Myosins are molecular motor proteins involved in cell movement, vesicle and organelle transport by moving along the cytoskeletal actin filaments. They include a myosin heavy chain and at least one myosin light chain (LC). The latter are typically bilobal proteins like calmodulin, where each lobe comprises a pair of EF-hand Ca2+-binding motifs. The LCs bind to ~25-residue IQ motifs that loosely conform to an IQXXXRGXXXR consensus sequence, and impart rigidity that is crucial for myosin function. The highly motile amoeba Dictyostelium discoideum expresses seven class I myosins, two of which (MyoD and MyoB) recruit the specific LCs MlcD and MlcB, with MlcB being the first observed single-lobe LC. However, the LCs for the remaining D. discoideum class I myosins are unknown. Identifying and characterizing these LCs is one focus of this thesis, with an overall goal of understanding their role in myosin function and regulation. Nuclear magnetic resonance spectroscopy, site-directed mutagenesis, and computational modeling were used to determine the solution structure of apo-MlcB and identify the MyoB IQ motif-binding site. Apo-MlcB differs from the typical closed conformation of an EF-hand Ca2+-binding protein in the apo-state as helix 1 in its structure is splayed from the remaining helices. The MyoB IQ motif-binding surface is not altered by Ca2+, involves residues from helices 1 and 4, and from residues in the N-terminal canonical EF-hand Ca2+-binding loop, and represents a unique mode of IQ recognition by a myosin LC. Calmodulin was identified as the LC for MyoA and MyoE while another single-lobe LC, MlcC, bound to two of three IQ motifs in MyoC. The solution structure of MlcC was more similar to the C-terminal lobe of apo-calmodulin than to apo-MlcB. Chemical shift perturbation studies suggest that like apo-CaM, MlcC undergoes a global MyoC IQ motif-induced conformational change. Computational modeling of the MlcC-MyoC IQ complex indicates that this is a feasible mode of IQ recognition. The structures of MlcB and MlcC, with their different modes of IQ motif binding, provide novel insights into IQ motif binding specificity and begin to illustrate their role in myosin function and regulation. / Thesis (Ph.D, Biochemistry) -- Queen's University, 2013-01-29 11:42:03.428

The major purpose of this thesis is to present a discussion of the motif of the faithful wife as it appears in the domestic drama of the Elizabethan Age; in addition, an account of the literary history of the theme will be given, in order that the use made of the story in Elizabethan drama may be correctly evaluated.

The present study examines the pictorial style of pottery made in Thera and Crete in the LCI/LMIA period. The work is in two volumes. Volume I is divided into three parts. Part I comprises the introductory chapter in which there is a summary of previous research on the subject and the aims of the thesis are set out. Chapter II the context of the pictorial style of pottery is examined. Chapter III contains analysis of the forms of vases with pictorial decoration. Part II includes three chapters dealing with the Analysis of Motifs. The plants are analysed in Chapter IV, the living creatures in Chapter V and the sacred symbols in Chapter VI. Part III comprises the Synthesis. In Chapter VII an attempt is made to identify pottery workshops specializing in different vase forms and decoration. Chapter VIII examines the origin and character of the pictorial style of pottery in the Cyclades and Crete. Finally in the last Chapter IX, conclusions regarding the character, context, forms and motifs, workshops and development of the pictorial style pottery are presented. A possible ritual function of the pottery is discussed. Interrelations and influences between the cultures Of Thera and Crete on various Levels are demonstrated. Volume II contains a Catalogue Of the available pottery, presented in two groups: the first from Thera and the second from Crete. The illustrations — figures and photographic plates — come at the end of Volume II.

I present a novel method for the unsupervised discovery of behavioural motifs in larval Drosophila melanogaster and Caenorhabditis elegans. Most current approaches to behavioural annotation suffer from the requirement of training data. As a result, automated programs carry the same observational biases as the humans who have annotated the data. The key novel element of my work is that it does not require training data; rather, behavioural motifs are discovered from the data itself. The method is based on an eigenshape representation of posture. Hence, my approach is called the eigenshape annotator (ESA). First, I examine the annotation consistency for a specific behaviour, the Omega turn of C. elegans, and find significant inconsistency in both expert annotation and the various Omega turn detection algorithms. This finding highlights the need for unbiased tools to study behaviour. A behavioural motif is defined as a particular sequence of postures that recurs frequently. In ESA, posture is represented by an eigenshape time series, and motifs are discovered in this representation. To find motifs, the time series is segmented, and the resulting segments are then clustered. The result is a set of self-similar time series segments, i.e. motifs. The advantage of this novel framework over the popular sliding windows approaches is twofold. First, it does not rely on the ‘closest neighbours’ definition of motifs, by which every motif has exactly two instances. Second, it does not require the assumption of exactly equal length for motifs of the same class. Behavioural motifs discovered using the segmentation-clustering framework are used as the basis of the ESA annotator. ESA is fully probabilistic, therefore avoiding rigid threshold values and allowing classification uncertainty to be quantified. I apply eigenshape annotation to both larval Drosophila and C. elegans, and produce a close match to hand annotation of behavioural states. However, many behavioural events cannot be unambiguously classified. By comparing the results to eigenshape annotation of an artificial agent’s behaviour, I argue that the ambiguity is due to greater continuity between behavioural states than is generally assumed for these organisms.

La recherche de motifs approchée consiste à identifier les occurrences d’un motif modulo une certaine distance au sein d’un texte. Ce problème trouve de nombreuses applications en bio-informatique pour l’analyse de séquences biologiques. Par exemple, les microARN sont des petits ARN qui régulent l’expression des gènes par reconnaissance d’un motif similaire. Comprendre le mode d’action des microARN demande de pouvoir localiser de courts motifs, environ 21 nucléotides, comprenant jusqu’à 3 ou 4 erreurs dans un texte de l’ordre de 108 à 109 nucléotides, représentant un génome. Dans cette thèse, nous proposons un algorithme efficace pour la recherche de motifs approchée, qui se base sur la définition d’un nouveau type de graines avec erreurs, les graines 01*0, et qui exploite une structure d’index compressée, le FM-index. Cet algorithme a été mis en œuvre dans un logiciel librement disponible, appelé Bwolo. Nous démontrons expérimentalement l’avantage de cette approche en nous comparant à l’état de l’art des outils existants. Nous montrons également comment utiliser Bwolo pour mettre en place une analyse originale sur l’étude de la distribution des cibles potentielles de miARN dans deux génomes de plantes, Arabidopsis thaliana et Arabidopsis lyrata. / Approximate string matching consists in identifying the occurrences of a motif within a text, modulo a given distance. This problem has many applications in bioinformatics for the analysis of biological sequences. For instance, microRNAs are short RNA molecules regulating the expression of genes by specific recognition of their sequence motif on the target gene. Understanding the mode of action of microRNAs requires the ability to identify short motifs, around 21 nucleotides in size, comprising up to 3-4 errors in a text whose size is in the order of 108-109 , representing a genome. In this thesis, I have proposed an efficient algorithm for the approximate search of short motifs. This algorithm is based on a new type of seeds containing errors, the 01*0 seeds, and uses a compressed index structure, the FM-index. I have implemented this algorithm in a freely available software, Bwolo. I demonstrate experimentally the advantage of this approach and compare it to the state of the art of existing tools. I also show how Bwolo can be used and have set up an original study on the distribution of potential miRNA target sites in two plant genomes, Arabidopsis thaliana and Arabidopsis lyrata.

La recherche d'occurrences de gènes d'ARN dans les séquences<br /> génomiques est un problème dont l'importance est renouvelée par la<br /> découverte récente de très nombreux ARN fonctionnels, opérant<br /> souvent en interaction avec d'autres molécules.<br /><br />Le formalisme des réseaux de contraintes est approprié à cette problématique aussi bien sur le plan de la modélisation que sur les développements algorithmiques qu'il permet de proposer. <br /><br /> Après une analyse et une comparaison des outils existants plongés dans le cadre des réseaux de contraintes, nous<br /> montrons comment l'utilisation conjointe des réseaux de contraintes,<br /> des techniques de résolution associées et des algorithmes et<br /> structures de données du "pattern matching" permet de modéliser et de<br /> rechercher efficacement des motifs structurés en interaction (faisant<br /> intervenir plusieurs textes génomiques simultanément).

Dans cette thèse, je relie la théorie, plutôt arithmétique, des modules de cycles de M.Rost à la théorie plus géométrique des faisceaux avec transferts invariants par homotopie de V.Voevodsky. Je montre précisément que cette dernière catégorie est une localisation de la catégorie des modules de cycles. De plus, en s'inspirant de la construction des spectres de la topologie algébrique, j'introduit la notion de module homotopique avec transferts à partir des faisceaux invariants par homotopie avec transferts. La catégorie formée par ces modules est équivalente à la catégorie des modules de cycles, prolongeant ainsi l'affirmation concernant les faisceaux homotopiques. Ceci me permet de redémontrer à l'aide des résultats de M.Rost que les faisceaux invariants par homotopie avec transferts ont une cohomologie invariante par homotopie, résultat déjà obtenu par V.Voevodsky. Par ailleurs, j'en déduis que la catégorie des modules de cycles est abélienne de Grothendieck, et munie d'une structure monoïdale telle que la K-théorie de Milnor est l'élément neutre. Par ailleurs, nous montrons comment les techniques employées se prolongent à la catégorie des motifs, obtenant ainsi des formules qui mettent en jeu les triangles de Gysin. On donne ainsi un lemme qui permet d'interpréter géométriquement la ramification au sens des anneaux de valuations discrètes d'égales caractéristiques. Le travail s'achève sur la définition de certains pro-motifs baptisés motifs génériques. Ce sont des pro-objets de la catégorie dérivée des motifs mixtes, associés à des extensions de type fini du corps de base (supposé parfait). On considère aussi que ces motifs peuvent être "twistés" par le motif Z(1)[1] ou une de ses puissances par un entier relatif n quelconque. De manière surprenante, chacune des données des pré-modules de cycles a en fait son analogue en tant que morphisme de motifs génériques. Et par ailleurs, les relations structurales sur les données des pré-modules de cycles sont vraies dans la catégorie des motifs génériques, réalisant ainsi l'incarnation géométrique des axiomes plutôt arithmétiques des pré-modules de cycles.

Thesis (Ph. D.)--University of Texas at Austin, 2000. / Vita. Includes bibliographical references (leaves 151-164). Available also in a digital version from Dissertation Abstracts.

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Thesis (Ph. D.)--University of Hong Kong, 2007. / Title proper from title frame. Also available in printed format.