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The affective experience of moral decision makingCreel, Laura Haley, Stadler, Holly A. January 2006 (has links) (PDF)
Dissertation (Ph.D.)--Auburn University, 2006. / Abstract. Vita. Includes bibliographic references (p.176-188).
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Acyloxyacyl hydrolase : studies on its regulation and function in mus musculusLu, Mingfang. January 2003 (has links) (PDF)
Thesis (Ph. D.) -- University of Texas Southwestern Medical Center at Dallas, 2003. / Vita. Bibliography: 162-207.
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Macrolide resistance and its linkage to tetracycline resistance /Chung, Whasun Oh. January 1999 (has links)
Thesis (Ph. D.)--University of Washington, 1999. / Vita. Includes bibliographical references (leaves 112-144).
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Αρνητική διωνυμική κατανομή και εκτίμηση των παραμέτρων τηςΔίκαρος, Ανδρέας 29 December 2010 (has links)
Η παρούσα μεταπτυχιακή διατριβή εντάσσεται ερευνητικά στην περιοχή της Στατιστικής θεωρίας Αποφάσεων και ειδικότερα στη μελέτη της αρνητικής διωνυμικής κατανομής καθώς επίσης και στην εκτίμηση των παραμέτρων της.
Στο Κεφάλαιο 1 παρουσιάζονται κάποιοι χρήσιμοι, για την πορεία της μελέτης μας, ορισμοί και θεωρήματα.
Στο Κεφάλαιο 2 μελετάται το μοντέλο της αρνητικής διωνυμικής κατανομής, δίνονται τα χαρακτηριστικά μεγέθη αυτής και παρουσιάζονται οι διαφορετικές παραμετρικοποιήσεις της.
Στο Κεφάλαιο 3, εξετάζεται το πρόβλημα εκτίμησης των παραμέτρων της αρνητικής διωνυμικής κατανομής και πιο ειδικά η εκτίμηση για τις διάφορες παραμετρικοποιήσης της. Για περισσότερη ανάλυση χρησιμοποιούνται η εκτίμηση μέγιστης πιθανοφάνειας, η εκτίμηση με τη μέθοδο των ροπών και πιο εξειδικευμένες υπολογιστικές μέθοδοι εκτίμησης.
Στο Κεφάλαιο 4, και για το ίδιο πρόβλημα εκτίμησης που πραγματεύεται το προηγούμενο κεφάλαιο, επιλέγεται ο βέλτιστος εκτιμητής των παραμέτρων της αρνητικής διωνυμικής κατανομής και παρουσιάζεται ένα παράδειγμα για την κατανόηση των μεθόδων εκτίμησης. / The master thesis we are going to introduce takes place in the region of Statistical Decision Theory and particularly in studying the Negative Binomial Distribution and the estimation of its parameters.
In Chapter 1 some useful definitions and theorems are presented.
In Chapter 2 the model of negative binomial distribution is studied and its different parameterizations are discussed.
In Chapter 3 we examine the problem of estimating the parameters of our model and for its parameterizations. In particular we give the method of Maximum Likelihood Estimation, the Method of Moments and more specified Estimation Methods.
In Chapter 4 and for the same estimation problem, as in previous chapter, it’s been chosen the best estimator of the parameters in our model and it’s been derived an example for the better understanding of the above methods.
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Δυσλειτουργικές σκέψεις σταδιοδρομίας, δυσθυμικά συναισθήματα και επαγγελματική αναποφασιστικότηταΘωμοπούλου, Ιωάννα 14 February 2012 (has links)
Η συμβουλευτική και ανάπτυξη της σταδιοδρομίας παρουσιάζει έντονο ερευνητικό ενδιαφέρον, το οποίο εστιάζεται στην μελέτη των παραγόντων που παρεμποδίζουν την επιτυχή λήψη απόφασης. Λαμβάνοντας υπόψη την σύνθετη αλληλλεπίδραση μεταξύ σκέψεων, συναισθημάτων, αποφάσεων και δράσης, στην παρούσα μελέτη διερευνήσαμε την σχέση των δυσλειτουργικών σκέψεων σταδιοδρομίας και των δυσθυμικών συναισθημάτων με την επαγγελματική αναποφασιστικότητα. Η μετανεωτερικότητα και ο κονστρουκτιβισμός μάς έδωσαν το πρόδηλο πλεονέκτημα να αξιοποιήσουμε ποιοτικές μεθοδολογικές προσεγγίσεις, προκειμένου να διερευνήσουμε τις εμφανείς και κυρίως τις λανθάνουσες εσωτερικές διεργασίες, νοητικές και συναισθηματικές, οι οποίες αλληλλεπιδρούν και επενεργούν στην διαδικασία λήψης αποφάσεων για την σταδιοδρομία. Ως μέθοδο έρευνας προκρίναμε την μελέτη περίπτωσης ενός μεμονωμένου προσώπου, προϊουσών των συμβουλευτικών παρεμβάσεων. Η τριγωνοποίηση περισσότερων μεθοδολογικών εργαλείων αποτέλεσε έναν ισχυρό τρόπο εφαρμογής της ταυτόχρονης εγκυρότητας. Το μοναδικό παράδειγμα ενός πραγματικού προσώπου, ως επίκεντρο της ερευνητικής στρατηγικής, μας έδωσε την δυνατότητα να διερευνήσουμε και να κατανοήσουμε σε βάθος τις δυσλειτουργικές σκέψεις και τα δυσθυμικά συναισθήματα, τα οποία οδηγούν σε αναποφασιστικότητα σχετικά με την ανάπτυξη σταδιοδρομίας. Το ερευνητικό υποκείμενο, στην αρχή της ενηλικιότητας, ενώ είχε φτάσει με επιτυχία σε λήψη απόφασης, δεν ακολούθησε την προεπιλεγμένη σταδιοδρομία. Η μελέτη κατέδειξε την παρουσία δυσλειτουργικών σκέψεων και δυσθυμικών συναισθημάτων, τα οποία δεν σχετίζονταν με την έλλειψη πληροφόρησης ή την απουσία δομής και εμπιστοσύνης αλλά με προσωπικές συγκρούσεις, στην προσπάθεια συμβιβασμού και ταυτόχρονης ικανοποίησης των προσωπικών προτιμήσεων και των δυσλειτουργικών πεποιθήσεων για την επιλογή σταδιοδρομίας. Η παρούσα μελέτη παρουσιάζει ιδιαίτερο ενδιαφέρον, καταδεικνύοντας ότι τα γεγονότα ζωής και οι τραυματικές εμπειρίες επηρεάζουν σε σημαντικό βαθμό την επαγγελματική αναποφασιστικότητα, επιδρώντας τόσο σε γνωστικό όσο και σε συναισθηματικό επίπεδο. Επιπρόσθετα, η συγκαιρινή οικονομιοκοινωνική πραγματικότητα ενισχύει τις δυσλειτουργικές σκέψεις, οι οποίες αφορούν στον εαυτό, στον εξωτερικό κόσμο και στο μέλλον. Τα δυσθυμικά συναισθήματα, όπως θλίψη, απαισιοδοξία, θυμός, άγχος, αίσθημα αποτυχίας, απώλεια ικανοποίησης και απουσία νοήματος, αποβαίνουν δυσλειτουργικά, όταν παρεμβαίνουν στην ικανότητα του ατόμου να επιλύει προβλήματα, να προβαίνει σε λήψη αποφάσεων και να δρα αποτελεσματικά. Η διερεύνηση των γνωστικών και συναισθηματικών παραγόντων σχετικά με την επαγγελματική αναποφασιστικότητα των νέων, αποσκοπεί στον εμπλουτισμό των θεωριών συμβουλευτικής και στην βελτίωση των παρεχόμενων συμβουλευτικών παρεμβάσων. Ωστόσο, απαιτείται περαιτέρω θεωρητικά στηριγμένη έρευνα για την πλήρη κατανόηση της επαγγελματικής αναποφασιστικότητας. / Career counselling and development is of considerable interest in terms of research, which focuses on the study of the factors which hinder successful decision-making. Taking into consideration the complex interaction between thoughts, feelings, decisions and action, in the present study we investigated the relationship between dysfunctional career thoughts and negative feelings and career indecision. Postmodernism and Constructivism have given us the clear advantage of being able to make use of qualitative methodological approaches in our study in order to investigate the visible but mainly the latent internal processes, both mental and emotional, which interact and affect the procedure of career decision-making. As a method of research we selected the case study of an isolated individual, during the course of counselling activities. The triangulation of a number of methodological tools constituted a powerful means of implementing simultaneous validity. The only example of a real person as the focus of a research strategy enabled us to explore and comprehend in depth the dysfunctional thoughts and negative feelings which lead to indecision in relation to career development. The subject of the research, at the outset of adulthood, while having successfully reached a career decision, did not follow the chosen career. The study clearly demonstrated the presence of dysfunctional thoughts and negative feelings, which were not related to a lack of information or a lack of structure or confidence, but to personal conflicts, in an attempt to reconcile and simultaneously satisfy personal preferences and dysfunctional beliefs concerning the choice of career. The present study is of particular interest, since it clearly demonstrates that the events of life and traumatic experiences influence career indecision to a great extent, with consequences both on cognitive and emotional levels. In addition, the contemporary socio-economic reality intensifies dysfunctional thoughts which concern the self, the internal world and the future. Negative feelings, such as sadness, pessimism, anger, stress, a sense of failure, lack of satisfaction and lack of meaning, prove to be dysfunctional when they interfere with the individual’s ability to resolve problems to take a decision and to act effectively. The investigation of cognitive and emotional factors in relation to career indecision among young people aims to enrich counselling theory and improve the counselling which is offered. Nevertheless, further theoretically supported research is required so as to achieve a full understanding of career indecision.
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Θεωρητική και πειραματική μελέτη της απόκρισης ζεολίθων σε μεταβολές θερμοκρασίας, πίεσης και συγκέντρωσης ροφημένων ουσιώνΚροκιδάς, Παναγιώτης 10 May 2012 (has links)
Οι ζεόλιθοι ανήκουν στα νανοπορώδη υλικά ή αλλιώς και μοριακά κόσκινα. Βρίσκουν δε εφαρμογή σε πληθώρα εφαρμογών, καλύπτοντας ένα μεγάλο θερμοκρασιακό φάσμα. Η γνώση της απόκρισής τους κατά τις μεταβολές της θερμοκρασίας είναι καθοριστικής σημασίας για την αποδοτικότητά τους, ακόμα περισσότερο όταν εμφανίζονται ανώμαλα φαινόμενα, όπως αρνητικός συντελεστής θερμικής διαστολής. Η παρούσα εργασία επικεντρώνεται στην ερμηνεία αυτού του φαινομένου με την χρήση προσομοιώσεων και πειραμάτων σκέδασης ακτίνων Χ. Ένα νέο πεδίο δυνάμεων αναπτύχθηκε και χρησιμοποιήθηκε σε προσομοιώσεις δυναμικής πλέγματος, όπου για πρώτη φορά προβλέπεται η συστολή της μοναδιαίας κυψελίδας του σιλικαλίτη, όπως και η διαστολή της μοναδιαίας κυψελίδας του αργιλοπυριτικού φωγιασίτη (NaX) πάνω από την θερμοκρασία δωματίου. Περαιτέρω ανάλυση των αποτελεσμάτων δείχνει πως υπεύθυνες για την συστολή κατά την θέρμανση είναι οι περιστροφές των τετραέδρων SiO4 και AlO4 από τα οποία απαρτίζεται η δομή. Αυτό το αποτέλεσμα είναι σύμφωνο με τον μηχανισμό των περιστροφών άκαμπτων μονάδων που προτείνεται στην βιβλιογραφία (R.U.M.). Στη συνέχεια υπολογίζονται μηχανικές ιδιότητες του υλικού, όπως το μέτρο Young και το μέτρο ελαστικότητας όγκου. Τέλος μελετήθηκε η απόκριση της δομής των ζεολίθων σε ερεθίσματα πέραν της θερμοκρασίας, όπως μεταβολή πίεσης και ρόφηση μορίων. Χαρακτηριστικά καταλήγουμε πως η δομή αποκρίνεται στην άσκηση της πίεσης μέσω του ίδιου μηχανισμού που καθορίζει της θερμοκρασιακή της απόκριση, δηλαδή τις περιστροφές των άκαμπτων ή σχεδόν άκαμπτων τετραέδρων. Επίσης, σε ό, τι αφορά την επίδραση της ρόφησης, η παρουσία των μορίων εξανίου, παρόλο επιφέρει δομικές αλλαγές που βελτιώνουν την αποδοτικότητα των ζεολιθικών μεμβρανών, αυτές οι αλλαγές δεν επηρεάζουν τις ροφητικές ιδιότητες στο εσωτερικό του κρυστάλλου. / Zeolites are nanoporous materials, otherwise called molecular sieves. The knowledge of the response of a zeolite structure to temperature changes or to the presence of host molecules in the pore system is of critical significance for the performance of zeolites as molecular sieves, especially if they are prepared in the form of membranes. Crack formation or grain boundary openings may appear between the substrate and the membrane due to a mismatch between the thermal expansion coefficient of the two materials, affecting the sorption and selectivity properties of the membrane. The problem is enhanced when the zeolite shows negative thermal expansion coefficient. The present work focuses in the mechanism that lies behind contraction upon heating, with the use of simulations and powder XRD experiments. A new force field was developed and was implemented in lattice dynamics simulations. It’s the first time that simulations predict the contraction of silicalite unit cell as well as the expansion of aluminosilicate faujasite (NaX) unit cell above room temperature. Further analysis of the simulation data shows that the Rigid Unit Mode (R.U.M.) mechanism that is proposed in the literature is the dominant mechanism of thermal contraction of the zeolite. Furthermore, mechanical properties such as Young modulus and bulk modulus were computed with the use of the newly derived force field. Finally, the response of framework upon pressure change and sorption of molecules was investigated. The zeolite structure response upon pressure change is similar to this of the temperature response, meaning that the volume and atomic positions change with the help of the rotations of the rigid AlO2/SiO2 tetrahedra. Concerning the response upon sorption, is was found with the help of theoretical calculations that although unit cell size variations that are induced by temperature changes and/or sorption may affect the efficiency of silicalite-1 membrane performance through alteration of the size of the non-zeolitic pores, such changes appear to affect negligibly the bulk sorption capacity of the silicalite-1 crystals.
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Uso de detectores de dimensões variáveis aplicados na detecção de anomalias através de sistemas imunológicos artificiais. / Use of varying lengths implemented in detecting anomalies by artificial immunological detection systems.Daniel dos Santos Morim 15 July 2009 (has links)
O presente trabalho investiga um método de detecção de anomalias baseado em
sistemas imunológicos artificiais, especificamente em uma técnica de reconhecimento
próprio/não-próprio chamada algoritmo de seleção negativa (NSA). Foi utilizado um esquema
de representação baseado em hiperesferas com centros e raios variáveis e um modelo capaz de
gerar detectores, com esta representação, de forma eficiente. Tal modelo utiliza algoritmos
genéticos onde cada gene do cromossomo contém um índice para um ponto de uma
distribuição quasi-aleatória que servirá como centro do detector e uma função decodificadora
responsável por determinar os raios apropriados. A aptidão do cromossomo é dada por uma
estimativa do volume coberto através uma integral de Monte Carlo. Este algoritmo teve seu
desempenho verificado em diferentes dimensões e suas limitações levantadas. Com isso,
pode-se focar as melhorias no algoritmo, feitas através da implementação de operadores
genéticos mais adequados para a representação utilizada, de técnicas de redução do número de
pontos do conjunto próprio e de um método de pré-processamento baseado em bitmaps de
séries temporais. Avaliações com dados sintéticos e experimentos com dados reais
demonstram o bom desempenho do algoritmo proposto e a diminuição do tempo de execução. / This work investigates a novel detection method based on Artificial Immune Systems,
specifically on a self/non-self recognition technique called negative selection algorithm
(NSA). A representation scheme based on hyperspheres with variable center and radius and a
model that is able to generate detectors, based on that representation scheme, have been used.
This model employs Genetic Algorithms where each chromosome gene represents an index to
a point in a quasi-random distribution, which serves as a detector center, and a decoder
function that determines the appropriate radius. The chromosome fitness is given by an
estimation of the covered volume, which is calculated through a Monte Carlo integral. This
algorithm had its performance evaluated for different dimensions, and more suitable genetic
operators for the used representation, techniques of reducing self-points number and a preprocessing
method based on bitmap time series have been therefore implemented. Evaluations
with synthetic data and experiments with real data demonstrate the performance of the
proposed algorithm and the decrease in execution time.
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La dynamique du momentum psychologique en sport / The dynamics of psychological momentum in sportBriki, Walid 11 October 2012 (has links)
L'objet de la présente thèse était d'examiner les caractéristiques de complexité et de dynamique du momentum psychologique (MP) en sport. Une première série d'études a tenté d'explorer qualitativement (étude 1) et quantitativement (études 2, 3 et 4) ces caractéristiques en situations naturelles de compétitions sportives. L'étude 1 a mis en évidence la richesse des contenus du MP, la diversité de ses mécanismes de déclenchement (dissonance, consonance, perturbation du flux de pensées), ainsi que ses formes de développement au cours du temps (processus d'amplification). Ces résultats témoignent de l'enracinement du MP dans une histoire d'événements signifiante. Les études 2, 3 et 4 ont montré que certains contenus affectifs du MP, tels que l'anxiété compétitive et la confiance en soi, peuvent subir des changements abrupts au cours des phases de MP, ce qui suggère le caractère non linéaire du phénomène. Par conséquent, une seconde série d'études (études 5, 6, 7 et 8) a ensuite été réalisée afin de tester expérimentalement les propriétés potentielles de non linéarité et de dépendance à l'histoire du MP en adoptant l'approche des systèmes dynamiques. Ces études étaient basées sur des scénarios de performance de prise d'ascendant (momentum positif) ou de décrochage (momentum négatif) impliquant des situations d'acteur en position virtuelle (études 5 et 6) ou réelle (étude 7), ou encore des situations de spectateur (étude 8). Le MP est apparu évoluer sous la forme d'un patron d'hystérésis négative (études 5, 6 et 8) ou d'un patron de limite critique décalée (étude 7) dans le sens où le MP négatif se déclenchait plus rapidement que le MP positif. L'hystérésis négative observée chez les spectateurs (étude 8) présentait, quant à elle, une asymétrie évoquant un déclenchement plus rapide du MP positif. Ces résultats attestent des propriétés de non linéarité et de dépendance à l'histoire du MP, montrent l'influence du degré d'implication dans la situation sur sa dynamique et confirment l'hypothèse générale selon laquelle le MP est un phénomène complexe et dynamique. / The present thesis aimed to examine the characteristics of complexity and dynamics of psychological momentum (PM) in sport. A first series of studies attempted to explore qualitatively (Study 1) and quantitatively (Studies 2, 3, and 4) these characteristics in natural situations of sport competition. Study 1 evidenced the richness of PM contents, its mechanisms of emergence (dissonance, consonance, and thought flow disturbance), as well as its forms of development over time (amplification processes). These findings suggest that PM is rooted in a meaningful history of events. Studies 2, 3, and 4 showed that certain affective contents, such as competitive anxiety and self-confidence, can change abruptly during PM phases, which suggests the nonlinear character of PM. Consequently, a second series of studies (Studies 5, 6, 7, and 8) was then conducted in order to experimentally test the potential properties of non linearity and history-dependence of PM through the lens of the dynamical systems approach. These studies were based on ascending (positive momentum) versus descending (negative momentum) scenarios of performance that were virtually (Studies 5 and 6) or actually (Study 7) experienced by actors, or that were seen from the point of view of a spectator (Study 8). Variations of PM displayed patterns of negative hysteresis (Studies 5, 6, and 8) and critical boundary that was lagged so that negative PM was triggered faster than positive PM. The negative hysteresis that was found among spectators (Study 8) displayed an asymmetry that reflected a faster triggering for positive PM. These findings evidence the properties of non linearity and history-dependence of PM, show the influence of the degree of involvement in the situation on PM dynamics, and support the general hypothesis that PM is a complex and dynamical phenomenon.
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Embolie dans les plantes : dynamique de l'invasion d'air dans des réseaux hydrauliques naturels et artificiels sous pression négative / Embolism in plants : dynamics of air invasion in natural and artificial hydraulic networks under negative pressureBienaime, Diane 07 October 2016 (has links)
Pour assurer le transport de la sève des racines vers les feuilles, les plantes vasculaires génèrent de très fortes dépressions dans le liquide, pouvant atteindre -200 bar, au niveau des feuilles. Cette dépression « tire » sur la colonne d'eau contenue dans l'appareil vasculaire de l'arbre. La cohésion de l'eau maintient la sève sous forme liquide. Cet état métastable peut se rompre : des bulles de cavitation apparaissent. Elles créent un « bouchon » d'air dans le réseau hydraulique de la plante et gênent la circulation de la sève. C'est ce que l'on appele l'embolie. Si ce phénomène se généralise, il peut provoquer la mort de la plante.Ce travail de thèse est consacré à 'invasion d'air dans des réseaux hydrauliques naturels ou artificiels initialement à pression négative. Nous avons d'abord étudié l'embolie dans les feuilles. Nous avons développé une technique novatrice permettant de relever la propagation spatiale de l'embolie dans le réseau hydraulique des feuilles. Nous montrons que l'embolie, quelque soit l'espèce, se propage par à-coups des plus grosses nervures aux plus petites.Afin de comprendre les lois physiques sous-jacentes, nous utilisons deux systèmes modèles. Nous réalisons d'abord des réseaux artificiels dans un hydrogel reproduisant les caractéristiques de la circulation de la sève ascendante. Après la relaxation de la tension dans le réseau par l'apparition de la bulle, nous observons des oscillations de surface et une croissance lente de la bulle, liée à l'évacuation de l'eau à travers l'hydrogel. Cette croissance peut atteindre un régime quasi-stationnaire. Ce systèmes ne nous permettant pas de reproduire toutes les caractéristiques géométriques du xylème, nous présentons une modélisation informatique reposant sur l'analogie entre réseaux hydrauliques et électrocinétique. Nous reproduisons les caractéristiques du xylème dans lequel circule la sève : les éléments conducteurs sont reliées par les ponctuations, des valves protégeant la plante de l'embolie. Nous retrouvons les à-coups caractéristiques de la propagation de l'embolie dans les feuilles.Enfin, nous discutons l'application des résultats précèdents dans le cas du bois et nous présentons quelques résultats obtenus sur du pin sylvestre. / To assure the transport from the roots to the leaves, vascular plants create strong depressions in the sap, next to -200 bars. This depression pulls the water column contained by the tree vascular system. The water cohesion keeps the sap under liquid state. This metastable state can breaks: cavitation bubbles appear. They create an air plug inside the plant hydraulic network and impede sap flow. This phenomena called embolism could lead to the plant death by preventing the sap transport.This thesis is dedicated to the air invasion into hydraulics networks under negative pressure. First, we study the leaf embolism. We developed a new technique which allows us to record the spatial propagation of embolism in leaves hydraulic network. We show that the embolism propagates by steps from biggest veins to smallest veins.Next, in order to understand the underlying physical laws, we use two model systems. We build artificial networks in a hydrogel which mimics the sap flow characteristics. After the relaxation of the negative pressure in the network by the nucleation of a bubble, we observe surface oscillations and the slow growth of the bubble. This growth is linked to the water transport through the hydrogel and can reach a stationary regime.As we are not able to reproduce all the characteristics of the leaf network with the hydrogel, we create a computer modeling based on the Ohm analogy between hydraulics networks and electrical circuits. We reproduce the specific features of the xylem which transport the sap: the conduits are linked by pits, small valves which limit the progression of the embolism. We were able to recover the distinctiveness steps in embolism.Finally, we discuss the application of the preceding results to wood and we present some results on Pinus sylvestris.
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An approach for analyzing and classifying microarray data using gene co-expression networks cycles / Uma abordagem para analisar e classificar dados microarrays usando ciclos de redes de co-expressão gênicaDillenburg, Fabiane Cristine January 2017 (has links)
Uma das principais áreas de pesquisa em Biologia de Sistemas refere-se à descoberta de redes biológicas a partir de conjuntos de dados de microarrays. Estas redes consistem de um grande número de genes cujos níveis de expressão afetam os outros genes de vários modos. Nesta tese, apresenta-se uma nova maneira de analisar os conjuntos de dados de microarrays, com base nos diferentes tipos de ciclos encontrados entre os genes das redes de co-expressão construídas com dados quantificados obtidos a partir dos microarrays. A entrada do método de análise é formada pelos dados brutos, um conjunto de genes de interesse (por exemplo, genes de uma via conhecida) e uma função (ativador ou inibidor) destes genes. A saída do método é um conjunto de ciclos. Um ciclo é um caminho fechado com todos os vértices (exceto o primeiro e o último) distintos. Graças à nova forma de encontrar relações entre os genes, é possível uma interpretação mais robusta das correlações dos genes, porque os ciclos estão associados a mecanismos de feedback, que são muito comuns em redes biológicas. A hipótese é que feedbacks negativos permitem encontrar relações entre os genes que podem ajudar a explicar a estabilidade do processo regulatório dentro da célula. Ciclos de feedback positivo, por outro lado, podem mostrar a quantidade de desequilíbrio de uma determinada célula em um determinado momento. A análise baseada em ciclos permite identificar a relação estequiométrica entre os genes da rede. Esta metodologia proporciona uma melhor compreensão da biologia do tumor. Portanto, as principais contribuições desta tese são: (i) um novo método de análise baseada em ciclos; (ii) um novo método de classificação; (iii) e, finalmente, aplicação dos métodos e a obtenção de resultados práticos. A metodologia proposta foi utilizada para analisar os genes de quatro redes fortemente relacionadas com o câncer - apoptose, glicólise, ciclo celular e NF B - em tecidos do tipo mais agressivo de tumor cerebral (Gliobastoma multiforme - GBM) e em tecidos cerebrais saudáveis. A maioria dos pacientes com GBM morrem em menos de um ano, essencialmente nenhum paciente tem sobrevivência a longo prazo, por isso estes tumores têm atraído atenção significativa. Os principais resultados nesta tese mostram que a relação estequiométrica entre genes envolvidos na apoptose, glicólise, ciclo celular e NF B está desequilibrada em amostras de GBM em comparação as amostras de controle. Este desequilíbrio pode ser medido e explicado pela identificação de um percentual maior de ciclos positivos nas redes das primeiras amostras. Esta conclusão ajuda a entender mais sobre a biologia deste tipo de tumor. O método de classificação baseado no ciclo proposto obteve as mesmas métricas de desempenho como uma rede neural, um método clássico de classificação. No entanto, o método proposto tem uma vantagem significativa em relação às redes neurais. O método de classificação proposto não só classifica as amostras, fornecendo diagnóstico, mas também explica porque as amostras foram classificadas de uma certa maneira em termos dos mecanismos de feedback que estão presentes/ausentes. Desta forma, o método fornece dicas para bioquímicos sobre possíveis experiências laboratoriais, bem como sobre potenciais genes alvo de terapias. / One of the main research areas in Systems Biology concerns the discovery of biological networks from microarray datasets. These networks consist of a great number of genes whose expression levels affect each other in various ways. We present a new way of analyzing microarray datasets, based on the different kind of cycles found among genes of the co-expression networks constructed using quantized data obtained from the microarrays. The input of the analysis method is formed by raw data, a set of interest genes (for example, genes from a known pathway) and a function (activator or inhibitor) of these genes. The output of the method is a set of cycles. A cycle is a closed walk, in which all vertices (except the first and last) are distinct. Thanks to the new way of finding relations among genes, a more robust interpretation of gene correlations is possible, because cycles are associated with feedback mechanisms that are very common in biological networks. Our hypothesis is that negative feedbacks allow finding relations among genes that may help explaining the stability of the regulatory process within the cell. Positive feedback cycles, on the other hand, may show the amount of imbalance of a certain cell in a given time. The cycle-based analysis allows identifying the stoichiometric relationship between the genes of the network. This methodology provides a better understanding of the biology of tumors. As a consequence, it may enable the development of more effective treatment therapies. Furthermore, cycles help differentiate, measure and explain the phenomena identified in healthy and diseased tissues. Cycles may also be used as a new method for classification of samples of a microarray (cancer diagnosis). Compared to other classification methods, cycle-based classification provides a richer explanation of the proposed classification, that can give hints on the possible therapies. Therefore, the main contributions of this thesis are: (i) a new cycle-based analysis method; (ii) a new microarray samples classification method; (iii) and, finally, application and achievement of practical results. We use the proposed methodology to analyze the genes of four networks closely related with cancer - apoptosis, glucolysis, cell cycle and NF B - in tissues of the most aggressive type of brain tumor (Gliobastoma multiforme – GBM) and in healthy tissues. Because most patients with GBMs die in less than a year, and essentially no patient has long-term survival, these tumors have drawn significant attention. Our main results show that the stoichiometric relationship between genes involved in apoptosis, glucolysis, cell cycle and NF B pathways is unbalanced in GBM samples versus control samples. This dysregulation can be measured and explained by the identification of a higher percentage of positive cycles in these networks. This conclusion helps to understand more about the biology of this tumor type. The proposed cycle-based classification method achieved the same performance metrics as a neural network, a classical classification method. However, our method has a significant advantage with respect to neural networks. The proposed classification method not only classifies samples, providing diagnosis, but also explains why samples were classified in a certain way in terms of the feedback mechanisms that are present/absent. This way, the method provides hints to biochemists about possible laboratory experiments, as well as on potential drug target genes.
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