Aplicação de redes neurais artificiais na predição de diâmetro e rugosidade durante o processo de furação

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Aplicação de redes NeuroFuzzy ao processamento de peças automotivas por meio de injeção de polímeros

The injection molding of automotive parts is a complex process due to the many non-linear and multivariable phenomena that occur simultaneously. Commercial software applications exist for modeling the parameters of polymer injection but can be prohibitively expensive. It is possible to identify these parameters analytically, but applying classical theories of transport phenomena requires accurate information about the injection machine, product geometry, and process parameters. However, neurofuzzy networks, which achieve a synergy by combining the learning capabilities of an artificial neural network with a fuzzy set's inference mechanism, have shown success in this field. The purpose of this paper was to use a multilayer perceptron artificial neural network and a radial basis function artificial neural network combined with fuzzy sets to produce an inference mechanism that could predict injection mold cycle times. The results confirmed neurofuzzy networks as an effective alternative to solving such problems.

Classificador Fisherface Fuzzy para o reconhecimento de faces

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Robust Switched Control Design for Nonlinear Systems Using Fuzzy Models

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

On Switched Regulator Design of Uncertain Nonlinear Systems Using Takagi-Sugeno Fuzzy Models

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

Evolutionary History of the PER3 Variable Number of Tandem Repeats (VNTR): Idiosyncratic Aspect of Primate Molecular Circadian Clock

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

Interaction among nitric oxide (NO)-related genes in migraine susceptibility

The pathogenic mechanisms involved in migraine are complex and not completely clarified. Because there is evidence for the involvement of nitric oxide (NO) in migraine pathophysiology, candidate gene approaches focusing on genes affecting the endothelial function have been studied including the genes encoding endothelial NO synthase (eNOS), inducible NO synthase (iNOS), and vascular endothelial growth factor (VEGF). However, investigations on gene-gene interactions are warranted to better elucidate the genetic basis of migraine. This study aimed at characterizing interactions among nine clinically relevant polymorphisms in eNOS (T-786C/rs2070744, the 27 bp VNTR in intron 4, the Glu298Asp/rs1799983, and two additional tagSNPs rs3918226 and rs743506), iNOS (C(-1026)A/rs2779249 and G2087A/rs2297518), and VEGF (C(-2578)A/rs699947 and G(-634)C/rs2010963) in migraine patients and control group. Genotypes were determined by real-time polymerase chain reaction using the Taqman(A (R)) allele discrimination assays or PCR and fragment separation by electrophoresis in 99 healthy women without migraine (control group) and in 150 women with migraine divided into two groups: 107 with migraine without aura and 43 with aura. The multifactor dimensionality reduction method was used to detect and characterize gene-gene interactions. We found a significant interaction between eNOS rs743506 and iNOS 2087G/A polymorphisms in migraine patients compared to control group (P < 0.05), suggesting that this combination affect the susceptibility to migraine. Further studies are needed to determine the molecular mechanisms explaining this interaction.

Tecniche di elaborazione di dati macrosismici per la definizione di sorgenti sismogenetiche

La valutazione dell’intensità secondo una procedura formale trasparente, obiettiva e che permetta di ottenere valori numerici attraverso scelte e criteri rigorosi, rappresenta un passo ed un obiettivo per la trattazione e l’impiego delle informazioni macrosismiche. I dati macrosismici possono infatti avere importanti applicazioni per analisi sismotettoniche e per la stima della pericolosità sismica. Questa tesi ha affrontato il problema del formalismo della stima dell’intensità migliorando aspetti sia teorici che pratici attraverso tre passaggi fondamentali sviluppati in ambiente MS-Excel e Matlab: i) la raccolta e l’archiviazione del dataset macrosismico; ii), l’associazione (funzione di appartenenza o membership function) tra effetti e gradi di intensità della scala macrosismica attraverso i principi della logica dei fuzzy sets; iii) l’applicazione di algoritmi decisionali rigorosi ed obiettivi per la stima dell’intensità finale. L’intera procedura è stata applicata a sette terremoti italiani sfruttando varie possibilità, anche metodologiche, come la costruzione di funzioni di appartenenza combinando le informazioni macrosismiche di più terremoti: Monte Baldo (1876), Valle d’Illasi (1891), Marsica (1915), Santa Sofia (1918), Mugello (1919), Garfagnana (1920) e Irpinia (1930). I risultati ottenuti hanno fornito un buon accordo statistico con le intensità di un catalogo macrosismico di riferimento confermando la validità dell’intera metodologia. Le intensità ricavate sono state poi utilizzate per analisi sismotettoniche nelle aree dei terremoti studiati. I metodi di analisi statistica sui piani quotati (distribuzione geografica delle intensità assegnate) si sono rivelate in passato uno strumento potente per analisi e caratterizzazione sismotettonica, determinando i principali parametri (localizzazione epicentrale, lunghezza, larghezza, orientazione) della possibile sorgente sismogenica. Questa tesi ha implementato alcuni aspetti delle metodologie di analisi grazie a specifiche applicazioni sviluppate in Matlab che hanno permesso anche di stimare le incertezze associate ai parametri di sorgente, grazie a tecniche di ricampionamento statistico. Un’analisi sistematica per i terremoti studiati è stata portata avanti combinando i vari metodi per la stima dei parametri di sorgente con i piani quotati originali e ricalcolati attraverso le procedure decisionali fuzzy. I risultati ottenuti hanno consentito di valutare le caratteristiche delle possibili sorgenti e formulare ipotesi di natura sismotettonica che hanno avuto alcuni riscontri indiziali con dati di tipo geologico e geologico-strutturale. Alcuni eventi (1915, 1918, 1920) presentano una forte stabilità dei parametri calcolati (localizzazione epicentrale e geometria della possibile sorgente) con piccole incertezze associate. Altri eventi (1891, 1919 e 1930) hanno invece mostrato una maggiore variabilità sia nella localizzazione dell’epicentro che nella geometria delle box: per il primo evento ciò è probabilmente da mettere in relazione con la ridotta consistenza del dataset di intensità mentre per gli altri con la possibile molteplicità delle sorgenti sismogenetiche. Anche l’analisi bootstrap ha messo in evidenza, in alcuni casi, le possibili asimmetrie nelle distribuzioni di alcuni parametri (ad es. l’azimut della possibile struttura), che potrebbero suggerire meccanismi di rottura su più faglie distinte.

Funktionelle Analyse der Polaritäts- und Tumorsuppressorgene hugl-1 und hugl-2 mittels siRNA-vermitteltem Gen-Silencing und konditionalem Gen-Knockout

Das menschliche Gen human giant larvae (hugl) ist ein Homolog des hochkonservierten Drosophila Gens lethal giant larvae (lgl), welches in Epithelzellen die Funktion eines neoplastischen Tumorsuppressors und Polaritätsregulators einnimmt. Ein Verlust oder eine verminderte Expression beider Homologe des Gens, hugl-1 und hugl-2, geht einher mit dem Auftreten und der Progression verschiedener epithelialer Tumorerkrankungen wie malignen Melanomen und Brust-, Kolon- oder Lungentumoren. Die exakte Funktion der Homologe Hugl-1 und Hugl-2 bezüglich der Regulation und Aufrechterhaltung der epithelialen Zellpolarität sowie ihre Rolle in der Genese humaner Tumore ist jedoch weitgehend unbekannt. Gänzlich unbekannt ist auch die Bedeutung von Hugl-1 und Hugl-2 als Polaritätsregulatoren für die Ausbildung und den Erhalt der T-Zellmorphologie und -funktion. Ziel der vorliegenden Arbeit war es daher, die Polaritäts- und Tumorsuppressorgene hugl-1 und hugl-2 in funktionellen Analysen mittels siRNA-vermitteltem Gen-Silencing in Epithelzellen und T-Lymphozyten zu charakterisieren. Darüber hinaus wurden die Funktionen und Eigenschaften von mgl-2, dem murinen Homologen von hugl-2, im Cre/loxP-vermittelten konditionalen Knockout Mausmodell in vivo analysiert.rnrnZur Charakterisierung der biologischen Effekte von Hugl-1 und Hugl-2 auf das Wachstumsverhalten, Migration und Invasion von Epithelzellen wurden in dieser Arbeit erfolgreich unterschiedliche shRNA-Expressionskonstrukte generiert sowie Hugl-supprimierte Zelllinien etabliert. In vitro Studien sowie in vivo Tumorigenizitätsanalysen lieferten übereinstimmend Hinweise darauf, dass verminderte Hugl-1- und Hugl-2-Expressionsspiegel eine signifikante Rolle in der Vermittlung invasiver und tumorigener Eigenschaften von Epithelzellen spielen. Dabei rief der Verlust beider Homologe deutlich stärkere Reaktionen hervor als die Suppression eines einzelnen Homologen. Zudem wiesen die Überexpression des Zellzyklusregulators Cyclin D1 sowie die Hyperproliferation von Hugl-1- und/oder Hugl-2-depletierten Epithelzellen auf eine wichtige Rolle der beiden Homologe in der Zellzyklusprogression und Zellproliferation hin. Ein geringer Expressionsstatus von Hugl-1 und -2 schien darüber hinaus mit einer verstärkten Resistenzbildung gegenüber Chemotherapeutika zu korrelieren. Im Rahmen dieser Arbeit konnte weiterhin gezeigt werden, dass die untersuchten T-Lymphozyten nur Hugl-1 exprimieren und dass letzteres notwendig für den F-Aktin-vermittelten Erhalt der T-Zellpolarität und -morphologie ist. Hugl-1-supprimierte, über voneinander unabhängige Signalwege (TCR- oder Chemokinrezeptor) stimulierte T-Lymphozyten wiesen eine bedeutende Störung der Lamellipodien- und Uropodausbildung auf und ließen eine Interaktion von Hugl-1 auf Ebene des F Aktins vermuten. Des Weiteren zeigte sich, dass der Polaritätsregulator Hugl-1 die CD3/TCR-induzierte Zelladhäsion positiv beeinflusst. Die Analyse der T-Zellmigration und -motilität offenbarte in Übereinstimmung dazu die Wichtigkeit von Hugl-1 für die Polarisierung und Migration der T-Zellen sowohl im Chemokingradienten als auch auf mDCs. rnrnFür die Aufklärung der funktionellen Rolle von mgl-2 in vivo wurde in dieser Arbeit eine Tamoxifen-induzierbare, Cre/loxP-vermittelte konditionale Mauslinie generiert und analysiert. Die mgl-2-deletierten Tiere wiesen weder signifikante phänotypische Unterschiede noch Abweichungen in der Organanatomie auf und ließen daher auf eine Kompensation durch das im Darmepithel koexprimierte und möglicherweise funktionell redundante mgl-1 Gen schließen.rn

Endothelial survival factors and spatial completion, but not pericyte coverage of retinal capillaries determine vessel plasticity

Pericyte loss and capillary regression are characteristic for incipient diabetic retinopathy. Pericyte recruitment is involved in vessel maturation, and ligand-receptor systems contributing to pericyte recruitment are survival factors for endothelial cells in pericyte-free in vitro systems. We studied pericyte recruitment in relation to the susceptibility toward hyperoxia-induced vascular remodeling using the pericyte reporter X-LacZ mouse and the mouse model of retinopathy of prematurity (ROP). Pericytes were found in close proximity to vessels, both during formation of the superficial and the deep capillary layers. When exposure of mice to the ROP was delayed by 24 h, i.e., after the deep retinal layer had formed [at postnatal (p) day 8], preretinal neovascularizations were substantially diminished at p18. Mice with a delayed ROP exposure had 50% reduced avascular zones. Formation of the deep capillary layers at p8 was associated with a combined up-regulation of angiopoietin-1 and PDGF-B, while VEGF was almost unchanged during the transition from a susceptible to a resistant capillary network. Inhibition of Tie-2 function either by soluble Tie-2 or by a sulindac analog, an inhibitor of Tie-2 phosphorylation, resensitized retinal vessels to neovascularizations due to a reduction of the deep capillary network. Inhibition of Tie-2 function had no effect on pericyte recruitment. Our data indicate that the final maturation of the retinal vasculature and its resistance to regressive signals such as hyperoxia depend on the completion of the multilayer structure, in particular the deep capillary layers, and are independent of the coverage by pericytes.

Neural reprogramming in retinal degeneration.

PURPOSE: Early visual defects in degenerative diseases such as retinitis pigmentosa (RP) may arise from phased remodeling of the neural retina. The authors sought to explore the functional expression of ionotropic (iGluR) and group 3, type 6 metabotropic (mGluR6) glutamate receptors in late-stage photoreceptor degeneration. METHODS: Excitation mapping with organic cations and computational molecular phenotyping were used to determine whether retinal neurons displayed functional glutamate receptor signaling in rodent models of retinal degeneration and a sample of human RP. RESULTS: After photoreceptor loss in rodent models of RP, bipolar cells lose mGluR6 and iGluR glutamate-activated currents, whereas amacrine and ganglion cells retain iGluR-mediated responsivity. Paradoxically, amacrine and ganglion cells show spontaneous iGluR signals in vivo even though bipolar cells lack glutamate-coupled depolarization mechanisms. Cone survival can rescue iGluR expression by OFF bipolar cells. In a case of human RP with cone sparing, iGluR signaling appeared intact, but the number of bipolar cells expressing functional iGluRs was double that of normal retina. CONCLUSIONS: RP triggers permanent loss of bipolar cell glutamate receptor expression, though spontaneous iGluR-mediated signaling by amacrine and ganglion cells implies that such truncated bipolar cells still release glutamate in response to some nonglutamatergic depolarization. Focal cone-sparing can preserve iGluR display by nearby bipolar cells, which may facilitate late RP photoreceptor transplantation attempts. An instance of human RP provides evidence that rod bipolar cell dendrite switching likely triggers new gene expression patterns and may impair cone pathway function.

Identification and characterization of new genes involved in Drosophila heart development

Heart development is a crucial and conserved process that is related to the major type of human birth defects. Dorsal vessel, the Drosophila heart, has been regarded as an insightful system to identify new genes and study gene functions involved in heart development. Using heart-specific GFP transgenes, I did a genetic screen for cardiogenic genes on Drosophila chromosome II. Drosophila mutants that carry chromosome II deficiencies were tested for their phenotypes of heart development. Based on the screen results, chromosome regions containing genes required for heart development were identified. Fly strains with single gene mutations located within the defined deficiency regions were tested further. Seven genes have been identified to be involved in heart development. ^ The LIM homeodomain transcription factor gene tailup (tup) was further studied for its function in heart development. Based on this study, tup is expressed in cardioblasts and pericardial cells of the heart tube, as well as in associated lymph glands and alary muscles. In depth analysis of tup mutant phenotypes demonstrated tup is required for normal development of both heart and lymph glands. Tup was shown to bind to two DNA recognition sequences in the dorsal vessel enhancer of the Hand bHLH transcription factor gene, with one site proven essential for the expression of Hand in lymph glands, pericardial cells, and Svp/Doc cardioblasts. Together, these studies demonstrate that Tup is a critical new transcription factor in dorsal vessel morphogenesis and lymph gland formation, and strongly suggest Tup is a direct regulator of the expression of Hand in these developmental processes. ^

Characterization of cellular and molecular functions of the p21 -activated kinase, Shk1, in the fission yeast, Schizosaccharomyces pombe

The p21-activated kinase, Shk1, is an essential serine/threonine kinase required for normal cell polarity, proper mating response, and hyperosmotic stress response, in the fission yeast, Schizosaccharomyces pombe. This study has established a novel role for Shk1 as a microtubule regulator in fission yeast and, in addition, characterized a potential biological substrate of Shk1. Cells defective in Shk1 function were found to exhibit malformed interphase and mitotic microtubules, are hypersensitive to the microtubule disrupting drug thiabendazole (TBZ), and are cold sensitive for growth. Microtubule disruption by TBZ results in a significant reduction of Shk1 kinase activity, which is restored after cells are released from the drug, thus providing a correlation between Shk1 kinase activity and active microtubule polymerization. Consistent with a role for Shk1 as a microtubule regulator, GFP-Shk1 fusion proteins localize to interphase microtubules and mitotic microtubule spindles. Furthermore, loss of Tea1, a presumptive microtubule regulator in fission yeast, exacerbates the growth and microtubule defects of cells deficient in Shk1 function, and results in illicit Shk1 localization. Moreover, loss of the Cdc2 inhibitory kinase Wee1, which has been implicated as a mediator of the Shk1 pathway, leads to significant microtubule defects. Intriguingly, Wee1 protein levels are markedly reduced both by partial loss of Shk1 function and by treatment with TBZ. These results suggest that Shk1 is required for proper regulation of microtubule dynamics in fission yeast and may interact with Tea1 and Wee1 in this regulatory process. ^ To further understand Shk1 function in fission yeast, a yeast two-hybrid screen for proteins that interact with the Shk1 catalytic domain was performed. This screen led to the identification of a novel protein, Skb10 (for S&barbelow;hk1 k&barbelow;inase b&barbelow;inding protein 10). Coprecipitation experiments demonstrated that Skb10 associates with Shk1 in S. pombe cells. (Abstract shortened by UMI.) ^

New methods for the estimation of Takagi-Sugeno model based extended Kalman filter and its applications to optimal control for nonlinear systems

This paper describes new approaches to improve the local and global approximation (matching) and modeling capability of Takagi–Sugeno (T-S) fuzzy model. The main aim is obtaining high function approximation accuracy and fast convergence. The main problem encountered is that T-S identification method cannot be applied when the membership functions are overlapped by pairs. This restricts the application of the T-S method because this type of membership function has been widely used during the last 2 decades in the stability, controller design of fuzzy systems and is popular in industrial control applications. The approach developed here can be considered as a generalized version of T-S identification method with optimized performance in approximating nonlinear functions. We propose a noniterative method through weighting of parameters approach and an iterative algorithm by applying the extended Kalman filter, based on the same idea of parameters’ weighting. We show that the Kalman filter is an effective tool in the identification of T-S fuzzy model. A fuzzy controller based linear quadratic regulator is proposed in order to show the effectiveness of the estimation method developed here in control applications. An illustrative example of an inverted pendulum is chosen to evaluate the robustness and remarkable performance of the proposed method locally and globally in comparison with the original T-S model. Simulation results indicate the potential, simplicity, and generality of the algorithm. An illustrative example is chosen to evaluate the robustness. In this paper, we prove that these algorithms converge very fast, thereby making them very practical to use.

Contribución al estudio de dos conceptos básicos de la lógica fuzzy

La tesis doctoral CONTRIBUCIÓN AL ESTUDIO DE DOS CONCEPTOS BÁSICOS DE LA LÓGICA FUZZY constituye un conjunto de nuevas aportaciones al análisis de dos elementos básicos de la lógica fuzzy: los mecanismos de inferencia y la representación de predicados vagos. La memoria se encuentra dividida en dos partes que corresponden a los dos aspectos señalados. En la Parte I se estudia el concepto básico de «estado lógico borroso». Un estado lógico borroso es un punto fijo de la aplicación generada a partir de la regla de inferencia conocida como modus ponens generalizado. Además, un preorden borroso puede ser representado mediante los preórdenes elementales generados por el conjunto de sus estados lógicos borrosos. El Capítulo 1 está dedicado a caracterizar cuándo dos estados lógicos dan lugar al mismo preorden elemental, obteniéndose también un representante de la clase de todos los estados lógicos que generan el mismo preorden elemental. El Capítulo finaliza con la caracterización del conjunto de estados lógicos borrosos de un preorden elemental. En el Capítulo 2 se obtiene un subconjunto borroso trapezoidal como una clase de una relación de indistinguibilidad. Finalmente, el Capítulo 3 se dedica a estudiar dos tipos de estados lógicos clásicos: los irreducibles y los minimales. En el Capítulo 4, que inicia la Parte II de la memoria, se aborda el problema de obtener la función de compatibilidad de un predicado vago. Se propone un método, basado en el conocimiento del uso del predicado mediante un conjunto de reglas y de ciertos elementos distinguidos, que permite obtener una expresión general de la función de pertenencia generalizada de un subconjunto borroso que realice la función de extensión del predicado borroso. Dicho método permite, en ciertos casos, definir un conjunto de conectivas multivaluadas asociadas al predicado. En el último capítulo se estudia la representación de antónimos y sinónimos en lógica fuzzy a través de auto-morfismos. Se caracterizan los automorfismos sobre el intervalo unidad cuando sobre él se consideran dos operaciones: una t-norma y una t-conorma ambas arquimedianas. The PhD Thesis CONTRIBUCIÓN AL ESTUDIO DE DOS CONCEPTOS BÁSICOS DE LA LÓGICA FUZZY is a contribution to two basic concepts of the Fuzzy Logic. It is divided in two parts, the first is devoted to a mechanism of inference in Fuzzy Logic, and the second to the representation of vague predicates. «Fuzzy Logic State» is the basic concept in Part I. A Fuzzy Logic State is a fixed-point for the mapping giving the Generalized Modus Ponens Rule of inference. Moreover, a fuzzy preordering can be represented by the elementary preorderings generated by its Fuzzy Logic States. Chapter 1 contemplates the identity of elementary preorderings and the selection of representatives for the classes modulo this identity. This chapter finishes with the characterization of the set of Fuzzy Logic States of an elementary preordering. In Chapter 2 a Trapezoidal Fuzzy Set as a class of a relation of Indistinguishability is obtained. Finally, Chapter 3 is devoted to study two types of Classical Logic States: irreducible and minimal. Part II begins with Chapter 4 dealing with the problem of obtaining a Compa¬tibility Function for a vague predicate. When the use of a predicate is known by means of a set of rules and some distinguished elements, a method to obtain the general expression of the Membership Function is presented. This method allows, in some cases, to reach a set of multivalued connectives associated to the predicate. Last Chapter is devoted to the representation of antonyms and synonyms in Fuzzy Logic. When the unit interval [0,1] is endowed with both an archimedean t-norm and a an archi-medean t-conorm, it is showed that the automorphisms' group is just reduced to the identity function.