Synthesis and analgesic profile of conformationally constrained N-acylhydrazone analogues: Discovery of novel N-arylideneamino quinazolin-4(3H)-one compounds derived from natural safrole

In this work we reported the synthesis and evaluation of the analgesic, anti-inflammatory, and platelet anti-aggregating properties of new 3-(arylideneamino)-2-methyl-6,7-methylenedioxy-quinazolin-4 (3H)-one derivatives (3a-j), designed as conformationally constrained analogues of analgesic 1,3- benzodioxolyl-N- acylhydrazones (1) previously developed at LASSBio. Target compounds were synthesized in very good yields exploiting abundant Brazilian natural product safrole (2) as starting material. The pharmacological assays lead us to identify compounds LASSBio-1240 (3b) and LASSBio-1272 (3d) as new analgesic prototypes, presenting an antinociceptive pro. le more potent and effective than dipyrone and indomethacin used, respectively, as standards in AcOH-induced abdominal constrictions assay and in the formalin test. These results confirmed the success in the exploitation of conformation restriction strategy for identification of novel cyclic N-acylhydrazone analogues with optimized analgesic profile (C) 2009 Elsevier Ltd. All rights reserved.

Acanthoscurrin Fragment 101-132: Total Synthesis at 60 degrees C of a Novel Difficult Sequence

Glycine-rich proteins (GRP), serve a variety of biological functions. Acanthoscurrin is an antimicrobial GRP isolated front hemocytes-of the Brazilian spider Acanthoscurria gomesiana. Aiming to contribute to the knowledge of the secondary structure and stepwise solid-phase synthesis of GRPs` glycine-rich domains, we attempted to prepare G(101)GGLGGGRGGGYG(113) GGGGYGGGYG(123)GGy(126)GGGKYK(132)-NH(2), acanthoscurrin C-terminal amidated fragment. Although a theoretical prediction did not indicate high aggregation potential for this peptide, repetitive incomplete aminoacylations were observed after incorporating Tyr(126) to the growing peptide-MBHA resin (Boc chemistry) at 60 degrees C. The problem was not solved by varying the coupling reagents or solvents, adding chaotropic salts to the reaction media or changing the resin/chemistry (Rink amide resin/Fmoc chemistry). Some improvement was mode when CLEAR amide resin (Fmoc chemistry) was 32 used, as it allowed for obtaining fragment (G(113)-K(132) NIR-FT-Raman spectra collected for samples of the growing peptide-MBHA, -Rink amide resin and -CLEAR amide resin revealed the presence of beta-sheet structures. Only the combination of CLEAR-amide resin, 60 degrees C, Fmoc-(Fmoc-Hmb)Gly-OH and LiCl (the last two used alternately) was able to inhibit the phenomenon, as proven by NIR-FT-Raman analysis of the growing peptide-resin, allowing the total synthesis of desired 132 fragment Gly(101)-K(132). In summary, this work describes a new difficult sequence, contributes to understanding stepwise solid-phase synthesis of this type of peptide and shows that, at least while protected and linked to a resin, this GRPs glycine-rich motif presents all early tendency to assume beta-sheet structures. (c) 2008 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 92: 65-75, 2009.

Sequential IRMPD of XGe(OEt)(4)(-) ions: Gas-phase synthesis of novel oxy-germanium anions

The gas-phase ion/molecule reactions of F(-) and EtO(-) with Ge(OEt)(4) yield readily and exclusively pentacoordinated complexes XGe(OEt)(4)(-) (X = F, EtO) at pressures in the 10(-8) T range as observed by FT-ICR techniques. These hypervalent species are prone to undergo sequential fragmentations induced by infrared multiphoton excitation that lead to a variety of germyl and germanate anions. In the case of FGe(OEt)(4)(-), three primary competitive channels are observed in the IRMPD process that can be identified as (EtO)(3)GeO(-), F(EtO)(2)GeO(-) and (EtO)(3)Ge(-). Ab initio calculations have been carried out to characterize the primary fragmentation paths induced by IRMPD and the most favorable structure of the resulting anions. The gas-phase acidity of a number of these germanium-containing ions have been estimated by bracketing experiments and by theoretical calculations. Germanate anions such as (EtO)(3)GeO(-) undergo some interesting reactions with H(2)S to give rise to anions such as (EtO)(3)GeS(-) and (EtO)(2)Ge(OH)S(-). (C) 2010 Elsevier B.V. All rights reserved.

Studies toward the structural optimization of novel thiazolylhydrazone-based potent antitrypanosomal agents

In previous studies, we identified promising anti-Trypanosoma cruzi cruzain inhibitors based on thiazolylhydrazones. To optimize this series, a number of medicinal chemistry directions were explored and new thiazolylhydrazones and thiosemicarbazones were thus synthesized. Potent cruzain inhibitors were identified, such as thiazolylhydrazones 3b and 3j, which exhibited IC(50) of 200-400 nM. Furthermore, molecular docking studies showed concordance with experimentally derived structure-activity relationships (SAR) data. In the course of this work, lead compounds exhibiting in vitro activity against both the epimastigote and trypomastigote forms of T. cruzi were identified and in vivo general toxicity analysis was subsequently performed. Novel SAR were documented, including the importance of the thiocarbonyl carbon attached to the thiazolyl ring and the direct comparison between thiosemicarbazones and thiazolylhydrazones. (C) 2010 Elsevier Ltd. All rights reserved.

Representation and interpretation : textbooks, teachers, and historical culture

This article presents a study of how contemporary Swedish lower secondary school textbooks present the emergence of the Cold War and how 10 active lower secondary school history teachers interpreted a quotation that was ambiguous in relation to the general narrative in the studied Swedish textbooks, seeking to analyse textbooks both from the perspectives of content and reception. Applying a theoretical framework of uses of history, the study finds that the narratives presented in the studied textbooks are what could be called traditional in the sense that they do not acknowledge perspective and representation in history. While the interviewed teachers generally acknowledged that textbook narratives are representations of history and contingent on perspective, few teachers extended this to include how their own views affect their interpretations, suggesting an intermediary appreciation of the contextual contingency of historical narratives.

Primitive art as it relates to contemporary design

For the most part, my project has been of an individually rewarding nature due to an extensive amount of reading and studio work. My paper functions as the major means of communication of my own experiences and findings. It is an attempt to share with others the ideas which I have found particularly stimulating and worthwhile during the course of the year. In other words, the written portion does not intend to summarize all of the phases of primitive art which I have studied during the past year; rather, it is indicative of the type of pursuit with which I became involved. It is neither a historical survey nor a specific and thorough study of one area of primitive art. Instead, my paper is a series of essays focusing upon primitive art in general, and upon some of the aspects of primitive art with which I became concerned in particular.

The Brazilian social security program:diagnosis and proposal for reform

The Brazilian pay-as-you-go social security program is analyzed in a historical perspective. Its contribution to income inequality, and the role played by the inflation as a balancing variable are discussed. It is shown that budgetary constraints due to the increasing informalization of the labor force can no longer be reconciled with protligate eligibility criteria. A tailor-made proposal for reform is presented as well as a plan for financing the transition from today's system to the proposed one.

William Gaddis's aesthetics of recognitions

William Gaddis’s The Recognitions (1955) is a selfreflexive novel that portrays Wyatt Gwyon’s trajectory from childhood to maturity, as he rejects and searches for originality. The present work bestows an analysis of William Gaddis’s The Recognitions focusing on the problematization of originality and authorship proposed by the novel by means of the central issues of forgery and plagiarism, which bring with them two larger and more important sister-notions: authorship and originality. The novel questions the prevailing demand for originality and discusses the possibility of being original. It formulates an aesthetics of recognitions defended in the novel and used by the author in the making of this text. In order to do that, this work provides a view on the different concepts associated with the terms originality and original, as well as some of the main infringements related to them in contemporary society. It also offers an account of the development of the concepts of originality and authorship in Western society, showing the growing importance of the figure of the author and the parallel development of the concepts of plagiarism and copyright. The next three chapters are dedicated to attempt to provide an account of William Gaddis’s The Recognitions focusing on the main artist characters and an analysis of the novel in the light of the theoretical and historical background provided. The first of these chapters focuses on Wyatt’s trajectory and his visions of art. The second identifies and analyses Wyatt’s mirrors in the narrative, which reinforce the self-reflective structure of the novel. And the third chapter exemplifies and analyses Wyatt’s aesthetics of recognitions, which turns out to be Gaddis’s own aesthetics in the making of his fiction.

Thinking from the South: brazilian social thought and the case of Euclides da Cunha

The article presents the main ideas of Euclides da Cunha (1866-1909), a famous Brazilian intellectual from the beginning of the twentieth-century. Da Cunha was one of the first writers to provide a proto-sociological account of subaltern people in Brazil. The aim of the article is to review his contributions in the light of contemporary discussions concerning postcolonialism and decolonisation.

Uma investigação das relações familiares na peça "Do Fundo do Lago Escuro (Assunto de Família)", de Domingos de Oliveira

A partir de três conceitos fundamentais para a compreensão da dinâmica das relações familiares: a pseudo-mutualidade, elaborada por Wynne, nos Estados Unidos, o postulado fusional, desenvolvido por Hochmann, na França e a mistificação, por Laing, na Inglaterra, investigou-se a estrutura de relações familiares em um texto teatral brasileiro, atual, "Do Fundo do Lago Escuro", de Domingos de Oliveira. Os três conceitos acima citados, fundamentais para a compreensão da dinâmica das relações familiares dentro de uma perspectiva sistêmica (não-psicanalítica),estão interrelacionados entre si e surgiram apartir de estudos realizados com famílias com um membro esquizofrênico, em três diferentes paises. Buscou-se estabelecer os pontos de contato, as divergências metodológicas, teóricas e ideológicas e os aspectos complementares dos referidos conceitos, bem como verificar sua aplicabilidade a uma estrutura familiar considerada representativa de certa parcela da sociedade brasileira, em determinada ocasião. Concluiu-se pela aplicabilidade dos conceitos, desenvolvidos em três diferentes países, a uma dada estrutura familiar brasileira em um dado momento histórico, e pela aplicabilidade dos conceitos a um grupo familiar que não apresenta, através de qualquer de seus membros, um quadro esquizofrênico manifesto.

The effects of trust in Brazilian PNPs: interpersonal and interorganizational trust in the cultural sector social organizations in São Paulo, Brazil

This study seeks to evaluate how enterorganizational and interpersonal trust affects the degree of State interference in the operations of public-nonprofit partnerships (PNPs). We conducted a qualitative case study in two Brazilian PNPs, Projeto Guri and Orquestra Sinfônica do Estado de São Paulo, through documental analysis and semi-structured interviews. Content analysis of the data yielded a trust framework that begins to explain how a variety of factors, including the protective qualities of the management contract and the strength of the board, moderate the relationship between interpersonal and interorganizational trust in PNPs. The study reveals that unlike Zaheer et al (1998), interpersonal trust had a unique and prominent effect on State interference and types of collaboration in PNPs. Parting from the suggestions by previous authors to contextualize PNP literature findings, the framework takes into account the highly personalistic qualities of Brazilian culture as well as historical and institutional context while highlighting the crucial role of interpersonal trust in Brazilian PNPs.

A monthly indicator of Brazilian GDP. The Brazilian business cycle and growth cycle

This paper constructs an indicator of Brazilian GDP at the monthly ftequency. The peculiar instability and abrupt changes of regimes in the dynamic behavior of the Brazilian business cycle were explicitly modeled within nonlinear ftameworks. In particular, a Markov switching dynarnic factor model was used to combine several macroeconomic variables that display simultaneous comovements with aggregate economic activity. The model generates as output a monthly indicator of the Brazilian GDP and real time probabilities of the current phase of the Brazilian business cycle. The monthly indicator shows a remarkable historical conformity with cyclical movements of GDP. In addition, the estimated filtered probabilities predict ali recessions in sample and out-of-sample. The ability of the indicator in linear forecasting growth rates of GDP is also examined. The estimated indicator displays a better in-sample and out-of-sample predictive performance in forecasting growth rates of real GDP, compared to a linear autoregressive model for GDP. These results suggest that the estimated monthly indicator can be used to forecast GDP and to monitor the state of the Brazilian economy in real time.

Perspectivas sobre o teletrabalho no contexto da administração pública brasileira: um anteprojeto

The job market today, undergoes transformations necessary for employees and employers. Coupled with technological progress, a large degree of connectivity and a new profile of workers opened up many opportunities and relevant aspects that have changed the way of working and their relations in several countries, including Brazil. This technological progress has provided contemporary workers to pursue alternative working outside of the workplace, the office and outside your residence without physical boundaries. Also provided the change in culture of both organizations, as employees, without compromising the Brazilian formal contractual character played by CLT or the Unified Contracting Regime. The emergence of this new type of worker needs to be inserted in the labor market respecting their peculiarities, either by private or public companies. Through a historical review of labor relations and their transformations over time, this research makes a brief reflection and analysis about telework in the Brazilian public administration, implementation, acceptance, advantages, disadvantages, difficulties, external and internal reflections, cultural impact, among others, that this "new" way of working brings to Brazilian society and the various levels of government.

Intergovernmental transfers and public spending in Brazilian municipalities

We estimate the effects of unconditional (full fiscal decentralization) versus conditional (partial fiscal decentralization) block grants on local public spending in Brazilian municipalities. Our results suggest that the effect of unconditional and conditional transfers do not differ statistically. Their combination promotes a full crowding-in effect on aggregate public spending — i.e., for $1 of unconditional and conditional grant receipts; we find $1 of additional local public expenditures, greater than the corresponding effect of local income, providing further evidence for the flypaper effect. Moreover, the effect of unconditional transfers on education (health) spending is smaller than the effect of conditional education (health) transfers but greater than the corresponding effect of local income. We consider four strategies to identify causal effects of federal grants and the local income on fiscal responses regarding Brazilian local governments: (i) a fuzzy regression discontinuity design, (ii) Redistributive rules of education funds, (iii) Oil and Gas production, and (iv) Rainfall deviations from the historical mean.

O impulso renovador: a atuação da Missão Indígena na Escola Militar do Realengo (1919-1922)

O presente trabalho tem por objetivo realizar uma análise da atuação de um grupo de instrutores na Escola Militar do Realengo no período compreendido entre os anos de 1919 e 1922, tomando por objeto as representações feitas por esses sujeitos, do que foi por eles atribuída como Missão Indígena. Os efeitos de sua atuação foram marcantes e se fizeram sentir por toda uma geração de oficiais do Exército Brasileiro, que ficou conhecida como a “geração do Realengo”. Embora constantemente lembrada pela historiografia militar, a Missão Indígena ainda foi muito pouco explorada em trabalhos acadêmicos, no que tange ao seu surgimento, à sua atuação na Escola Militar e ao envolvimento de alguns de seus membros no movimento tenentista. Dessa forma, o foco da pesquisa se concentrou na maneira como esse grupo de instrutores atuou e nas mudanças provocadas e percebidas pelos alunos em função dessa atuação, tanto na instrução como no regime militar diário da Escola Militar, estabelecimento de ensino que pretendia formar oficias “apolíticos” e que serviu de laboratório do Exército para experiências acerca de qual educação militar seria a ideal para a formação de seus quadros. A escolha do tema repousa no fato de a Missão ter sido constituída por um grupo de jovens oficiais subalternos e intermediários do Exército, dotados de elevada capacidade técnico-profissional e cujo perfil psicológico lhes conduziam a atuar em consonância com o ensino prático de caráter militar, inteiramente de acordo com as normas e regulamentos do Exército, sob a influência do rígido modelo alemão de instrução. Como instrumentos metodológicos foram utilizados os trabalhos de Michael Pollak, no que se refere à construção da memória e à institucionalização de determinadas narrativas, e de Maurice Halbwachs, no tocante à relação existente entre memória coletiva e espaço. Uma pesquisa realizada nos acervos documentais da Escola Militar do Realengo, pertencentes ao Arquivo Histórico do Exército, e nos arquivos pessoais e acervos de história oral do Centro de Pesquisa e Documentação História Contemporânea do Brasil, da Fundação Getúlio Vargas, possibilitou o acesso às fontes. Conclui-se que o esforço da Missão Indígena, voltado para a formação profissional da oficialidade do Exército Brasileiro, não esteve dissociado das inclinações para agir politicamente da geração que passou pela Escola do Realengo na década de 1920.