Designing Novel Antitrypanosomal Agents from a Mixed Graph-Theoretical Substructural Approach

Chagas disease is nowadays the most serious parasitic health problem. This disease is caused by Trypanosoma cruzi. The great number of deaths and the insufficient effectiveness of drugs against this parasite have alarmed the scientific community worldwide. In an attempt to overcome this problem, a model for the design and prediction of new antitrypanosomal agents was obtained. This used a mixed approach, containing simple descriptors based on fragments and topological substructural molecular design descriptors. A data set was made up of 188 compounds, 99 of them characterized an antitrypanosomal activity and 88 compounds that belong to other pharmaceutical categories. The model showed sensitivity, specificity and accuracy values above 85%. Quantitative fragmental contributions were also calculated. Then, and to confirm the quality of the model, 15 structures of molecules tested as antitrypanosomal compounds (that we did not include in this study) were predicted, taking into account the information on the abovementioned calculated fragmental contributions. The model showed an accuracy of 100% which means that the ""in silico"" methodology developed by our team is promising for the rational design of new antitrypanosomal drugs. (C) 2009 Wiley Periodicals, Inc. J Comput Chem 31: 882-894. 2010

Microwave-Assisted Derivatization of Cellulose in an Ionic Liquid: An Efficient, Expedient Synthesis of Simple and Mixed Carboxylic Esters

Microwave (MW)-assisted cellulose dissolution in ionic liquids (ILs) has routinely led either to incomplete biopolymer solubilization, or its degradation. We show that these problems can be avoided by use of low-energy MW heating, coupled with efficient stirring. Dissolution of microcrystalline cellulose in the IL 1-allyl-3-methylimidazolium chloride has been achieved without changing its degree of polymerization; regenerated cellulose showed pronounced changes in its index of crystallinity, surface area, and morphology. MW-assisted functionalization of MCC by ethanoic, propanoic, butanoic, pentanoic, and hexanoic anhydrides has been studied. Compared with conventional heating, MW irradiation has resulted in considerable decrease in dissolution and reaction times. The value of the degree of substitution (DS) was found to be DS(ethanoate) > DS(propanoate) > DS(butanoate). The values of DS(pentanoate) and DS(hexanoate) were found to be slightly higher than DS(ethanoate). This surprising dependence on the chain length of the acylating agent has been reported before, but not rationalized. On the basis of the rate constants and activation parameters of the hydrolysis of ethanoic, butanoic, and hexanoic anhydrides in aqueous acetonitrile (a model acyl transfer reaction), we suggest that this result may be attributed to the balance between two opposing effects, namely, steric crowding and (cooperative) hydrophobic interactions between the anhydride and the cellulosic surface, whose lipophilicity has increased, due to its partial acylation. Four ethanoate-based mixed esters were synthesized by the reaction with a mixture of the two anhydrides; the ethanoate moiety predominated in all products. The DS is reproducible and the IL is easily recycled. (C) 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 134-143, 2010

Feasible estimation of generalized linear mixed models (GLMM) with weak dependency between groups

This paper presents a two-step pseudo likelihood estimation technique for generalized linear mixed models with the random effects being correlated between groups. The core idea is to deal with the intractable integrals in the likelihood function by multivariate Taylor's approximation. The accuracy of the estimation technique is assessed in a Monte-Carlo study. An application of it with a binary response variable is presented using a real data set on credit defaults from two Swedish banks. Thanks to the use of two-step estimation technique, the proposed algorithm outperforms conventional pseudo likelihood algorithms in terms of computational time.

Likelihood prediction for generalized linear mixed models under covariate uncertainty

This paper presents the techniques of likelihood prediction for the generalized linear mixed models. Methods of likelihood prediction is explained through a series of examples; from a classical one to more complicated ones. The examples show, in simple cases, that the likelihood prediction (LP) coincides with already known best frequentist practice such as the best linear unbiased predictor. The paper outlines a way to deal with the covariate uncertainty while producing predictive inference. Using a Poisson error-in-variable generalized linear model, it has been shown that in complicated cases LP produces better results than already know methods.

A Modular and digitally programmable interface based on band-pass sigma-delta modulator for mixed-signal systems-on-chip

The focus of this thesis is to discuss the development and modeling of an interface architecture to be employed for interfacing analog signals in mixed-signal SOC. We claim that the approach that is going to be presented is able to achieve wide frequency range, and covers a large range of applications with constant performance, allied to digital configuration compatibility. Our primary assumptions are to use a fixed analog block and to promote application configurability in the digital domain, which leads to a mixed-signal interface. The use of a fixed analog block avoids the performance loss common to configurable analog blocks. The usage of configurability on the digital domain makes possible the use of all existing tools for high level design, simulation and synthesis to implement the target application, with very good performance prediction. The proposed approach utilizes the concept of frequency translation (mixing) of the input signal followed by its conversion to the ΣΔ domain, which makes possible the use of a fairly constant analog block, and also, a uniform treatment of input signal from DC to high frequencies. The programmability is performed in the ΣΔ digital domain where performance can be closely achieved according to application specification. The interface performance theoretical and simulation model are developed for design space exploration and for physical design support. Two prototypes are built and characterized to validate the proposed model and to implement some application examples. The usage of this interface as a multi-band parametric ADC and as a two channels analog multiplier and adder are shown. The multi-channel analog interface architecture is also presented. The characterization measurements support the main advantages of the approach proposed.

Proposal of an alternative transmission line model for symmetrical and asymmetrical configurations

This article shows a transmission line model for simulation of fast and slow transients, applied to symmetrical or asymmetrical configurations. A transmission line model is developed based on lumped elements representation and state-space techniques. The proposed methodology represents a practical procedure to model three-phase transmission lines directly in time domain, without the explicit or implicit use of inverse transforms. In three-phase representation, analysis modal techniques are applied to decouple the phases in their respective propagation modes, using a correction procedure to set a real and constant matrix for untransposed lines with or without vertical symmetry plane. The proposed methodology takes into account the frequency-dependent parameters of the line and in order to include this effect in the state matrices, a fitting procedure is applied. To verify the accuracy of the proposed state-space model in frequency domain, a simple methodology is described based on line distributed parameters and transfer function associated with input/output signals of the lumped parameters representation. In addition, this article proposes the use of a fast and robust integration procedure to solve the state equations, enabling transient and steady-state simulations. The results obtained by the proposed methodology are compared with several established transmission line models in EMTP, taking into account an asymmetrical three-phase transmission line. The principal contribution of the proposed methodology is to handle a steady fundamental signal mixed with fast and slow transients, including impulsive and oscillatory behavior, by a practical procedure applied directly in time domain for symmetrical or asymmetrical representations. (C) 2011 Elsevier Ltd. All rights reserved.

Sulcus vocalis: evidence for autosomal dominant inheritance

We found evidence of autosomal dominant hereditary transmission of sulcus vocalis. Four dysphonic patients from three generations of the same family were submitted to videolaryngoscopic examination (three patients) and to direct laryngoscopy ( one patient) to diagnose the hoarseness. Sulcus vocalis was diagnosed in all four patients. The finding of four affected individuals in three generations, with vertical transmission affecting man and women, is more consistent with autosomal dominant inheritance pattern; it is an etiological model that we propose for the sulcus vocalis in this pedigree.

Supernumerary chromosome inheritance in the curimbata (Prochilodus lineatus) of the Mogi-Guacu River

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

Nonabelian Toda theories from parafermionic reductions of the WZW model

We investigate a class of conformal nonabelian-Toda models representing noncompact SL(2, R)/U(1) parafermions (PF) interacting with specific abelian Toda theories and having a global U(1) symmetry. A systematic derivation of the conserved currents, their algebras, and the exact solution of these models are presented. An important property of this class of models is the affine SL(2, R)(q) algebra spanned by charges of the chiral and antichiral nonlocal currents and the U(1) charge. The classical (Poisson brackets) algebras of symmetries VG(n), of these models appear to be of mixed PF-WG(n) type. They contain together with the local quadratic terms specific for the W-n-algebras the nonlocal terms similar to the ones of the classical PF-algebra. The renormalization of the spins of the nonlocal currents is the main new feature of the quantum VA(n)-algebras. The quantum VA(2)-algebra and its degenerate representations are studied in detail. (C) 1999 Academic Press.

Nonautonomous mixed mKdV-sinh-Gordon hierarchy

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

A class of mixed integrable models

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Notes on the two-brane model with variable tension

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

A family of crisis in a dissipative Fermi accelerator model

The Fermi accelerator model is studied in the framework of inelastic collisions. The dynamics of this problem is obtained by use of a two-dimensional nonlinear area-contracting map. We consider that the collisions of the particle with both periodically time varying and fixed walls are inelastic. We have shown that the dissipation destroys the mixed phase space structure of the nondissipative case and in special, we have obtained and characterized in this problem a family of two damping coefficients for which a boundary crisis occurs. (c) 2006 Elsevier B.V. All rights reserved.

Parameter space for a dissipative Fermi-Ulam model

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

Stickiness in a bouncer model: A slowing mechanism for Fermi acceleration

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)