Cheaper Faster Drug Development Validated By The Repositioning Of Drugs Against Neglected Tropical Diseases.

There is an urgent need to make drug discovery cheaper and faster. This will enable the development of treatments for diseases currently neglected for economic reasons, such as tropical and orphan diseases, and generally increase the supply of new drugs. Here, we report the Robot Scientist 'Eve' designed to make drug discovery more economical. A Robot Scientist is a laboratory automation system that uses artificial intelligence (AI) techniques to discover scientific knowledge through cycles of experimentation. Eve integrates and automates library-screening, hit-confirmation, and lead generation through cycles of quantitative structure activity relationship learning and testing. Using econometric modelling we demonstrate that the use of AI to select compounds economically outperforms standard drug screening. For further efficiency Eve uses a standardized form of assay to compute Boolean functions of compound properties. These assays can be quickly and cheaply engineered using synthetic biology, enabling more targets to be assayed for a given budget. Eve has repositioned several drugs against specific targets in parasites that cause tropical diseases. One validated discovery is that the anti-cancer compound TNP-470 is a potent inhibitor of dihydrofolate reductase from the malaria-causing parasite Plasmodium vivax.

Development And Characterization Of Microsatellite Markers For Piptadenia Gonoacantha (fabaceae).

• Microsatellite primers were designed for Piptadenia gonoacantha (Fabaceae) and characterized to estimate genetic diversity parameters. The species is a native tree from the Atlantic Forest biome commonly used in forest restoration; it has medicinal potential and the wood is economically useful. • Twenty-eight microsatellite loci were identified from an enriched genomic library. Fifteen loci resulted in successful amplifications and were characterized in a natural population of 94 individuals. Twelve loci were polymorphic, with allele numbers ranging from three to 15 per locus, and expected and observed heterozygosities ranging from 0.2142 to 0.8325 and 0.190 to 0.769, respectively. • The developed markers will be used in further studies of population genetics of P. gonoacantha, aimed at conservation and management of the species in natural populations and in forest restoration projects.

Towards A Deeper Understanding Of Structural Biomass Recalcitrance Using Phase-contrast Tomography.

The development of technological routes to convert lignocellulosic biomass to liquid fuels requires an in-depth understanding of the cell wall architecture of substrates. Essential pretreatment processes are conducted to reduce biomass recalcitrance and usually increase the reactive surface area. Quantitative three-dimensional information about both bulk and surface structural features of substrates needs to be obtained to expand our knowledge of substrates. In this work, phase-contrast tomography (PCT) was used to gather information about the structure of a model lignocellulosic biomass (piassava fibers). The three-dimensional cellular organization of piassava fibers was characterized by PCT using synchrotron radiation. This technique enabled important physical features that describe the substrate piassava fibers to be visualized and quantified. The external surface area of a fiber and internal surface area of the pores in a fiber could be determined separately. More than 96% of the overall surface area available to enzymes was in the bulk substrate. The pore surface area and length exhibited a positive linear relationship, where the slope of this relationship depended on the plant tissue. We demonstrated that PCT is a powerful tool for the three-dimensional characterization of the cell wall features related to biomass recalcitrance. Original and relevant quantitative information about the structural features of the analyzed material were obtained. The data obtained by PCT can be used to improve processing routes to efficiently convert biomass feedstock into sugars.

Development Of Egg Pc/cholesterol/α-tocopherol Liposomes With Ionic Gradients To Deliver Ropivacaine.

Ropivacaine (RVC) is an aminoamide local anesthetic widely used in surgical procedures. Studies with RVC encapsulated in liposomes and complexed in cyclodextrins have shown good results, but in order to use RVC for lengthy procedures and during the postoperative period, a still more prolonged anesthetic effect is required. This study therefore aimed to provide extended RVC release and increased upload using modified liposomes. Three types of vesicles were studied: (i) large multilamellar vesicle (LMV), (ii) large multivesicular vesicle (LMVV) and (iii) large unilamellar vesicle (LUV), prepared with egg phosphatidylcholine/cholesterol/α-tocopherol (4:3:0.07 mol%) at pH 7.4. Ionic gradient liposomes (inside: pH 5.5, pH 5.5 + (NH4)2SO4 and pH 7.4 + (NH4)2SO4) were prepared and showed improved RVC loading, compared to conventional liposomes (inside: pH 7.4). An high-performance liquid chromatography analytical method was validated for RVC quantification. The liposomes were characterized in terms of their size, zeta potential, polydispersion, morphology, RVC encapsulation efficiency (EE(%)) and in vitro RVC release. LMVV liposomes provided better performance than LMV or LUV. The best formulations were prepared using pH 5.5 (LMVV 5.5in) or pH 7.4 with 250 mM (NH4)2SO4 in the inner aqueous core (LMVV 7.4in + ammonium sulfate), enabling encapsulation of as much as 2% RVC, with high uptake (EE(%) ∼70%) and sustained release (∼25 h). The encapsulation of RVC in ionic gradient liposomes significantly extended the duration of release of the anesthetic, showing that this strategy could be a viable means of promoting longer-term anesthesia during surgical procedures and during the postoperative period.

Development Plates For Stable Internal Fixation: Study Of Mechanical Resistance In Simulated Fractures Of The Mandibular Condyle.

To develop Y-shaped plates with different thicknesses to be used in simulated fractures of the mandibular condyle. Ten plates were developed in Y shape, containing eight holes, and 30 synthetic polyurethane mandible replicas were developed for the study. The load test was performed on an Instron Model 4411 universal testing machine, applying load in the mediolateral and anterior-posterior positions on the head of the condyle. Two-way ANOVA with Tukey testing with a 5% significance level was used. It was observed that when the load was applied in the medial-lateral plate of greater thickness (1.5 mm), it gave the highest strength, while in the anteroposterior direction, the plate with the highest resistance was of the lesser thickness (0.6 mm). A plate with a thickness of 1.5 mm was the one with the highest average value for all displacements. In the anteroposterior direction, the highest values of resistance were seen in the displacement of 15 mm. After comparing the values of the biomechanical testing found in the scientific literature, it is suggested that the use of Y plates are suitable for use in subcondylar fractures within the limitations of the study.

PARAFAC: uma ferramenta quimiométrica para tratamento de dados multidimensionais. Aplicações na determinação direta de fármacos em plasma humano por espectrofluorimetria

Since the last decade, the combined use of chemometrics and molecular spectroscopic techniques has become a new alternative for direct drug determination, without the need of physical separation. Among the new methodologies developed, the application of PARAFAC in the decomposition of spectrofluorimetric data should be highlighted. The first objective of this article is to describe the theoretical basis of PARAFAC. For this purpose, a discussion about the order of chemometric methods used in multivariate calibration and the development of multi-dimensional methods is presented first. The other objective of this article is to divulge for the Brazilian chemical community the potential of the combination PARAFAC/spectrofluorimetry for the determination of drugs in complex biological matrices. For this purpose, two applications aiming at determining, respectively, doxorrubicine and salicylate in human plasma are presented.

Polímeros biomiméticos em química analítica. Parte 2: aplicações de MIP (Molecularly Imprinted Polymers) no desenvolvimento de sensores químicos

The aim of this paper is the description of the strategies and advances in the use of MIP in the development of chemical sensors. MIP has been considered an emerging technology, which allows the synthesis of materials that can mimic some highly specific natural receptors such as antibodies and enzymes. In recent years a great number of publications have demonstrated a growth in their use as sensing phases in the construction of sensors . Thus, the MIP technology became very attractive as a promising analytical tool for the development of sensors.

Desenvolvimento de um algoritmo para identificação e correção de spikes em espectroscopia Raman de imagem

Raman imaging spectroscopy is a highly useful analytical tool that provides spatial and spectral information on a sample. However, CCD detectors used in dispersive instruments present the drawback of being sensitive to cosmic rays, giving rise to spikes in Raman spectra. Spikes influence variance structures and must be removed prior to the use of multivariate techniques. A new algorithm for correction of spikes in Raman imaging was developed using an approach based on comparison of nearest neighbor pixels. The algorithm showed characteristics including simplicity, rapidity, selectivity and high quality in spike removal from hyperspectral images.

Identificação eletrônica para avaliação do comportamento dos suínos na fase de gestação

The efficiency of swine production performance depends on the herd administration, such as good nutrition, sanitary control, facilities and appropriate environmental conditions. The concept of this production model is directly related with the reduction of selective losses and the process control. Each production segment is controlled to reach the optimization in the system totality, it is necessary to apply animals handling concepts, environmental control implementation, diseases control, nutrition control, information concerning in guaranteeing the animal welfare and individual identification. The present work presents as objective the development of the mathematical model to evaluate interactions among the internal atmosphere of the installation and the thermal animals preference, in the expectation of detecting a relationship among the frequency access to the drinking fountain and the atmosphere conditions - temperature, black globe temperature and relative humidity, using as tool the electronic identification. The results obtained by the mathematical model, allowed to conclude accurately the evaluation of the swine thermal preference correlating with the climatic variables in the pregnancy stage.

Uso de redes neurais artificiais na identificação de vocalização de suínos

Animal welfare has been an important research topic in animal production mainly in its ways of assessment. Vocalization is found to be an interesting tool for evaluating welfare as it provides data in a non-invasive way as well as it allows easy automation of process. The present research had as objective the implementation of an algorithm based on artificial neural network that had the potential of identifying vocalization related to welfare pattern indicatives. The research was done in two parts, the first was the development of the algorithm, and the second its validation with data from the field. Previous records allowed the development of the algorithm from behaviors observed in sows housed in farrowing cages. Matlab® software was used for implementing the network. It was selected a retropropagation gradient algorithm for training the network with the following stop criteria: maximum of 5,000 interactions or error quadratic addition smaller than 0.1. Validation was done with sows and piglets housed in commercial farm. Among the usual behaviors the ones that deserved enhancement were: the feed dispute at farrowing and the eventual risk of involuntary aggression between the piglets or between those and the sow. The algorithm was able to identify through the noise intensity the inherent risk situation of piglets welfare reduction.

Perfis temporais NDVI MODIS, na cana-soca, de maturação tardia

This paper describes the development of a relational database and a tool for viewing MODIS NDVI temporal profile, using data from MOD09Q1 product, specifically the surface bidirectional reflectance factor relative to the RED and NIR wavelength, mosaic of 8-day temporal composition, and the quality band, in sugarcane fields in the state of São Paulo, for analysis of the late stubble-cane maturation. From sugarcane farms were obtained the historical data about yield, soil, variety, location of the each pixel for each subregion monitored. All data were integrated in a database developed in PostgreSQL. The tool was implemented using Java language and allowed a fast and automatic way of analyzing sugarcane phenological patterns. It concluded that the MODIS NDVI temporal profile using data from MOD09Q1 product is able to subsidize the monitoring of phenological changes in the sugarcane.

Multifunctional role of steroidogenic factor 1 and disorders of sex development

Disorders of sex development (DSD) involve several conditions that result from abnormalities during gonadal determination and differentiation. Some of these disorders may manifest at birth by ambiguous genitalia; others are diagnosed only at puberty, by the delayed onset of secondary sexual characteristics. Sex determination and differentiation in humans are processes that involve the interaction of several genes such as WT1, NR5A1, NR0B1, SOX9, among others, in the testicular pathway, and WNT4, DAX1, FOXL2 and RSPO1, in the ovarian pathway. One of the major proteins in mammalian gonadal differentiation is the steroidogenic nuclear receptor factor 1 (SF1). This review will cover some of the most recent data on SF1 functional roles and findings related to mutations in its coding gene, NR5A1.

Interação entre alunos com e sem deficiencia na educação fisica escolar : validação de instrumento

Universidade Estadual de Campinas. Faculdade de Educação Física

Jogos infantis da cultura : uma avaliação da educação fisica escolar na 1a. fase do 1o. grau

Universidade Estadual de Campinas. Faculdade de Educação Física

Modelo de inclusão digital para construção do conhecimento em qualidade de vida e atividade fisica

Universidade Estadual de Campinas. Faculdade de Educação Física