Natural products biological screening and ligand-based virtual screening for the discovery of new antileishmanial agents

In the course of our research program to discover novel antileishmanial agents, a biological screening of natural products against Leishmania major promastigotes allowed the identification of a furoquinoline alkaloid (1) and a furanocoumarin (2) as new hits. Subsequently, an integrated ligand-based virtual screening approach was employed to search for new antileishmanial compounds using these naturally occurring molecules as templates. Fourteen out of 40 compounds selected from a database of about 800,000 compounds (extracted from ZINC, a free database for virtual screening) were experimentally confirmed to possess significant in vitro antileishmanial properties. The application of ligand-based virtual screening as a complementary approach to experimental natural product screening was a useful strategy to facilitate the identification of new promising lead candidates.

Classical and fragment-based hologram structure-activity relationships for a series of analgesic cyclic imides

Cyclic imides have been widely employed in drug design research due to their multiple pharmacological and biological properties. In the present study, two-dimensional quantitative structure-activity relationship (2D QSAR) studies were conducted on a series of potent analgesic cyclic imides using both classical and hologram QSAR (HQSAR) methods, yielding significant statistical models (classical QSAR, q(2) = 0.80; HQSAR, q(2) = 0.84). The models were then used to evaluate an external data test, and the predicted values were in good agreement with the experimental results, indicating their consistency for untested compounds.

A reparametrization of Triangular Distribution based on the Skew-Symmetric Distributions

In this paper a new approach is considered for studying the triangular distribution using the theoretical development behind Skew distributions. Triangular distribution are obtained by a reparametrization of usual triangular distribution. Main probabilistic properties of the distribution are studied, including moments, asymmetry and kurtosis coefficients, and an stochastic representation, which provides a simple and efficient method for generating random variables. Moments estimation is also implemented. Finally, a simulation study is conducted to illustrate the behavior of the estimation approach proposed.

Development of Highly Selective Enzymatic Devices Based on Deposition of Permselective Membranes on Aligned Nanowires

We describe a simple and efficient strategy to fabricate enzymatic devices based on the deposition of glucose oxidase on aligned and highly oriented CoNiMo metallic nanowires. CoNiMo nanowires with an average diameter of 200 nm and length of 50 mu m were electrodeposited on Au-covered alumina substrates via electrodeposition, using alumina membranes as templates. Enzyme-modified electrodes were fabricated via enzyme immobilization using a cross-linker. To minimize nonspecific reactions in the presence of interfering agents, a permselective membrane composed of poly(vinylsulfonic acid) and polyamidoamine dendrimer was deposited via electrostatic interaction. The formation of hydrogen peroxide as a product of the enzymatic reaction was monitored at low overpotential, 0.0 V (vs Ag/AgCl). The detection limit was estimated at 22 mu M under an applied potential of 0.0 V. The apparent Michaelis-Menten constant determined from the Lineweaver-Burke plot was 2 mM.

Optimization of performances of gelatin/LiBF(4)-based polymer electrolytes by plasticizing effects

Gelatin is a cheap and abundant natural product with very good biodegradation properties and can be used to obtain acetic acid or LiClO(4)-based gel polymer electrolytes (GPEs) with high ionic conductivity and good stability. This article presents results of GPEs obtained by the plasticization of gelatin and addition of LiBF(4), where the optimization of the system was achieved by using a factorial design type 22 with two variables: glycerol and LiBF(4). From this analysis it was stated that the effect of glycerol as a plasticizer on the ionic conductivity results is much more important than the effect obtained by varying the lithium salt content or the effect of the interaction of both variables. Also all the samples were characterized by X-ray diffraction measurements, UV-vis-NIR spectroscopy and scanning electron microscopy (SEM) and impedance spectroscopy. The ionic conductivity results of all analyzed samples as a function of temperature obey predominantly an Arrhenius relationship and the samples are stable up to 160 degrees C. Good conductivity results combined with transparency and good adhesion to the electrodes have shown that gelatin-based GPEs are very promising materials to be used as solid electrolytes in electrochromic devices. (C) 2009 Elsevier Ltd. All rights reserved.

GENOTYPE CHARACTERIZATION OF THE Haematobia irritans (DIPTERA: MUSCIDAE) FROM BRAZIL, DOMINICAN REPUBLIC AND COLOMBIA BASED ON RANDOMLY AMPLIFIED POLYMORPHIC DNA (RAPD) ANALYSIS

Blood-sucking flies are important parasites in animal production systems, especially regarding confinement conditions. Haematobia irritans, the horn fly, is one of the most troublesome species within bovine production systems, due to the intense stress imposed to the animals. H. irritans is one of the parasites of cattle that cause significant economic losses in many parts of the world, including South America. In the present work, Brazilian, Colombian and Dominican Republic populations of this species were studied by Random Amplified Polymorphic DNA(RAPD) to assess basically genetic variability between populations. Fifteen different decamer random primers were employed in the genomic DNA amplification, yielding 196 fragments in the three H. irritans populations. Among h. irritans samples, that from Colombia produced the smallest numbers of polymorphic hands. This high genetic homogeneity may be ascribed to its geographic origin, which causes high isolation, low gene flow, unlike the other American populations, from Brazil and Dominican Republic. Molecular marker fragments, which its produced exclusive bands, detected in every sample enabled the population origin to be characterized, but they are also potentially useful for further approaches such as the putative origin of Brazilian, Colombian and Dominican Republic populations of horn fly from South America. Similarity indices produced by chemo metric analysis showed the closest relationships between flies from Brazil and Dominican Republic, while flies from Colombia showed the greatest genotypic differentiation relative to the others populations.

An approach to evaluate product verifications

Companies implement a module product assortment as a part of their strategy to, among others, shorten lead-times, increase the product quality and to create more product variants with fever parts. However, the increased number of variants becomes a challenging task for the personnel responsible for the product verifications. By implementing verifications at module level, so called MPV (Module Property Verification) several advantages ensue. The advantages is not only a decrease in cost of verifications, but also a decrease in repair times, occupied space, storages with spare parts, and repair tools. Further, MPV also give an increased product quality due to an increased understanding of which defects that may occur. As an approach to implement MPV, this paper discusses defects and verification processes based on a study at a Swedish company. It also describes a matrix which is used to map relations between company specific cost drivers and so called verification factors. The matrix may indicate cost drivers which have a large impact on the total cost of product verifications.

Salesperson’s Personality, Motivation and Selling Performance : The Study of New Product Selling

In the highly competitive environment businesses invest big amounts of money into the new product development. New product success potentially depends on different factors among which salespeople play an important role. The aim of this paper is to explore the potential link between salespeople’s personality, motivation to sell new products and performance in selling new products. Based on the theoretical background of the Big Five personality dimensions, motivation and selling performance hypotheses were formulated and tested using statistical methods of correlation and regression analysis. The data was collected within one technologically intensive organization – ABB AB in Sweden using online web questionnaire and self-assessment measurements. Total investigation was conducted among organization’s salesforce. The findings confirm the importance of salesperson’s personality empirically showing that the latter significantly predicts both motivation and performance in selling new products. From all the Big Five Extraversion was confirmed to be the most important predictor of both motivation and performance in selling new products. Extraversion was found positively related with both motivation and performance in selling new products. Salespeople scoring high in Extraversion and especially possessing such characteristics as confident, energetic and sociable tend to be more motivated to sell new products and show higher performance results. Other personality dimensions such as Agreeableness, Conscientiousness, Neuroticism, and Openness to experience complexly approached are not proved to be significantly related neither with motivation nor performance in selling new products. The results are explained by the extreme importance of Extraversion in new product selling situation which analyzing in combination with the other personality dimensions suppresses the others. Finding regarding controlling for certain demographical characteristics of salespeople reveal that performance in selling new products is determined by selling experience. Salespeople’s age is not proved to be significantly related neither with motivation nor performance in selling new products. Findings regarding salespeople’s gender though proposing that males are more motivated to sell new products cannot be generalized due to the study limitations.

Health system context and implementation of evidence-based practices-development and validation of the Context Assessment for Community Health (COACH) tool for low- and middle-income settings

Background: The gap between what is known and what is practiced results in health service users not benefitting from advances in healthcare, and in unnecessary costs. A supportive context is considered a key element for successful implementation of evidence-based practices (EBP). There were no tools available for the systematic mapping of aspects of organizational context influencing the implementation of EBPs in low- and middle-income countries (LMICs). Thus, this project aimed to develop and psychometrically validate a tool for this purpose. Methods: The development of the Context Assessment for Community Health (COACH) tool was premised on the context dimension in the Promoting Action on Research Implementation in Health Services framework, and is a derivative product of the Alberta Context Tool. Its development was undertaken in Bangladesh, Vietnam, Uganda, South Africa and Nicaragua in six phases: (1) defining dimensions and draft tool development, (2) content validity amongst in-country expert panels, (3) content validity amongst international experts, (4) response process validity, (5) translation and (6) evaluation of psychometric properties amongst 690 health workers in the five countries. Results: The tool was validated for use amongst physicians, nurse/midwives and community health workers. The six phases of development resulted in a good fit between the theoretical dimensions of the COACH tool and its psychometric properties. The tool has 49 items measuring eight aspects of context: Resources, Community engagement, Commitment to work, Informal payment, Leadership, Work culture, Monitoring services for action and Sources of knowledge. Conclusions: Aspects of organizational context that were identified as influencing the implementation of EBPs in high-income settings were also found to be relevant in LMICs. However, there were additional aspects of context of relevance in LMICs specifically Resources, Community engagement, Commitment to work and Informal payment. Use of the COACH tool will allow for systematic description of the local healthcare context prior implementing healthcare interventions to allow for tailoring implementation strategies or as part of the evaluation of implementing healthcare interventions and thus allow for deeper insights into the process of implementing EBPs in LMICs.

Nonparametric entropy-based tests of independence between stochastic processes

This paper develops nonparametric tests of independence between two stationary stochastic processes. The testing strategy boils down to gauging the closeness between the joint and the product of the marginal stationary densities. For that purpose, I take advantage of a generalized entropic measure so as to build a class of nonparametric tests of independence. Asymptotic normality and local power are derived using the functional delta method for kernels, whereas finite sample properties are investigated through Monte Carlo simulations.

Novel catalyst systems based on Ni(II), Ti(IV), and Cr(III) complexes for oligo-and polymerization of ethylene

The complex of Brookhart Ni(α-diimine)Cl2 (1) (α-diimine = 1,4-bis(2,6- diisopropylphenyl)-acenaphthenediimine) has been characterized after impregnation on silica (S1) and MAO-modified silicas (4.0, 8.0 and 23.0 wts.% Al/SiO2 called S2, S3 and S4, respectively). The treatment of these heterogeneous systems with MAO produces some active catalysts for the polymerization of the ethylene. A high catalytic activity has been gotten while using the system supported 1/S3 (196 kg of PE/mol[Ni].h.atm; toluene, Al/Ni = 1000, 30ºC, 60 min and atmospheric pressure of ethylene). The effects of polymerization conditions have been tested with the catalyst supported in S2 and the best catalytic activity has been gotten with solvent hexane, MAO as cocatalyst, molar ratio Al/Ni of 1000 and to the temperature of 30°C (285 kg of PE/mol[Ni].h.atm). When the reaction has been driven according to the in situ methodology, the activity practically doubled and polymers showed some similar properties. Polymers products by the supported catalysts showed the absence of melting fusion, results similar to those gotten with the homogeneous systems by DSC analysis. But then, polymers gotten with the transplanted system present according to the GPC’s curves the polydispersity (MwD) varies between 1.7 and 7.0. A polyethylene blend (BPE/LPE) was prepared using the complex Ni(α-diimine)Cl2 (1) (α-diimine = 1,4-bis(2,6-diisopropylphenyl)-acenaphthenediimine) and {TpMs*}TiCl3 (2) (TpMs* = hydridobis(3-mesitylpyrazol-1-yl)(5-mesitylpyrazol-1-yl)) supported in situ on MAO-modified silica (4.0 wts. -% Al/SiO2, S2). Reactions of polymerization of ethylene have been executed in the toluene in two different temperatures (0 and 30°C), varying the molars fraction of nickel (xNi), and using MAO as external cocatalyst. To all temperatures, the activities show a linear variation tendency with xNi and indicate the absence of the effect synergic between the species of nickel and the titanium. The maximum of activity have been found at 0°C. The melting temperature for the blends of polyethylene produced at 0 °C decrease whereas xNi increases indicating a good compatibility between phases of the polyethylene gotten with the two catalysts. The melting temperature for the blends of polyethylene showed be depend on the order according to which catalysts have been supported on the MAO-modified silica. The initial immobilization of 1 on the support (2/1/S2) product of polymers with a melting temperature (Tm) lower to the one of the polymer gotten when the titanium has been supported inicially (1/2/S2). The observation of polyethylenes gotten with the two systems (2/1/S2 and 1/2/S2) by scanning electron microscopy (SEM) showed the spherical polymer formation showing that the spherical morphology of the support to been reproduced. Are described the synthesis, the characterization and the catalytic properties for the oligomerization of the ethylene of four organometallics compounds of CrIII with ligands ([bis[2-(3,5-dimethyl-1-pyrazolyl)ethyl]amine] chromium (III) chloride (3a), [bis[2-(3,5- dimethyl-l-pyrazolyl)ethyl]benzylamine] chromium (III) chloride (3b), [bis[2-(3,5-dimethyl-lpyrazolyl) ethyl]ether] chromiun(III)chloride (3c), [bis[2-(3-phenyl-lpyrazolyl) ethyl]ether]chromiun(III)chloride (3d)). In relation of the oligomerization, at exception made of the compounds 3a, all complex of the chromium showed be active after activation with MAO and the TOF gotten have one effect differentiated to those formed with CrCl3(thf)3. The coordination of a tridentate ligand on the metallic center doesn't provoke any considerable changes on the formation of the C4 and C6, but the amount of C8 are decrease and the C10 and C12+ have increased. The Polymers produced by the catalyst 3a to 3 and 20 bar of ethylene have, according to analyses by DSC, the temperatures of fusion of 133,8 and 136ºC respectively. It indicates that in the two cases the production of high density polyethylene. The molar mass, gotten by GPC, is 46647 g/mols with MwD = 2,4 (3 bar). The system 3c/MAO showed values of TOF, activity and selectivity to different α-olefins according to the pressure of ethylene uses. Himself that shown a big sensibility to the concentration of ethylene solubilized.

Advertising new product categories to new geographical markets

Em um ambiente global dinâmico e competitivo, muitas empresas notam que constante desenvolvimento e lançamento de novos produtos são atividades-chave para seu crescimento e sobrevivência. Hoje, um dos maiores desafios enfrentados por tais empresas envolve saber como agir em um mundo em que tanto o escopo como a estrutura do ambiente competitivo estão em constante mudança, e em que reestruturações e mudanças de portfólio são centrais para as companhias que visam capitalizar com o crescimento global. Tanto o rápido ritmo de inovação tecnológica quando a crescente afluência de economias emergentes apresentam riscos e oportunidades para as empresas, o que torna importante não apenas que estas estejam atentas ao lançamento de produtos de última geração para mercados desenvolvidos: faz-se também necessário que saibam como lançar produtos antigos para novos mercados. Usando o mercado brasileiro como um exemplo, esta dissertação procurou estudar como multinacionais têm utilizado anúncios publicitários no lançamento, para novos mercados, de categorias e subcategorias de produtos já vendidas em outros países. Após uma revisão da literatura disponível, do desenvolvimento de proposições, e da avaliação destas através de três estudos de caso, foi possível verificar a existência de alguma linearidade entre os casos e a literatura estudada, incluindo: uma busca pela legitimação da categoria que precede àquela pela da marca; o uso de “especialistas” para a legitimação da categoria; o uso de apelos baseados em argumentos; e a divulgação de mais de uma característica de produto por anúncio. No entanto, dadas algumas discrepâncias entre o que foi observado nos casos e aquilo descrito na literatura consultada, também foi possível verificar que a maneira como os anúncios são feitos em diferentes lugares depende igualmente do cenário competitivo enfrentado pela empresa, bem como de variantes econômicas e culturais específicas da localidade em questão.

Product placement in movies: a cross cultural study between Brazil and the USA

The broader objective of this study undertaking can briefly be articulated in particulate aims as follows: to measure the attitudes of consumers regarding the brand displayed by this strategy as well as to highlight recall, recognition and purchase intentions generated by product placement on consumers. In addition, check the differences and similarities between the behavior of Brazilian and American consumers caused by the influence of product placements. The study was undertaken targeting consumer audience in Brazil and the U.S. A rang3 modeling set ups were performed in order to realign study instruments and hypothesis towards the research objectives. This study gave focus on the following hypothesized models. H1: Consumers / Participants who viewed the brands / products in the movie have a higher brand / product recall compared to the consumers / participants who did not view the brands / products in the movie. H2: US Consumers / Participants are able to recognize and recall brands / products which appear in the background of the movie than Brazil. H3: Consumers / participants from USA are more accepting of product placements compared to their counterparts in Brazil. H4: There are discernible similarities in consumer / participant brand attitudes and purchase intentions in consumers / participants from USA and Brazil in spite of the fact that their country of origin is different. Cronbach’s Alpha Coefficient ensured the reliability of survey instruments. The study involved the use of the Structural Equation Modeling (SEM) for the hypothesis testing. This study used the Confirmatory Factor Analysis (CFA) to assess both the convergent and discriminant validities instead of using the Exploratory Factor Analysis (EFA) or the Principal Component Analysis (PCA). This reinforced for the use of the regression Chi Square and T statistical tests in further. Only hypothesis H3 was rejected, the rest were not. T test provided insight findings on specific subgroup significant differences. In the SEM testing, the error variance for product placement attitudes was negative for both the groups. On this The Heywood Case came in handy to fix negative values. The researcher used both quantitative and qualitative approach where closed ended questionnaires and interviews respectively were used to collect primary data. The results were additionally provided with tabulations. It can be concluded that, product placement varies markedly in the U.S. from Brazil based on the influence a range of factors provided in the study. However, there are elements of convergence probably driven by the convergence in technology. In order, product placement to become more competitive in the promotional marketing, there will be the need for researchers to extend focus from the traditional variables and add knowledge on the conventional marketplace factors that is the sell-ability of the product placement technologies and strategies.

Estimation of Maximal Work Rate Based on the 6-Minute Walk Test and Fat-Free Mass in Chronic Obstructive Pulmonary Disease

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