Apesar do crescimento nas exportações de açúcar, a conjuntura atual do setor sucroalcooleiro e a instabilidade do mercado externo têm feito com que as usinas busquem mais competitividade. A Tecnologia da Informação (TI) tem participação nesta busca, visto que, hoje, é impossível uma empresa apresentar um gerenciamento integrado eficaz sem a utilização de sistemas informatizados. Alguns desses sistemas, os ERP, têm se desenvolvido muito nos últimos anos, chegando, por exemplo, a ponto de possuírem módulos específicos para determinados tipos de empresas. Um dos desenvolvedores desses sistemas criou módulos específicos para o Planejamento e Controle da Produção (PCP) em indústrias de processo contínuo. Os conceitos envolvidos em tais módulos são apresentados nesta dissertação e comparados com os módulos tradicionais de Planejamento e Controle de Produção. Depois do embasamento conceitual, e da apresentação dos processos industriais de uma determinada usina de açúcar e álcool, é desenvolvida a configuração de tais módulo, para análise da compatibilidade desses ao processo produtivo da usina. / In spite of the growth in the sugar exports, the current situation of the sector responsible for the production of sugar and alcohol, as well as the instability of the external market, responsible for the fact that sugar and alcohol mills are looking for an increase competitiveness. The Information Technology (IT) has a great degree of participation in this search for competitiveness, because it is impossible for a company to introduce an effective integrated management network without the utilization of computerized systems. Some of these systems, called Enterprise Resources Planning, have developed remarkably in the last years, reaching, for instance, the point of having their own specific modules for certain industry types. One of the developers of these systems developed specific modules for the production planning and control in industries of continuous process. The concepts involved in such modules are introduced in this dissertation, and compared with the traditional modules of production planning and control. Basic concepts are introduced at first, then the industrial processes of a plant are explained, and the modeling of such company is presented for the analysis of the compatibility of the modules to the productive process of the plant.

Cilia are small microtubule based protrusions found on most cells of the vertebrate body. In humans, defects in the structure or function of cilia results in a large class of developmental and homeostatic diseases known collectively as the ciliopathies. Ciliogenesis is accomplished by the concerted action of a number of molecular pathways including the intraflagellar transport (IFT) system. IFT is a group of ~20 highly conserved proteins that assemble into large macromolecular complexes known as trains. These trains act to carry cargo bi-directionally between the cell body and ciliary tip, via interaction with the microtubule motors kinesin and dynein. IFT train dynamics are required for both cilia structure and function, however the controls on these dynamics are still incompletely understood. Here, I present the first platform for study of IFT dynamics within vertebrate multiciliated cells, an understudied population with critical functions in development and homeostasis. Using this platform, I demonstrate that the planar cell polarity effector protein Fuz is required for IFT dynamics via its control of the cytoplasmic localization of a subset of IFT proteins. Subsequently, I find that a Fuz binding partner, the putative small GTPase Rsg1, is also required for IFT protein localization and dynamics. Additionally, I describe a role for Rsg1 in basal body docking, one of the earliest events of ciliogenesis. Finally, I show that the poorly studied protein TTC29 is required for a specific subset of IFT dynamic behaviors. These data reveal novel regulatory motifs for ciliogenesis and demonstrate, specifically, the complexities of IFT regulation in the cytoplasm and within the cilium itself. Finally, they suggest that multiciliated cells provide a tractable platform for generating robust datasets for the investigation ciliary dynamics. Such studies are critical for informing our understanding of the molecular etiology of human ciliopathic diseases. / text

Apesar do crescimento nas exportações de açúcar, a conjuntura atual do setor sucroalcooleiro e a instabilidade do mercado externo têm feito com que as usinas busquem mais competitividade. A Tecnologia da Informação (TI) tem participação nesta busca, visto que, hoje, é impossível uma empresa apresentar um gerenciamento integrado eficaz sem a utilização de sistemas informatizados. Alguns desses sistemas, os ERP, têm se desenvolvido muito nos últimos anos, chegando, por exemplo, a ponto de possuírem módulos específicos para determinados tipos de empresas. Um dos desenvolvedores desses sistemas criou módulos específicos para o Planejamento e Controle da Produção (PCP) em indústrias de processo contínuo. Os conceitos envolvidos em tais módulos são apresentados nesta dissertação e comparados com os módulos tradicionais de Planejamento e Controle de Produção. Depois do embasamento conceitual, e da apresentação dos processos industriais de uma determinada usina de açúcar e álcool, é desenvolvida a configuração de tais módulo, para análise da compatibilidade desses ao processo produtivo da usina. / In spite of the growth in the sugar exports, the current situation of the sector responsible for the production of sugar and alcohol, as well as the instability of the external market, responsible for the fact that sugar and alcohol mills are looking for an increase competitiveness. The Information Technology (IT) has a great degree of participation in this search for competitiveness, because it is impossible for a company to introduce an effective integrated management network without the utilization of computerized systems. Some of these systems, called Enterprise Resources Planning, have developed remarkably in the last years, reaching, for instance, the point of having their own specific modules for certain industry types. One of the developers of these systems developed specific modules for the production planning and control in industries of continuous process. The concepts involved in such modules are introduced in this dissertation, and compared with the traditional modules of production planning and control. Basic concepts are introduced at first, then the industrial processes of a plant are explained, and the modeling of such company is presented for the analysis of the compatibility of the modules to the productive process of the plant.

As empresas fornecedoras para o segmento automotivo estão inseridas em um mercado de constante variação e sujeitas às oscilações da economia. As montadoras, principais influenciadoras do restante da cadeia de suprimentos, aderiram às práticas do just in time, que objetiva a alta eficiência e estoques reduzidos. Este trabalho procura identificar como os fornecedores ao longo da cadeia automotiva se adequaram às novas práticas das montadoras no que se refere ao planejamento e controle da produção e estoques. É realizado um survey, em que se verifica que os profissionais de PCP dos fornecedores respondem satisfatoriamente à demanda, porém de maneira não uniforme, com baixa coordenação com o elo mais próximo, baixa acuracidade de estoque e nível de estoque de produto acabado e matéria-prima elevado. É realizada uma comparação entre o desempenho dos fornecedores mais próximos da montadora com os mais longes, verificando-se que não há diferenças significativas entre ambos / Automotive segment suppliers are part of a constant changing that is subject to oscillations in the economy. Automobile assemblers, the major influence over the rest of the supply chain, have adopted Japanese just in time practices,in order to achieve high levels of efficiency and low inventory. This paper seeks to identify how suppliers along the chain have adjusted to these new practices relating to production and inventory planning and control activities. A survey is conducted, showing that suppliers PPCs fulfill demand requests satisfactorily, although in a non-uniform way, with poor coordination between adjacent links in the chain, low inventory accuracy and high stock level of raw materials and finnished goods. It is concluded that there are no significant performance differences between the suppliers close to the assemblers and those further from them.

L’emploi d’adjuvants fluidifiants est courant pour tout béton. Ceci permet d’améliorer les propriétés rhéologiques à l’état frais: la fluidité initiale et son maintien pendant les 2-3 premières heures de la vie d’un béton. La compréhension de ce mécanisme d’action est encore partielle pour les PCP (copolymères greffés). Ici, le but a été de tester l’hypothèse selon laquelle l’évolution de la quantité de PCP adsorbé par unité de surface minérale instantanée explique quantitativement l’évolution temporelle de la fluidité au cours de la période d’ouvrabilité.Sur un système inerte (calcite), nous avons confirmé que la fluidité est bien gouvernée par l’adsorption: à même adsorption surfacique, la fluidité de la pâte est quasiment identique quelle que soit la structure du PCP. Par ailleurs sur un système inerte (calcite ou ettringite), la modification de la fonction ionique du PCP fournit une solution pour améliorer la résistance de l’adsorption à la variation de la concentration en sulfates.Deux techniques ont été utilisées pour mesurer l’aire interfaciale au cours de l’hydratation d’un système réactif modèle (aluminate tricalcique, gypse, hémihydrate et calcite): l’adsorption de N2 et la relaxométrie du proton de l’eau. L’adsorption du PCP par unité de surface réelle a été calculée et corrélée à la fluidité de la pâte. La relation simple fluidité/adsorption n’est plus vérifiée ici. La présence de PCP a un impact sur l’hydratation du système et l’augmentation de l’étendue de la surface minérale associée. Les PCP vont augmenter la surface spécifique de l’ettringite qui précipite en modifiant sa morphologie. Cet effet est plus marqué quand la densité de greffage du PCP diminue. / Nowadays the use of superplasticizers admixtures becomes unavoidable for concrete. It allows enhancing the rheological properties at the fresh state: the initial flow and slump retention during the 2-3 first hours of the life of a concrete. The understanding of this mechanism is still partly elucidated for PCE (grafted copolymers). The aim of this thesis was to challenge the assumption of the evolution of the adsorbed amount of PCE per instantaneous mineral surface unit as origin of the fluidity temporal evolution during the workability period.On an inert system (calcite), we confirmed that the fluidity is mainly governed by the adsorption level. Thus for a same surface adsorption density, the fluidity of the paste is roughly similar whatever the structure of the PCE. On an inert system also (calcite or ettringite), the modification of the anionic function provides a technological way to improve the resistance of the adsorption against the variation of the sulfate ions concentration.The surface area of a reactive model system (tricalcium aluminate, gypsum, hemihydrate and calcite) has been measured by two techniques during the workability period: the N2 adsorption (BET) and the water proton relaxometry (RMN). The PCE adsorption per surface unit has been calculated and analysed in link with the fluidity of the paste. In that case, the simple relation, shown on the inert system, is not verified because the presence of PCE has also an impact on the hydration and on the extent of the surface area. Especially PCE lead to increase the surface by changing the morphology of ettringite. The specific surface area of ettringite increases when the grafting density of PCE decreases.

We sought to investigate the role of the Planar Cell Polarity (PCP) pathway in neuronal positioning along the Anterior-Posterior (AP) axis of C. elegans, and chose the worm’s DD-type motor neurons as a model. The six DD neurons (DD1-DD6) are evenly spaced in the ventral nerve cord of wild type animals. Here we showed that mutations in core PCP genes caused DD neuron spacing and positioning defects. prkl-1 double mutant combinations with vang-1 and fmi-1 showed a suppression of the more severe prkl-1 single mutant defects, which was evidence of genetic interactions between these PCP components. We also conducted a candidate screen of Frizzled, Dishevelled, Wnt, and ROCK genes, and found that dsh-1/Dishevelled, mom-2/Wnt and let-502/ROCK also played roles in DD neuronal positioning. Both vang-1 and prkl-1 were found to function within the nervous system to guide DD neuronal positioning, and prkl-1 was further identified as playing a cell autonomous role. The origins of observed DD neuron anterior positioning defects were investigated during embryogenesis, in which 1.5 fold stage prkl-1(ok3182) embryos displayed delayed intercalation of the DD neurons. This represents a novel role for the PCP pathway in mediating DD neuronal intercalation.

TSN has for many years been the staple of reliable communication over traditional switched Ethernet and, has been used to advance the industrial automation sector. However, TSN is not mobile, which is needed to fully enable Industry 4.0. The development of 5G and its promised URLLC combined with TSN would give both a mobile and reliable heterogeneous network. The 3GPP has suggested different designs for a 5G and TSN integration. This thesis investigates the different proposed integration designs. Besides the integration design, one of the most essential steps towards validity of the integration is to evaluate the TSN-5G networks based on simulation. Currently, this simulation environment is missing. The investigation in this thesis shows that the most exhaustive work had been done on the Logical TSN Bridge design for simulators, such as the ones based on OMNeT++. Capabilities of the simulator itself are also investigated, where aspects such as the lack of a 5G medium and clock synchronization are presented. In this thesis, we implement the 5G-TSN component that results in a translator which sets different 5G channel parameters depending on the Ethernet packet's priority and its corresponding value. To verify the functionality of the translator that is developed within the simulator, it is tested in a use case inspired by the vehicle industry, containing both TSN and 5G devices. Results from the use case indicate that the translation is performed correctly.

Since 2008, physician-led primary care practices have decreased as physician's encounter sustainability challenges because of government regulations and the requirements of the Affordable Care Act. The problem is that some physician-led primary care practice leaders lack strategies to sustain a medical practice longer than 5 years. The purpose of this study was to explore strategies primary-care practice leaders use to sustain a practice longer than 5 years. This study followed a case study design, including a purposeful sampling of 3 physician-led primary care practice leaders in southern Indiana. Open-ended semistructured interviews were conducted and triangulated with company policies and procedures as well as government statistics. Coded data and themes were identified using the complex adaptive systems theory. Three sustainability themes emerged: (1) patient engagement, (2) relationship development and retention, and (3) adaptation and innovation. The recommended action is for physician leaders to apply the strategies to develop their primary care medical practices. Results from the study may contribute a positive social change by presenting strategies to develop and sustain physician-led primary care practices, which could lead to an increase of primary care medical practices, resulting in more patients having access to primary care physicians.

Final publication is available at http://www.plosgenetics.org/article/related/info%3Adoi%2F10.1371%2Fjournal.pgen.1005802 / 京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19627号 / 医博第4134号 / 新制||医||1016(附属図書館) / 32663 / 京都大学大学院医学研究科医学専攻 / (主査)教授 萩原 正敏, 教授 松田 秀一, 教授 瀬原 淳子 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Indiana University-Purdue University Indianapolis (IUPUI) / Dishevelled-associated activator of morphogenesis 1 (Daam1), a member of the formin protein family, has been implicated in the non-canonical Wnt mediated Planar Cell Polarity (PCP) signaling pathway. Although the studies in Drosophila Daam1 and Xenopus Daam1 generated inconsistent conclusions regarding the function of Daam1, the biological function of mammalian Daam1 was not evaluated. In this study, we used a mouse promoter trap technology to create Daam1 deficient mice to analyze the role of Daam1 in embryonic development and organogenesis. Daam1 is highly expressed in the developing heart. The majority of Daam1 mutant mice died between embryonic day 14.5 and birth, exhibiting a variety of heart defects, which include ventricular noncompaction, ventricular septal defects, and double outlet right ventricle. About 10% mutant mice survive to adulthood, and these survivors do not show significantly compromised heart function based on echocardiographic analyses. However, all of these mutant survivors have ventricular noncompaction with a range of severities. A conditional rescue experiment using a cardiac specific Cre mouse line, Nkx2-5Cre, confirmed that the cardiac defects are the primary cause of death in Daam1 mutants. Both in vivo and ex vivo analyses revealed that Daam1 is essential for regulating non-sarcomeric filamentous actin assembly in cardiomyocytes, which likely contributes to cardiac morphogenesis and ventricular wall maturation. Biochemical studies further suggested that Daam1 is not a key signaling component in regulating the activation of small GTPases, such as RhoA, Rac1 and Cdc42. In conclusion, our studies demonstrated that Daam1 is essential for cardiac morphogenesis likely through its regulation of cytoskeletal architecture in the developing cardiomyocytes. / indefinitely