Cis-configured aziridines are new pseudo-irreversible dual-mode inhibitors of Candida albicans secreted aspartic protease 2

A series of cis-configured epoxides and aziridines containing hydrophobic moieties and amino acid esters,were synthesized as new potential inhibitors of the secreted aspartic protease 2 (SAP2) of Candida albicans. Enzyme assays revealed the N- benzyl-3-phenyl-substituted aziridines 11 and 17 as the most potent inhibitors, with second-order inhibition, rate constants (k(2)) between 56000 and 12-1000 M-1 min(-1). The compounds were shown to be pseudo-irreversible dual-mode, inhibitors: the interm ediate esterified enzyme resulting from nucleophilic ring opening was hydrolyzed and yielded amino alcohols as transition state-mimetic reversible inhibitors. The results of docking studies with the ring-closed aziridine forms of the inhibitors suggest binding modes mainly dominated by hydrophobic interactions with the S1, S1' S2, and S2' subsites of the protease, and docking studies with the processed amino alcohol forms predict additional hydrogen bonds of the new hydroxy group to the active site Asp residues. C. albicans growth assays showed the compounds to decrease SAP2-dependent growth while not affecting SAP2-independent growth.

Study of the combined radial post-feeding dispersion of the blowflies Chrysomya megacephala (Fabricius) and C. albiceps (Wiedemann) (Diptera, Calliphoridae)

Blowflies use discrete and ephemeral substrates to feed their larvae. After they run out of food, the larvae begin to disperse in order to find adequate places for pupation or additional food sources, a process named post-feeding larval dispersion. Some important aspects of this process were studied in a circular arena allowing the combined radial post-feeding dispersion from the center of the arena of C. albiceps and C. megacephala larvae. To determine the location of each pupa, the arena was divided in 72 identical sections starting from the center. The distance from the center, the depth and weight of each pupa were evaluated. Statistical tests were done to verify the relation between weight, depth and distance for pupation. From the total an average of 976 larvae released (488 for each species) were collected considering both experiments 456 C. megacephala pupae and 488 of C. albiceps. This demonstrates that C. albiceps probably preyed on 32 C. megacephala larvae during post-feeding dispersion. The study of this dispersion process can be used to estimate the postmortem interval (PMI) of human cadavers in legal medicine.

Why ethnic fractionalization? Polarization, ethnic conflict and growth

This paper ia an attempt to clarify the relationship between fractionalization,polarization and conflict. The literature on the measurement of ethnic diversityhas taken as given that the proper measure for heterogeneity can be calculatedby using the fractionalization index. This index is widely used in industrialeconomics and, for empirical purposes, the ethnolinguistic fragmentation isready available for regression exercises. Nevertheless the adequacy of asynthetic index of hetergeneity depends on the intrinsic characteristicsof the heterogeneous dimension to be measured. In the case of ethnicdiversity there is a very strong conflictive dimension. For this reasonwe argue that the measure of heterogeneity should be one of the class ofpolarization measures. In fact the intuition of the relationship betweenconflict and fractionalization do not hold for more than two groups. Incontrast with the usual problem of polarization indices, which are ofdifficult empirical implementation without making some arbitrary choiceof parameters, we show that the RQ index, proposed by Reynal-Querol (2002),is the only discrete polarization measure that satisfies the basic propertiesof polarization. Additionally we present a derivation of the RQ index froma simple rent seeking model. In the empirical section we show that whileethnic polarization has a positive effect on civil wars and, indirectly ongrowth, this effect is not present when we use ethnic fractionalization.

L’insertion commerciale internationale du Cap-Vert : obstacles, stratégies et mode d’insertion

Le Cap-Vert se présente comme une Petite Economie Insulaire, très ouverte à l’extérieur. En effet, parmi les principales spécificités géographiques, économiques et commerciales on pourrait mettre en exergue d’une part l’insularité et l’éloignement ainsi que la petitesse de la population et d’autre part la primauté du secteur des services, le déficit de la balance commerciale ainsi que l’importance des transferts des émigrants, les investissements étrangers, l’aide internationale. L’insertion commerciale internationale de cette PEI est contrainte par de nombreux obstacles. Il s’agit, notamment, de l’impossibilité de réaliser des économies d’échelle, les surcoûts des transports dus à l’insularité et l’éloignement, de la faible diversification de l’offre exportable ainsi que certains obstacles commerciaux internationaux dont les mesures SPS, les OTC et les règles d’origine. Cherchant à remédier à ces obstacles et à améliorer les conditions de son insertion commerciale internationale, le Cap-Vert a fait recours à un ensemble de stratégies. Ainsi, cette insertion est fondée sur des partenariats stratégiques et l’exportation des services.

Econometrics and decision making: Effects of presentation mode

Much of empirical economics involves regression analysis. However, does thepresentation of results affect economists ability to make inferences for decision makingpurposes? In a survey, 257 academic economists were asked to make probabilisticinferences on the basis of the outputs of a regression analysis presented in a standardformat. Questions concerned the distribution of the dependent variable conditional onknown values of the independent variable. However, many respondents underestimateduncertainty by failing to take into account the standard deviation of the estimatedresiduals. The addition of graphs did not substantially improve inferences. On the otherhand, when only graphs were provided (i.e., with no statistics), respondents weresubstantially more accurate. We discuss implications for improving practice in reportingresults of regression analyses.

Ethnic polarization, potential conflict and civil wars

This paper analyzes the relationship between ethnic fractionalization, polarization, and conflict. In recent years many authors have found empirical evidence that ethnic fractionalization has a negative effect on growth. One mechanism that can explain this nexus is the effect of ethnic heterogeneity on rent-seeking activities and the increase in potential conflict, which is negative for investment. However the empirical evidence supporting the effect of ethnic fractionalization on the incidence of civil conflicts is very weak. Although ethnic fractionalization may be important for growth, we argue that the channel is not through an increase in potential ethnic conflict. We discuss the appropriateness of indices of polarization to capture conflictive dimensions. We develop a new measure of ethnic heterogeneity that satisfies the basic properties associated with the concept of polarization. The empirical section shows that this index of ethnic polarization is a significant variable in the explanation of the incidence of civil wars. This result is robust to the presence of other indicators of ethnic heterogeneity, other sources of data for the construction of the index, and other data structures.

Dispersion of natural arsenic in the Malcantone watershed, Southern Switzerland: field evidence for repeated sorption-desorption and oxidation-reduction processes

In recent years, elevated arsenic concentrations have been found in waters and soils of many, countries, often resulting in a health threat for the local population. Switzerland is not an exception and this paper deals with the release and subsequent fate of arsenic in a 200-km(2) mountainous watershed, characterized by crystalline silicate rocks (gneisses, schists, amphibolites) that contain abundant As-bearing sulfide ore deposits, some of which have been mined for iron and gold in the past. Using analytical methods common for mineralogical, ground water and soil studies (XRD, XRF, XAS-XANES and -EXAFS, electron microprobe, extraction, ICP, AAS with hydride generator, ion chromatography), seven different field situations and related dispersion processes of natural arsenic have been studied: (1) release by rock weathering, (2) transport and deposition by water and ice; (3) release of As to the ground and surface water due to increasing pH; (4) accumulation in humic soil horizons; (5) remobilization by reduction in water-saturated soils and stagnant ground waters; (6) remobilization by using P-rich fertilizers or dung and (7) oxidation, precipitation and dilution in surface waters. Comparison of the results with experimental adsorption studies and speciation diagrams from the literature allows us to reconstruct and identify the typical behavior of arsenic in a natural environment under temperate climatic conditions. The main parameters identified are: (a) once liberated from the primary minerals, sorption processes on Fe-oxy-hydroxides dominate over Al-phases, such as Al-hydroxides or clay minerals and limit the As concentrations in the spring and well waters between 20 and 300 mug/l. (b) Precipitation as secondary minerals is limited to the weathering domain, where the As concentrations are still high and not yet too diluted by rain and soils waters. (c) Although neutral and alkaline pH conditions clearly increase the mobility of As, the main factor to mobilize As is a low redox potential (Eh close or below 0 mV), which favors the dissolution of the Fe-oxy-hydroxides on which the As is sorbed. (d) X-ray absorption spectroscopy (XAS) of As in water-logged humic forest soils indicates that the reduction to As III only occurs at the solid-water interface and that the solid contains As as As V (e) A and Bh horizons of humic cambisols can effectively capture As when As-rich waters flow through them. Complex spatial and temporal variation of the various parameters in a watershed results in repeated mobilization and immobilization of As, which continuously transports As from the upper to the lower part of a watershed and ultimately to the ocean. (C) 2004 Elsevier B.V. All rights reserved.

Comprendre la dispersion des espèces dans l'espace et dans le temps : un défi pour les biogéographes

De tout temps, l'homme s'est interrogé sur les facteurs qui régissent la distribution des espèces. Comment se dispersent-elles? Comment occupent-elles un milieu? Pourquoi certaines caractéristiques biologiques d'une même entité spécifique varient-elles en différents points de l'espace? Pour répondre à ces questions, il faut faire appel à de nombreuses disciplines scientifiques, telles que l'écologie, la géologie, la climatologie ou la paléontologie. Comprendre la distribution spatiale de la vie, quel que soit le niveau taxonomique, tel est l'objectif de la biogéographie

Microscopic and macroscopic polarization within a combined quantum mechanics and molecular mechanics model

A polarizable quantum mechanics and molecular mechanics model has been extended to account for the difference between the macroscopic electric field and the actual electric field felt by the solute molecule. This enables the calculation of effective microscopic properties which can be related to macroscopic susceptibilities directly comparable with experimental results. By seperating the discrete local field into two distinct contribution we define two different microscopic properties, the so-called solute and effective properties. The solute properties account for the pure solvent effects, i.e., effects even when the macroscopic electric field is zero, and the effective properties account for both the pure solvent effects and the effect from the induced dipoles in the solvent due to the macroscopic electric field. We present results for the linear and nonlinear polarizabilities of water and acetonitrile both in the gas phase and in the liquid phase. For all the properties we find that the pure solvent effect increases the properties whereas the induced electric field decreases the properties. Furthermore, we present results for the refractive index, third-harmonic generation (THG), and electric field induced second-harmonic generation (EFISH) for liquid water and acetonitrile. We find in general good agreement between the calculated and experimental results for the refractive index and the THG susceptibility. For the EFISH susceptibility, however, the difference between experiment and theory is larger since the orientational effect arising from the static electric field is not accurately described

Limitations of stimulated echo acquisition mode (STEAM) techniques in cardiac applications.

Stimulated echoes are widely used for imaging functional tissue parameters such as diffusion coefficient, perfusion, and flow rates. They are potentially interesting for the assessment of various cardiac functions. However, severe limitations of the stimulated echo acquisition mode occur, which are related to the special dynamic properties of the beating heart and flowing blood. To the well-known signal decay due to longitudinal relaxation and through-plane motion between the preparation and the read-out period of the stimulated echoes, additional signal loss is often observed. As the prepared magnetization is fixed with respect to the tissue, this signal loss is caused by the tissue deformation during the cardiac cycle, which leads to a modification of the modulation frequency of the magnetization. These effects are theoretically derived and corroborated by phantom and in vivo experiments.

Energy investment in gynes of the Argentine ant Iridomyrmex humilis (Mayr) in relation to the mode of colony founding in ants (Hymenoptera, Formicidae)

The increase in weight, fat and energy content of queens was studied in Iridomyrmex humilis (Mayr) in relation to the mode of colony founding in ants. The increase in energy content of gynes during the time between emergence and mating reaches only 80% in this species in which queens found colonies with the help of workers (dependent mode), whereas it can reach 470% in species in which queens found colonies without the help of workers (independent mode). These results are discussed with regard to the investment in energy required by each mode of colony founding.