KAI407, a potent non-8-aminoquinoline compound that kills Plasmodium cynomolgi early dormant liver stage parasites in vitro.

Preventing relapses of Plasmodium vivax malaria through a radical cure depends on use of the 8-aminoquinoline primaquine, which is associated with safety and compliance issues. For future malaria eradication strategies, new, safer radical curative compounds that efficiently kill dormant liver stages (hypnozoites) will be essential. A new compound with potential radical cure activity was identified using a low-throughput assay of in vitro-cultured hypnozoite forms of Plasmodium cynomolgi (an excellent and accessible model for Plasmodium vivax). In this assay, primary rhesus hepatocytes are infected with P. cynomolgi sporozoites, and exoerythrocytic development is monitored in the presence of compounds. Liver stage cultures are fixed after 6 days and stained with anti-Hsp70 antibodies, and the relative proportions of small (hypnozoite) and large (schizont) forms relative to the untreated controls are determined. This assay was used to screen a series of 18 known antimalarials and 14 new non-8-aminoquinolines (preselected for blood and/or liver stage activity) in three-point 10-fold dilutions (0.1, 1, and 10 μM final concentrations). A novel compound, designated KAI407 showed an activity profile similar to that of primaquine (PQ), efficiently killing the earliest stages of the parasites that become either primary hepatic schizonts or hypnozoites (50% inhibitory concentration [IC50] for hypnozoites, KAI407, 0.69 μM, and PQ, 0.84 μM; for developing liver stages, KAI407, 0.64 μM, and PQ, 0.37 μM). When given as causal prophylaxis, a single oral dose of 100 mg/kg of body weight prevented blood stage parasitemia in mice. From these results, we conclude that KAI407 may represent a new compound class for P. vivax malaria prophylaxis and potentially a radical cure

Replicability of data collected for empirical estimation of relative pollen productivity

The effects of repeated survey and fieldwork timing on data derived from a recently proposed standard field methodology for empirical estimation of relative pollen productivity (RPP) have been tested. Seasonal variations in vegetation and associated pollen assemblages were studied in three contrasting cultural habitat types; semi-natural ancient woodlands, lowland heaths, and unimproved, traditionally managed hay meadows. Results show that in woodlands and heathlands the standard method generates vegetation data with a reasonable degree of similarity throughout the field season, though in some instances additional recording of woodland canopy cover should be undertaken, and differences were greater for woodland understorey taxa than for arboreal taxa. Large differences in vegetation cover were observed over the field season in the grassland community, and matching the phenological timing of surveys within and between studies is clearly important if RPP estimates from these sites are to be comparable. Pollen assemblages from closely co-located moss polsters collected on different visits are shown to be variable in all communities, to a greater degree than can be explained by the sampling error associated with pollen counting, and further study of moss polsters as pollen traps is recommended

Exchange Rate Dynamics and Fundamental Equilibrium Exchange Rates

The paper investigates if the most popular alternative to the purchasing parity power approach (PPP) to estimate equilibrium exchange rates, the fundamental equilibrium exchange rate (FEER) influences exchange rate dynamics in the long run. For a large panel of industrialized and emerging countries and on the period 1982-2007, we detect the presence of unit roots in the series of real effective exchange rates and in the series of FEERs. We find and estimate a cointegration relationship between real effective exchange rates and FEERs. The results show that the FEER has a positive and significant influence on exchange rate dynamics in the long run.Fundamental equilibrium exchange rates; Panel unit root tests; Global imbalances; Fully modified ordinary least square; Dynamic ordinary least square; Pooled Mean Group

Exchange Rate Dynamics and Fundamental Equilibrium Exchange Rates

The paper investigates if the most popular alternative to the purchasing parity power approach (PPP) to estimate equilibrium exchange rates, the fundamental equilibrium exchange rate (FEER) influences exchange rate dynamics in the long run. For a large panel of industrialized and emerging countries and on the period 1982-2007, we detect the presence of unit roots in the series of real effective exchange rates and in the series of FEERs. We find and estimate a cointegration relationship between real effective exchange rates and FEERs. The results show that the FEER has a positive and significant influence on exchange rate dynamics in the long run.Fundamental equilibrium exchange rates, Panel unit root tests, Global imbalances, Fully modified ordinary least square, Dynamic ordinary least square

Exchange Rate Misalignments at World and European Levels: a FEER Approach

Since the mid-1990s, we observe an increase of world current account imbalances. These imbalances have only been partially reduced since the burst of the crisis in 2007. They reflect, to some extent, exchange rate misalignments, an issue which has been frequently studied in the literature. However, these imbalances, which have reinforced in the 2000s, are also important inside the Euro area. This analysis cannot be reduced to simple estimates of euro misalignment at the world level because of the specific constraints that exist for each member of the Euro area. This article aims to examine to what extent the intra-European imbalances reflect exchange rate misalignments for each "national euro".Equilibrium Exchange Rate; Current Account Balance; Macroeconomic Balance

Modelling Spatial Compositional Data: Reconstructions of past land cover and uncertainties

In this paper, we construct a hierarchical model for spatial compositional data, which is used to reconstruct past land-cover compositions (in terms of coniferous forest, broadleaved forest, and unforested/open land) for five time periods during the past $6\,000$ years over Europe. The model consists of a Gaussian Markov Random Field (GMRF) with Dirichlet observations. A block updated Markov chain Monte Carlo (MCMC), including an adaptive Metropolis adjusted Langevin step, is used to estimate model parameters. The sparse precision matrix in the GMRF provides computational advantages leading to a fast MCMC algorithm. Reconstructions are obtained by combining pollen-based estimates of vegetation cover at a limited number of locations with scenarios of past deforestation and output from a dynamic vegetation model. To evaluate uncertainties in the predictions a novel way of constructing joint confidence regions for the entire composition at each prediction location is proposed. The hierarchical model's ability to reconstruct past land cover is evaluated through cross validation for all time periods, and by comparing reconstructions for the recent past to a present day European forest map. The evaluation results are promising and the model is able to capture known structures in past land-cover compositions

Anticipations of the Crisis: On the Similarities Between Post Keynesian Economics and Regulation Theory

The purpose of this paper is to explore the similarities between Post Keynesian Economics (PKE) and Regulation Theory (RT). It is argued that, despite important differences between these traditions, the analytical contents of PKE and RT display broad similarities with respect to their treatments of the income-generating process, the crisis-prone nature of capitalism, and the institutional contingency of capitalist growth and development. This thesis is then exemplified and substantiated with reference to the 2007—2009 financial crisis and “Great Recession”. Specifically, it is shown that important strands of both PKE and RT characterize and were successful in anticipating the crisis as the result of the exhaustion of a financialized growth process.Post Keynesian Economics, Regulation Theory, Great Recession, financial crisis

Modelling Transition And International Opening In Asia: The Case Of Vietnam With A Comparison With China And The "Asian Tigers"

This paper describes the multisectoral macroeconomic model of a small developing economy in transition, in order to highlight linkages between agriculture and the rest of the economy, and consequences of external opening up. Agriculture is a supply sector, sticky in the short range with market clearing by price adjustment. The non agricultural sector is demand-led, with imperfect competition (and hence sticky prices and indexed nominal wages). According to this dual theoretical pattern, labor market is segmented with an unlimited supply in the rural area. This part of labor force is employed in the agricultural sector and in the rural non agricultural one. Urban workers are employed in the non agricultural sector but may face unemployment. The wage gap between urban and ruralareas induces migration, according to a Harris Todaro mechanism. This framework is applied to the Vietnam case. A calibrated quantitative model performs a base line simulation from 1993 to 2010, following approximately the path designed by the Vietnamese government. Finally, this model is used to sketch various scenarios, among which traditional macroeconomic packages, structural reforms, and external shocks.Vietnam; multisectoral models; development; transition