Modeling of hybrid systems by piecewise decomposition

Piecewise linear models systems arise as mathematical models of systems in many practical applications, often from linearization for nonlinear systems. There are two main approaches of dealing with these systems according to their continuous or discrete-time aspects. We propose an approach which is based on the state transformation, more particularly the partition of the phase portrait in different regions where each subregion is modeled as a two-dimensional linear time invariant system. Then the Takagi-Sugeno model, which is a combination of local model is calculated. The simulation results show that the Alpha partition is well-suited for dealing with such a system

Structural analysis of narratives produced by normal-hearing and deaf children

This dissertation presents two experiments investigating the structural analysis of narratives produced by normal-hearing and hearing-impaired children. The results suggest that the evaluation of deaf children’s language at a discourse level is both possible and more relevant to academic achievement than traditional assessment procedures that focus on assessing language at a word, phrase or sentence level.

The structural component of linguistic meaning and the reading of normally hearing and deaf children

This paper discusses an experiment in psycholinguistic method and its application to the field of education.

Subjective versus objective measures of daily listening environments

This study examined hearing impaired listeners’ subjective perceptions of listening environments through a listening questionnaire and compared these results to objective measures mimicked by the questionnaire in the datalogging device SAM (Sound Activity Meter). Results indicate audiologists should not rely on patient reports of “typical” listening environments for hearing aid selection as significant discrepancies were present between several of the subjective and objective measures.

Molecule modeling of human pentameric alpha(7) neuronal nicotinic acetylcholine receptor and its interaction with its agonist and competitive antagonist

The nicotinic Acetylcholine Receptor (nAChR) is the major class of neurotransmitter receptors that is involved in many neurodegenerative conditions such as schizophrenia, Alzheimer's and Parkinson's diseases. The N-terminal region or Ligand Binding Domain (LBD) of nAChR is located at pre- and post-synaptic nervous system, which mediates synaptic transmission. nAChR acts as the drug target for agonist and competitive antagonist molecules that modulate signal transmission at the nerve terminals. Based on Acetylcholine Binding Protein (AChBP) from Lymnea stagnalis as the structural template, the homology modeling approach was carried out to build three dimensional model of the N-terminal region of human alpha(7)nAChR. This theoretical model is an assembly of five alpha(7) subunits with 5 fold axis symmetry, constituting a channel, with the binding picket present at the interface region of the subunits. alpha-netlrotoxin is a potent nAChR competitive antagonist that readily blocks the channel resulting in paralysis. The molecular interaction of alpha-Bungarotoxin, a long chain alpha-neurotoxin from (Bungarus multicinctus) and human alpha(7)nAChR seas studied. Agonists such as acetylcholine, nicotine, which are used in it diverse array of biological activities, such as enhancements of cognitive performances, were also docked with the theoretical model of human alpha(7)nAChR. These docked complexes were analyzed further for identifying the crucial residues involved in interaction. These results provide the details of interaction of agonists and competitive antagonists with three dimensional model of the N-terminal region of human alpha(7)nAChR and thereby point to the design of novel lead compounds.

Syntheses, structural analyses, and magneto-structural correlations of three polymeric Fe(II) complexes with azide ligand

Three new metal-organic polymeric complexes, [Fe(N-3)(2)(bPP)(2)] (1), [Fe(N-3)(2)(bpe)] (2), and [Fe(N-3)(2)(phen)] (3) [bpp = (1,3-bis(4-pyridyl)-propane), bpe = (1,2-bis(4-pyridyl)-ethane), phen = 1,10-phenanthroline], have been synthesized and characterized by single-crystal X-ray diffraction studies and low-temperature magnetic measurements in the range 300-2 K. Complexes 1 and 2 crystallize in the monoclinic system, space group C2/c, with the following cell parameters: a = 19.355(4) Angstrom, b = 7.076(2) Angstrom, c = 22.549(4) Angstrom, beta = 119.50(3)degrees, Z = 4, and a = 10.007(14) Angstrom, b = 13.789(18) Angstrom, c = 10.377(14) Angstrom, beta = 103.50(1)degrees, Z = 4, respectively. Complex 3 crystallizes in the triclinic system, space group P (1) over bar, with a = 7.155(12) Angstrom, b = 10.066(14) Angstrom, c = 10.508(14) Angstrom, alpha = 109.57(1)degrees, beta = 104.57(1)degrees, gamma = 105.10(1)degrees, and Z = 2. All coordination polymers exhibit octahedral Fe(II) nodes. The structural determination of 1 reveals a parallel interpenetrated structure of 2D layers of (4,4) topology, formed by Fe(II) nodes linked through bpp ligands, while mono-coordinated azide anions are pendant from the corrugated sheet. Complex 2 has a 2D arrangement constructed through 1D double end-to-end azide bridged iron(11) chains interconnected through bpe ligands. Complex 3 shows a polymeric arrangement where the metal ions are interlinked through pairs of end-on and end-to-end azide ligands exhibiting a zigzag arrangement of metals (Fe-Fe-Fe angle of 111.18degrees) and an intermetallic separation of 3.347 Angstrom (through the EO azide) and of 5.229 Angstrom (EE azide). Variable-temperature magnetic susceptibility data suggest that there is no magnetic interaction between the metal centers in 1, whereas in 2 there is an antiferromagnetic interaction through the end-to-end azide bridge. Complex 3 shows ferro- as well as anti-ferromagnetic interactions between the metal centers generated through the alternating end-on and end-to-end azide bridges. Complex I has been modeled using the D parameter (considering distorted octahedral Fe(II) geometry and with any possible J value equal to zero) and complex 2 has been modeled as a one-dimensional system with classical and/or quantum spin where we have used two possible full diagonalization processes: without and with the D parameter, considering the important distortions of the Fe(II) ions. For complex 3, the alternating coupling model impedes a mathematical solution for the modeling as classical spins. With quantum spin, the modeling has been made as in 2.

Top-down systems biology modeling of host metabotype-microbiome associations in obese rodents

Covariation in the structural composition of the gut microbiome and the spectroscopically derived metabolic phenotype (metabotype) of a rodent model for obesity were investigated using a range of multivariate statistical tools. Urine and plasma samples from three strains of 10-week-old male Zucker rats (obese (fa/fa, n = 8), lean (fal-, n = 8) and lean (-/-, n = 8)) were characterized via high-resolution H-1 NMR spectroscopy, and in parallel, the fecal microbial composition was investigated using fluorescence in situ hydridization (FISH) and denaturing gradient gel electrophoresis (DGGE) methods. All three Zucker strains had different relative abundances of the dominant members of their intestinal microbiota (FISH), with the novel observation of a Halomonas and a Sphingomonas species being present in the (fa/fa) obese strain on the basis of DGGE data. The two functionally and phenotypically normal Zucker strains (fal- and -/-) were readily distinguished from the (fa/fa) obese rats on the basis of their metabotypes with relatively lower urinary hippurate and creatinine, relatively higher levels of urinary isoleucine, leucine and acetate and higher plasma LDL and VLDL levels typifying the (fa/fa) obese strain. Collectively, these data suggest a conditional host genetic involvement in selection of the microbial species in each host strain, and that both lean and obese animals could have specific metabolic phenotypes that are linked to their individual microbiomes.

Four novel mononuclear and polynuclear Cu(I) thiosaccharinates with triphenylphosphane and bis(diphenylposphino)methane. Synthesis and structural study of Cu(4)(tsac)(4)(PPh(3))(3), Cu(tsac)(PPh(3))(2), Cu(4)(tsac)(4)(dppm)(2), and Cu(2)(tsac)(2)(dppm)(2)

Four new ternary complexes of copper(I) with thiosaccharin and phosphanes were prepared. The reaction of [Cu(4)(tsac)(4)(CH(3)CN)(2)] (1) (tsac: thiosaccharinate anion) with PPh(3) in molar ratios Cu(I)/PPh(3) 1:075 and 1:2 gave the complexes [Cu(4)(tsac)(4)(PPh(3))(3)] center dot CH(3)CN (2) and Cu(tsac)(PPh(3))(2) (3), respectively. The reaction of 1 with Ph(2)PCH(2)PPh(2) (dppm) in molar ratios Cu(I)/dppm 2:1 and 1:1 gave the complexes [Cu(4) (tsac)(4)(dppm)(2)] center dot 2CH(2)Cl(2) (4) and [Cu(2)(tsac)(2)(dppm)(2)] center dot CH(2)Cl(2) (5), respectively. All the compounds have been characterized by spectroscopic and X-ray crystallographic methods. Complex 2 presents a tetra-nuclear arrangement with three metal centers in distorted tetrahedral S(2)NP environments, the fourth one with the Cu(I) ion in a distorted trigonal S(2)N coordination sphere, and the tsac anions acting as six electron donor ligands in mu(3)-S(2)N coordination forms. Complex 3 shows mononuclear molecular units with copper(I) in a distorted trigonal planar coordination sphere, built with the exocyclic S atom of a mono-coordinated thiosaccharinate anion and two P-atoms of triphenylphosphane molecules. With dppm as secondary ligand the structures of the complexes depends strongly on the stoicheometry of the preparation reaction. Complex 4 has a centrosymmetric structure. Two triply bridged Cu(2)(tsac)(2)(dppm) units are joined together by the exocyclic S-atoms of two tsac anions acting effectively as bridging tridentate ligands. Complex 5 is conformed by asymmetric dinuclear moieties where the two dppm and one tsac ligands bridge two Cu(I) atoms and the second tsac anion binds one of the metal centers through its exocyclic S-atom. (C) 2009 Elsevier B.V. All rights reserved.

Structural studies of prephenate dehydratase from Mycobacterium tuberculosis H37Rv by SAXS, ultracentrifugation, and computational analysis

Tuberculosis (TB) is one of the most common infectious diseases known to man and responsible for millions of human deaths in the world. The increasing incidence of TB in developing countries, the proliferation of multidrug resistant strains, and the absence of resources for treatment have highlighted the need of developing new drugs against TB. The shikimate pathway leads to the biosynthesis of chorismate, a precursor of aromatic amino acids. This pathway is absent from mammals and shown to be essential for the survival of Mycobacterium tuberculosis, the causative agent of TB. Accordingly, enzymes of aromatic amino acid biosynthesis pathway represent promising targets for structure-based drug design. The first reaction in phenylalanine biosynthesis involves the conversion of chorismate to prephenate, catalyzed by chorismate mutase. The second reaction is catalyzed by prephenate dehydratase (PDT) and involves decarboxylation and dehydratation of prephenate to form phenylpyruvate, the precursor of phenylalanine. Here, we describe utilization of different techniques to infer the structure of M. tuberculosis PDT (MtbPDT) in solution. Small angle X-ray scattering and ultracentrifugation analysis showed that the protein oligomeric state is a tetramer and MtbPDT is a flat disk protein. Bioinformatics tools were used to infer the structure of MtbPDT A molecular model for MtbPDT is presented and molecular dynamics simulations indicate that MtbPDT i.s stable. Experimental and molecular modeling results were in agreement and provide evidence for a tetrameric state of MtbPDT in solution.

Syntheses of Cross-Linking Agents, Molecular Modeling of Oligonucleotides and Polypeptide-Ion Complexes

Each section of this thesis will be subdivided into three parts encompassing all of the research in which I have been involved during the past three years. These will be referred to under the headings "Syntheses:' "Molecular Modeling," and "Cross-linking Efficiencies." Each of these subdivisions may have divisions within them when necessary in order to fully detail the research.

Purification, characterization, crystallization and theoretical molecular modeling of gyroxin fraction from Crotalus durissus terrificus venom (Laurenti, 1768)

The venom of Crotalus durissus terrificus snakes presents various substances, including a serine protease with thrombin-like activity, called gyroxin, that clots plasmatic fibrinogen and promote the fibrin formation. The aim of this study was to purify and structurally characterize the gyroxin enzyme from Crotalus durissus terrificus venom. For isolation and purification, the following methods were employed: gel filtration on Sephadex G75 column and affinity chromatography on benzamidine Sepharose 6B; 12% SDS-PAGE under reducing conditions; N-terminal sequence analysis; cDNA cloning and expression through RT-PCR and crystallization tests. Theoretical molecular modeling was performed using bioinformatics tools based on comparative analysis of other serine proteases deposited in the NCBI (National Center for Biotechnology Information) database. Protein N-terminal sequencing produced a single chain with a molecular mass of similar to 30 kDa while its full-length cDNA had 714 bp which encoded a mature protein containing 238 amino acids. Crystals were obtained from the solutions 2 and 5 of the Crystal Screen Kit (R), two and one respectively, that reveal the protein constitution of the sample. For multiple sequence alignments of gyroxin-like B2.1 with six other serine proteases obtained from snake venoms (SVSPs), the preservation of cysteine residues and their main structural elements (alpha-helices, beta-barrel and loops) was indicated. The localization of the catalytic triad in His57, Asp102 and Ser198 as well as S1 and S2 specific activity sites in Thr193 and Gli215 amino acids was pointed. The area of recognition and cleavage of fibrinogen in SVSPs for modeling gyroxin B2.1 sequence was located at Arg60, Arg72, Gln75, Arg81, Arg82, Lis85, Glu86 and Lis87 residues. Theoretical modeling of gyroxin fraction generated a classical structure consisting of two alpha-helices, two beta-barrel structures, five disulfide bridges and loops in positions 37, 60, 70, 99, 148, 174 and 218. These results provided information about the functional structure of gyroxin allowing its application in the design of new drugs.

Modeling of interfaces in two-dimensional problems using solid finite elements with high aspect ratio

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Generating VHDL-AMS models of digital-to-analogue converters from MATLAB (R)/SIMULINK (R)

Today, the trend within the electronics industry is for the use of rapid and advanced simulation methodologies in association with synthesis toolsets. This paper presents an approach developed to support mixed-signal circuit design and analysis. The methodology proposed shows a novel approach to the problem of developing behvioural model descriptions of mixed-signal circuit topologies, by construction of a set of subsystems, that supports the automated mapping of MATLAB (R)/SINIULINK (R) models to structural VHDL-AMS descriptions. The tool developed, named (MSSV)-S-2, reads a SIMULINK (R) model file and translates it to a structural VHDL-AMS code. It also creates the file structure required to simulate the translated model in the SystemVision (TM). To validate the methodology and the developed program, the DAC08, AD7524 and AD5450 data converters were studied and initially modelled in MATLAB (R)/SIMULINK (R). The VHDL-AMS code generated automatically by (MSSV)-S-2, (MATLAB (R)/SIMULINK (R) to SystemVision (TM)), was then simulated in the SystemVision (TM). The simulation results show that the proposed approach, which is based on VHDL-AMS descriptions of the original model library elements, allows for the behavioural level simulation of complex mixed-signal circuits.