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Chagas disease, caused by Trypanosoma cruzi (T. cruzi), is a serious public health problem. Current treatment is restricted to two drugs, benznidazole and nifurtimox, displaying serious efficacy and safety drawbacks. Nucleoside analogues represent a promising alternative as protozoans do not biosynthesize purines and rely on purine salvage from the hosts. Protozoan transporters often present different substrate specificities from mammalian transporters, justifying the exploration of nucleoside analogues as therapeutic agents. Previous reports identified nucleosides with potent trypanocidal activity; therefore, two 7-derivatized tubercidins (FH11706, FH10714) and a 3′-deoxytubercidin (FH8513) were assayed against T. cruzi. They were highly potent and selective, and the uptake of the tubercidin analogues appeared to be mediated by the nucleoside transporter TcrNT2. At 10 μM, the analogues reduced parasitemia >90% in 2D and 3D cardiac cultures. The washout assays showed that FH10714 sterilized the infected cultures. Given orally, the compounds did not induce noticeable mouse toxicity (50 mg/kg), suppressed the parasitemia of T. cruzi-infected Swiss mice (25 mg/kg, 5 days) and presented DNA amplification below the limit of detection. These findings justify further studies with longer treatment regimens, as well as evaluations in combination with nitro drugs, aiming to identify more effective and safer therapies for Chagas disease.

The reaction 17O(n, α)14C was studied using virtual neutrons coming from the quasi-free deuteron break-up in the three body reaction 17O+d → α+14C+p. This technique, called virtual neutron method, extends the Trojan Horse method to neutron-induced reactions allowing to study the reaction cross section avoiding the suppression effects coming from the penetrability of the centrifugal barrier. For incident neutron energies from thermal up to a few hundred keV, direct experiments have shown the population of two out of three expected excited states at energies 8213 keV and 8282 keV and the influence of the sub-threshold level at 8038 keV. In the present experiment the 18O excited state at E* = 8.125 MeV, missing in the direct measurement, is observed. The angular distributions of the populated resonances have been measured for the first time. The results unambiguously indicate the ability of the method to overcome the centrifugal barrier suppression effect and to pick out the contribution of the bare nuclear interaction.

The question of whether language affects our categorization of perceptual continua is of particular interest for the domain of color where constraints on categorization have been proposed both within the visual system and in the visual environment. Recent research (Roberson, Davies, & Davidoff, 2000; Roberson et al., in press) found substantial evidence of cognitive color differences between different language communities, but concerns remained as to how representative might be a tiny, extremely remote community. The present study replicates and extends previous findings using additional paradigms among a larger community in a different visual environment. Adult semi-nomadic tribesmen in Southern Africa carried out similarity judgments, short-term memory and long-term learning tasks. They showed different cognitive organization of color to both English and another language with the five color terms. Moreover, Categorical Perception effects were found to differ even between languages with broadly similar color categories. The results provide further evidence of the tight relationship between language and cognition.

Leishmania is a trypanosomatid parasite that causes skin lesions in its cutaneous form. Current therapies rely on old and expensive drugs, against which the parasites have acquired considerable resistance. Trypanosomatids are unable to synthesize purines relying on salvaging from the host, and nucleoside analogues have emerged as attractive antiparasitic drug candidates. 4-Methyl-7-β-D-ribofuranosyl-7H-pyrrolo[2,3-d]pyrimidine (CL5564), an analogue of tubercidin in which the amine has been replaced by a methyl group, demonstrates activity against Trypanosoma cruzi and Leishmania infantum. Herein, we investigated its in vitro and in vivo activity against L. amazonensis. CL5564 was 6.5-fold (P = 0.0002) more potent than milteforan™ (ML) against intracellular forms in peritoneal mouse macrophages, and highly selective, while combination with ML gave an additive effect. These results stimulated us to study the activity of CL5564 in mouse model of cutaneous Leishmania infection. BALB/c female and male mice infected by L. amazonensis treated with CL5564 (10 mg kg−1, intralesional route for five days) presented a >93% reduction of paw lesion size likely ML given orally at 40 mg kg−1, while the combination (10 + 40 mg kg−1 of CL5564 and ML, respectively) caused >96% reduction. The qPCR confirmed the suppression of parasite load, but only the combination approach reached 66% of parasitological cure. These results support additional studies with nucleoside derivatives.

We investigate the [L.sub.2] gain of periodic linear switched systems under fast switching. For systems that possess a suitable notion of a time-average system, we characterize the relationship between the [L.sub.2] gain of the switched system and the [L.sub.2] gain of its induced time-average system when the switching rate is sufficiently fast. We show that the switched system [L.sub.2] gain is in general different from the average system [L.sub.2] gain if the input or output coefficient matrix switches. If only the state coefficient matrix switches, the input-output energy gain for a fixed [L.sub.2] input signal is bounded by the [L.sub.2] gain of the average system as the switching rate grows large. Additionally, for a fixed [L.sub.2] input, the maximum pointwise in time difference between the switched and average system outputs approaches zero as the switching rate grows. Index Terms--Fast switching, [L.sub.2] gain analysis, switched systems.

Nesta obra, o autor apresenta uma proposta teórico-metodológica para a pesquisa sócio-espacial. Aqui, ressalta-se que o termo apresentado com o “hífen” se refere não apenas ao espaço produzido pela sociedade, mas sim, a todas as relações e interações que se estabelecem a partir de um determinado processo, seja qual ele produtivo, de lazer, enfim, desde que delimitado por uma espacialidade.