A Novel Diagnostic Target in the Hepatitis C Virus Genome

BackgroundDetection and quantification of hepatitis C virus (HCV) RNA is integral to diagnostic and therapeutic regimens. All molecular assays target the viral 5'-noncoding region (59-NCR), and all show genotype-dependent variation of sensitivities and viral load results. Non-western HCV genotypes have been under-represented in evaluation studies. An alternative diagnostic target region within the HCV genome could facilitate a new generation of assays.Methods and FindingsIn this study we determined by de novo sequencing that the 3'-X-tail element, characterized significantly later than the rest of the genome, is highly conserved across genotypes. To prove its clinical utility as a molecular diagnostic target, a prototype qualitative and quantitative test was developed and evaluated multicentrically on a large and complete panel of 725 clinical plasma samples, covering HCV genotypes 1-6, from four continents (Germany, UK, Brazil, South Africa, Singapore). To our knowledge, this is the most diversified and comprehensive panel of clinical and genotype specimens used in HCV nucleic acid testing (NAT) validation to date. The lower limit of detection (LOD) was 18.4 IU/ml (95% confidence interval, 15.3-24.1 IU/ml), suggesting applicability in donor blood screening. The upper LOD exceeded 10(-9) IU/ml, facilitating viral load monitoring within a wide dynamic range. In 598 genotyped samples, quantified by Bayer VERSANT 3.0 branched DNA (bDNA), X-tail-based viral loads were highly concordant with bDNA for all genotypes. Correlation coefficients between bDNA and X-tail NAT, for genotypes 1-6, were: 0.92, 0.85, 0.95, 0.91, 0.95, and 0.96, respectively; X-tail-based viral loads deviated by more than 0.5 log10 from 5'-NCR-based viral loads in only 12% of samples (maximum deviation, 0.85 log10). The successful introduction of X-tail NAT in a Brazilian laboratory confirmed the practical stability and robustness of the X-tail-based protocol. The assay was implemented at low reaction costs (US$8.70 per sample), short turnover times (2.5 h for up to 96 samples), and without technical difficulties.ConclusionThis study indicates a way to fundamentally improve HCV viral load monitoring and infection screening. Our prototype assay can serve as a template for a new generation of viral load assays. Additionally, to our knowledge this study provides the first open protocol to permit industry-grade HCV detection and quantification in resource-limited settings.

Dinâmica Costeira dos Campos petrolíferos Macau/Serra, litoral setentrional do Estado do Rio Grande do Norte

This thesis describes the general behavior of the northern shore of the State of Rio Grande do Norte relating beach profile morphology with hydrodynamic and sedimentological parameters. The Macau and Serra Oil Field are inserted on this area and are under accelerated coastal erosion. At these oil fields are installed oil wells from PETROBRAS, nowadays located directly in the shoreline, under constant attacks of coastal processes (e.g. waves, tides and currents), which promote an intense morphodynamic variability of this sandy coast. The area was monitored for 24 months in three different stations (P01, P02 and P03). The methodology applied involved current techniques of beach profiles, hydrodynamical processes, remote sensing and geophysics. A synthesis of results obtained through the use of different time scales (monthly, lunar cycle, seasonal, annual) from a coastal dynamics study is presented. The average wind direction corresponded to 77ºAz (NE). The steepness of the berm and of the shoreface, as well as coastal current direction, do not present major changes, with an average of 36º for the steepness of the berm, 15º for the shoreface and 15º for the coastal current direction. This data set allows us to infer that the months of larger coastal erosion were November/2000 and April/2001, because of the largest wave parameter during this time. The months of worse coastal erosion in this area are related with the increasing wavy energy. This in turn, seems to be related to seasonal climatic variations, with the wave energy and tide currents speed increasing during months of minor precipitations (June to January). The months of worse coastal erosion were September and November, when the largest wave parameters and speed currents are measured in the area. Since these months are included on the period of minor precipitations, we related the coastal erosion to seasonal climatic variations. The results obtained during these 24 months of monitoring confirms a situation of accentuated erosion, mainly in Profile 03 (Barra do Corta-Cachorro), where the wave height, period, and coastal current speed are always larger than the values found in Profile 02 (Macau5). Probably these values are more expressive in Profile 03, because it does not present any natural structure of protection against the wave impacts, as the barrier island located at Ponta do Tubarão, or the sand banks in front of Macau5. The transport of the sediments occurs from East to West, and the sand accumulation is more pronounced on Profile 03 intertidal zone, where there are embrionary dunes in dryer months. The tidal currents speed, on the other hand, is more accentuated in the Macau5 area (Profile 02). At Ponta do Tubarão, the tidal currents presented a preferential direction for NE, at times of flood, currents and for NW, at times of ebb current; at Barra do Corta-Cachorro the direction of the currents were predominantly for NW, independent of the tide phase, coinciding with the preferential direction of the longshore current. This currents inversion at Ponta do Tubarão is attributed to the presence of the Ponta do Tubarão island barrier and by the communication channel of the lagoon with the sea. The tide currents are better observed in protected areas, as in the Ponta do Tubarão, when they present inversion in their direction accordingly to the flood and ebb tide. In open areas, as in Barra do Corta-Cachorro, the tide currents are overprinted by the longshore currents. Sediment analysis does not show important modifications in grain size related to seasonality (dry- and rainy seasons). On the foreshore and backshore zones, the sediments vary from fine to medium sand, while in the shoreface they very from fine to very sands. The grains are mostly spheres, varying from sub rounded to sub angled. Quartz is the main component alongside Feldspat and heavy minerals as accessory components. Biogenic content is also present and mainly represented by mollusks fragments. The calculated sediment transport show values around 100 m3/day. The morphodynamic studies indicated that this is a reflexive area from October to April, and intermediate from May to September. The Relative Tide Range-RTR for this area is 4 < RTR < 15, and so classified in the mixed wave-tide group. Having this exposed we can affirm that the more active natural factors in this area are the currents, followed by the tides and the winds. The anthropic factors are exclusively local and punctual (Macau and Serra Oil Field). Taking in account the economic importance of the area, as well as the intensity of coastal processes acting on this shore, it is important a continuity of the monthly environmental monitoring looking for variations on longer-period cycles. These data have been stored on the geo-referenced database of the projects MARPETRO and PETRORISCO (REDE 05), aiming to model the coastal and sea environment, susceptible to oil spills and their derivatives

Litoestratigrafia e deformação cenzóica na região de Icapuí, Ceará, e implicações para a estruturação de campos de petróleo na borda ocidental da bacia Potiguar(NE do Brasil)

This thesis deals with the sedimentological/stratigraphic and structural evolution of the sedimentary rocks that occur in the NW continental border of the Potiguar Basin. These rocks are well exposed along coastal cliffs between the localities of Lagoa do Mato and Icapuí, Ceará State (NE Brazil). The sedimentological/stratigraphic study involved, at the outcrop scale, detailed facies descriptions, profile mapping of the vertical succession of different beds, and columnar sections displaying inferred lateral relationships. The approach was complemented by granulometric and petrographic analyses, including the characterization of heavy mineral assemblages. The data set allowed to recognize two kinds of lithological units, a carbonate one of very restricted occurrence at the base of the cliffs, and three younger, distinct siliciclastic units, that predominate along the cliffs, in vertical and lateral extent. The carbonate rocks were correlated to the late Cretaceous Jandaíra Formation, which is covered by the siliciclastic Barreiras Formation. The Barreiras Formation occurs in two distinct structural settings, the usual one with nondeformed, subhorizontal strata, or as tilted beds, affected by strong deformation. Two lithofacies were recognized, vertically arranged or in fault contacts. The lower facies is characterized by silty-argillaceous sandstones with low-angle cross bedding; the upper facies comprises medium to coarse grained sandstones, with conglomeratic layers. The Tibau Formation (medium to coarse-grained sandstones with argillite intercalations) occurs at the NW side of the studied area, laterally interlayered with the Barreiras Formation. Eolic sediments correlated to the Potengi Formation overly the former units, either displaying an angular unconformity, or simply an erosional contact (stratigraphic unconformity). Outstanding structural features, identified in the Barreiras Formation, led to characterize a neocenozoic stress field, which generated faults and folds and/or reactivated older structures in the subjacent late cretaceous (to paleogene, in the offshore basin) section. The structures recognized in the Barreiras Formation comprise two distinct assemblages, namely a main extensional deformation between the localities of Ponta Grossa and Redonda, and a contractional style (succeeded by oblique extensional structures) at Vila Nova. In the first case, the structural assemblage is dominated by N-S (N±20°Az) steep to gently-dipping extensional faults, displaying a domino-style or listric geometry with associated roll-over structures. This deformation pattern is explained by an E-W/WNW extension, contemporaneous with deposition of the upper facies of the Barreiras Formation, during the time interval Miocene to Pleistocene. Strong rotation of blocks and faults generated low-angle distensional faults and, locally, subvertical bedding, allowing to estimate very high strain states, with extension estimates varying between 40% up to 200%. Numerous detachment zones, parallel to bedding, help to acommodate this intense deformation. The detachment surfaces and a large number of faults display mesoscopic features analoguous to the ones of ductile shear zones, with development of S-C fabrics, shear bands, sigmoidal clasts and others, pointing to a hydroplastic deformation regime in these cases. Local occurrences of the Jandaíra limestone are controled by extensional faults that exhume the pre-Barreiras section, including an earlier event with N-S extension. Finally, WNWtrending extensional shear zones and faults are compatible with the Holocene stress field along the present continental margin. In the Vila Nova region, close to Icapuí, gentle normal folds with fold hinges shallowly pluging to SSW affect the lower facies of the Barreiras Formation, displaying an incipient dissolution cleavage associated with an extension lineation at high rake (a S>L fabric). Deposition of the upper facies siliciclastics is controlled by pull-apart graben structures, bordered by N-NE-trending sinistral-normal shear zones and faults, characterizing an structural inversion. Microstructures are compatible with tectonic deformation of the sedimentary pile, burried at shallow depths. The observed features point to high pore fluid pressures during deformation of the sediments, producing hydroplastic structures through mechanisms of granular flow. Such structures are overprinted by microfractures and microfaults (an essentially brittle regime), tracking the change to microfracturing and frictional shear mechanisms accompanying progressive dewatering and sediment lithification. Correlation of the structures observed at the surface with those present at depth was tested through geophysical data (Ground Penetrating Radar, seismics and a magnetic map). EW and NE-trending lineaments are observed in the magnetic map. The seismic sections display several examples of positive flower structures which affect the base of the cretaceous sediments; at higher stratigraphic levels, normal components/slips are compatible with the negative structural inversion characterized at the surface. Such correlations assisted in proposing a structural model compatible with the regional tectonic framework. The strong neogenepleistocene deformation is necessarily propagated in the subsurface, affecting the late cretaceous section (Açu and Jandaíra formations), wich host the hydrocarbon reservoirs in this portion of the Potiguar Basin. The proposed structural model is related to the dextral transcurrent/transform deformation along the Equatorial Margin, associated with transpressive terminations of E-W fault zones, or at their intersections with NE-trending lineaments, such as the Ponta Grossa-Fazenda Belém one (the LPGFB, itself controlled by a Brasiliano-age strike-slip shear zone). In a first step (and possibly during the late Cretaceous to Paleogene), this lineament was activated under a sinistral transpressional regime (antithetic to the main dextral deformation in the E-W zones), giving way to the folds in the lower facies of the Barreiras Formation, as well as the positive flower structures mapped through the seismic sections, at depth. This stage was succeeded (or was penecontemporaneous) by the extensional structures related to a (also sinistral) transtensional movement stage, associated to volcanism (Macau, Messejana) and thermal doming processes during the Neogene-Pleistocene time interval. This structural model has direct implications to hydrocarbon exploration and exploitation activities at this sector of the Potiguar Basin and its offshore continuation. The structure of the reservoirs at depth (Açu Formation sandstones of the post-rift section) may be controlled (or at least, strongly influenced) by the deformation geometry and kinematics characterized at the surface. In addition, the deformation event recognized in the Barreiras Formation has an age close to the one postulated for the oil maturation and migration in the basin, between the Oligocene to the Miocene. In this way, the described structural cenario represents a valid model to understand the conditions of hydrocarbon transport and acummulation through space openings, trap formation and destruction. This model is potentially applicable to the NW region of the Potiguar Basin and other sectors with a similar structural setting, along the brazilian Equatorial Atlantic Margin

Uma abordagem no ensino de frações baseadas em atividades para o 6º ano do ensino fundamantal

The objective of this work if constitutes in creation a proposal for activities, in the discipline of mathematics, for the 6th year of Elementary School, that stimulates the students the develop the learning of the content of fractions, from the awareness of the insufficiency of the natural numbers for solve several problems. Thus, we prepared a set with twelve activities, starting by the comparison between measures, presenting afterward some of the meanings of fractions and ending with the operations between fractions. For so much, use has been made of materials available for use in the classroom, of forma ludic, for resolution of challenges proposed. Through these activities, it becomes possible students to recognize the necessity of using fractions for solve a amount larger of problems

Análise multitemporal dos elementos geoambientais da região da Ponta do Tubarão, área de influência dos campos petrolíferos de Macau e Serra, município de Macau/RN

The study area is inserted in Ponta do Tubarão region, Macau City, setentrional littoral of Rio Grande do Norte State, composed of Tertiary and Quatemary sedimentary rocks and sediments. This region is characterized for the intense action of the coastal processes, causing the morphologic instability in part of the area, beyond the interference of human activities, as the Petroliferous Industrial Polo, salt companies and shrimp farms. This justifies the integration of multidisciplinary and multitemporal detailed scientific studies dealing with the evaluation of the changing behavior of this coastal environment by geoenvironments elements characterization, identifying protected and recuperation areas, mainly those under socioeconomic intervention. The main objective was the coastal monitoring using geoprocessing techniques to prepare thematic maps useful for oil spilling environment risk areas survey. The methodology was based on multitemporal interpretation of remote sensing images and field checking, integrated in a Geographical Information System (GIS). The Geologic, Geomorphologic, Vegetation, Soil and Land Use maps were prepared, and later on they allowed the generation of the Natural Vulnerability and Environmental Vulnerability maps. These maps had been classified in accordance with vulnerability degrees: very low, low, medi um, high and very high. Beyond these maps the GIS allowed the analysis of the shoreline evolution for 10 distinct dates, using Landsat 5 TM and 7 ETM+ and SPOT-HRVIR images. This analysis made possible the attendance of the coastal morphodynamic evolution, where the results had been represented by areasof erosion and accretion (or deposition) of sediments, pointing critical areas under erosive process to the petroliferous industry (Macau and Serra fields). The GIS also provided to prepare the Environmental Sensitivity Maps of Oil Spill (SAO Maps) in operational scale (1: 10.000), according to the norms ofthe Ministério do Meio Ambiente (MMA 2002). The SAO Map in operational scale was based on IKONOS images mosaic where the ESI (Environmental Sensitivity Index) was represented according with two tides phases of theregion. Therewere recognizedfiveESI (3, 4,7,9, 1O) for the low tide; to the high tide the ESI number increased to seven (3, 4, 5, 7, 8, 9, 10). All these information are necessary to the decisions making about oi! spill and its derivatives containment. These techniques application makes possible the optimization and implantation ofnew socioeconomics activities of low environmental impact, indicates areas for better productivity and security exploration, and benefits local communities with fauna and flora preservation. The development of these activities is inserted in the scope of Monitoramento Ambiental de Áreas de Risco a Derrames de Petróleo e Seus Derivados Cooperation Project (Rede 05/01 - PETRORISCO, FINEP/CTPETRO/PETROBRAS) of multidisciplinary and interinstitucional characteristics dealing with subjects involving the environmental monitoring and the petroliferous activity

Effect of obesity on rat reproduction and on the development of their adult offspring

The aim of the present study was to assess the reproductive parameters of obese Wistar rats and to determine the frequency of their obese adult offspring. Neonatal rats were divided into two groups: F-1 generation, induced to obesity by monosodium glutamate (MSG; F(1)MSG, N = 30), and rats given saline (F1CON, N = 13). At 90 days of age all animals were mated, producing the F-2 offspring (F2CON, N = 28; F(2)MSG, N = 15). Reproductive parameters (fertility, pregnancy, and delivery indexes) were evaluated in F-1 rats. F-2 newborns were weighed, and the obesity parameter for F-1 and F-2 generations was determined from months 5 to 7 of life. At month 7, periovarian fat was weighed and no differences were found. Mean newborn weight also did not differ. The F-1 and F(2)MSG groups presented approximately 90% of obese rats since month 5 of life, whereas F-1 and F2CON groups presented only 33%. There was no difference in periovarian weight among groups. Although obesity did not affect reproductive parameters, obese dams (F(1)MSG) were responsible for the appearance of obesity in the subsequent generation. Thus, obesity induced by neonatal MSG administration did not interfere with reproduction, but did provide a viable model for obesity in second-generation adult Wistar rats. This model might contribute to a better understanding of the pathophysiological mechanisms involved in transgenerational obesity.

Maternal-Fetal Outcome, Lipid Profile and Oxidative Stress of Diabetic Rats Neonatally Exposed to Streptozotocin

Background: There is no evidence about the integrated issue on glycemia, lipid profile, oxidative stress, and anomaly frequency of pregnant diabetic rats neonatally exposed to streptozotocin.Objective: Evaluating the impact of hyperglycemia in diabetic rats neonatally exposed to streptozotocin on maternal reproductive and fetal outcomes and the relationship with lipid profile and maternal oxidative stress.Material and Methods: Ten 90-day-old female Wistar rats were mated to obtain offspring. Some of these newborns received streptozotocin (70 mg/kg, i.p. - n5-STZ group) and the remainder given only citrate buffer (control group) on their day 5 of life. At adult life, these rats (n =13 animals/group) were mated and, at day 21 of pregnancy, they were killed to obtain a maternal blood samples for biochemical determinations. The gravid uterus was weighed with its contents and fetuses were analyzed.Results: At day 0 of pregnancy, glycemic means of n5-STZ rats were significantly greater compared to those of control rats, but presented fetuses classified as small for pregnancy age. The n5-STZ rats showed increased total cholesterol, triglycerides, MDA concentrations, lower SOD activity and increased frequency fetal visceral anomalies as compared to the control group.Conclusion: This study showed that the experimental model used led to mild hyperglycemia during pregnancy, although it did not lead to increased macrosomic fetus rates. The hyperglycemic maternal environment caused metabolic alterations, including increased triglyceride and total cholesterol concentrations, and elevated oxidative stress, contributing to increase fetal visceral anomalies.

Effects of exposure to cigarette smoke prior to pregnancy in diabetic rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of Passiflora edulis (Yellow Passion) on Serum Lipids and Oxidative Stress Status of Wistar Rats

The aim of this study was to evaluate the effects of Passiflora edulis f. flavicarpa Degener (yellow passion) juice on the lipid profile and oxidative stress status of Wistar rats. Adult male Wistar rats were divided in two groups (n = 8 animals per group): the control group, which received water, and the treated group, which was given P. edulis juice (1,000 mg/kg). Both groups received by gavage treatment twice a day for 28 days. The treated group showed an increased high-density lipoprotein-cholesterol level and decreased low-density lipoprotein-cholesterol and free fatty acid levels compared with the control group. Levels of triglycerides and and very low-density lipoprotein-cholesterol, superoxide dismutase activity, and total glutathione concentration were not statistically different between the two groups, but the thiobarbituric acid-reactive substances concentration (indicating lipid peroxidation) decreased in the treated group. These findings suggests that P. edulis juice in the experimental conditions used showed beneficial effects on lipid profile and improved lipid peroxidation in Wistar rats.

Avaliação do efeito do exercício físico no metabolismo de ratas diabéticas prenhes

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Neonatally-induced diabetes: lipid profile outcomes and oxidative stress status in adult rats

INTRODUÇÃO: Modelos experimentais são desenvolvidos com propósito de ampliar o entendimento dos mecanismos fisiopatológicos envolvidos no diabete. Os achados experimentais levam ao desenvolvimento de tratamentos alternativos para a manutenção das condições metabólicas normais. Existem vários estudos sobre o diabete induzido por streptozotocin mimetizando o quadro clínico do DM2. No entanto, a interação entre os níveis de glicose, perfil lipídico e estresse oxidativo nestes animais são escassos. Portanto, o objetivo do trabalho foi avaliar estes parâmetros em ratas Wistar adultas com diabete induzido com streptozotocin no período neonatal. MÉTODOS: Fêmeas recém-nascidas receberam streptozotocin (70mg/Kg, ip) no 5º dia de vida (n5-STZ). A glicemia foi medida no terceiro e quarto meses de vida dos animais. No final do quarto mês de vida, amostras de sangue foram coletadas e processadas para a dosagem de lipídios e marcadores de estresse oxidativo. RESULTADOS: A glicemia das ratas do grupo n5-STZ foi significativamente maior comparada às ratas do grupo controle (p<0,05). Não houve alteração nos níveis de colesterol total e triglicérides, peroxidação lipídica (TBARS), atividade da SOD e determinação da GSH-t (p>0,05) nas ratas n5-STZ em relação às ratas do grupo controle. No entanto, houve diminuição significativa no HDL-colesterol (p<0,05). CONCLUSÃO: Este modelo de indução de diabete em ratas causou hiperglicemia (120-360mg/dL), caracterizando o diabete moderado. Essa glicemia levou a alterações no HDL-colesterol, a qual não foi suficiente para prejudicar a atividade das enzimas antioxidantes ou marcadores da peroxidação lipídica na vida adulta. Além disso, esta investigação experimental contribuiu para entender os diferentes resultados encontrados em outros modelos deindução do diabete moderado em animais de laboratório, como também para a melhor compreensão dos mecanismos fisiopatológicos do diabete moderado ou da hiperglicemia em humanos.

Effect of Morus nigra aqueous extract treatment on the maternal-fetal outcome, oxidative stress status and lipid profile of streptozotocin-induced diabetic rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Commissural nucleus of the solitary tract is important for cardiovascular responses to caudal pressor area activation

The nucleus of the solitary tract (NTS) is the site of the first synapse of cardiovascular afferent fibers in the central nervous system. Important mechanisms for cardiovascular regulation are also present in the caudal pressor area (CPA) localized at the caudal end of the ventrolateral medulla. In the present study we sought to investigate the role of the commissural subnucleus of the NTS (commNTS) on pressor and tachycardic responses induced by L-glutamate injected into the CPA. Male Holtzman rats (n=8 rats/group) anesthetized with urethane (1.2 g/kg of body weight, iv) received injections of the GABAA receptor agonist muscimol into the commNTS. Unilateral injection of L-glutamate (10 nmol/ 100 nL) into the CPA increased mean arterial pressure (MAP, 31 4 mm Hg, vs. saline: 3 +/- 2 mm Hg) and heart rate (HR, 44 8 bpm, vs. saline: 10 7 bpm). inhibition of commNTS neurons with muscimol (120 pmol/60 nL) abolished the increase in MAP (9 4 mm Hg) and HR (17 7 bpm) produced by L-glutamate into the CPA. The present results suggest that the pressor and tachycardic responses to CPA activation are dependent on commNTS mechanisms.

Customized fiber glass posts. Fatigue and fracture resistance

Purpose: To evaluate the root fracture strength of human single-rooted premolars restored with customized fiberglass post-core systems after fatigue simulation. Methods: 40 human premolars had their crowns cut and the root length was standardized to 13 mm. The teeth were endodontically treated and embedded in acrylic resin. The specimens were distributed into four groups (n=10) according to the restorative material used: prefabricated fiber post (PFP), PFP+accessory fiber posts (PFPa), PFP+unidirectional fiberglass (PFPf), and unidirectional fiberglass customized post (CP). All posts were luted using resin cement and the cores were built up with a resin composite. The samples were stored for 24 hours at 37 degrees C and 100% relative humidity and then submitted to mechanical cycling. The specimens were then compressive-loaded in a universal testing machine at a crosshead speed of 0.5 mm/minute until fracture. The failure patterns were analyzed and classified. Data was submitted to one-way ANOVA and Tukey's test (alpha= 0.05). Results: The mean values of maximum load (N) were: PFP - 811.4 +/- 124.3; PFPa - 729.2 +/- 157.2; PFPf - 747.5 +/- 204.7; CP - 762.4 +/- 110. Statistical differences were not observed among the groups. All groups showed favorable restorable failures. Fiberglass customized post did not show improved fracture resistance or differences in failure patterns when compared to prefabricated glass fiber posts. (Am J Dent 2012;25:35-38).

High-Intensity Resistance Training with Insufficient Recovery Time Between Bouts Induce Atrophy and Alterations in Myosin Heavy Chain Content in Rat Skeletal Muscle

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)