Two New Ternary Complexes of Copper(II) with Tetracycline or Doxycycline and 1,10-Phenanthroline and Their Potential as Antitumoral: Cytotoxicity and DNA Cleavage

This paper reports on the synthesis and characterization of two new ternary copper(II) complexes: [Cu(doxy-cycline)(1,10-phenanthroline)(H(2)O)(ClO(4))](ClO(4)) (1) and [Cu(tetracycline)(1,10-phenanthroline)(H(2)O)(ClO(4))](ClO(4)) (2). These compounds exhibit a distorted tetragonal geometry around copper, which is coordinated to two bidentate ligands, 1,10-phenanthroline and tetracycline or doxycyline, a water molecule, and a perchlorate ion weakly bonded in the axial positions. In both compounds, copper(II) binds to tetracyclines`. via the oxygen of the hydroxyl group and oxygen of the amide group at ring A and to 1,10-phenanthroline via its two heterocyclic nitrogens. We have evaluated the binding of the new complexes to DNA, their capacity to cleave it, their cytotoxic activity, and uptake in tumoral cells. The complexes bind to DNA preferentially by the major groove, and then cleave its strands by an oxidative mechanism involving the generation of ROS. The cleavage of DNA was inhibited by radical inhibitors and/or trappers such as superoxide dismutase, DMSO, and the copper(I) chelator bathocuproine. The enzyme T4 DNA ligase was not able to relegate the products of DNA cleavage, which indicates that the cleavage does not occur via a hydrolytic mechanism. Both complexes present an expressive plasmid DNA cleavage activity generating single- and double-strand breaks, under mild reaction conditions, and even in the absence of any additional oxidant or reducing agent. In the same experimental conditions, [Cu(phen)(2)](2+) is approximately 100-fold less active than our complexes. These complexes are among the most potent DNA cleavage agents reported so far. Both complexes inhibit the growth of K562 cells With the IC(50) values of 1.93 and 2.59 mu mol L(-1) for compounds I and 2, respectively. The complexes are more active than the free ligands, and their cytotoxic activity correlates with intracellular copper concentration and the number of Cu-DNA adducts formed inside cells.

Catalytic oxidation of hydrocarbons by trinuclear mu-oxo-bridged ruthenium-acetate clusters: Radical versus non-radical mechanisms

The [Ru(3)O(H(3)CCO(2))(6)(py)(2)(L)]PF(6) clusters, where L=methanol or dimethyl sulfoxide, can be activated by peroxide or oxygen donor species, such as tert-butyl hydroperoxide (TBHP) or iodosylbenzene (PhIO), respectively, generating reactive intermediates of the type [Ru(3)(IV,IV,III)=0](+). In this way, they catalyse the oxidation of cyclohexane or cyclohexene by TBHP and PhIO, via oxygen atom transfer, rather than by the alternative oxygen radical mechanism characteristic of this type of complexes. In addition to their ability to perform efficient olefin epoxydation catalysis, these clusters also promote the cleavage of the C-H bond in hydrocarbons, resembling the oxidation catalysis by metal porphyrins. (C) 2008 Elsevier Inc. All rights reserved.

Double-strand DNA cleavage induced by oxindole-Schiff base copper(II) complexes with potential antitumor activity

Some oxindole-Schiff base copper(II) complexes have already shown potential antitumor activity towards different cells, inducing apoptosis in a process modulated by the ligand, and having nuclei and mitochondria as main targets. Here, three novel copper(II) complexes with analogous ligands were isolated and characterized by spectroscopic techniques, having their reactivity compared to the so far most active complex in this class. Cytotoxicity experiments carried out toward human neuroblastoma SH-SY5Y cells confirmed its proapoptosis property. DNA cleavage studies were then performed in the presence of these complexes, in order to verify the influence of ligand structural features in its nuclease activity. All of them were able to cause double-strand DNA scissions, giving rise to nicked circular Form II and linear Form III species, in the presence of hydrogen peroxide. Additionally, DNA Form II was also detected in the absence of peroxide when the most active complex, [Cu(isaepy)(2)](2+) 1, was used. In an effort to better elucidate their interactions with DNA, solutions of the different complexes titrated with DNA had their absorption spectra monitored. An absorbance hyperchromism observed at 260 nm pointed to the intercalation of these complexes into the DNA structure. Further, investigations of 2-deoxy-D-ribose (DR) oxidation catalyzed by each of those complexes, using 2-thiobarbituric acid reactive species (TBARS) method, and detection of reactive oxygen species (ROS) formation by spin-trapping EPR, suggested that their mechanism of action in performing efficiently DNA cleavage occurs preferentially, but not only by oxidative pathways. (C) 2007 Elsevier Inc. All rights reserved.

Methanol and ethanol electro-oxidation on Pt-SnO(2) and Pt-Ta(2)O(5) sol-gel-modified boron-doped diamond surfaces

The search for more efficient anode catalyst than platinum to be used in direct alcohol fuel cell systems is an important challenge. In this study, boron-doped diamond film surfaces were modified with Pt, Pt-SnO(2) and Pt-Ta(2)O(5) nano-crystalline deposits by the sol-gel method to study the methanol and ethanol electro-oxidation reactions in acidic medium. Electrochemical experiments carried out in steady-state conditions demonstrate that the addition of SnO(2) to Pt produces a very reactive electrocatalyst that possibly adsorbs and/or dissociate ethanol more efficiently than pure Pt changing the onset potential of the reaction by 190 mV toward less positive potentials. Furthermore, the addition of Ta(2)O(5) to Pt enhances the catalytic activity toward the methanol oxidation resulting in a negative shift of the onset potential of 170 mV. These synergic effects indicate that the addition of these co-catalysts inhibits the poisoning effect caused by strongly adsorbed intermediary species. Since the SnO(2) catalyst was more efficient for ethanol oxidation, it could probably facilitate the cleavage of the C-C bond of the adsorbed intermediate fragments of the reaction. (C) 2009 Elsevier B.V. All rights reserved.

James Bond-temats musikaliska förändringar : Från Dr. No till Casino Royale

I denna uppsats har den musikaliska förändringen i James Bond-temat, sett över de 21 filmer som gjorts fram till denna uppsats genomförande, analyserats och tolkats. Syftet är att dela med mig av mina tankar och analyser om hur temat framförts och utvecklats, samt därmed också bidra till att utveckla kunskapen om James Bond-världen.Efter en litteraturbaserad del, där bakgrunden till James Bond-temats uppkomst behandlas, så analyseras sedan film för film i Bond-serien från Dr. No till Casino Royale. Analysen tar främst upp delarna synkronisering, instrumentering och influenser.Analyserna visar på att James Bond-temat i grund och botten bygger på samma melodi genom alla filmer, men också har förändrats i stor utsträckning i utförandet.

What is the role of bookbuilding in bond allocation ? : evidence from Brazil

A dissertação tem como objetivo analisar dois aspectos do processo de bookbuilding nas emissões de debêntures no mercado brasileiro. O primeiro aspecto é verificar se o underwriter utiliza, a exemplo do que ocorre no Initial Public Offering (IPO) de ações, o poder discricionário nas alocações das debêntures entre os investidores. O segundo consiste em encontrar as características, tanto do emissor quanto do investidor, que influenciam na eficiência do bidder no processo de bookbuilding. Para realizar os testes empíricos foi utilizada uma base de dados composta por 40 books1 (totalizando 727 bids) fornecidos por um banco de investimento.Verifica-se que o underwriter não beneficia nenhum investidor na alocação final das debêntures. Essa afirmação fica evidenciada quando se calcula a diferença entre alocação final (efetivamente recebida pelo investidor) e alocação teórica (estimada com base no método pro-rata) para os 27 books (totalizando 557 bids) que apresentam demanda superior a oferta. A diferença é nula para 96.6% da amostra, sendo que das 19 observações não nulas, 15 possuem diferença absoluta de uma debênture entre a alocação teórica e a final, resultado explicado em função do arredondamento das alocações.Contrariando a teoria de leilão de titulos públicos, onde autores, como Scott and Wolf (1979), defendem que os investidores devem utilizar o step bid como estratégia ótima de bid, este trabalho verificou que no caso de bookbuilding de debêntures no mercado brasileiro, os investidores usuários de step bid posssuem menos chances de ter seu bid atendido plenamente pelo underwriter. Quando o investidor é um gestor de recursos de terceiros (asset management), aumenta-se a possibilidade de ter sua demanda atendida. O maior sucesso do asset management no bookbuilding deve-se às peculiaridades do mercado brasileiro: (i) somente investidores locais participam dos bookbuilding, já que investidores estrangeiros possuem preferência e incentivos por títulos públicos; (ii) gestores de recursos de terceiros representam 75% da demanda por debêntures; (iii) o mercado de gestão de recursos é concentrado: os 5 maiores gestores concentram 60% da indústria. Com isso os gestores de recursos podem desenvolver uma expertise própria, já que são os principais demandadores e frequentemente participam dos bookbuilding. As características do emissor também influenciam no desempenho dos bidders: as debêntures de baixo e médio risco aumentam a possibilidade do bidder ter seu pedido atendido na íntegra. Além disso, como era esperado, quanto maior for a demanda do título, mais dificil é para o investor conseguir a quantidade desejável.

Re-framing risk transfer to assess integrative partnership opportunities: the S.A.R. approach and the AIG/BID/CNO regional surety bond facility of 2007

Identificar, compartilhar e gerenciar os riscos de contratar são preocupações que impedem o estabelicmento e a administração das Parcerias Públicos Particulares (PPP). Porem, gerentes das entidades públicas, bancos de formento, construtoras e seguradoras pesquisam e utilizam muitas técnicas para enfrentar a avaliação e gerenciamento dos riscos. A transferência de risco é uma indicação dos chamados benefícios que são inspirados pelos PPP, contudo devido às realidades contratuais e conceptuais, a entidade de cede o risco (o partido público) permanece quase sempre como o portador final do risco. Conseqüentemente, o partido público retem um interesse de resistência na gerência total destes riscos cedidos. Esta dissertação explora alguns defeitos das aproximações comuns a conceituar a gestão de risco no contexto de um PPP. Focalizando os conceitos da interdependência e da reciprocidade e usando na decisão para transferir o risco do projeto, esta dissertação molda a decisão para transferir o risco nos termos das realidades interdependentes de relacionamentos sistemáticos, alargam os conceitos técnicos do risco e da avaliação de risco, considerando o uso reflexivo das diferenças na analise de um estudo de caso. O autor explora estes conceitos em uma análise da decisão de um gerente de risco da empresa de construção civil brasileira Construtora Norberto Odebrecht (ODB) para projetar uma facilidade inovadora da ligação de garantia com Inter-American Development Bank (BID) e uma seguradora, American International Group (AIG), um negócio que ganhe o reconhecimento Trade Finance Magazine’s 2007 deal of the year. O autor mostra que por compreender a transferência de risco nos termos abordados nesta dissertação, um atore que transfere o risco pode identificar e criar mais oportunidades de estabelecer relacionamentos em longo prazo, através dos processos que a literatura atual do PPP ainda não considere. Os resultados devem fornecer contribuições para a pesquisas sobre a transferência do risco do projeto, na cooperação entre organizações e na seleção do sócio do projeto do potencial.

The role of bond covenants and short-term debt: evidence from Brazil

Esta dissertação tem como objetivo analisar a relação entre covenants e alavancagem financeira no curto e longo prazo com oportunidades de crescimento. A partir de uma amostra de 159 debêntures, encontramos evidência de que: 1) Covenants e dívida de curto-prazo podem ser considerados substitutos na atenuação do conflito de agência, uma vez que apresentaram relação negativa e significante e; 2) A relação negativa existente entre dívida de curto prazo e oportunidades de crescimento pode ser reduzida através da utilização de covenants.

Electoral institutions,cleavage structures,and the number of parties

Theory: A classic question in political science concems ",hat deteImines the number of parties that compete in a given polity. Broadly speaking, there are two approaches to answering this question, one that emphasizes the role of electorallaws in structuring coalitional incentives, another that emphasizes the importance of pre-existing social cleavages. In tbis paper, we view the number of parties as a product of the interaction between these two forces, following Powell (1982) and Ordeshook and Shvetsova (1994). Hypotheses: The effective number of parties in a polity should be a multiplicative rather than an additive function ofthe peImissiveness ofthe electoral system and the heterogeneity ofthe society. Methods: Multiple regression on cross-sectional aggregate electoral statistics. Unlike previous studies, we (1) do not confine attention to developed democracies; (2) explicitly control for the influence of presidential elections, taking account of whether they are concurrent or nonconcurrent, and ofthe effective number ofpresidential candidates; and (3) also control for the presence and operation of upper tiers in legislative elections. Results: The hypothesis is confiImed, both as regards the number of legislative and the number of presidential parties .

Do options contain information about excess bond returns ?

There is strong empirical evidence that risk premia in long-term interest rates are time-varying. These risk premia critically depend on interest rate volatility, yet existing research has not examined the im- pact of time-varying volatility on excess returns for long-term bonds. To address this issue, we incorporate interest rate option prices, which are very sensitive to interest rate volatility, into a dynamic model for the term structure of interest rates. We estimate three-factor affine term structure models using both swap rates and interest rate cap prices. When we incorporate option prices, the model better captures interest rate volatility and is better able to predict excess returns for long-term swaps over short-term swaps, both in- and out-of-sample. Our results indicate that interest rate options contain valuable infor- mation about risk premia and interest rate dynamics that cannot be extracted from interest rates alone.

Por que James Bond, o engenheiro, desistiu do Brasil

Após oito anos e meio, James Arthur Bond, de 48 anos, a contragosto, foi levado de volta às origens. A crise tirou-o do Rio de Janeiro, terra que escolheu para viver com a família, forçando-o a buscar estabilidade em solo britânico.

Social impact bond feasibility study APAC Portugal: enhancing ex-offenders’ lives

Este estudo é uma análise à eficácia de um Social Impact Bond como como instrumento financeiro no modelo de intervenção da APAC Portugal. O objetivo é o de melhorar a vida de ex-criminosos e reduzir os índices de reincidência de modo a apoiar a sua reinserção na sociedade após a libertação. Enquanto os custos de funcionamento de um estabelecimento prisional forem suportados pelo sector público, como é de lei, o modelo inovador de intervenção terá de encontrar um meio alternativo de financiamento. Sendo assim, testámos a rentabilidade de um Social Impact Bond através de um bem estruturado modelo Excel que simula o mecanismo de investimento, tendo os resultados demonstrado que um Social Impact Bond pode, de facto, financiar o modelo de intervenção da APAC Portugal de forma eficaz.

The Pair-Bond Formation and Its Role in the Stimulation of Reproductive Function in Female Common Marmosets (Callithrix jacchus)

SILVA, H.P.A.; SOUSA, M.B.C. The pair-bond formation and its role in the stimulation of reproductive function in female common marmosets (collithrix Jacchus). International Journal of Primatology, v, 18, n.3, p.387-400, 1997.

The zymogen-enteropeptidase system: A practical approach to study the regulation of enzyme activity by proteolytic cleavage

The present research describes an efficient procedure to obtain high levels of trypsinogen and chymotrypsinogen by using a simple, rapid, and easily reproducible method. The extraction process and the time-course of activation of zymogens can be carried out in a single laboratory period, without sophisticated equipment. The main objective was to prepare a laboratory class that would stimulate student interest in enzyme regulation, exploring the fact that the catalytic activity of some enzymes is regulated by different mechanisms. The regulation of proteolytic enzymes requires the synthesis of an inactive zymogen and its being irreversibly switched on by specific proteolytic cleavage.