Algoritmo híbrido neural-imuno aplicado ao diagnóstico de distúrbios de tensão em sistemas de distribuição de energia elétrica

Pós-graduação em Engenharia Elétrica - FEIS

Alocação ótima de chaves de interconexão nas redes de distribuição de energia elétrica

Pós-graduação em Engenharia Elétrica - FEIS

Analysis of the genotoxic potential of low concentrations of Malathion on the Allium cepa cells and rat hepatoma tissue culture

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

Meta-heurísticas para o problema de planejamento de expansão da rede de transmissão de energia elétrica considerando restrições de segurança

Pós-graduação em Engenharia Elétrica - FEIS

Fluxo de potência continuado baseado em equações de injeção de corrente expressas em coordenadas polares

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Optimal reactive power flow via the modified barrier Lagrangian function approach

A new approach called the Modified Barrier Lagrangian Function (MBLF) to solve the Optimal Reactive Power Flow problem is presented. In this approach, the inequality constraints are treated by the Modified Barrier Function (MBF) method, which has a finite convergence property: i.e. the optimal solution in the MBF method can actually be in the bound of the feasible set. Hence, the inequality constraints can be precisely equal to zero. Another property of the MBF method is that the barrier parameter does not need to be driven to zero to attain the solution. Therefore, the conditioning of the involved Hessian matrix is greatly enhanced. In order to show this, a comparative analysis of the numeric conditioning of the Hessian matrix of the MBLF approach, by the decomposition in singular values, is carried out. The feasibility of the proposed approach is also demonstrated with comparative tests to Interior Point Method (IPM) using various IEEE test systems and two networks derived from Brazilian generation/transmission system. The results show that the MBLF method is computationally more attractive than the IPM in terms of speed, number of iterations and numerical conditioning. (C) 2011 Elsevier B.V. All rights reserved.

A modified Primal-Dual Logarithmic-Barrier Method for solving the Optimal Power Flow problem with discrete and continuous control variables

The aim of solving the Optimal Power Flow problem is to determine the optimal state of an electric power transmission system, that is, the voltage magnitude and phase angles and the tap ratios of the transformers that optimize the performance of a given system, while satisfying its physical and operating constraints. The Optimal Power Flow problem is modeled as a large-scale mixed-discrete nonlinear programming problem. This paper proposes a method for handling the discrete variables of the Optimal Power Flow problem. A penalty function is presented. Due to the inclusion of the penalty function into the objective function, a sequence of nonlinear programming problems with only continuous variables is obtained and the solutions of these problems converge to a solution of the mixed problem. The obtained nonlinear programming problems are solved by a Primal-Dual Logarithmic-Barrier Method. Numerical tests using the IEEE 14, 30, 118 and 300-Bus test systems indicate that the method is efficient. (C) 2012 Elsevier B.V. All rights reserved.

Use of solvents and environmental friendly materials for applications in Green Chemistry

The present Thesis studies three alternative solvent groups as sustainable replacement of traditional organic solvents. Some aspects of fluorinated solvents, supercritical fluids and ionic liquids, have been analysed with a critical approach and their effective “greenness” has been evaluated from the points of view of the synthesis, the properties and the applications. In particular, the attention has been put on the environmental and human health issues, evaluating the eco-toxicity, the toxicity and the persistence, to underline that applicability and sustainability are subjects with equal importance. The “green” features of fluorous solvents and supercritical fluids are almost well-established; in particular supercritical carbon dioxide (scCO2) is probably the “greenest” solvent among the alternative solvent systems developed in the last years, enabling to combine numerous advantages both from the point of view of industrial/technological applications and eco-compatibility. In the Thesis the analysis of these two classes of alternative solvents has been mainly focused on their applicability, rather than the evaluation of their environmental impact. Specifically they have been evaluated as alternative media for non-aqueous biocatalysis. For this purpose, the hydrophobic ion pairing (HIP), which allows solubilising enzymes in apolar solvents by an ion pairing between the protein and a surfactant, has been investigated as effective enzymatic derivatisation technique to improve the catalytic activity under homogeneous conditions in non conventional media. The results showed that the complex enzyme-surfactant was much more active both in fluorous solvents and in supercritical carbon dioxide than the native form of the enzyme. Ionic liquids, especially imidazolium salts, have been proposed some years ago as “fully green” alternative solvents; however this epithet does not take into account several “brown” aspects such as their synthesis from petro-chemical starting materials, their considerable eco-toxicity, toxicity and resistance to biodegradation, and the difficulty of clearly outline applications in which ionic liquids are really more advantageous than traditional solvents. For all of these reasons in this Thesis a critical analysis of ionic liquids has been focused on three main topics: i) alternative synthesis by introducing structural moieties which could reduce the toxicity of the most known liquid salts, and by using starting materials from renewable resources; ii) on the evaluation of their environmental impact through eco-toxicological tests (Daphnia magna and Vibrio fischeri acute toxicity tests, and algal growth inhibition), toxicity tests (MTT test, AChE inhibition and LDH release tests) and fate and rate of aerobic biodegradation in soil and water; iii) and on the demonstration of their effectiveness as reaction media in organo-catalysis and as extractive solvents in the recovery of vegetable oil from terrestrial and aquatic biomass. The results about eco-toxicity tests with Daphnia magna, Vibrio fischeri and algae, and toxicity assay using cultured cell lines, clearly indicate that the difference in toxicity between alkyl and oxygenated cations relies in differences of polarity, according to the general trend of decreasing toxicity by decreasing the lipophilicity. Independently by the biological approach in fact, all the results are in agreement, showing a lower toxicity for compounds with oxygenated lateral chains than for those having purely alkyl lateral chains. These findings indicate that an appropriate choice of cation and anion structures is important not only to design the IL with improved and suitable chemico-physical properties but also to obtain safer and eco-friendly ILs. Moreover there is a clear indication that the composition of the abiotic environment has to be taken into account when the toxicity of ILs in various biological test systems is analysed, because, for example, the data reported in the Thesis indicate a significant influence of salinity variations on algal toxicity. Aerobic biodegradation of four imidazolium ionic liquids, two alkylated and two oxygenated, in soil was evaluated for the first time. Alkyl ionic liquids were shown to be biodegradable over the 6 months test period, and in contrast no significant mineralisation was observed with oxygenated derivatives. A different result was observed in the aerobic biodegradation of alkylated and oxygenated pyridinium ionic liquids in water because all the ionic liquids were almost completely degraded after 10 days, independently by the number of oxygen in the lateral chain of the cation. The synthesis of new ionic liquids by using renewable feedstock as starting materials, has been developed through the synthesis of furan-based ion pairs from furfural. The new ammonium salts were synthesised in very good yields, good purity of the products and wide versatility, combining low melting points with high decomposition temperatures and reduced viscosities. Regarding the possible applications as surfactants and biocides, furan-based salts could be a valuable alternative to benzyltributylammonium salts and benzalkonium chloride that are produced from non-renewable resources. A new procedure for the allylation of ketones and aldehydes with tetraallyltin in ionic liquids was developed. The reaction afforded high yields both in sulfonate-containing ILs and in ILs without sulfonate upon addition of a small amount of sulfonic acid. The checked reaction resulted in peculiar chemoselectivity favouring aliphatic substrates towards aromatic ketones and good stereoselectivity in the allylation of levoglucosenone. Finally ILs-based systems could be easily and successfully recycled, making the described procedure environmentally benign. The potential role of switchable polarity solvents as a green technology for the extraction of vegetable oil from terrestrial and aquatic biomass has been investigated. The extraction efficiency of terrestrial biomass rich in triacylglycerols, as soy bean flakes and sunflower seeds, was comparable to those of traditional organic solvents, being the yield of vegetable oils recovery very similar. Switchable polarity solvents as been also exploited for the first time in the extraction of hydrocarbons from the microalga Botryococcus braunii, demonstrating the efficiency of the process for the extraction of both dried microalgal biomass and directly of the aqueous growth medium. The switchable polarity solvents exhibited better extraction efficiency than conventional solvents, both with dried and liquid samples. This is an important issue considering that the harvest and the dewatering of algal biomass have a large impact on overall costs and energy balance.

2,3-Divinyl- und 2-Aryl-3-vinylindole als Bausteine zu Carbazolen und Versuche zur photochemischen und Ultraschall-induzierten 1,6-Elektrocyclisierung

Es wurden neue funktionalisierte Carbazole und anellierte Benzo[a]carbazole als potentielle pharmakologische Therapeutika durch 1,6-pi-Elektrocyclisierung auf photo-chemischem, thermischem und sonochemischem Weg synthetisiert und die Synthesemethoden der 1,6-pi-Elektrocyclisierung sowie der 2,3-Divinylindole und der 2-Aryl-3-vinylindole als entsprechende Ausgangsprodukte validiert und evaluiert. Es gelang weder das nach den Woodward-Hoffmann-Regeln erwartete primäre Cyclisierungsprodukt mit Indolochinodimethanstruktur noch die Existenz des in einer photochemischen Abfangreaktion daraus resultierenden Cycloprodukts NMR-spektroskopisch nachzuweisen, um den stereochemischen Verlauf der Cyclisierung vorherzusagen. Ergebnisse der quantenchemischen Berechnungen der Eduktmoleküle (AO-Koeffizienten der MO's, HOMO/LUMO-Energien) sowie der Übergangszustandsgeometrien der Cyclisierungen decken sich mit den experimentellen Daten. Divinyl- und 2-Aryl-3-vinylindole sind als Systeme mit Hexatriensymmetrie aufzufassen, deren Cyclisierungsverhalten sich mit den Woodward-Hoffmann-Regeln beschreiben läßt. Im Vergleich der verschiedenen 1,6-pi-Elektrocyclisierungsmethoden zeigte sich, daß die photochemische Variante eine elegante Synthesemethode darstellt, um funktionalisierte Carbazole und Benzo[a]carbazole mit unterschiedlichen pharmakologischen Aktivitäten unter schonenden Reaktionsbedingungen mit den vergleichbar höchsten Ausbeuten zu erhalten. Demgegenüber lieferten die Ultraschallreaktionen keine nachweisbaren Cyclisierungsprodukte. Die thermische Cyclisierung führte zur Gruppe der 1,2-Dihydrocarbazole. Sie bildeten sich in einer Folgereaktion durch [1,5s]-H-Verschiebung aus dem primär entstandenen Woodward-Hoffmann-Cyclisierungsprodukt. In abschließenden DNA-Bindestudien mit verschiedenen Testsystemen zeigte keine der synthetisierten Testsubstanzen DNA-Bindungsaktivität.

Entwicklung eines immunologischen Testsystems zur Detektion des marinen Biotoxins Domoinsäure

Domoinsäure ist ein von mehreren Arten mariner Kieselalgen der Gattung Pseudonitzschia produziertes Toxin, welches während einer Algenblüte in Molluscen wie z.B. der Miesmuschel Mytilus sp. akkumuliert werden kann. Beim Verzehr solch kontaminierter Muscheln können sowohl beim Menschen als auch bei Tieren erhebliche Vergiftungserscheinungen auftreten, die von Übelkeit, Kopfschmerzen und Orientierungsstörungen bis hin zum Verlust des Kurzzeitgedächtnisses (daher auch als amnesic shellfish poisoning bekannt) reichen und in einigen Fällen tödlich enden. rnDie heute gängigen Methoden zur Detektion von Domoinsäure in Muschelgewebe wie Flüssigkeitschromatographie und Maus-Bioassay sind zeit- und kostenintensiv bzw. in Anbetracht einer Verbesserung des Tierschutzes aus ethischer Sicht nicht zu vertreten. Immunologische Testsysteme stellen eine erstrebenswerte Alternative dar, da sie sich durch eine vergleichsweise einfache Handhabung, hohe Selektivität und Reproduzierbarkeit auszeichnen.rnDas Ziel der vorliegenden Arbeit war es, ein solches immunologisches Testsystem zur Detektion von Domoinsäure zu entwickeln. Hierfür wurden zunächst Antikörper gegen Domoinsäure gewonnen, wofür das Toxin wiederum als erstes über die Carbodiimid-Methode an das Trägerprotein keyhole limpet hemocyanin (KLH) gekoppelt wurde, um eine Immunantwort auslösen zu können. Kaninchen und Mäuse wurden mit KLH-DO-Konjugaten nach vorgegebenen Immunisierungsschemata immunisiert. Nach vier Blutabnahmen zeigte das polyklonale Kaninchenantiserum eine ausreichend hohe Sensitivität zum Antigen; das nachfolgende Detektionssystem wurde mit Hilfe dieses polyklonalen Antikörpers aufgebaut. Zwar ist es gegen Ende der Arbeit auch gelungen, einen spezifischen monoklonalen Antikörper aus der Maus zu gewinnen, jedoch konnte dieser aus zeitlichen Gründen nicht mehr im Detektionssystem etabliert werden, was durchaus wünschenswert gewesen wäre. rnWeiterhin wurde Domoinsäure im Zuge der Entwicklung eines neuartigen Testsystems an die Trägerproteine Ovalbumin, Trypsininhibitor und Casein sowie an Biotin konjugiert. Die Kopplungserfolge wurden im ELISA, Western Blot bzw. Dot Blot nachgewiesen. Die Ovalbumin-gekoppelte sowie die biotinylierte Domoinsäure dienten im Folgenden als die zu messenden Größen in den Detektionsassays- die in einer zu untersuchenden Probe vorhandende, kompetitierende Domoinsäure wurde somit indirekt nachgewiesen. rnDer zulässige Höchstwert für Domoinsäure liegt bei 20 µg/g Muschelgewebe. Sowohl mit Biotin-DO als auch mit OVA-DO als den zu messenden Größen waren Domoinsäurekonzentrationen unterhalb dieses Grenzwertes nachweisbar; allerdings erwies sich der Aufbau mit Biotin-DO um das ca. 20-fache empfindlicher als jener mit OVA-DO. rnDie in dieser Arbeit präsentierten Ergebnisse könnten als Grundlage zur Etablierung eines kommerzialisierbaren immunologischen Testsystems zur Detektion von Domoinsäure und anderen Biotoxinen dienen. Nach erfolgreicher Validierung wäre ein solches Testsystem in seiner Handhabung einfacher als die gängige Flüssigkeitschromatographie und besser reproduzierbar als der Maus-Bioassay.rn

Synthese und Testung von COX-1-, COX-2- und 5-LOX-Inhibitoren zur topischen Anwendung

Das Ziel der Dissertation war die Synthese und pharmakologische Charakterisierung von COX-1-, COX-2- und 5-LOX-Inhibitoren, die zur Behandlung entzündlicher Dermatosen für die topische Anwendung geeignet sein sollten. Hierfür wurden zwei Strukturklassen - die sogenannten Imidazothiazole und die Chalcone-Derivate - entworfen und synthetisiert sowie in verschiedenen in vitro-Testsystemen auf ihre pharmakologische Wirksamkeit untersucht. rnDie Leitsubstanz der ersten Strukturklasse wurde in Anlehnung an die Struktur von Licofelon entworfen. Licofelon ist ein dualer COX/LOX-Inhibitor, der für die Indikation Osteoarthritis eingesetzt werden soll. Durch den Austausch einzelner Substituenten an den Phenylringen wurde die Leitstruktur schrittweise verändert, um die Wirksamkeit zu optimieren. Die Substituentenvariation erfolgte anhand des sogenannten Topliss-Schemas. Bei der zweiten Substanzklasse wurde durch Kombination zweier antiinflammatorisch wirksamer Molekülgruppen - mit dem Ziel eines synergistischen Effekts - eine Grundstruktur entwickelt, die zur Optimierung der Wirksamkeit derivatisiert wurde. Als Komponenten dienten 4,5-Bis(4-methoxyphenyl)-1H-imidazol-2-thiol (Z11) und ein Chalcon. Z11 ist sowohl in der Literatur als auch in vorangegangen Arbeiten des Arbeitskreises als dualer COX/LOX-Inhibitor beschrieben. Chalcone besitzen eine 1,3-Diphenylpropenon-Partialstruktur und können über einen der beiden Phenylringe mit Z11 verknüpft werden. In der Literatur wurde vielfach über die vielfältigen pharmakologischen Eigenschaften der Chalcone berichtet; im Rahmen dieser Arbeit stand deren antiinflammatorische Eigenschaft im Vordergrund. rnZur Beurteilung der Effektivität und Toxizität der Substanzen wurden diese anschließend pharmakologisch charakterisiert werden. Hierfür standen verschiedene in vitro-Testsysteme zur Verfügung, die Aufschluss über die COX-1-, COX-2- und 5-LOX-Inhibition der synthetisierten Substanzen gaben. Des Weiteren wurden die Substanzen auf eine mögliche inhibitorische Aktivität gegenüber TNF- untersucht. Da die Entwicklung der Testverbindungen mit dem Ziel der topischen Anwendung erfolgte, wurde eine log P-Wert-Bestimmung durchgeführt, um eine Aussage über die Lipophilie der Verbindungen treffen zu können.rn

Mechanistic study of the effects of 8-oxo-7,8-dihydroguanine (8-oxoG) on reporter gene expression in mammalian cells

DNA damage causes replication errors, leading to genetic instability or cell death. Besides that, many types of DNA base modifications have been shown to interfere with transcriptional elongation if they are located in the transcribed DNA strand of active genes, acting as roadblocks for RNA polymerases. It is widely assumed that transcription blockage by endogenous DNA damage is responsible for the early cell senescence in organs and accelerated ageing observed in individuals with compromised nucleotide excision repair.rnThe aims of this work were to design new experimental systems for testing transcription blocking potentials of DNA base modifications in an individual gene and to apply these test systems to the investigation of the effects of a frequent endogenously generated base modification, namely 8-oxo-7,8-hydroxyguanine (8-oxoG), on the gene transcription in cells. Several experimental strategies were employed for this purpose. First, I constructed an episomal vector encoding for a short-lived EGFP-ODC fusion protein and measured expression of the reporter gene in permanently transfected clonal cell lines exposed to DNA damaging agents. Second, the expression of plasmid-borne EGFP gene damaged with photosensitisers to obtain one or several oxidative purine modifications per plasmid molecule was determined in transiently transfected human and mouse host cells in an approach known as “host cell reactivation”. As a prerequisite for these experiments, a robust method of precise quantitative measurement of the EGFP gene expression in transiently transfected cells by flow cytometry was developed and validated. Third, I elaborated a very efficient procedure for insertion of synthetic oligonucleotides carrying 8-oxoG into plasmid DNA, avoiding any unwanted base damage and strand breaks. The consequences of 8-oxoG placed in defined positions in opposing DNA strands of the EGFP gene for transcription were measured by host cell reactivation in cells with functional 8-oxoguanine DNA glycosylase (OGG1) gene and in OGG1 null cells.rnThe results obtained in Ogg1-/- cells demonstrated that unrepaired 8-oxoG, even if situated in the transcribed DNA strand, does not have any negative effect on the reporter gene transcription. On the other hand, as few as one 8-oxoG was sufficient to cause a significant decrease of the gene expression in OGG1-proficient cell lines, i.e. in the presence of base excision repair. For two analysed positions of 8-oxoG in the plasmid DNA, the inhibition of gene transcription by the base modification correlated with the efficiency of its excision by purified OGG1 protein under cell-free conditions. Based on these findings, it has to be concluded that the observed decrease of transcription is mediated by excision of the base modification by OGG1 and probably caused by the repair-induced single-strand breaks. The mechanism of transcription inhibition by 8-oxoG is therefore clearly distinct from stalling of elongating RNA polymerase II complexes at the modified base.

A simple tool for stereological assessment of digital images: the STEPanizer

STEPanizer is an easy-to-use computer-based software tool for the stereological assessment of digitally captured images from all kinds of microscopical (LM, TEM, LSM) and macroscopical (radiology, tomography) imaging modalities. The program design focuses on providing the user a defined workflow adapted to most basic stereological tasks. The software is compact, that is user friendly without being bulky. STEPanizer comprises the creation of test systems, the appropriate display of digital images with superimposed test systems, a scaling facility, a counting module and an export function for the transfer of results to spreadsheet programs. Here we describe the major workflow of the tool illustrating the application on two examples from transmission electron microscopy and light microscopy, respectively.

Comparison of three strip-type tests and two laboratory methods for salivary buffering analysis

This study evaluated the correlation between three strip-type, colorimetric tests and two laboratory methods with respect to the analysis of salivary buffering. The strip-type tests were saliva-check buffer, Dentobuff strip and CRT(®) Buffer test. The laboratory methods included Ericsson's laboratory method and a monotone acid/base titration to create a reference scale for the salivary titratable acidity. Additionally, defined buffer solutions were prepared and tested to simulate the carbonate, phosphate and protein buffer systems of saliva. The correlation between the methods was analysed by the Spearman's rank test. Disagreement was detected between buffering capacity values obtained with three strip-type tests that was more pronounced in case of saliva samples with medium and low buffering capacities. All strip-type tests were able to assign the hydrogencarbonate, di-hydrogenphosphate and 0.1% protein buffer solutions to the correct buffer categories. However, at 0.6% total protein concentrations, none of the test systems worked accurately. Improvements are necessary for strip-type tests because of certain disagreement with the Ericsson's laboratory method and dependence on the protein content of saliva.

Disruption of glucocorticoid action by environmental chemicals: potential mechanisms and relevance

Glucocorticoids play an essential role in the regulation of key physiological processes, including immunomodulation, brain function, energy metabolism, electrolyte balance and blood pressure. Exposure to naturally occurring compounds or industrial chemicals that impair glucocorticoid action may contribute to the increasing incidence of cognitive deficits, immune disorders and metabolic diseases. Potentially, "glucocorticoid disruptors" can interfere with various steps of hormone action, e.g. hormone synthesis, binding to plasma proteins, delivery to target cells, pre-receptor regulation of the ratio of active versus inactive hormones, glucocorticoid receptor (GR) function, or export and degradation of glucocorticoids. Several recent studies indicate that such chemicals exist and that some of them can cause multiple toxic effects by interfering with different steps of hormone action. For example, increasing evidence suggests that organotins disturb glucocorticoid action by altering the function of factors that regulate the expression of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) pre-receptor enzymes, by direct inhibition of 11beta-HSD2-dependent inactivation of glucocorticoids, and by blocking GR activation. These observations emphasize on the complexity of the toxic effects caused by such compounds and on the need of suitable test systems to assess their effects on each relevant step.