Three-Dimensional Quantitative Structure-Activity Relationship Study of Antitumor 2-Formylpyridine Thiosemicarbazones Derivatives as Inhibitors of Ribonucleotide Reductase

In order to extend previous SAR and QSAR studies, 3D-QSAR analysis has been performed using CoMFA and CoMSIA approaches applied to a set of 39 alpha-(N)-heterocyclic carboxaldehydes thiosemicarbazones with their inhibitory activity values (IC(50)) evaluated against ribonucleotide reductase (RNR) of H.Ep.-2 cells (human epidermoid carcinoma), taken from selected literature. Both rigid and field alignment methods, taking the unsubstituted 2-formylpyridine thiosemicarbazone in its syn conformation as template, have been used to generate multiple predictive CoMFA and CoMSIA models derived from training sets and validated with the corresponding test sets. Acceptable predictive correlation coefficients (Q(cv)(2) from 0.360 to 0.609 for CoMFA and Q(cv)(2) from 0.394 to 0.580 for CoMSIA models) with high fitted correlation coefficients (r` from 0.881 to 0.981 for CoMFA and r(2) from 0.938 to 0.993 for CoMSIA models) and low standard errors (s from 0.135 to 0.383 for CoMFA and s from 0.098 to 0.240 for CoMSIA models) were obtained. More precise CoMFA and CoMSIA models have been derived considering the subset of thiosemicarbazones (TSC) substituted only at 5-position of the pyridine ring (n=22). Reasonable predictive correlation coefficients (Q(cv)(2) from 0.486 to 0.683 for CoMFA and Q(cv)(2) from 0.565 to 0.791 for CoMSIA models) with high fitted correlation coefficients (r(2) from 0.896 to 0.997 for CoMFA and r(2) from 0.991 to 0.998 for CoMSIA models) and very low standard errors (s from 0.040 to 0.179 for CoMFA and s from 0.029 to 0.068 for CoMSIA models) were obtained. The stability of each CoMFA and CoMSIA models was further assessed by performing bootstrapping analysis. For the two sets the generated CoMSIA models showed, in general, better statistics than the corresponding CoMFA models. The analysis of CoMFA and CoMSIA contour maps suggest that a hydrogen bond acceptor near the nitrogen of the pyridine ring can enhance inhibitory activity values. This observation agrees with literature data, which suggests that the nitrogen pyridine lone pairs can complex with the iron ion leading to species that inhibits RNR. The derived CoMFA and CoMSIA models contribute to understand the structural features of this class of TSC as antitumor agents in terms of steric, electrostatic, hydrophobic and hydrogen bond donor and hydrogen bond acceptor fields as well as to the rational design of this key enzyme inhibitors.

Asymmetric phase-transfer catalytic sulfanylation of some 2-methylsulfinyl cyclanones. Modeling of the stereochemical course of the aldol reaction of (SS,2S)-2-methylsulfinyl-2-methylsulfanylcyclohexanone

Increased diastereoisomeric excesses are obtained for the sulfanylation reactions of some 2-methylsulfinyl cyclanones under phase-transfer catalysis using the chiral catalyst QUIBEC instead of TEBA. The optically pure (SS,2S)-2-methylsulfinyl-2-methylsulfanylcyclohexanone thus prepared reacts with ethyl acetate lithium enolate affording, after hydrolysis, (R)-2-[(ethoxycarbonyl)methyl]-2-hydroxycyclohexanone in 60% ee. Density functional theory calculations (at the B3LYP/6-311++G(d,p) level) can successfully explain the origin of this result as the kinetically favored axial attack of the nucleophile to the carbonyl group of the most stable conformer of the cyclanone, in which the CH(3)SO and CH(3)S groups are at the equatorial and axial positions, respectively. (C) 2010 Elsevier Ltd. All rights reserved.

Desenvolvimento de um teste de Elisa-LPS para Salmonella e sua aplicação em rebanhos suínos na identificação de fatores de risco associados à infecção.

A implementação de programas de controle de salmonela em suínos, com objetivo de diminuir os riscos de infecção alimentar em humanos, exige métodos rápidos e baratos para medir a intensidade da infecção, bem como reduzir seus fatores de risco. A partir disso, desenvolveu-se um teste de ELISA, utilizando antígeno lipopolissacarídeo do sorovar Typhimurium, pela sua similaridade antigênica com os sorovares prevalentes em suínos no Rio Grande do Sul. O teste padronizado foi utilizado na determinação da soroprevalência em 65 rebanhos suínos, os quais participaram de estudo para identificação de fatores de risco. As granjas foram classificadas em três categorias de soroprevalência, baixa (até 40%), média (40-70%) e alta (mais de 70%) prevalência, estabelecidas como variável explicada. As respostas do questionário contituíram as variáveis explicativas. Aquelas associadas à variável explicada pelo teste de χ2 (p ≤ 0,1) foram submetidas à análise fatorial de correspondência múltipla (AFCM). Paralelamente, foram avaliados seis desinfetantes (amônia quaternária, glutaraldeído, iodóforo, hipoclorito de sódio (1 e 0,1%), fenol e ácido peracético) frente a amostras de Salmonella Typhimurium isoladas de suínos. Os produtos foram testados na presença e ausência de matéria orgânica, sob duas diferentes temperaturas e, posteriormente, frente a 8 isolados com diferentes perfis de resistência antimicrobiana, por um tempo de contato de 5 minutos. O teste de ELISA identificou a soroconversão nos animais inoculados (7 dias p.i.) e contatos (21 dias p.i.), bem como o aumento no número de animais positivos após infecção natural (28,6% para 76,9%). A sensibilidade e a especificidade do teste foram respectivamente de 92 e 100%. Após adaptações para suco de carne, estabelecendo o soro como referência, a sensibilidade do teste para suco de carne foi de 88,12% e a especificidade 70,43%. Em análise de concordância entre os testes, o índice kappa foi de 5,78, com p=0,002 no teste MacNemar. A AFCM identificou a associação da maior soroprevalência com o seguinte grupo de variáveis: nas granjas terminadoras, uso de ração peletizada, distribuição de dejetos a menos de 100m do local de captação de água, não utilização de comedouro do modelo comedouro/bebedouro, transporte com freteiro misturando animais de várias granjas; enquanto nas granjas de ciclo completo apareceram ingredientes de ração desprotegidos de outros animais, ausência de controle de roedores, ração seca, ausência de cerca, não uso da pintura com cal após lavagem e desinfecção e a entrada de outras pessoas além do técnico na granja. Todos os desinfetantes foram eficazes na ausência de matéria orgânica, nas duas temperaturas testadas. Entretanto, quando na presença de matéria orgânica ou após cinco minutos de contato, somente o hipoclorito de sódio (1%), fenol e o ácido peracético foram eficazes. Dessa forma, ao estabelecer uma ferramenta sorológica para medir a infecção pelos principais sorovares de Salmonella que afetam os suínos no sul do Brasil e identificar fatores de risco associados à alta soroprevalência, será possível dar início à implementação e validação de protocolos de controle da infecção em rebanhos.

Crescimento aéreo e radicular de arroz de terras altas em função da adubação fosfatada e bioestimulante

The use of plant regulators that stimulate root growth can increase phosphorus uptake by upland rice. The objective of this study was to evaluate shoot and root growth of upland rice fertilized with different phosphorus doses with and without biostimulant. The experiment was carried out in greenhouse in the Faculdade de Ciencias Agronomicas-UNESP, in Botucatu-SP. The treatments consisted of six phosphorus doses applied in sowing (0, 12,5, 25, 50, 100 and 200 mg dm(-3)), with and without Stimulate (R) applied in the seeds (cv. Primavera). The plants were grown for 78 days and then cut at soil level to evaluate leaf area and leaves and collar dry matter. Root samples that were harvested on the same day had their root diameter and dry matter evaluated. The experimental design was the completely randomized, with three replications, arranged as a factorial 2x6. Variance analysis and regression were used to data evaluation. Linear and quadratic equations were adjusted at a probability level of 5%, using those with higher determination coefficient (R(2)). The increase on the phosphorus dose contributed to the lower matter production and leaf area of the plants when the biostimulant was applied. For shoot phosphorus accumulation and root evaluations, the same behavior was observed. It was concluded that the use of Stimulate (R) in seeds, for fitomass production or root system evaluation, was only efficient in low phosphorus doses.

Quadratic gravity theories in 2+1 dimensions and the topological Chern-Simons term

The addition of a topological Chern-Simons term to three-dimensional higher-derivative gravity is not a good therapy to cure the nonunitarity of the aforementioned theory. Moreover, R+R-2 gravity in (2+1)D, which is unitary at the tree level, becomes tree-level nonunitary when it is augmented by the abovementioned topological term. Therefore, unlike what is claimed in the literature, topological higher-derivative gravity in (2+1)D is not tree-level unitary and neither is topological three-dimensional R+R-2 gravity.

Curvas de lactação em rebanhos da raça holandesa no estado de Minas Gerais. Escolha do modelo de melhor ajuste

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

D-n-forced symmetry breaking of O(2)-equivariant problems

We use singularity theory to classify forced symmetry-breaking bifurcation problemsf(z, lambda, mu) = f(1)(z, lambda) + muf(2)(z, lambda, mu) = 0,where f(1) is O(2)-equivariant and f(2) is D-n-equivariant with the orthogonal group actions on z is an element of R-2. Forced symmetry breaking occurs when the symmetry of the equation changes when parameters are varied. We explicitly apply our results to the branching of subharmonic solutions in a model periodic perturbation of an autonomous equation and sketch further applications.

2,3-Dihydrobenzofuran neolignans from Aristolochia pubescens

From a hexane extract of stems and roots of Aristolochia pubescens, the new neolignans (2S,3S,1'R,2'R)- and (2S,3S, 1'S,2'R)-2,3-dihydro-5-(1',2'-dihydroxypropyl)-2-(4-hydroxy-3-methylbenzofuran) and (2S,3S,1'R,2'R)- and (2S,3S,1'S,2'R)-2,3-dihydro-5-(1',2'-dihydroxypropyl)-2-(3,4-dimethoxyphenyl)-7-methoxy-3-methyl-benzofuran were isolated, together with the known neolignan licarin A, and its bisnor-neolignan aldehyde and acid derivatives. In addition, sitosterol, 8R,9R-oxide-beta-caryophyllene, kobusone, ent-kauran-16 alpha, 17-diol, vanillin, vanillic acid, (+)-sesamin, (+)eudesmin, and (-)-cubebin were isolated. The structures of the new compounds have been elucidated by spectroscopic methods and by chemical transformation using Mosher's acid chloride. (C) 1999 Elsevier B.V. Ltd. All rights reserved.

Predicting body and carcass characteristics of 2 broiler chicken strains using support vector regression and neural network models

As a new modeling method, support vector regression (SVR) has been regarded as the state-of-the-art technique for regression and approximation. In this study, the SVR models had been introduced and developed to predict body and carcass-related characteristics of 2 strains of broiler chicken. To evaluate the prediction ability of SVR models, we compared their performance with that of neural network (NN) models. Evaluation of the prediction accuracy of models was based on the R-2, MS error, and bias. The variables of interest as model output were BW, empty BW, carcass, breast, drumstick, thigh, and wing weight in 2 strains of Ross and Cobb chickens based on intake dietary nutrients, including ME (kcal/bird per week), CP, TSAA, and Lys, all as grams per bird per week. A data set composed of 64 measurements taken from each strain were used for this analysis, where 44 data lines were used for model training, whereas the remaining 20 lines were used to test the created models. The results of this study revealed that it is possible to satisfactorily estimate the BW and carcass parts of the broiler chickens via their dietary nutrient intake. Through statistical criteria used to evaluate the performance of the SVR and NN models, the overall results demonstrate that the discussed models can be effective for accurate prediction of the body and carcass-related characteristics investigated here. However, the SVR method achieved better accuracy and generalization than the NN method. This indicates that the new data mining technique (SVR model) can be used as an alternative modeling tool for NN models. However, further reevaluation of this algorithm in the future is suggested.

Epidemiologia da mancha de phaeosphaeria e da cercosporiose em milho

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Adaptação transcultural do Preschool Language Assessment Instrument (PLAI-2) em falantes do português brasileiro com desenvolvimento típico de linguagem

Pós-graduação em Fonoaudiologia - FFC

Microencapsulation of turmeric oleoresin in binary and ternary blends of gum arabic, maltodextrin and modified starch

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

Silsesquioxane organofunctionalized with 4-amino-3-hydrazino-5-mercapto-1,2,4-triazole: preparation and subsequent reaction with silver and potassium hexacyanoferrate(III) for detection of l-cysteine

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

Avaliação do desperdício de alimentos prontos para o consumo em Unidade de Alimentação e Nutrição (UAN), do interior do estado de São Paulo

Pós-graduação em Engenharia e Ciência de Alimentos - IBILCE

TOPOLOGY OF SINPLE SINGULARITIES OF RULED SURFACES IN R-p

In this work we compare the simple singularities of germs from R-2 to R-p with multiplicity 2 or 3 with the singularities appearing in the set of 2-ruled surfaces. We also study the topological type of all finitely determined singularities by studying generic projections of these singularities in R-3. (C) 2011 Elsevier B.V. All rights reserved.