The molecular mechanisms that coordinate postnatal brain enlargement, synaptic properties and cognition remain an enigma. This study demonstrates that neuronal complexity controlled by p21-activated kinases (PAKs) is a key determinant for postnatal brain enlargement and synaptic properties. Double knockout (DK) mice lacking both PAK1 and PAK3 were severely impaired in postnatal brain growth, resulting in a dramatic reduction in brain volume at maturity. Remarkably, the reduced brain was accompanied by minimal changes in total cell count, due to a significant increase in cell density. However, the DK neurons have smaller soma, markedly simplified dendritic arbors/axons and reduced synapse density. Surprisingly, the DK mice were elevated in basal synaptic responses due to enhanced individual synaptic potency, but severely impaired in bi-directional synaptic plasticity. The PAK1/3 action is likely mediated by cofilin-dependent actin regulation because the activity of cofilin and the properties of actin filaments were specifically altered in the DK mice.

Thesis (Ph.D.)--Case Western Reserve University, 2009 / Title from PDF (viewed on 30 July 2009) Department of Organizational Behavior Includes abstract Includes bibliographical references Available online via the OhioLINK ETD Center

Thesis (Ph. D.)--Division of Geography, School of Geosciences, Faculty of Science, University of Sydney, 2006. / Title from title screen (viewed 15 January 2009). Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the School of Geosciences, Faculty of Science. Includes bibliographical references. Also available in print form.

TESIS PARA OPTAR AL GRADO DE MAGÍSTER EN MARKETING / Singh, Daljit [Parte I], Burillo, Michelle [Parte II] / Como trabajo final para optar por el grado de Magister en Marketing, hemos decidido realizar un Plan de Marketing para la marca Del Monte® en el mercado panameño, específicamente para el Maíz en Grano en formato Tetra Pak®, debido a la importancia que tiene la marca en esta categoría y línea de producto. En los últimos años, Del Monte® ha sufrido de escasez de varios productos procedentes de las plantas ubicadas en Estados Unidos de América, entre ellos el maíz en grano. Considerando estos factores, se desarrolló un plan para importar al mercado panameño, maíz en grano procedente de plantas de producción de Del Monte® en otras regiones, que tuvieran un diferenciador importante para el consumidor y de esta forma, desarrollar la línea. Por otro lado, la categoría de vegetales enlatados, tiene poco apoyo por parte de la mayoría de las marcas, lo que hace que las consumidoras no realicen el valor o beneficios del producto que están comprando y la versatilidad que muchos de estos productos tienen. De igual forma, la falta de dinamismo por parte de las marcas, al no innovar o renovar empaques, nuevas referencias o líneas de producto; hacen que sea más difícil crear ese compromiso entre una marca y el consumidor. Tomando en cuenta que el maíz en grano es un producto cotidiano y a la vez muy versátil, con potencial para crear contenido dinámico y de utilidad para sus consumidoras; y que la propuesta diferenciadora de Del Monte®, no ha tenido una exposición adecuada que le permita tener un crecimiento en la categoría, creemos oportuno aprovechar la oportunidad para presentar un plan que permita crear conocimiento del producto para desarrollar la línea en un corto a mediano plazo. Como líderes de la categoría, Del Monte®, debe mantenerse a la vanguardia y realizar cambios en el comportamiento de la categoría que le permitan captar la atención del target, buscando siempre ser ese aliado dinámico que les brinde solución en el momento de preparar la comida para la familia.

The significance in Jung-Sun Park's Arirang Mass is the discovery of artistic value in folk song and its applicability to art music. By using fragments of the Arirang folk songs, or by imitating its musical character, composer could create and develop musical characteristics that are recognizably Korean. The work exhibits his remarkable compositional style, which shows a relationship between Korean traditional style and Western style. This analysis demonstrates specific examples of the elements of Korean traditional folksong, such as Sikimsae, Jangdan, Han, and pentatonic scales which are permeated into this mass setting, and how composer uses fragments of the Arirang tune.

Biomimetic tactile sensing was previously mostly performed in medical situations, such as when locating tumors in patients’ bodies. This thesis examined the effectiveness of using a biomimetic tactile sensory equipment for examining pressure distribution throughout carton board packages, made in two different carton board qualities. The purpose was to examine to what extent biomimetic tactile sensing was able to mimic the results of a group of human test subjects evaluations. Eight packages, made from two different materials, were tested. There were four packages of each of the materials. Each package had four points where displacement measurements with a force of 6N were conducted. The packages were then measured twice on a single point on the edge of the package, with the force of 12N.  The packages at disposal were compressed using a uniaxial-tensile-testing machine alongside with the aforementioned equipment. The pressure sensitive film was placed on top of the packages and a limit on the maximum force to be applied was set on the testing machine. Two limits on the applied forces were set, the first to see the distribution of pressure within the range of elastic deformation, so that no lasting deformation would have occurred. The second force limit was set to see the moment where the elastic deformation area transformed into the plastic deformation area, to see whether or not there was a difference in the distribution of pressure pre- or post-plastic deformation. From the results from compression tests, it was clear that there was a difference in pressure distribution before and after the plastic deformation had occurred. The experimental diagrams showed that the curves were vastly different in both cases. It was also clear that there was a significant difference in the distribution of pressure, depending on if the pressure was applied closer to the middle compared to closer to the center of the package (single vs multiple concentration of forces, respectively). Inspecting results from packages made in both carton board qualities, there were no clear results as the same trends could be seen throughout the tests.  It was concluded that the BioTac could be used to accurately identify concentrations of forces, differences in pressure distribution and the location of deformation. This means that the BioTac will be useful in future experiments, when objectively evaluating and defining grip stiffness, with the help of methods such as the finite-element method. / Biomimetiskt taktilt avkännande var något som tidigare mestadels utfördes för medicinala syften, såsom för att lokalisera tumörer i patienters kroppar. Detta examensarbete undersökte effektiviteten av att använda en biomimetisk taktil avkännare för att granska tryckfördelningen genom kartongförpackningar, gjorda av material från två olika kartongkvaliteter. Totalt åtta förpackningar, gjorda av två olika material, provades. Det var fyra av varje materialtyp. Varje förpackning mättes på fyra punkter med 6N och sedan två gånger på samma punkt med 12N. Förpackningarna till förfogande trycktes ihop med en enaxlad drag- och tryckprovare samt den tidigare nämnda avkännaren. En tryckkänslig film användes mellan avkännaren och förpackningen för att tydligt se tryckfördelningen på alla förpackningarna. Två gränser på den maximala tillåtna kraften upprättades i tryckmaskinen, 6N och 12N. Den lägre nivån sattes för att undersöka tryckfördelningen inom det elastiska deformationsområdet, utan att en kvarstående plastisk deformation uppstått. Den högre gränsen sattes för att undersöka skedet där det elastiska deformationsområdet övergår till det plastiska. Båda gränsvärdena valdes för att undersöka om det gick att urskilja en skillnad i tryckfördelningen innan och efter plastisk deformation, eller inte.  Från resultaten av dessa kompressionstest var det tydligt att det fanns en skillnad i tryckfördelning före och efter den plastiska deformationen uppstått. De uppställda diagrammen visade att kurvorna var mycket annorlunda i båda fallen. Det var, dessutom, relativt tydligt att det fanns en skillnad i tryckfördelning beroende av om trycket var applicerat närmre mitten av paketet jämfört med om det var applicerat närmre kanten av paketet (enskilda kraftkoncentrationer vid mitten av förpackningarna och multipla koncentrationer vid kanten av förpackningarna). Genom att undersöka resultat från förpackningar gjorda av båda kartongkvaliteter, upptäcktes ingen tydlig skillnad i förpackningarna, då liknande trender uppstod i båda materialen. Slutsatsen drogs att BioTac kunde användas för att finna kraftkoncentrationer, skillnader i tryckfördelning, samt området för deformation. Detta betyder att BioTac-sensorn kan vara nyttig vid framtida experiment, för att objektivt utvärdera och definiera greppstyvhet, med metoder som finita-element-metoden.

L'adhérence cellulaire à la matrice extracellulaire joue un rôle clé dans leur prolifération,leur différenciation ou l'apoptose. Par conséquent ce processus est critique pour undéveloppement normal et pour l'homéostasie tissulaire. La dérégulation de ce mécanismecontribue souvent à des situations pathologiques. Ainsi, la dérégulation de nombreux gènesimpliqués dans les adhérences cellule-cellule ou cellule-matrice extracellulaire sont liés à despathologies conduisant à un défaut de développement, la progression tumorale, oul'inflammation.Les intégrines sont des récepteurs transmembranaires hétéro dimériques jouant un rôlemajeur dans les interactions cellule-matrice extracellulaire. Ce rôle n'est pas limité à unesimple interaction mécanique puisqu'elles permettent également la transduction dessignaux de la matrice extracellulaire à la cellule afin de permettre à cette dernière des'adapter à son micro environnement. Dans le but d’étudier le rôle des intégrines à chaîneβ1 dans le développement osseux, le laboratoire a mis en place un modèle murind'inactivation conditionnelle du gène Itgb1 basée sur l'expression de la recombinase Cre austade pré-ostéoblastique. Les souris mutées présentent un défaut de développementosseux, dû à une faible prolifération des ostéoblastes.Contrairement à ce qui était généralement admis, cette faible prolifération desostéoblastes est indépendante de la voie classique mettant en jeu la voie classique des MAPkinases. En revanche, elle est contrôlée par la voie Hippo: cette signalisation a étérécemment identifiée chez la Drosophile et les Mammifères comme un mécanismeinhibiteur majeur de la prolifération cellulaire. Le cofacteur de transcription YAP, effecteurfinal de cette voie, est une navette nucléo-cytoplasmique. Son expression est amplifiée dansdivers cancers dont l'ostéosarcome où cette surexpression associée à celle de l’Itgb1 est unfacteur de mauvais pronostique.Mes travaux consistent à comprendre comment les intégrines à chaîne β1 contrôlent lavoie Hippo, et donc la prolifération. Nous avons confirmé que la délétion des intégrines β16active la phosphorylation de YAP et sa séquestration dans le cytoplasme. En utilisant destechniques de Biologie Cellulaire et de Biochimie, nous avons montré que suite à la délétionde l’Itgb1, les cellules présentent un défaut de trafic vésiculaire réduisant la translocationmembranaire de Rac1. La séquestration cytoplasmique de Rac1 diminue l’activation de soneffecteur majeur la kinase PAK responsable de la dissociation d'un complexe membranaired'inactivation composé de la protéine adaptatrice NF2, la kinase LATS et de son effecteurprincipal YAP. Les intégrines en provocant la perte de ce complexe induisent ladéphosphorylation de YAP, sa translocation nucléaire et donc stimulent la proliférationcellulaire. / Cell adhesion to the extracellular matrix plays a key role in their proliferation,differentiation or apoptosis. Therefore, this process is critical for normal development andtissue homeostasis. The deregulation of this mechanism often contributes to pathologicalsituations. Thus, the deregulation of many genes involved in cell-cell or cell-extracellularmatrix adhesions are linked to pathologies leading to developmental defects, tumorprogression, or inflammation.Integrins are heterodimeric transmembrane receptors that play a major role in cellextracellularmatrix interactions. This role is not limited to a simple mechanical interactionsince integrins also allow the transduction of the signals from the extracellular matrix to thecell in order to permit the latter to adapt to its microenvironment. In order to study the roleof β1 integrins in bone development, the laboratory has implemented a mouse model withconditional inactivation of the Itgb1 gene based on the expression of recombinase Cre at thepre-osteoblastic stage. The mutated mice show a defect in bone development due to a lowproliferation rate of osteoblasts.Contrary to what was generally accepted, this reduced proliferation is independent of theclassical pathway involving the classical pathway of MAP kinases. On the other hand, it iscontrolled by Hippo: this signaling pathway has recently been identified in Drosophila andMammals as a major inhibitory mechanism of cell proliferation. The transcription cofactorYAP, the end effector of this pathway, is a nucleo-cytoplasmic shuttle. Its expression isamplified in various cancers including osteosarcoma where this overexpression associatedwith that of Itgb1 is a factor of poor prognosis.My work involves understanding how β1 integrins control the Hippo pathway, and thusproliferation. We confirmed that deletion of β1 integrins activates the phosphorylation ofYAP and its sequestration in the cytoplasm. Using Cell Biology and Biochemistry techniques,we showed that following the deletion of Itgb1, the cells exhibit a defect in vesicular trafficthat reduces the membrane translocation of Rac1. The cytoplasmic sequestration of Rac18decreases the activation of its major effector, the PAK kinase. PAK is responsible for thedissociation of an inactivating membrane complex composed of the adaptor protein NF2,the LATS kinase, and its main effector YAP. The integrins by provoking the loss of thiscomplex induce the dephosphorylation of YAP, its nuclear translocation, and thus stimulatecell proliferation.

L'élongation embryonnaire de C. elegans a lieu en deux étapes. La première phase est permise par les contractions d’actomyosine et régulée par les kinases let-502 et pak-1. La seconde dépend des contractions musculaires (après le stade 1,7-fold). La tension fournie par ces contractions permet le recrutement de GIT-1 aux hémidesmosomes, facilitant la poursuite de l’élongation via l’activation de PAK-1 (Nature, 2011). Étonnamment, en l'absence de git-1 ou pak-1, l'élongation se poursuit, nous conduisant à émettre l'hypothèse de voies de régulation parallèles. Un crible ARNi a été réalisé pour rechercher les candidats impliqués. La majorité des candidats interagissant fortement avec git-1 appartenait au complexe dynéine-dynactine. En utilisant des allèles sensibles à la température et des protéines affectant les microtubules, nous avons décrit un rôle de la dynactine indépendant des microtubules dans l'épiderme ainsi que son interaction avec la spectraplakine vab-10 et la spectrine spc-1. / C. elegans embryonic elongation is driven by 2 forces: Actomyosin contractility and Muscle contraction (after 1.7-fold). Actomyosin contraction is regulated by the Rho kinase and the serine/threonine p21 activated kinase pak-1. Tension provided by muscle contraction recruits GIT-1 to hemidesmosomes (HD), which in turn facilitates further elongation by activating proteins such as PAK-1 (Nature 2011). Surprisingly in absence of git-1/pak-1, elongation still continues, which led us to hypothesize parallel pathways. An RNAi screen was performed to get the candidates in the parallel pathway/s. Candidates interacting strongly with git-1 belonged to the Dynein Dynactin complex. By use of temperature sensitive alleles and microtubule severing proteins, we found a microtubule independent role of Dynactin in epidermis and that dynactin functionally interacts with spectraplakin vab-10 and spectrin spc-1, which allows us to portray the role of Dynein Dynactin complex during embryonic elongation.

published_or_final_version / Architecture / Master / Master of Landscape Architecture

Mon travail se concentre sur la morphogenèse épithéliale pendant l’élongation embryonnaire de C. elegans. Ce processus s’appuie sur la transmission de signaux mécaniques, jouent un rôle essentiel également au cours de l’homéostasie tissulaire. Le gène pak-1 joue un rôle essentiel au cours des tels processus à la fois chez l’homme et dans l’élongation chez C. elegans. Nous avons montré que α-spectrine (SPC-1) est un nouveau partenaire de la kinase PAK-1. Pendant mon doctorat, j’ai confirmé que la perte simultanée de PAK-1 et de SPC-1 induit des défauts sévères d’élongation, impliquant une rétractation et un collapse général de l’embryon et suggèrent la présence de défauts biomécaniques. Mon travail était destiné à déterminer comment la perte de PAK-1 et SPC-1 influence le comportement mécanique des cellules épidermales. Cette étude permettra de mieux d’établir le rôle de SPC-1 et de PAK-1 dans la morphogenèse épithéliale et de mieux comprendre la régulation des propriétés mécaniques des cellules dans un contexte vivant. / I study epithelial morphogenesis during C. elegans embryonic elongation. This process depends on mechanical cues that also influence tissue homeostasis. The pak-1 gene plays an essential role equally during such processes in human and during C. elegans elongation. Our work identified α-spectrin (SPC-1) as a new interactor of the kinase PAK-1. During my PhD I confirmed that the simultaneous lack of PAK-1 and SPC-1 induces serious elongation defects, including a retraction and general collapse of the embryo and suggests that the mechanical properties of the epidermis are modified. My work aimed to determine how the simultaneous lack of PAK-1 and SPC-1 could influence these processes. Such studies would allow to better establish the role of SPC-1 and PAK-1 during epithelial morphogenesis and to better understand the regulation of cellular mechanical properties in the living organisms.