timings. Our study shows that individual-based, genetically explicit models provide a promising way of evaluating the accuracy of demographic models of effective size and delineate their field of applicability.

Dynamics of the control of Aedes (Stegomyia) aegypti Linnaeus (Diptera, Culicidae) by Bacillus thuringiensis var israelensis, related with temperature, density and concentration of insecticide

The dynamics of the control of Aedes (Stegomyia) aegypti Linnaeus, (Diptera, Culicidae) by Bacillus thuringiensis var israelensis has been related with the temperature, density and concentration of the insecticide. A mathematical model for biological control of Aedes aegypti with Bacillus thuringiensis var israelensis (Bti) was constructed by using data from the literature regarding the biology of the vector. The life cycle was described by differential equations. Lethal concentrations (LC50 and LC95) of Bti were determined in the laboratory under different experimental conditions. Temperature, colony, larvae density and bioinsecticide concentration presented marked differences in the analysis of the whole set of variables; although when analyzed individually, only the temperature and concentration showed changes. The simulations indicated an inverse relationship between temperature and mosquito population, nonetheless, faster growth of populations is reached at higher temperatures. As conclusion, the model suggests the use of integrated control strategies for immature and adult mosquitoes in order to achieve a reduction of Aedes aegypti.

Is altruism important for understanding the long-run effects of social security?

This paper quantifies the effects of social security on capital accumulation and wealth distribution in a life cycle framework with altruistic individuals. The main findings of this paper are that the current U.S. social security system has a significant impact on capital accumulation and wealth distribution. I find that social security crowds out 8\% of the capital stock of an economy without social security. This effect is driven by the distortions of labor supply due to the taxation of labor income rather than by the intergenerational redistribution of income imposed by the social security system. In contrast to previous analysis of social security, I found that social security does not affect the savings rate of the economy. Another interesting finding is that even though the current U.S. social security system is progressive in its benefits, it may lead to a more disperse distribution of wealth.