Clopidogrel, independent of the vascular P2Y(12) receptor, improves arterial function in small mesenteric arteries from Angll-hypertensive rats

The P2Y(12) receptor antagonist clopidogrel blocks platelet aggregation, improves systemic endothelial nitric oxide bioavailability and has anti-inflammatory effects. Since P2Y(12) receptors have been identified in the vasculature, we hypothesized that clopidogrel ameliorates Angll (angiotensin II)-induced vascular functional changes by blockade of P2Y(12) receptors in the vasculature. Male Sprague Dawley rats were infused with Angll (60 ng/min) or vehicle for 14 days. The animals were treated with clopidogrel (10 mg . kg(-1) of body weight . day(-1)) or vehicle. Vascular reactivity was evaluated in second-order mesenteric arteries. Clopidogrel treatment did not change systolic blood pressure [(mmHg) control-vehicle, 117 +/- 7.1 versus control-clopidogrel, 125 +/- 4.2; Angll vehicle, 197 +/- 10.7 versus Angll clopidogrel, 198 +/- 5.2], but it normalized increased phenylephrine-induced vascular contractions [(%KCI) vehicle-treated, 182.2 +/- 18% versus clopidogrel, 133 +/- 14%), as well as impaired vasodilation to acetylcholine [(%) vehicle-treated, 71.7 +/- 2.2 versus clopidogrel, 85.3 +/- 2.8) in Angll-treated animals. Vascular expression of P2Y(12) receptor was determined by Western blot. Pharmacological characterization of vascular P2Y(12) was performed with the P2Y(12) agonist 2-MeS-ADP [2-(methylthio) adenosine 5`-trihydrogen diphosphate trisodium]. Although 2-MeS-ADP induced endothelium-dependent relaxation [(Emax %) = 71 +/- 12%) as well as contractile vascular responses (Emax % = 83 +/- 12%), these actions are not mediated by P2Y(12) receptor activation. 2-MeS-ADP produced similar vascular responses in control and Angll rats. These results indicate potential effects of clopidogrel, such as improvement of hypertension-related vascular functional changes that are not associated with direct actions of clopidogrel in the vasculature, supporting the concept that activated platelets contribute to endothelial dysfunction, possibly via impaired nitric oxide bioavailability.

On the Hartman-Grobman Theorem with Parameters

The Hartman-Grobman Theorem of linearization is extended to families of dynamical systems in a Banach space X, depending continuously on parameters. We prove that the conjugacy also changes continuously. The cases of nonlinear maps and flows are considered, and both in global and local versions, but global in the parameters. To use a special version of the Banach-Caccioppoli Theorem we introduce equivalent norms on X depending on the parameters. The functional setting is suitable for applications to some nonlinear evolution partial differential equations like the nonlinear beam equation.

Numerical solution of the PTT constitutive equation for unsteady three-dimensional free surface flows

This work deals with the development of a numerical technique for simulating three-dimensional viscoelastic free surface flows using the PTT (Phan-Thien-Tanner) nonlinear constitutive equation. In particular, we are interested in flows possessing moving free surfaces. The equations describing the numerical technique are solved by the finite difference method on a staggered grid. The fluid is modelled by a Marker-and-Cell type method and an accurate representation of the fluid surface is employed. The full free surface stress conditions are considered. The PTT equation is solved by a high order method, which requires the calculation of the extra-stress tensor on the mesh contours. To validate the numerical technique developed in this work flow predictions for fully developed pipe flow are compared with an analytic solution from the literature. Then, results of complex free surface flows using the FIT equation such as the transient extrudate swell problem and a jet flowing onto a rigid plate are presented. An investigation of the effects of the parameters epsilon and xi on the extrudate swell and jet buckling problems is reported. (C) 2010 Elsevier B.V. All rights reserved.

A general Trotter-Kato formula for a class of evolution operators

In this article we prove new results concerning the existence and various properties of an evolution system U(A+B)(t, s)0 <= s <= t <= T generated by the sum -(A(t) + B(t)) of two linear, time-dependent, and generally unbounded operators defined on time-dependent domains in a complex and separable Banach space B. In particular, writing L(B) for the algebra of all linear bounded operators on B, we can express U(A+B)(t, s)0 <= s <= t <= T as the strong limit in C(8) of a product of the holomorphic contraction semigroups generated by -A (t) and - B(t), respectively, thereby proving a product formula of the Trotter-Kato type under very general conditions which allow the domain D(A(t) + B(t)) to evolve with time provided there exists a fixed set D subset of boolean AND(t is an element of)[0,T] D(A(t) + B(t)) everywhere dense in B. We obtain a special case of our formula when B(t) = 0, which, in effect, allows us to reconstruct U(A)(t, s)0 <=(s)<=(t)<=(T) very simply in terms of the semigroup generated by -A(t). We then illustrate our results by considering various examples of nonautonomous parabolic initial-boundary value problems, including one related to the theory of timedependent singular perturbations of self-adjoint operators. We finally mention what we think remains an open problem for the corresponding equations of Schrodinger type in quantum mechanics.

Single Synapse Information Coding in Intraburst Spike Patterns of Central Pattern Generator Motor Neurons

Burst firing is ubiquitous in nervous systems and has been intensively studied in central pattern generators (CPGs). Previous works have described subtle intraburst spike patterns (IBSPs) that, despite being traditionally neglected for their lack of relation to CPG motor function, were shown to be cell-type specific and sensitive to CPG connectivity. Here we address this matter by investigating how a bursting motor neuron expresses information about other neurons in the network. We performed experiments on the crustacean stomatogastric pyloric CPG, both in control conditions and interacting in real-time with computer model neurons. The sensitivity of postsynaptic to presynaptic IBSPs was inferred by computing their average mutual information along each neuron burst. We found that details of input patterns are nonlinearly and inhomogeneously coded through a single synapse into the fine IBSPs structure of the postsynaptic neuron following burst. In this way, motor neurons are able to use different time scales to convey two types of information simultaneously: muscle contraction (related to bursting rhythm) and the behavior of other CPG neurons (at a much shorter timescale by using IBSPs as information carriers). Moreover, the analysis revealed that the coding mechanism described takes part in a previously unsuspected information pathway from a CPG motor neuron to a nerve that projects to sensory brain areas, thus providing evidence of the general physiological role of information coding through IBSPs in the regulation of neuronal firing patterns in remote circuits by the CNS.

Ring Contraction of 1,2-Dihydronaphthalenes Promoted by Thallium(III) in Acetonitrile: A Diastereoselective Approach to Indanes

trans-1,3-Disubstituted indanes are conveniently accessed by a stereoselective ring contraction of 1,2-dihydronaphthalenes upon treatment with thallium(III) nitrate (TTN) in acetonitrile. Under these conditions, the oxidative rearrangement of either di- or trisubstituted double bonds is possible.

Relative durations of post-vocalic consonants in readaloud Spanish by native Swedish L2-learners

Prosody is said to be a persistent feature in foreign accents, particularly in the speech of adult learners. Native Swedish speakers have been reported to lengthen vowels in Spanish as well as post-vocalic consonants in English and German, more than native speakers of the respective languages. The aim of the present study is to examine whether native Swedish learners of Spanish produce increased postvocalic consonant durations in a reading aloud exercise. The text contains certain words that could be expected to trigger complementary consonant lengthening in native Swedish speakers. The result shows that there is no general tendency for native Swedes to lengthen post-vocalic consonants more than native speakers of Spanish in the present speech material. There are examples of longer consonant durations in the speech of the native,Swedish subjects, but it could be a coincidence. A conclusion is that the text used in the study, and probably Spanish as a language, contains few words that are ideal for triggering lengthening of post-vocalic consonants in native Swedish speakers.

The priority of temporal aspects in L2-Swedish prosody : Studies in perception and production

Foreign accent can be everything from hardly detectable to rendering the second language speech unintelligible. It is assumed that certain aspects of a specific target language contribute more to making the foreign accented speech intelligible and listener friendly, than others. The present thesis examines a teaching strategy for Swedish pronunciation in second language education. The teaching strategy “Basic prosody” or BP, gives priority to temporal aspects of Swedish prosody, which means the temporal phonological contrasts word stress and quantity, as well as the durational realizations of these contrasts. BP does not prescribe any specific tonal realizations. This standpoint is based on the great regional variety in realization and distribution of Swedish word accents. The teaching strategy consists virtually of three directives: · Stress the proper word in the sentence. · Stress proper syllables in stressed words and make them longer. · Lengthen the proper segment – vowel or subsequent consonant – in the stressed syllable. These directives reflect the view that all phonological length is stress-induced, and that vowel length and consonant length are equally important as learning goals. BP is examined in the light of existing findings in the field of second language pronunciation and with respect to the phonetic correlates of Swedish stress and quantity. Five studies examine the relation between segment durations and the categorization made by native Swedish listeners. The results indicate that the postvocalic consonant duration contributes to quantity categorization as well as giving the proper duration to stressed syllables. Furthermore, native Swedish speakers are shown to apply the complementary /V: C/ - /VC:/ pattern also when speaking English and German, by lengthening postvocalic consonants. The correctness of the priority is not directly addressed but important aspects of BP are supported by earlier findings as well as the results from the present studies.

Isquemia silenciosa e arritmias ventriculares são preditores independentes de evenos no pós-infarto do miocárdio de baixo risco

pós-infarto agudo do miocárdio (IAM) têm mostrado baixo valor preditivo positivo quando estudados isoladamente. A possibilidade da Eletrocardiografia Dinâmica de 24 horas (ECGD) fornecer dados referentes a isquemia silenciosa (IS), arritmias ventriculares e modulação autonômica do coração pelo estudo da variabilidade da freqüência cardíaca (VFC), levou o autor a empregar este método em pacientes acometidos de IAM com o objetivo de avaliar se estas três variáveis estariam relacionadas a presença de eventos desfavoráveis em evolução a médio prazo. Material e Métodos – Foram selecionados 91 pacientes acometidos de um primeiro IAM não-complicado e realizados exames de ECGD de 24 h por dois dias consecutivos, antes da alta hospitalar. Os parâmetros pesquisados nos exames foram: isquemia silenciosa, identificação e quantificação de arritmias ventriculares e determinação dos índices de VFC pelos métodos do domínio do tempo e do mapa de retorno tridimensional. Foram considerados como desfechos: re-infarto, angina instável, taquicardia ventricular sustentada e morte. Resultados – No seguimento médio de 27,7 meses (DP=15,45), 23 (25%) dos pacientes apresentaram eventos, sendo nove fatais. Os eventos foram mais freqüentes entre os pacientes que apresentaram extra-sístoles ventriculares ≥10/hora (p=0,01) e também naqueles com IS (p=0,02). Em modelo de análise multifatorial, a presença de dislipidemia elevou o valor preditivo positivo dessas variáveis. Nenhum dos índices de VFC esteve significativamente relacionado ao surgimento de eventos. Conclusões – Em pacientes pós-IAM de baixo risco, a presença de arritmias ventriculares freqüentes ou de isquemia silenciosa está relacionada a um prognóstico desfavorável. O estudo da VFC não mostrou utilidade na estratificação de risco destes pacientes.

Resposta urodinamica ao cateterismo vesical intermitente e cloreto de oxibutinina em crianças com mielomeningocele

Examinamos urodinamicamente 46 crianças com mielomeningocele que foram classificadas em pressão de perda do detrusor maior de 40 cmH2O (33 pacientes) ou menor de 40 cmH2O (13 pacientes). As variáveis estudadas foram: idade, sexo, pressão intravesical, complacência vesical, contrações vesicais não-inibidas, capacidade vesical, tipo de esfíncter, hidronefrose, refluxo vesicoureteral e cicatriz renal. Os pacientes com pressão de perda do detrusor maior de 40 cmH2O foram tratados com cateterismo vesical intermitente limpo 4 x/dia e cloreto de oxibutinina na dose de 0,2 mg/kg/dose 3 x/dia. Após 30 dias de tratamento, avaliamos a resposta urodinâmica da pressão intravesical, complacência vesical, contrações vesicais não-inibidas e capacidade vesical. A idade dos pacientes com pressão de perda alta é significativamente maior. O sexo não foi significativamente diferente entre os dois grupos. A pressão intravesical e contrações vesicais não-inibidas são significativamente maiores nos pacientes com pressão de perda alta e a complacência vesical é significativamente menor nestes casos. Não houve correlação significativa entre capacidade vesical e pressão de perda. Também não houve correlação significativa entre o tipo de esfíncter e a capacidade vesical, contrações não-inibidas e pressão intravesical. Os pacientes com dissinergia apresentam significativamente menor complacência vesical e aqueles com sinergia apresentam significativamente maior complacência vesical. A dissinergia esteve significativamente associada aos pacientes com pressão de perda alta. Os pacientes com hidronefrose apresentam significativamente maior capacidade vesical e estão correlacionados significativamente com dissinergia e cicatriz renal. Não houve correlação significativa entre hidronefrose e pressão intravesical, complacência vesical, contrações vesicais não-inibidas e pressão de perda.Também não houve correlação significativa entre refluxo vesicoureteral e capacidade vesical, pressão intravesical, complacência vesical, contrações vesicais não-inibidas, tipo de esfíncter e pressão de perda, mas houve associação significativa com hidronefrose e cicatriz renal. Os pacientes com cicatriz renal apresentam significativamente maior capacidade vesical, mas não houve correlação significativa entre cicatriz renal e pressão intravesical, complacência vesical, contrações vesicais não-inibidas, tipo de esfíncter e pressão de perda. A média da pressão intravesical inicial era 60,5 cmH2O e diminuiu significativamente para 50,2 cmH2O após o tratamento. A complacência vesical média era 2,8 ml/cmH2O inicialmente e aumentou significativamente para 5,2 ml/cmH2O. A média das contrações vesicais não-inibidas inicial era 37 cmH2O e diminuiu significativamente para 11,4 cmH2O. A capacidade vesical média inicial era 133,9 ml e aumentou significativamente para 215,3 ml. Houve significativa melhora nos parâmetros urodinâmicos com o tratamento que, contudo, não conseguiu atingir valores considerados normais. Isto pode ser explicado pelas alterações viscoelásticas que já tenham ocorrido nestas bexigas e pela provável presença de outros neurotransmissores envolvidos na neurofisiologia patológica. Este trabalho deixa em aberto a possibilidade de que doses mais elevadas de cloreto de oxibutinina usadas por períodos mais prolongados possam ter efeitos benéficos adicionais aos aqui demonstrados.

Economic recovery from the Argentine great depression : institutions, expectations, and the change of macroeconomic regime

This work explores how Argentina overcame the Great Depression and asks whether active macroeconomic interventions made any contribution to the recovery. In particular, we study Argentine macroeconomic policy as it deviated from gold-standard orthodoxy after the final suspension of convertibility in 1929. As elsewhere, fiscal policy in Argentina was conservative, and had little power to smooth output. Monetary policy became heterodox after 1929. The first and most important stage of institutional change took place with the switch from a metallic monetary regime to a fiduciary regime in 1931; the Caja de Conversión (Conversion Office, a currency board) began rediscounting as a means to sterilize gold outflows and avoid deflationary pressures, thus breaking from orthodox "mIes of the game." However, the actual injections of liquidity were small' and were not enough to fully offset the incipient monetary contractions: the "Keynes" effect was weak or negative. Rather, recovery derived from changes in beliefs and expectations surrounding the shift in the monetary and exchange-rate regime,and the delinking of gold flows and the money base. Agents perceivod a new regime, as shown by the path of consumption, investment, and estimated ex ante real interest rates: the "Mundell" effect was dominant. Notably, this change of regime predated a later, and supposedly more significant, stage of institutional reform, namely the creation of the central bank in 1935. Still, the extent of intervention was weak, and insufficient to fully offset externaI shocks to prices and money. Argentine macropolicy was heterodox in terms of the change of regime, but still conservative in terms of the tentative scope of the measures taken .

O desafio na contratação e elaboração de projetos para execução de obras rodoviárias: “o fator projeto”

O Governo brasileiro criou a partir de 2007 o PAC – Programa de Aceleração do Crescimento, um conjunto de projetos de infraestrutura no qual o DNIT ocupa posição de destaque com volume de recursos superior a R$ 58 bilhões. Desde o início do Programa o principal obstáculo é a insuficiência de projetos de qualidade. Projetos de engenharia são etapa crucial para o lançamento de licitações para obras de infraestrutura. Este gargalo de projeto, associado ao processo licitatório, é chamado de “fator projeto”. Em 2011 foi instituído o RDC – Regime Diferenciado de Contratações com o objetivo de remover estes entraves. Este trabalho surge da necessidade da Secretaria do Programa de Aceleração do Crescimento, vinculada ao Ministério do Planejamento, e do Departamento Nacional de Infraestrutura de Transportes, vinculado ao Ministério dos Transportes, de entender os desafios impostos pelo “fator projeto” na execução dos projetos relacionados às obras rodoviárias no âmbito do PAC. Para tanto, foram analisados os aspectos de contratação pela Administração Pública, enfatizando as mudanças ocorridas no processo licitatório corridas depois da vigência do Regime Diferenciado de Contratação (RDC) e as formas contemporâneas de relacionamentos pré-contratuais, abordando as parcerias publico-privadas (PPP), as manifestações de interesse da iniciativa privada (PMI) e os diálogos concorrenciais. Após uma apresentação do DNIT e do processo de institucionalização do RDC no âmbito da autarquia concluiu-se que três aspectos tem contribuído para minimizar os efeitos do “fator projeto”: O primeiro, de natureza procedimental, está diretamente relacionado com o efeito da implementação do novo regime licitatório. Em projetos complexos, como os da área de infraestrutura, o desenvolvimento de relações pré-contratuais trazem ganhos consideráveis, tanto para Administração Pública quanto para o ente privado, por promover a redução das assimetrias de informação e a lapidação do objeto a ser contratado. O segundo aspecto está relacionado com a natureza do DNIT. Trata-se de uma Autarquia com acúmulo de conhecimentos na área de engenharia e gestão de projetos. Ao adotar intensamente o RDC, mostrou capacidade instalada e avançou nos parâmetros de monitoramento e gestão de risco e gerou um conjunto normativo atual e adequado para enfrentar os desafios do novo regime de contrações. O terceiro aspecto também está relacionado com o aspecto institucional do DNIT. Trata-se de sua estrutura organizacional, que influencia a governança dos processos licitatórios e que agrega dois predicados: segurança na responsabilização entre os diretores-membros quando partilham uma decisão e salvaguarda do corpo técnico para uma postura mais republicana. Estes tres aspectos levaram a uma maior eficácia e efetividade da Autarquia, minimizaram o "fator projeto". O Relatório de Gestão do DNIT de 2012 cita que no RDC há a redução de até 50% no tempo do processo licitatório em relação às modalidades concorrência e Tomada de Preços. A implementação do RDC Eletrônico, que possibilita a participação de empresas de todo o país, aumentou a competitividade e ajudou a executar R$ 10,2 bilhões em obras e serviços em infraestrutura de transportes.

Debt management in Brazil: evaluation of the Real Plan and challenges ahead

The Brazilian domestic debt has posed two challenges to policy-makers: it has grown very fast and its maturity is extremely short. This has prompted fears that a default or a compulsory lengthening scheme would be imposed. Here, we analyse the domestic public debt management experience in Brazil, searching for policy prescriptions for the next few years. After briefiy reviewing the recent domestic public debt history, we decompose the large rise in federal bonded debt during 1995-2000, searching for its macroeconomic causes. The main culprits are the extremely high interest payments-which, unti11998, were caused by the weak fiscal stance and the quasi-fixed exchange-rate regime; and since 1999, by the impact ofthe currency depreciation On the dollar-indexed and the externai debt-, and the accumulation of assets of doubtful value, much of which may have to be written off in the future. Simulation exercises of the net debt path for the near future underscore the importance of a tighter fiscal stance to prevent the debt-GDP ratio from growing further. Given the need to quickly lengthen the debt maturity, our main policy advice is to foster, and rely more on, infiation-linked bonds.

On theory multiple contraction

The one which is considered the standard model of theory change was presented in [AGM85] and is known as the AGM model. In particular, that paper introduced the class of partial meet contractions. In subsequent works several alternative constructive models for that same class of functions were presented, e.g.: safe/kernel contractions ([AM85, Han94]), system of spheres-based contractions ([Gro88]) and epistemic entrenchment-based contractions ([G ar88, GM88]). Besides, several generalizations of such model were investigated. In that regard we emphasise the presentation of models which accounted for contractions by sets of sentences rather than only by a single sentence, i.e. multiple contractions. However, until now, only two of the above mentioned models have been generalized in the sense of addressing the case of contractions by sets of sentences: The partial meet multiple contractions were presented in [Han89, FH94], while the kernel multiple contractions were introduced in [FSS03]. In this thesis we propose two new constructive models of multiple contraction functions, namely the system of spheres-based and the epistemic entrenchment-based multiple contractions which generalize the models of system of spheres-based and of epistemic entrenchment-based contractions, respectively, to the case of contractions (of theories) by sets of sentences. Furthermore, analogously to what is the case in what concerns the corresponding classes of contraction functions by one single sentence, those two classes are identical and constitute a subclass of the class of partial meet multiple contractions. Additionally, and as the rst step of the procedure that is here followed to obtain an adequate de nition for the system of spheres-based multiple contractions, we present a possible worlds semantics for the partial meet multiple contractions analogous to the one proposed in [Gro88] for the partial meet contractions (by one single sentence). Finally, we present yet an axiomatic characterization for the new class(es) of multiple contraction functions that are here introduced.

Atividades antinociceptiva e anti-inflamatória de uma fração rica em heterogalactana sulfatada extraída da alga codium isthmocladum (vickers 1905)

Sulfated polysaccharides comprise a complex group of macromolecules with a range of several biological activities, including antiviral activity, anticoagulant, antiproliferative, antiherpética, antitumor, anti-inflammatory and antioxidant. These anionic polymers are widely distributed in tissues of vertebrates, invertebrates and algae. Seaweeds are the most abundant sources of sulfated polysaccharides in nature. The green algal sulfated polysaccharides are homo or heteropolysaccharides comprised of galactose, glucose, arabinose and/or glucuronic acid. They are described as anticoagulant, anti-inflammatory, antiviral, anti-angiogenic, antitumor compounds. However, there are few studies about elucidation and evaluation of biological/pharmacological effects of sulfated polysaccharides obtained from green algae, for example, there is only one paper reporting the antinociceptive activity of sulfated polysaccharides of these algae. Therefore this study aimed to obtain sulfated polysaccharides of green seaweed Codium isthmocladum and evaluates them as potential antinociceptive agents. Thus, in this study, the total extract of polysaccharides of green alga C. isthmocladum was obtained by proteolytic digestion, followed by fractionation resulting in five fractions (F0.3, F0.5, F0.7, F0.9 and F1.2) by sequential precipitation with acetone. Using the test of abdominal contractions we observed that the fraction F0.9 was the most potent antinociceptive aompound. F0.9 consists mainly of a sulfated heterogalactana. More specific tests showed that Fo.9 effect is dose and time dependent, reaching a maximum at 90 after administration (10 mg / kg of animal). F0.9 is associated with TRPV1 and TRPA1 receptors and inhibits painful sensation in animals. Furthermore, F0.9 inhibits the migration of lymphocytes induced peritonitis test. On the other hand, stimulates the release of NO and TNF-α. These results suggest that F0.9 has the potential to be used as a source of sulfated galactan antinociceptive and anti-inflammatory