A new class of survival regression models with heavy-tailed errors: robustness and diagnostics

Birnbaum-Saunders models have largely been applied in material fatigue studies and reliability analyses to relate the total time until failure with some type of cumulative damage. In many problems related to the medical field, such as chronic cardiac diseases and different types of cancer, a cumulative damage caused by several risk factors might cause some degradation that leads to a fatigue process. In these cases, BS models can be suitable for describing the propagation lifetime. However, since the cumulative damage is assumed to be normally distributed in the BS distribution, the parameter estimates from this model can be sensitive to outlying observations. In order to attenuate this influence, we present in this paper BS models, in which a Student-t distribution is assumed to explain the cumulative damage. In particular, we show that the maximum likelihood estimates of the Student-t log-BS models attribute smaller weights to outlying observations, which produce robust parameter estimates. Also, some inferential results are presented. In addition, based on local influence and deviance component and martingale-type residuals, a diagnostics analysis is derived. Finally, a motivating example from the medical field is analyzed using log-BS regression models. Since the parameter estimates appear to be very sensitive to outlying and influential observations, the Student-t log-BS regression model should attenuate such influences. The model checking methodologies developed in this paper are used to compare the fitted models.

Ultrasensitive Simultaneous Quantification of 1,N(2)-Etheno-2 `-deoxyguanosine and 1,N(2-)Propano-2 `-deoxyguanosine in DNA by an Online Liquid Chromatography-Electrospray Tandem Mass Spectrometry Assay

Exocyclic DNA adducts produced by exogenous and endogenous compounds are emerging as potential tools to study a variety of human diseases and air pollution exposure. A highly sensitive method involving online reverse-phase high performance liquid chromatography with electrospray tandem mass spectrometry detection in the multiple reaction monitoring mode and employing stable isotope-labeled internal standards was developed for the simultaneous quantification of 1,N(2)-etheno-2`-deoxyguanosine (1,N(2)-epsilon dGuo) and 1,N(2)-propano-2`-deoxyguanosine (1,N(2)-propanodGuo) in DNA. This methodology permits direct online quantification of 2`-deoxyguanosine and ca. 500 amol of adducts in 100 mu g of hydrolyzed DNA M the same analysis. Using the newly developed technique, accurate determinations of 1,N(2)-etheno-2`-deoxyguanosine and 1,N2-propano-2`-deoxyguanosine levels in DNA extracts of human cultured cells (4.01 +/- 0.32 1,N(2)-epsilon dGuo/10(8) dGuo and 3.43 +/- 0.33 1,N(2)-propanodGuo/10(8) dGuo) and rat tissue (liver, 2.47 +/- 0.61 1,N(2)-epsilon dGuo/10(8) dGuo and 4.61 +/- 0.69 1,N(2)-propanodGuo/108 dGuo; brain, 2.96 +/- 1.43,N(2)-epsilon dGuo/10(8) dGuo and 5.66 +/- 3.70 1,N(2)-propanoclGuo/10(8) dGuo; and lung, 0,87 +/- 0.34 1,N(2)-edGuo/ 10(8) dGuo and 2.25 +/- 1.72 1,N(2)-propanodGuo/10(8) dGuo) were performed. The method described herein can be used to study the biological significance of exocyclic DNA adducts through the quantification of different adducts in humans and experimental an with pathological conditions and after air pollution exposure.

Schistosoma mansoni: In vitro schistosomicidal activity of piplartine

Schistosomiasis is one of the world`s greatly neglected tropical diseases, and its control is largely dependent on a single drug, praziquantel. Here, we report the in vitro effect of piplartine, an amide isolated from Piper tuberculatum (Piperaceae), on Schistosoma mansoni adult worms. A piplartine concentration of 15.8 mu M reduced the motor activity of worms and caused their death within 24 h in a RPMI 1640 medium. Similarly, the highest sub-lethal concentration of piplartine (6.3 mu M) caused a 75% reduction in egg production in spite of coupling. Additionally, piplartine induced morphological changes on the tegument, and a quantitative analysis carried out by confocal microscopy revealed an extensive tegumental destruction and damage in the tubercles. This damage was dose-dependent in the range of 15.8-630.2 mu M. At doses higher than 157.6 mu M, piplartine induced morphological changes in the oral and ventral sucker regions of the worms. It is the first time that the schistosomicidal activity has been reported for piplartine. Published by Elsevier Inc.

Determination of lipophilic and hydrophilic antioxidants in Solanum Lycopersicum L. tomato from Gordal variety by LL-USAE combined with UHPLC-PDA/FLR

Tomato (Lycopersicon esculentum L.) is one of the main constituents of the Mediterranean diet. Its consumption has been proposed to reduce the risk of cardiovascular diseases and certain types of cancer. It is therefore one of the most popular and extensively consumed vegetable crop worldwide. To gain insights on the potential of Lycopersicon esculentum L. as bioactive food, two analytical methodologies were developed to determine the levels of the lipophilic -tocopherol, α-tocopherol, β-carotene, lycopene; and hydrophilic antioxidants ascorbic acid. The quantification of total carotenoids (β-carotene and lycopene) was assessed through a liquid–liquid ultrasound assisted extraction (LL-USAE) in combination with ultraviolet-visible spectroscopy (UV-Vis), according to method of mean, for total carotenoids (λmáx = 450 nm. The ultra-high performance liquid chromatographic using both photodiode array and fluorescence detection (UHPLC-PDA/FLR), allows the identification and quantification of the target lipophilic and hydrophilic antioxidants. This methodology UHPLC-PDA/FLR is fast, simple and revealed a high sensitivity for the compounds under study. The limits of detection (LODs) and quantification (LOQs) obtained were much lower (about 10 times) than the reported in literature. The method LL-USAE/UV-Vis was validated and applied to different tomato foodstuffs. The results reveal a small increase of carotenoids content during maturation, reaching the maximum level when ripe. These results complement those obtained by the ORAC and TBARS assays that show an increase of antioxidant capacity during maturation. The LODs ans LOQs obtained were also about 10 times lower than reported in literature. The carotenoid content was also evaluated by LL-USAE/UV-Vis in different tomatoes varieties. Regional variety present the high carotenoid level, followed by campari and gordal, and at last grape. This methodology was also applied to different processed food samples containing tomatoes derivatives. Highest carotenoids content were obtained in concentrated tomato foodstuffs.

PEGylated polyethyleneimine-entrapped gold nanoparticles for enhanced and targeted gene delivery applications

Gene therapy, which involves the transfer of nucleic acid into target cells in patients, has become one of the most important and widely explored strategies to treat a variety of diseases, such as cancer, infectious diseases and genetic disorders. Relative to viral vectors that have high immunogenicity, toxicity and oncogenicity, non-viral vectors have gained a lot of interest in recent years. This is largely due to their ability to mimic viral vector features including the capacity to overcome extra- and intra-cellular barriers and to enhance transfection efficiency. Polyethyleneimine (PEI) has been extensively investigated as a non-viral vector. This cationic polymer, which is able to compact nucleic acid through electrostatic interactions and to transport it across the negatively charged cell membranes, has been shown to effectively transfect nucleic acid into different cell lines. Moreover, entrapment of gold nanoparticles (Au NPs) into such an amine-terminated polymer template has been shown to significantly enhance gene transfection efficiency. In this work, a novel non-viral nucleic acid vector system for enhanced and targeted nucleic acid delivery applications was developed. The system was based on the functionalization of PEI with folic acid (FA; for targeted delivery to cancer cells overexpressing FA receptors on their surface) using polyethylene glycol (PEG) as a linker molecule. This was followed by the preparation of PEI-entrapped Au NPs (Au PENPs; for enhancement of transfection efficiency). In the synthesis process, the primary amines of PEI were first partially modified with fluorescein isothiocyanate (FI) using a molar ratio of 1:7. The formed PEI-FI conjugate was then further modified with either PEG or PEGylated FA using a molar ratio of 1:1. This process was finally followed by entrapment of Au NPs into the modified polymers. The resulting conjugates and Au PENPs were characterized by several techniques, namely Nuclear Magnetic Resonance, Dynamic Light Scattering and Ultraviolet-Visible Spectroscopy, to assess their physicochemical properties. In the cell biology studies, the synthesized conjugates and their respective Au PENPs were shown to be non-toxic towards A2780 human ovarian carcinoma cells. The role of these materials as gene delivery agents was lastly evaluated. In the gene delivery studies, the A2780 cells were successfully transfected with plasmid DNA using the different vector systems. However, FA-modification and Au NPs entrapment were not determinant factors for improved transfection efficiency. In the gene silencing studies, on the other hand, the Au PENPs were shown to effectively deliver small interfering RNA, thereby reducing the expression of the B-cell lymphoma 2 protein. Based on these results, we can say that the systems synthesized in this work show potential for enhanced and targeted gene therapy applications.

The effectiveness of community-based interventions to improve maternal and infant health in the Northeast of Brazil

EMOND, Alan et al. The effectiveness of community-based interventions to improve maternal and infant health in the Northeast of Brazil. Revista Panamericana de Salud Pública/ Pan American Journal of Public Health , v.12, n.2, p.101-110, 2002

Clonagem e expressão do gene que codifica o inibidor de quimotripsina de Erythrina velutina WILLD. - caracterização e avaliação de seu potencial farmacológico

Proteinases are enzymes distributed widely founded in several organisms and perform many different functions, from maintaining homeostasis to the worsening of some diseases such as cancer, autoimmune diseases and infections. The proteins responsible of controlling the action of these enzymes are the inhibitors, that are classified based on their target proteases and are founded since simple organisms, such as bacteria, to higher organisms, such as larger plants and mammals. Plant proteinase inhibitors act by reducing or inactivating the activity of target proteases, thus, these proteins have been studied as potential tools in the treatment of diseases related to protease activities. In this context, an inhibitor of chymotrypsin from Erythrina velutina, called EvCI was previously purified and it was observed that this protein plays in vitro anticoagulant activity and anti-inflammatory activity in in vivo model. Aiming to reduce the environmental impact caused by the purification EvCI in high amounts and to facilitate the process of obtaining this protein, the recombinant chymotrypsin inhibitor from Eryhrina velutina was produced after cloning and expression in Escherichia coli. The bacteria were grown in LB medium and after induction of the expression this material was subjected to procedures for cell lysis and the product was applied on Nickel-affinity column. The proteins adsorbed were digested by thrombin and applied on Chymotrypsin-Sepharose affinity column, obtaining the purified inhibitor, named recEvCI. After electrophoresis, the recombinant inhibitor showed an approximately molecular mass of 17 kDa, and reduced the chymotrypsin and elastase activities in vitro. The recombinant inhibitor was sequenced and was found similar amino acids residues when compared to other inhibitors deposited in the database, with some modifications. recEvCI showed high stability under pH variations and reducing conditions, maintaining its activity around 80%. This protein increased the blood coagulation time in vitro by acting on the intrinsic pathway and did not show cytotoxicity against strains of mouse 3T3 fibroblasts and RAW 264.7 macrophages. recEvCI showed microbicide activity related to release of nitric oxide and consequently the activation of macrophages, futhermore having proinflammatory effects assessed by increased release of TNF-α. These results indicate that recEvCI can be biotechnologically used as a new tool in the control of coagulation-related diseases as well as can be an activating agent of the immune system in immunosuppressed individuals

Produção de mudas de maracujazeiro-amarelo por enxertia hipocotiledonar sobre sete espécies de passifloras

The yellow passion fruit (Passiflora edulis Sims f. flavicarpa Deg.) Passifloraceae is the main crop in Brazil, and the crop has found some difficulties, particularly concerned to the orchards longevity, which has been reduced due to diseases and nematodes that attack the root system. This study was carried out to establish technologies for the production of seedlings of yellow passion fruit by hypocotyledonary grafting on seven rootstocks. The treatments used as rootstocks were: P. edulis f. flavicarpa, P. caerulea, P. alata, P. giberti, P. coccinea, P. cincinnata and P. setacea. The experimental design was completely randomized, with 36 replications for each rootstock. The percentage of graft survival, plant height, number of leaves and rootstock diameter were the characteristics evaluated. The hypocotyledonary grafting methodology was successful for most species tested. P. caerulea, P. giberti, P. cincinnata and P. flavicarpa were the stood out rootstocks by their high conditions of plants growth, and by their early plants production.

Primeiro registro de Fidicinoides picea (Walker, 1850) e Fidicinoides poulaini Boulard & Martinelli, 1996 no Brasil

As cigarras são importantes pragas de diversas culturas, entre plantas cultivadas e ornamentais. Estudos de taxonomia e morfologia de insetos são primordiais para pesquisas etológicas e para o emprego de métodos de controle. Ao estudar coleções entomológicas de cigarras, foi constatado o primeiro registro de ocorrência de Fidicinoides picea e Fidicinoides poulaini (Hemiptera: Cicadidae) no Brasil, espécies coletadas nos Estados do Pará e de Manaus, respectivamente. Neste trabalho, são apresentadas as descrições morfológicas da cabeça, do tórax, do abdome e da asa.

Dinâmica populacional de ovos e lagartas e parasitismo de ovos de Curuquerê-do-algodoeiro por Trichogramma pretiosum em cultivares convencionais e transgênica de algodoeiro

The introduction of new cotton cultivars in the Midwest region of Brazil resulted in a significant increase in productivity, but the use of inappropriate farming techniques brought many problems to field, as the higher incidence of pests, diseases and weeds. The aim of this work was to study the population dynamics of eggs and larvae of cotton leafworm and natural egg parasitism of the pest by Trichogramma pretiosum Riley (Hymenoptera: Trichogrammatidae) at different phenological stages of conventional and transgenic cultivars (Bollgard I) of cotton was carried out this experiment from December 2007 to April 2008 in Ipameri, Goias State, Brazil. The experimental design was a randomized blocks with five trataments and four replications. The treatments consisting of the conventional cotton cultivars DeltaOPAL, FMX 966, FMX 993, FMX 910 and the cultivar transgenic NuOPAL. Allabama argillacea Hubner (Lepidoptera: Noctuidae) oviposited on all cultivars, not presented differences in relation to oviposition preference. Compared to the average number of eggs of A. argillacea parasitized by T. pretiosum, there were no differences between cultivars. In conventional cultivars, small, medium and large larvae occurred from 34 days after plant emergence until the end of the cycle, while in the transgenic cultivar were found only small caterpillars. Cultivar NuOPAL control cotton leafworm since the first larval stage, and does not interfere in egg parasitism by T. pretiosum compared with other cultivars.

Association between MUC1 gene polymorphism and expected progeny differences in Nelore cattle (Bos primigenius indicus)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação da esporulação de Bionectria ochroleuca em diferentes meios de culturas

The biological control of the plants diseases, caused by fungi, is carried out using others organisms (predator, parasite or pathogen). Among the possible agents of biocontrol, a fungus has been highlighting as promising and it is known as Clonostachys rosea, asexual form of Bionectria ochroleuca. For that, it is necessary the in vitro production of spores of this fungus. In this study were tested several culture media to select those with better conidia production. The study was conducted at Plant Protection Division, in the Plant Production Department, FCA - UNESP, Botucatu campus, São Paulo state, Brazil. We used the isolated CCR64 (Empresa Brasileira de Pesquisa Agropecuária (EMBRAPA)-CNPMA). The means of crops were: BDA; Oats-Agar; Mazeina-Agar; Rice-Agar; V8-5%; V8-10%; V8-20%; TJ-5 %; TJ-10, TJ-20%. The sporulation of the fungus in different culture media was estimated at 8 days after of the incubation. The data were analyzed using method of comparing averages, using the Tukey test, at 5% probability, and the data processed, using (X + 1) 0.5 transformation. All culture media tested were able to produce conidia. It was found that the best culture media for production of conidia of Bionectria ochroleuca is the TJ-5%, followed by TJ-20%, with an sporulation average of 3,5 x 106 conidia / ml.

Silicon leaf application and physiological quality of white oat and wheat seeds

Plant nutrition can positively influence quality of seeds by improving plant tolerance to adverse climate. In this context, silicon is currently considered a micronutrient and it is beneficial to plant growth, especially Poaceaes such as white oat and wheat, thereby improving physiological quality of seeds. This study had the objective of evaluating the effects of silicon leaf application on plant tillering, silicon levels and physiological quality of white oat and wheat seeds besides establishing correlations between them. Two experiments were carried out in winter with white oat and wheat. The experimental design was the completely randomized block with eight replications. Treatments consisted of foliar application of silicon (0.8% of soluble silicon, as stabilized orthosilicic acid) and a control (with no application). Silicon levels in leaves were determined at flowering whereas the number of plants and panicles/spikes per area was counted right before harvest. Seed quality was evaluated right after harvest through mass, germination and vigor tests. Data was submitted to variance analysis and means were compared by the Tukey test at a probability level of 5%. Person's linear correlation test was performed among silicon level in plants, tillering and seed quality data. Silicon leaf application increases root and total length of white oat seedlings as an effect of higher Si level in leaves. Silicon leaf application increases mass of wheat seeds without affecting germination or vigor.

Efficiency of intermittent exercise on adiposity and fatty liver in rats fed with high-fat diet

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

Culicídeos vetores em uma unidade de conservação da caatinga na região do seridó no Rio Grande do Norte aspectos da transmissão de doenças

The scarcity of occurrence records of culicid species, transmitting insects of etiologic agents for arboviruses, protozoan diseases and philarioses, and lack of information about their interactions with the forest environment make the Caatinga one of the most unknown biomes in Brazil. The aim of this study was to identify culicid species in a conservation unit located in a preserved area of the Caatinga and the possible associations with local abiotic factors, as well as characterize the natural and artificial ecotopes present in the Caatinga of Rio Grande do Norte state. The Ecological Station of Serido (ESEC-Seridó) is a Caatinga Conservation Unit located in a rural area of Rio Grande do Norte. The hot and dry climate of the Caatinga, along with a short rainy season, favor the adaptation and resistance of plants, resulting in completely distinct landscapes over the course of the year. The study took place over the course of one year, with monthly collections between 10h-12h, 14h-16h and 18h-20h. Adult mosquitoes were collected in a forest area using a manual suction trap with human bait as attractant at the three times and a Shannon trap for night collections. During the rainy season ovitraps were randomly distributed at different sites. The different capture sites were observed and photographed. Immature and adult insects captured were taken to the laboratory for identification. Of the 5081 insects collected in human-bait and Shannon traps, 75% were Mansonia wilsoni. In addition, Aedeomyia, Aedes, Anopheles, Coquillettidia, Culex, Haemagogus, Mansonia and Psorophora were identified. Of the 92 Haemagogus eggs found, 71 were collected on the banks of a reservoir. Mosquito larvae were found and photographed in an artificial breeding site of a neighboring rural area. Humidity had the greatest influence on culicid density in the Caatinga. Rain was important in the appearance of Haemagogus, Anopheles, Aedes and Psorophora. Temperature had a negative influence on Anopheles triannulatus. The occurence of important vector species of diseases in a little known preserved area of the Caatinga as well as environmental and sociocultural questions are factors that favor the emergence of transmitting insects, making these areas potential subject to the resurgence of diseases