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.

Dentistry and HIV: University professors' role in establishing a basis for judgment

The aim of this study was to determine whether there are differences in the attitudes of Dentistry School Professors from two universities, one private and one public concerning HIV-positive patients or HIV-positive health care professionals. A questionnaire Was handled to all profession at the Araçatuba Dental School of São Paulo State University - FOA-UNESP (public) and Lins Dental School of the Piracicaba Methodist University - FOL-UNIMEP (private). When asked if they would be willing to be treated by an HIV-infected health care professional, 38.9% of the 77 professors at FOA-UNESP replied that they would accept only non-invasive treatments and 13% would not accept any kind of treatment; the same applied to 42.4% and 15.2% of the 33 FOL-UNIMEP professors. Among the 54 professors at FOA-UNESP and 27 at FOL-UNIMEP providing clinical service, only 31.5% and 18.5% stated that they treat HIV-infected persons like any other patient. The results were very similar in both schools. Although they reported that they taught their students not to act in a discriminatory manner towards HIV-positive patient the professors themselves showed prejudice towards infected patients and professionals. Consequently, this topic trust be further debated in the academic milieu.

Radial basis function network applied to the linearization of a voltage controlled oscillator

An analog circuit that implements a radial basis function network is presented. The proposed circuit allows the adjustment of all shape parameters of the radial functions, i.e., amplitude, center and width. The implemented network was applied to the linearization of a nonlinear circuit, a voltage controlled oscillator (VCO). This application can be classified as an open-loop control in which the network plays the role of the controller. Experimental results have proved the linearization capability of the proposed circuit. Its performance can be improved by using a network with more basis functions. Copyright 2007 ACM.

Physical parameters and basis transformations in the two-Higgs-doublet model

A direct connection between physical parameters of general two-Higgs-doublet model (2HDM) potentials after electroweak symmetry breaking (EWSB) and the parameters that define the potentials before EWSB is established. These physical parameters, such as the mass matrix of the neutral Higgs bosons, have well-defined transformation properties under basis transformations transposed to the fields after EWSB. The relations are also explicitly written in a basis covariant form. Violation of these relations may indicate models beyond 2HDMs. In certain cases the whole potential can be defined in terms of the physical parameters. The distinction between basis transformations and reparametrizations is pointed out. Some physical implications are discussed. © 2008 The American Physical Society.

Radial basis function networks with quantized parameters

A RBFN implemented with quantized parameters is proposed and the relative or limited approximation property is presented. Simulation results for sinusoidal function approximation with various quantization levels are shown. The results indicate that the network presents good approximation capability even with severe quantization. The parameter quantization decreases the memory size and circuit complexity required to store the network parameters leading to compact mixed-signal circuits proper for low-power applications. ©2008 IEEE.

Radial basis function circuits using folded cascode differential pairs

In this paper, we propose new circuits for the implementation of Radial Basis Functions (RBF). These RBFs are obtained by the subtraction of two differential pair output currents in a folded cascode configuration. We also propose a multidimensional version based on the unidimensional circuits. SPICE simulation and experimental results indicate good functionality. These circuits are intended to be applied in the implementation of radial basis function networks. Possible applications of these networks include transducer signal conditioning and processing in onboard telemetry systems for aircraft and spacecraft vehicles. © 2010 IEEE.

Molecular basis for defining the pineal gland and pinealocytes as targets for tumor necrosis factor

The pineal gland, the gland that translates darkness into an endocrine signal by releasing melatonin at night, is now considered a key player in the mounting of an innate immune response. Tumor necrosis factor (TNF), the first pro-inflammatory cytokine to be released by an inflammatory response, suppresses the translation of the key enzyme of melatonin synthesis (arylalkylamine-N-acetyltransferase, Aanat). Here, we show that TNF receptors of the subtype 1 (TNF-R1) are expressed by astrocytes, microglia, and pinealocytes. We also show that the TNF signaling reduces the level of inhibitory nuclear factor kappa B protein subtype A (NFKBIA), leading to the nuclear translocation of two NFKB dimers, p50/p50, and p50/RelA. The lack of a transactivating domain in the p50/p50 dimer suggests that this dimer is responsible for the repression of Aanat transcription. Meanwhile, p50/RelA promotes the expression of inducible nitric oxide synthase (iNOS) and the production of nitric oxide, which inhibits adrenergically induced melatonin production. Together, these data provide a mechanistic basis for considering pinealocytes a target ofTNF and reinforce the idea that the suppression of pineal melatonin is one of the mechanisms involved in mounting an innate immune response. © 2011 Carvalho-Sousa, da Silveira Cruz-Machado, Tamura, Fernandes, Pinato, Muxel, Cecon and Markus.

DNA repair gene polymorphism is associated with the genetic basis of atherosclerotic coronary artery disease

Background: Atherosclerotic coronary artery disease (CAD) is a multifactorial process that appears to be caused by the interaction of environmental risk factors with multiple predisposing genes. It is nowadays accepted that increased levels of DNA damage induced by xenobiotics play an important role in the early phases of atherogenesis. Therefore, in this study, we focus on determining whether genetic variations in xenobiotic-metabolizing [glutathione-S-transferase theta 1 (GSTT1), glutathione-S-transferase mu 1 (GSTM1), cytochrome P450 IIEI (CYP2E1)] and DNA repair [X-ray cross-complementing group 1 (XRCC1)] genes might be associated with increased risk for CAD. Methods: A case-control study was conducted with 400 individuals who underwent subjected to coronary angiography. A total of 299 were patients diagnosed with effective coronary atherosclerosis (case group; >20% obstructive lesion), and 101 (control group) were individuals diagnosed as negative for CAD (<20% obstructive lesions). The polymorphism identifications for GSTM1 and GSTT1, and for CYP2E1 and XRCC1 genes were performed by polymerase chain reaction (PCR) amplification and by PCR-RFLP, respectively. Results and conclusions: The XRCC1 homozygous wild-type genotype Arg/Arg for codon 399 was statistically less pronounced in the case subjects (21.4%) than in controls (38.5%); individuals with the variant XRCC1 genotype had a 2.3-fold increased risk for coronary atherosclerosis than individuals with the wild-type genotype (OR=2.3, 95% CI=1.13-4.69). Conversely, no association between GSTM1, GSTT1, and CYP2E1gene polymorphisms and coronary atherosclerosis was detected. The results provide evidence of the role of DNA damage and repair in cardiovascular disease. © 2011 Elsevier Inc. All rights reserved.

The perfective aspect in english and portuguese: a constrative study on semantic basis

An exam of the occurrences of the PRESENT PERFECT in Englishwas made in such a way as to establish the prevailing semantic features ofthis verbal form. I t was verified up to what an extent the meaning of thePERFECTIVE thus characterized is expressed in the corresponding Portuguesesentences in the PRETÉRITO PERFEITO. It was found that in Portuguesethe verbal inflexion itself characterizes in a much smaller degree the PERFECTIVE ASPECT.

The phonological and visual basis of developmental dyslexia in Brazilian Portuguese reading children

Evidence from opaque languages suggests that visual attention processing abilities in addition to phonological skills may act as cognitive underpinnings of developmental dyslexia. We explored the role of these two cognitive abilities on reading fluency in Brazilian Portuguese, a more transparent orthography than French or English. Sixty-six children with developmental dyslexia and normal Brazilian Portuguese children participated. They were administered three tasks of phonological skills (phoneme identification, phoneme, and syllable blending) and three visual tasks (a letter global report task and two non-verbal tasks of visual closure and visual constancy). Results show that Brazilian Portuguese children with developmental dyslexia are impaired not only in phonological processing but further in visual processing. The phonological and visual processing abilities significantly and independently contribute to reading fluency in the whole population. Last, different cognitively homogeneous subtypes can be identified in the Brazilian Portuguese population of children with developmental dyslexia. Two subsets of children with developmental dyslexia were identified as having a single cognitive disorder, phonological or visual; another group exhibited a double deficit and a few children showed no visual or phonological disorder. Thus the current findings extend previous data from more opaque orthographies as French and English, in showing the importance of investigating visual processing skills in addition to phonological skills in children with developmental dyslexia whatever their language orthography transparency.

A radial basis function network (RBFN) for function approximation

A radial basis function network (RBFN) circuit for function approximation is presented. Simulation and experimental results show that the network has good approximation capabilities. The RBFN was a squared hyperbolic secant with three adjustable parameters amplitude, width and center. To test the network a sinusoidal and sine function,vas approximated.

An analog implementation of radial basis function network appropriate for transducer linearizer

A circuit for transducer linearizer tasks have been designed and built using discrete components and it implements by: a Radial Basis Function Network (RBFN) with three basis functions. The application in a linearized thermistor showed that the network has good approximation capabilities. The circuit advantages is the amplitude, width and center.

Structural basis for the inhibition of a phospholipase A2-like toxin by caffeic and aristolochic acids

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

Crystal structure of Staphylococcus aureus exfoliative toxin D-like protein: structural basis for the high specificity of exfoliative toxins

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