Chebyshev-Laurent polynomials and weighted approximation

Let (a, b) subset of (0, infinity) and for any positive integer n, let S-n be the Chebyshev space in [a, b] defined by S-n:= span{x(-n/2+k),k= 0,...,n}. The unique (up to a constant factor) function tau(n) is an element of S-n, which satisfies the orthogonality relation S(a)(b)tau(n)(x)q(x) (x(b - x)(x - a))(-1/2) dx = 0 for any q is an element of Sn-1, is said to be the orthogonal Chebyshev S-n-polynomials. This paper is an attempt to exibit some interesting properties of the orthogonal Chebyshev S-n-polynomials and to demonstrate their importance to the problem of approximation by S-n-polynomials. A simple proof of a Jackson-type theorem is given and the Lagrange interpolation problem by functions from S-n is discussed. It is shown also that tau(n) obeys an extremal property in L-q, 1 less than or equal to q less than or equal to infinity. Natural analogues of some inequalities for algebraic polynomials, which we expect to hold for the S-n-pelynomials, are conjectured.

A structure based model for liposome disruption and the role of catalytic activity in myotoxic phospholipase A(2)S

Venom phospholipase A(2)s (PLA(2)s) display a wide spectrum of pharmacological activities and, based on the wealth of biochemical and structural data currently available for PLA(2)S, mechanistic models can now be inferred to account for some of these activities. A structural model is presented for the role played by the distribution of surface electrostatic potential in the ability of myotoxic D49/K49 PLA(2)s to disrupt multilamellar vesicles containing negatively charged natural and non-hydrolyzable phospholipids. Structural evidence is provided for the ability of K49 PLA(2)s to bind phospholipid analogues and for the existence of catalytic activity in K49 PLA(2)s. The importance of the existence of catalytic activity of D49 and K49 PLA(2)s in myotoxicity is presented. (C) 2003 Elsevier Ltd. All rights reserved.

Integration of polyharmonic functions

The results in this paper are motivated by two analogies. First, m-harmonic functions in R(n) are extensions of the univariate algebraic polynomials of odd degree 2m-1. Second, Gauss' and Pizzetti's mean value formulae are natural multivariate analogues of the rectangular and Taylor's quadrature formulae, respectively. This point of view suggests that some theorems concerning quadrature rules could be generalized to results about integration of polyharmonic functions. This is done for the Tchakaloff-Obrechkoff quadrature formula and for the Gaussian quadrature with two nodes.

Fmoc-POAC: [(9-fluorenylmethyloxycarbonyl)-2,2,5,5-tetramethylpyrrolidine-N-oxyl-3-amino-4-carboxylic acid]: A novel protected spin labeled beta-amino acid for peptide and protein chemistry

The stable free radical 2,2,6,6-tetramethylpiperidine-N-oxyl-4-amino-4-carboxylic acid (TOAC) is the only spin labeled amino acid that has been used to date to successfully label peptide sequences for structural studies. However, severe difficulty in coupling the subsequent amino acid has been the most serious shortcoming of this paramagnetic marker. This problem stems from the low nucleophilicity of TOAC's amine group towards the acylation reaction during peptide chain elongation. The present report introduces the alternative beta -amino acid 2,2,5,5-tetramethylpyrrolidine-N-oxyl-3-amino-4-carboxylic acid (POAC), potentially useful in peptide and protein chemistry. Investigations aimed at addressing the stereochemistry of this cyclic molecule through X-ray diffraction measurements of crystalline and bulk samples revealed that it consists only of the trans conformer. The 9-fluorenylmethyloxyearbonyl group (Fmoc) was chosen for temporary protection of the POAC amine function, allowing insertion of the probe at any position in a peptide sequence. The vasoactive octapeptide angiotensin II (AII, DRVYIHPF) was synthesized by replacing Pro(7) with POAC. The reaction of Fmoc-POAC with the peptidyl-resin occurred smoothly, and the coupling of the subsequent amino acid showed a much faster reaction when compared with TOAC. POAC(7)-AII was obtained in good yield, demonstrating that, in addition to TOAC, POAC is a convenient amino acid for the synthesis of spin labeled peptide analogues. The present findings open the possibility of a wide range of chemical and biological applications for this novel beta -amino acid derivative, including structural investigations involving its differentiated bend-inducing characteristics.

Self-Structuring of Lamellar Bridged Silsesquioxanes with Long Side Spacers

Diurea cross-linked bridged silsesquioxanes (BSs) C(10)C(11)C(10) derived from organosilane precursors, including decylene chains as side spacers and alkylene chains with variable length as central spacers (EtO)(3)Si- (CH(2))(10)-Y(CH(2))(n)-Y-(CH(2))(10)-Si(OEt)(3) (n = 7, 9-12; Y = urea group and Et = ethyl), have been synthesized through the combination of self-directed assembly and an acid-catalyzed sol gel route involving the addition of dimethylsulfoxide (DMSO) and a large excess of water. This new family of hybrids has enabled us to conclude that the length of the side spacers plays a unique role in the structuring of alkylene-based BSs, although their morphology remains unaffected. All the samples adopt a lamellar structure. While the alkylene chains are totally disordered in the case of the C(10)C(7)C(10) sample, a variable proportion of all-trans and gauche conformers exists in the materials with longer central spacers. The highest degree of structuring occurs for n = 9. The inclusion of decylene instead of propylene chains as side spacers leads to the formation of a stronger hydrogen-bonded urea-urea array as evidenced by two dimensional correlation Fourier transform infrared spectroscopic analysis. The emission spectra and emission quantum yields of the C(10)C(n)C(10) Cm materials are similar to those reported for diurea cross-linked alkylene-based BSs incorporating propylene chains as side spacers and prepared under different experimental conditions. The emission of the C(10)C(n)C(10) hybrids is ascribed to the overlap of two distinct components that occur within the urea cross-linkages and within the siliceous nanodomains. Time-resolved photoluminescence spectroscopy has provided evidence that the average distance between the siliceous domains and the urea cross-links is similar in the C(10)C(n)C(10) BSs and in oxyethylene-based hybrid analogues incorporating propylene chains as side spacers (diureasils), an indication that the longer side chains in the former materials adopt gauche conformations. It has also allowed us to demonstrate for the first time that the emission features of the urea-related component of the emission of alkylene-based BSs depend critically on the length of the side spacers.

Generalized soldering of +/- 2 helicity states in D=2+1

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Chemical communication in Apis mellifera: Temporal modulation of alarm behaviors

The effect of pheromones and their chemical analogues in honeybee alarm behaviors was studied in observation boxes. Defensive behaviors, as follows: a) attraction to scent source, b) elevation of wings in 'V', c) abdomen elevation, d) abdomen elevation and pumping and e) first leg pair elevation had been temporarily registered when the following compounds were presented: isoamyl alcohol, octyl alcohol, benzyl alcohol, n-butyl acetate, n-octyl acetate, isopentyl acetate, benzyl acetate and 2-heptanone. The results were as follows: 1. the bees elicited some characteristic behaviors when chemical alarm messages were presented, 2. agression (stinging) was not completed with any compound tested, probably because there was not a target (visual stimulus), 3. in all situations the attraction to scent source was low, 4. all the behaviors were elicited in a temporarily different way, 5. the compounds that elicited stronger responses and a greater number of the investigated behaviors were: isopentyl acetate, 2-heptanone, octyl acetate and n-octyl alcohol. In all situations, the first behavior response (and the most intense one) was the elevation and pumping the abdomen. This suggests that the chemical message was promptly recognized and then transmitted to each worker. So, the results obtained in the present work, suggest that chemical alarm messages may be recognized by different mechanisms of neural integration.

Conformational basis for the biological activity of TOAC-labeled angiotensin II and bradykinin: Electron paramagnetic resonance, circular dichroism, and fluorescence studies

N-Terminally and internally labeled analogues of the hormones angiotensin (AII, DRVYIHPF) and bradykinin (BK, RPPGFSPFR) were synthesized containing the paramagnetic amino acid 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4- carboxylic acid (TOAC). TOAC replaced Asp 1 (TOAC 1-AII) and Val 3 (TOAC 3-AII) in AII and was inserted prior to Arg 1 (TOAC 0-BK) and replacing Pro 3 (TOAC 3-BK) in BK. The peptide conformational properties were examined as a function of trifluoroethanol (TFE) content and pH. Electron paramagnetic resonance spectra were sensitive to both variables and showed that internally labeled analogues yielded rotational correlation times (TC) considerably larger than N-terminally labeled ones, evincing the greater freedom of motion of the N-terminus. In TFE, τ C increased due to viscosity effects. Calculation of τ Cpeptide/τ CTOAC ratios indicated that the peptides acquired more folded conformations. Circular dichroism spectra showed that, except for TOAC 1-AII in TFE, the N-terminally labeled analogues displayed a conformational behavior similar to that of the parent peptides. In contrast, under all conditions, the TOAC 3 derivatives acquired more restricted conformations. Fluorescence spectra of All and its derivatives were especially sensitive to the ionization of Tyr 4. Fluorescence quenching by the nitroxide moiety was much more pronounced for TOAC 3-AII The conformational behavior of the TOAC derivatives bears excellent correlation with their biological activity, since, while the N-terminally labeled peptides were partially active, their internally labeled counterparts were inactive [Nakaie, C. R., et al., Peptides 2002, 23, 65-70]. The data demonstrate that insertion of TOAC in the middle of the peptide chain induces conformational restrictions that lead to loss of backbone flexibility, not allowing the peptides to acquire their receptor-bound conformation. © 2004 Wiley Periodicals, Inc.

Context-sensitive analysis of obfuscated x86 executables

A method for context-sensitive analysis of binaries that may have obfuscated procedure call and return operations is presented. Such binaries may use operators to directly manipulate stack instead of using native call and ret instructions to achieve equivalent behavior. Since definition of context-sensitivity and algorithms for context-sensitive analysis have thus far been based on the specific semantics associated to procedure call and return operations, classic interprocedural analyses cannot be used reliably for analyzing programs in which these operations cannot be discerned. A new notion of context-sensitivity is introduced that is based on the state of the stack at any instruction. While changes in 'calling'-context are associated with transfer of control, and hence can be reasoned in terms of paths in an interprocedural control flow graph (ICFG), the same is not true of changes in 'stack'-context. An abstract interpretation based framework is developed to reason about stack-contexts and to derive analogues of call-strings based methods for the context-sensitive analysis using stack-context. The method presented is used to create a context-sensitive version of Venable et al.'s algorithm for detecting obfuscated calls. Experimental results show that the context-sensitive version of the algorithm generates more precise results and is also computationally more efficient than its context-insensitive counterpart. Copyright © 2010 ACM.

Context-sensitive analysis without calling-context

Since Sharir and Pnueli, algorithms for context-sensitivity have been defined in terms of 'valid' paths in an interprocedural flow graph. The definition of valid paths requires atomic call and ret statements, and encapsulated procedures. Thus, the resulting algorithms are not directly applicable when behavior similar to call and ret instructions may be realized using non-atomic statements, or when procedures do not have rigid boundaries, such as with programs in low level languages like assembly or RTL. We present a framework for context-sensitive analysis that requires neither atomic call and ret instructions, nor encapsulated procedures. The framework presented decouples the transfer of control semantics and the context manipulation semantics of statements. A new definition of context-sensitivity, called stack contexts, is developed. A stack context, which is defined using trace semantics, is more general than Sharir and Pnueli's interprocedural path based calling-context. An abstract interpretation based framework is developed to reason about stack-contexts and to derive analogues of calling-context based algorithms using stack-context. The framework presented is suitable for deriving algorithms for analyzing binary programs, such as malware, that employ obfuscations with the deliberate intent of defeating automated analysis. The framework is used to create a context-sensitive version of Venable et al.'s algorithm for analyzing x86 binaries without requiring that a binary conforms to a standard compilation model for maintaining procedures, calls, and returns. Experimental results show that a context-sensitive analysis using stack-context performs just as well for programs where the use of Sharir and Pnueli's calling-context produces correct approximations. However, if those programs are transformed to use call obfuscations, a contextsensitive analysis using stack-context still provides the same, correct results and without any additional overhead. © Springer Science+Business Media, LLC 2011.

Agonistas do GnRH, antagonistas do GnRH e a reprodução assistida: Análogos do GnRH x fertilização in vitro

The agonists of gonadotropin-releasing hormone (GnRH) were introduced in ovarian stimulation for in vitro fertilization to avoid a premature surge of luteinizing hormone. Although they are accompanied by some disadvantages, GnRH agonists have become well accepted in clinical practice, and their use is associated with increased rates of pregnancy. The development of GnRH antagonists capable of blocking the pituitary immediately offered a therapeutic option. Comparative studies between the two analogs have suggested that the use of antagonists is associated with a shorter duration of ovulatory stimulus and a decreased incidence of ovarian hyperstimulation syndrome, while the type of GnRH analogues used show no significant effects on the rates of pregnancy and live birth. However, GnRH agonists have other applications in assisted reproductive technology cycles than the pituitary downregulation.

Determination of sildenafil and vardenafil by capillary zone electrophoresis using capacitively coupled contactless conductivity detection

A method based on capillary electrophoresis with capacitively coupled contactless conductivity detection (CE-C4D) for determination of two important phosphodiesterase type-5 inhibitors (sildenafil and vardenafil) is introduced. The background electrolyte (BGE) consisted of an aqueous solution of 500 mmol L-1 acetic acid, and the capillary was previously treated with polybrene solution to prevent cationic analytes from adsorbing onto the inner surface. Although the analytes migrate in the counter flow, the total time is short. An instrument with two C4D detectors allowed a seamless transition from a fast method (less than one minute) but of low-efficiency using the first detector to a more efficient method using the second detector. The analysis of commercial tablets showed no significant difference between CE-C4D and HPLC methods. Conductivity detection is a well-known low selectivity detection scheme, which in conjunction with the high mobility of the co-ion in the BGE (hydroxonium) allows one to predict that other cationic analogues of sildenafil can also be detected. This is an interesting feature given the increasing number of compounds in this class. © 2013 The Royal Society of Chemistry.

Dimerization of aurein 1.2: Effects in structure, antimicrobial activity and aggregation of Cândida albicans cells

Antimicrobial peptides (AMPs) are a promising solution to face the antibiotic-resistant problem because they display little or no resistance effects. Dimeric analogues of select AMPs have shown pharmacotechnical advantages, making these molecules promising candidates for the development of novel antibiotic agents. Here, we evaluate the effects of dimerization on the structure and biological activity of the AMP aurein 1.2 (AU). AU and the C- and N-terminal dimers, (AU)2K and E(AU)2, respectively, were synthesized by solid-phase peptide synthesis. Circular dichroism spectra indicated that E(AU)2 has a coiled coil structure in water while (AU)2K has an α-helix structure. In contrast, AU displayed typical spectra for disordered structures. In LPC micelles, all peptides acquired a high amount of α-helix structure. Hemolytic and vesicle permeabilization assays showed that AU has a concentration dependence activity, while this effect was less pronounced for dimeric versions, suggesting that dimerization may change the mechanism of action of AU. Notably, the antimicrobial activity against bacteria and yeast decreased with dimerization. However, dimeric peptides promoted the aggregation of C. albicans. The ability to aggregate yeast cells makes dimeric versions of AU attractive candidates to inhibit the adhesion of C. albicans to biological targets and medical devices, preventing disease caused by this fungus. © 2013 Springer-Verlag Wien.

Sistemas drug delivery aplicados a novos inibidores de topoisomerases estruturalmente derivados de toxinas bacterianas

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Síntese e estudos estrutura/função de um peptídeo extraído da rã Hypsiboas albopunctatus e análogos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)