High Content Screening of a Kinase-Focused Library Reveals Compounds Broadly-Active against Dengue Viruses

Dengue virus is a mosquito-borne flavivirus that has a large impact in global health. It is considered as one of the medically important arboviruses, and developing a preventive or therapeutic solution remains a top priority in the medical and scientific community. Drug discovery programs for potential dengue antivirals have increased dramatically over the last decade, largely in part to the introduction of high-throughput assays. In this study, we have developed an image-based dengue high-throughput/high-content assay (HT/HCA) using an innovative computer vision approach to screen a kinase-focused library for anti-dengue compounds. Using this dengue HT/HCA, we identified a group of compounds with a 4-(1-aminoethyl)-N-methylthiazol-2-amine as a common core structure that inhibits dengue viral infection in a human liver-derived cell line (Huh-7.5 cells). Compounds CND1201, CND1203 and CND1243 exhibited strong antiviral activities against all four dengue serotypes. Plaque reduction and time-of-addition assays suggests that these compounds interfere with the late stage of viral infection cycle. These findings demonstrate that our image-based dengue HT/HCA is a reliable tool that can be used to screen various chemical libraries for potential dengue antiviral candidates. © 2013 Cruz et al.

Ethopharmacological evaluation of the rat exposure test: A prey-predator interaction test

The rat exposure test (RET) is a prey (mouse)-predator (rat) situation that activates brain defensive areas and elicits hormonal and defensive behavior in the mouse. Here, we investigated possible correlations between the spatiotemporal [time spent in protected (home chamber and tunnel) and unprotected (surface) compartments and frequency of entries into the three compartments] and ethological [e.g., duration of protected and unprotected stretched-attend postures (SAP), duration of contact with the rat's compartment] measures (Experiment 1). Secondly, we investigated the effects of systemic treatment with pro- or anti-aversive drugs on the behavior that emerged from the factor analysis (Experiment 2). The effects of chronic (21 days) imipramine and fluoxetine on defensive behavior were also investigated (Experiment 3). Exp. 1 revealed that the time in the protected compartment, protected SAP and rat contacts loaded on factor 1 (defensive behavior), while the total entries and unprotected SAP loaded on factor 2 (locomotor activity). Exp. 2 showed that alprazolam (but not diazepam) selectively changed the defensive factor. Caffeine produced a mild proaversive-like effect, whereas yohimbine only decreased locomotor activity (total entries). Fluoxetine (but not imipramine) produced a weak proaversive-like effect. 5-HT1A/5-HT2 receptor ligands did not change any behavioral measure. In Exp. 3, chronic fluoxetine (but not imipramine) attenuated the defensive behavior factor without changing locomotion. Given that the defensive factor was sensitive to drugs known to attenuate (alprazolam and chronic fluoxetine) and induce (caffeine) panic attack, we suggest the RET as a useful test to assess the effects of panicolytic and panicogenic drugs. © 2012 Elsevier B.V.

Método de Lowry: validação e estimativa do cálculo da incerteza

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

As práticas e os saberes médicos no Brasil colonial (1677-1808)

Pós-graduação em História - FCHS

Otimização e validação de método cromatográfico para determinação de 17 'beta'- estradiol, estrona e estriol em solo tratado com esterco animal e iodo de ETE

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Análise microestrutural de tubos API P110, para prospecção de petróleo e gás, soldados pelo processo HF/ERW

On the grounds of the great advances achieved over recent years, the process HF/ERW (High-Frequency/Electric Resistance Welding)welded pipe have played an active role in the oil and gas industry for deep water applications, at high and extremely low temperatures, under high pressure and in highly corrosive environments, gradually replacing manufactured pipes by other processes. However, studies have shown that defects in the welded joints are a the leading causes of pipelines failures, which has required the determination of toughness values in this region, in compliance with the strict recommendations of the codes and standards with manufacturers and construction companies, on the oil and gas sector. As part of the validation process required toughness values, this research project focuses on a microstructural analysis in HF / ERW tubes microalloyed, steel grade API 5CT P110, designed to explore oil and gas in deep waters, the subject of strategic relevance to the country because of the recent discoveries in the Santos mega fields: Tupi and Libra (pre-salt). In this scientific work will be presented and discussed the results of mechanical tensile and Charpy, a few CTOD tests curves (showing the trend of toughness values to be obtained), and the microstructures of the base material obtained by optical microscopy, with special emphasis on the formation of nonmetallic inclusions in the welded joint

Análise microestrutural de tubos API N80 soldados pelo processo HF/ERW para prospecção de petróleo e gás

On the grounds of the great advances achieved over recent years, the process HF/ERW (High-Frequency/Electric Resistance Welding)welded pipe have played an active role in the oil and gas industry for deep water applications, at high and extremely low temperatures, under high pressure and in highly corrosive environments, gradually replacing manufactured pipes by other processes. However, studies have shown that defects in the welded joints are a the leading causes of pipelines failures, which has required the determination of toughness values in this region, in compliance with the strict recommendations of the codes and standards with manufacturers and construction companies, on the oil and gas sector. As part of the validation process required toughness values, this research project focuses on a microstructural analysis in HF / ERW tubes microalloyed, steel grade API 5CT N80, designed to explore oil and gas in deep waters, the subject of strategic relevance to the country because of the recent discoveries in the Santos mega fields: Tupi and Libra (pre-salt). In this scientific work will be presented and discussed the results of mechanical tensile and Charpy, a few CTOD tests curves (showing the trend of toughness values to be obtained), and the microstructures of the base material obtained by optical microscopy, with special emphasis on the formation of non-metallic inclusions in the welded joint

Método de quantificação da capacidade antioxidante total sérica: padronização e validação para espécie ovina

Pós-graduação em Ciência Animal - FMVA

Orientação motivacional de metas na modalidade do basquetebol

The present study aims to verify motivation of goals orientation using the scale TEOSQ (TEOSQ) developed by Duda (1992), translated, adapted and validated by Hirota and De Marco (2006), presenting as an experimental research methodology proposed (MARCONI and LAKATOS, 2006), with 37 practitioners basketball aged 11 to 17 (mean age 14.02 +1.42 years) of the City of Sao Caetano South – São Paulo, Brazil. Used for statistical software SPSS, version 15.0 in order to get the Cronbach's Alpha and the mean, standard deviation and median of each orientation – goal of Task and ego goal. Observed with the results that the scale has good values related to the statistic of Alpha showing Task 0.69 to 0.67 Ego. The mean age between 11 and 13 years old related to the orientation task was 4.60(+0.62) and ego orientation to 3.11(+0.84), for ages 14 to 15 years the average task was 4.23(+0.78) and 2.74(+1.02) for the ego and the age of 16 and 17 years the average orientation task was 4.78(+0.1) and ego of 2.66(+0.47). The total result of the group concerning the task was 4.36(+0.75) and ego of 2.83(+0.97). We conclude that the validation process was in line with expectations, showing consistent values of Alpha, which demonstrate that the students while learning basketball are more sure of their actions, but optimistic, persistent in their goals and adopt a position of responsibility the rest of the team

Estudo da mobilidade de micotoxinas em solo sob condições de clima tropical

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Estudo da mobilidade de micotoxinas em solo sob condições de clima tropical

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

SPATIAL VARIABILITY OF THE RAINFALL EROSIVE POTENTIAL IN THE STATE OF MATO GROSSO DO SUL, BRAZIL

Information about rainfall erosivity is important during soil and water conservation planning. Thus, the spatial variability of rainfall erosivity of the state Mato Grosso do Sul was analyzed using ordinary kriging interpolation. For this, three pluviograph stations were used to obtain the regression equations between the erosivity index and the rainfall coefficient EI30. The equations obtained were applied to 109 pluviometric stations, resulting in EI30 values. These values were analyzed from geostatistical technique, which can be divided into: descriptive statistics, adjust to semivariogram, cross-validation process and implementation of ordinary kriging to generate the erosivity map. Highest erosivity values were found in central and northeast regions of the State, while the lowest values were observed in the southern region. In addition, high annual precipitation values not necessarily produce higher erosivity values.

Sistema de observação proxémica do instrutor de fitness (soprox-fitness): desenvolvimento, validação e estudio piloto

[ES] The purpose of this study was to develop and validate the Observational System for the Proxemic Communication of the Fitness Instructor, as well as conduct a pilot application of the same. During the development and validation process of the new observation system it was employed five sequential phases. At the end of this process, it was established the validity and reliability of 5 coding dimensions and 23 categories of instructor proxemics behavior to create the final version of the observational system. This version of the observational system was applied in a pilot study conducted in a sample of 12 fitness instructors from four different group-exercise classes. The results indicated that instructor proxemics behaviour could be feasibly coded with the Observational System for the Proxemic Communication of the Fitness Instructor, having been held a comparative analysis about its intervention in the various activities, albeit with a small sample size.

Sviluppo di sperimentazioni per la produzione di getti in lega di alluminio a caratteristiche difettologiche e microstrutturali controllate, per la validazione di modelli di previsione delle porosità

Nei processi di progettazione e produzione tramite tecnologie di colata di componenti in alluminio ad elevate prestazioni, risulta fondamentale poter prevedere la presenza e la quantità di difetti correlabili a design non corretti e a determinate condizioni di processo. Fra le difettologie più comuni di un getto in alluminio, le porosità con dimensioni di decine o centinaia di m, note come microporosità, hanno un impatto estremamente negativo sulle caratteristiche meccaniche, sia statiche che a fatica. In questo lavoro, dopo un’adeguata analisi bibliografica, sono state progettate e messe a punto attrezzature e procedure sperimentali che permettessero la produzione di materiale a difettologia e microstruttura differenziata, a partire da condizioni di processo note ed accuratamente misurabili, che riproducessero la variabilità delle stesse nell’ambito della reale produzione di componenti fusi. Tutte le attività di progettazione delle sperimentazioni, sono state coadiuvate dall’ausilio di software di simulazione del processo fusorio che hanno a loro volta beneficiato di tarature e validazioni sperimentali ad hoc. L’apparato sperimentale ha dimostrato la propria efficacia nella produzione di materiale a microstruttura e difettologia differenziata, in maniera robusta e ripetibile. Utilizzando i risultati sperimentali ottenuti, si è svolta la validazione di un modello numerico di previsione delle porosità da ritiro e gas, ritenuto ad oggi allo stato dell’arte e già implementato in alcuni codici commerciali di simulazione del processo fusorio. I risultati numerici e sperimentali, una volta comparati, hanno evidenziato una buona accuratezza del modello numerico nella previsione delle difettologie sia in termini di ordini di grandezza che di gradienti della porosità nei getti realizzati.

Multiplex assays for biomarker research and clinical application: translational science coming of age

Over the last decade, translational science has come into the focus of academic medicine, and significant intellectual and financial efforts have been made to initiate a multitude of bench-to-bedside projects. The quest for suitable biomarkers that will significantly change clinical practice has become one of the biggest challenges in translational medicine. Quantitative measurement of proteins is a critical step in biomarker discovery. Assessing a large number of potential protein biomarkers in a statistically significant number of samples and controls still constitutes a major technical hurdle. Multiplexed analysis offers significant advantages regarding time, reagent cost, sample requirements and the amount of data that can be generated. The two contemporary approaches in multiplexed and quantitative biomarker validation, antibody-based immunoassays and MS-based multiple (or selected) reaction monitoring, are based on different assay principles and instrument requirements. Both approaches have their own advantages and disadvantages and therefore have complementary roles in the multi-staged biomarker verification and validation process. In this review, we discuss quantitative immunoassay and multiple reaction monitoring/selected reaction monitoring assay principles and development. We also discuss choosing an appropriate platform, judging the performance of assays, obtaining reliable, quantitative results for translational research and clinical applications in the biomarker field.