P8 est un gène lié au stress cellulaire qui a été identifié et caractérisé dans notre laboratoire. Il est surexprimé dans diverses pathologies, et plus particulièrement dans l'adénocarcinome pancréatique. Notre étude se focalise sur le rôle de p8 dans la progression tumorale et la formation des métastases du cancer du pancréas. Dans ce travail, nous avons démontré, dans un premier temps, que p8 régule la migration, l'adhésion et l'invasion cellulaire induites par diverses molécules dont le TGF-β1, par le biais de la GTPase CDC42, dont il contrôle l'expression et l'activité. Nous avons prouvé aussi que la présence de p8 est nécessaire pour la mise en place d'une transition épithélio-mésenchymateuse, facilitant ainsi l'action pro-tumorale du TGF-β1. Enfin, une analyse morphologique d'adénocarcinomes pancréatiques humains et murins nous a permis d'identifier la présence de cellules « cannibales », déficientes en p8, capables de phagocyter et ainsi limiter la prolifération d'autres cellules. Nous avons décortiqué ce mécanisme au niveau moléculaire. Son étude nous a permis de conclure, qu'en absence de p8, une nouvelle transition de type épithélio-phagocytaire est instaurée, ayant comme résultat un cannibalisme cellulaire, potentialisé notamment par le TGF-β1, qui agirait dans ce cas comme un agent anti-tumoral. L'avancée de ces résultats donne place à des nouvelles perspectives vis-à-vis de l'importance de p8, d'abord d'un point de vue moléculaire sur les actions pro et anti-tumorales du TGF-β1, ensuite en tant que potentielle cible thérapeutique dans le cancer du pancréas. / P8 is a gene related to cellular stress, identified and characterized in our laboratory, and overexpressed in several diseases, especially in pancreatic cancer (PDAC). Our study focuses on the role of p8 in tumor progression and metastasis formation in PDAC. In this work, we have demonstrated that firstly, p8 regulates pancreatic cancer cell migration, invasion and adhesion, induced by several molecules like TGF-β1, through CDC42, a small GTPase, whose expression and activation is controlled by p8. We also established that p8 is necessary to set up epithelial-to-mesenchymal transition, promoting TGF-β1 pro-tumoral effects. Finally, morphological analysis of human and murine pancreatic cancer, allowed us to identify “cannibal” cells, in which p8 expression was absent, able to phagocytose another cells and in this way limit its proliferation. We dissected the mechanism involved in this process at the molecular level. This study led us to conclude that when p8 is absent, a new epithelial-to-phagocytic transition takes place, resulting in cell cannibalism, maximized by TGF-β1 action that will play an anti-tumoral role. These results underscore, on one hand, the crucial role of p8, at the molecular level, over the pro and anti-tumoral effects of TGF-β1 and on the other hand its potential role in pancreatic cancer therapy.

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2016-02-15T14:17:14Z No. of bitstreams: 1 Jaqueline Goes de Jesus. Estudo...2014.pdf: 4655999 bytes, checksum: 99ee2ef801cc69dd80d0a344e8f01be2 (MD5) / Approved for entry into archive by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2016-02-15T14:18:33Z (GMT) No. of bitstreams: 1 Jaqueline Goes de Jesus. Estudo...2014.pdf: 4655999 bytes, checksum: 99ee2ef801cc69dd80d0a344e8f01be2 (MD5) / Made available in DSpace on 2016-02-15T14:18:33Z (GMT). No. of bitstreams: 1 Jaqueline Goes de Jesus. Estudo...2014.pdf: 4655999 bytes, checksum: 99ee2ef801cc69dd80d0a344e8f01be2 (MD5) Previous issue date: 2014 / Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / As ORFs I e IV do genoma do HTLV-1 codificam, respectivamente, as proteínas p12/p8 (acessória) e Tax (regulatória). p12/p8, de 99 aminoácidos, pode ser clivada em sua extremidade amino terminal gerando a proteína p8. A primeira clivagem proteolítica de p12 remove o sinal de retenção ao RE, enquanto a segunda clivagem, gera o produto de 8kDa, referido como p8. p12 localiza-se no sistema de endomembranes, residindo em RE e aparato de Golgi, enquanto p8 dirige-se para a membrana plasmática, onde é recrutada para a sinapse imunológica, através da ligação com o receptor de células T (TCR), além de participar da sinapse virológica e da formação de conduítes. A proteína Tax, por outro lado, atua como transativador transcricional do HTLV-1, sendo referida também na indução da expressão de diversos genes celulares, aumentando a proliferação e a migração das células infectadas. Na via de transporte de vesículas secretórias, vesículas produzidas como pós-Golgi são transportadas ao longo do citoesqueleto por motores celulares. A Miosina-Va, um motor não convencional, transporta diversos cargos, incluindo vesículas secretórias, vesículas sinápticas e de retículo endoplasmático. Outra proteína relacionada ao citoesqueleto é a Paxilina, que atua como molécula adaptadora nas adesões focais e cuja expressão está aumentada em indivíduos TSP-HAM. Na tentativa de compreender se Tax influencia no aumento da expressão de Paxilina e, paralelamente, se p8 trafega a partir de Golgi em direção à membrana, de maneira dependente de Miosina-Va, células de linhagem foram transfectadas, com o plasmídeo que expressa Tax ou com plasmídeos que expressam variantes da proteína p12 (pMEp12) fusionada a um tag de HA (hemaglutinina de influenza) e que expressam porções da Miosina-Va, incluindo a cauda completa neuronal conjugada com GFP (MyoVa FTNeu-eGFP), que funciona como dominante negativo e compete com a Miosina-Va constitutiva pelos seus ligantes intracelulares. A localização intracelular das proteínas foi realizada por ensaio de imunofluorescência indireta utilizando anticorpos contra a Paxilina ou contra o tag de HA e a cauda medial da Miosina-Va. Técnicas de microscopia confocal e obtenção de imagens foram realizadas utilizando o microscópio Zeiss LSM 780 (Carl Zeiss Optical, Chester, Va.) e o software Adobe Photoshop CC. Surpreendentemente, nas células que expressavam Tax, a expressão de Paxilina, avaliada por imunofluorescência, foi menor, necessitando de novos ensaios para confirmação dos resultados. Em relação à p12/p8, foi observada a sua sub-localização celular como já descrito na literatura, apresentando-se na região perinuclear (RE e aparato de Golgi), e co-localização entre p12/p8 e Miosina-Va, embora apenas quando o dominante negativo MyoVa FTNeu-eGFP foi expresso simultaneamente com as variantes de p12, a localização de p12/p8 mostrou-se alterada, de pontos dispersos por todo o citoplasma e superfície celular para apresentar-se em forma de grumos agregados independentemente da variante de p12 expressa, sugerindo que a Miosina-Va desempenha um importante papel no tráfego de p8 partindo de Golgi até a superfície celular. / HTLV-1 ORFs I and IV encode respectively p12/p8 (accessory protein) and Tax (regulatory protein). The 99 amino acid p12 protein can be proteolytically cleaved at the amino terminus to generate the p8 protein. The first proteolytic cleavage removes the ER retention/retrieval signal at the amino terminus of p12, while the second cleavage generates the p8 protein. The p12 protein localizes to cellular endomembranes, within the ER and Golgi apparatus, while p8 traffics to lipid rafts at the cell surface and is recruited to the immunological synapse upon T-cell receptor (TCR) ligation, virological synapse and conduits. Tax on the other hand acts as viral transactivator and induces expression of many cellular genes, increasing proliferation and migration of infected cells. In secretory vesicle transport, vesicles produced as post-Golgi are moved along the cytoskeleton by motor proteins. The unconventional myosin motor, Myosin-Va, moves several cargoes including secretory vesicles, synaptic vesicles, and the endoplasmic reticulum. Another cytoskeleton associated protein is Paxillin, an adapter on focal adhesions which expression is increased in TSP-HAM patients. To understand if Tax play a role on increased expression of Paxillin and parallel if p8 traffics from Golgi apparatus to cell surface on a myosin-Va dependent manner, lineage cells were transfected with Tax plasmids or pMEp12 plasmids which express variants (p12WT, p12Δ29 and p12G29S) of the fusion protein of HTLV-1 p12 tagged with the influenza hemagglutinin (HA1) tag and with the Myo-Va plasmids including full-tail neuronal-eGFP conjugated (MyoVa FTNeu-eGFP) plasmid which expresses a negative dominant of myosin Va and competes for intracellular ligands with cellular putative myosin. Proteins intracellular localization were analyzed by indirect immunofluorescence assay using antibodies against Paxillin or the HA-tag and the Myo-Va protein. Confocal microscopy and image collection was performed by using a Zeiss LSM 780 microscope (Carl Zeiss Optical, Chester, Va.) with Adobe Photoshop CC software. Surprisingly in Tax-expressing cells Paxillin fluorescence was decreased requiring another assay to confirm this find. It was reported that p12 expression in Jurkat T, as previous described, was shown in perinuclear region which might be RE and Golgi apparatus and that p12/p8 and MyoVa proteins colocalizes in lineage cells, however only when MyoVa FTNeu-eGFP was simultaneously expressed with pMEp12 plasmids, p12/p8 localization showed to be altered from dots dispersed all over cytoplasm and cell surface to form cytoplasmic aggregates independently on variant of p12 expressed, suggesting that myosin Va plays an important role on traffics of p8 from Golgi to cell surface.

Interconnection between various types of IT systems used in an enterprise is crucial in these days. Most of companies are using many different kinds of applications in their daily running of the enterprise which leads to necessity of sharing data across those applications to enable all employees to make a right decision upon correct information. In my diploma thesis I deal with interconnection of two systems -- Business Process Management (BPM) and Business Intelligence (BI). Both systems belong to group of top IT systems with big influence on ongoing business and right decision making on all levels from operational to strategic. My paper contains theoretical as well as practical part of the solution for interconnection of BI and BPM systems. First part is about presenting and describing basic concepts and technologies which are used in process of integration of BI and BPM. At the beginning there is a short introduction to BPM, BI and SOA. Following part is including analysis of three major ways of interconnection between BI and BPM systems. Last part of the first theoretical section presents two products. IBM FileNet P8 representative of BPM system and IBM Cognos 8 BI as a representative of BI system. Second part deals with the practical example of real integration between BI and BPM systems. In first part of this section is simple description of the scenario -- business case. After that there is a detail depiction of two different kinds of integration of BI and BPM. Analysis of benefits, advantages and further possibilities are at the end of work.

The presented work deals with the linking of software product EPLAN Electric P8 with production. The work briefly introduces the problems of computer-aided in manufacturing and control of software EPLAN. The work analyzed the equipment in production and created a solution for linking with output data of the program.

This thesis examines the working lives of foreign-born academics who come to work to the UK. Its main aim is to understand the degree and conditions of migrant scholars' inclusion in professional practice abroad. The thesis fulfils this aim by developing a conceptual approach to encapsulate how migrant professionals' working lives are conditioned by the pre-existing professional structures. Grounded in the principle of social closure, this framework proposes that migrant professionals' employment abroad is influenced by the different forms and rules of closure, as well as by the sites in which closure rules are applied. The synthesis of the theoretical framework with findings from sixty-two interviews with foreign-born scholars employed in thirteen British universities shows that migrant academics' working lives are explained by ‘modes of incorporation'. ‘Modes of incorporation' designate the distinct ways in which the academic profession has reacted to the increased presence of foreign incomers, and comprise integration, exclusion, subordination and indifference. The proposed framework extends the understanding of the demographic change in professions, and offers a way to capture migrant professionals' movement across countries.

Diploma thesis is dedicated to the analysis of threats and risks related with document management in a real enterprise -- big telco company. For document management company utilizes a complex solution called application DMS which is implemented on IBM FileNet P8 platform. In my work I will concentrate on risks linked with operation of DMS application. Along with the description of DMS application and document management I will mention problems perceived from the external supplier's point of view. These problems will be the basis for identification of the risks for the company emerging from the operation of DMS application. Subsequently I will evaluate risks and propose solutions to handle or avoid these risks. I will put proposed solutions into the sequence, in which they should be implemented while considering nature of the risk and financial demands of the proposed solution. Contributions of my work are list of identified risks and list of solutions which both can be used for assigning priorities of the change requests carried out in 2013 and possibly during discussions about budget increase for the DMS application operation.

The thesis deals with the optimization of project activities in the software EPLAN Electric P8. First part introduces electrotechnical software EPLAN, the basic functions, and explains the methodology of the work in the program environment. This is followed by an analysis of the state of the electrical documentation of the TAC 75 circular saw manufactured by Exactcut s. r. o., and the method of designing. The thesis is also focused on the individual problems that make barriers between the average and the high quality level of design and the ability to use the available features of the purchased software. Thereafter, individual optimization steps and partial methods of reaching aims are described. Part of the thesis is devoted to finding solutions for interconnection of two engineering branches, which are electric and fluid technologies and in the end are revealed expansion modules of software, which can be used to achieve a higher level of professional planning activity.

This presenting master’s thesis deals with a problem of digitaly controled room temperature using the software PLC. The result of this work was creating of an algorithm to control temperature on the requested leve ofl setpoint, minimizing operating costs of the building. The PLC softwares from different manufacturers were analyzed and compared with conventional PLC. The testing facility was disigned and used to control the temperature in the room and data visualization. Room temperature was regulated by PS controller or two point regulator.

This Graduation Theses dissertate about a creation of a drawing documentation at the professional CAE EPLAN Electric P8 system. One original solution of a remote control and of motor-generator monitoring with a mobile phone, short SMS-aided in this case, was used as an example of the drawing documentation. As has allready been noted in previous Bachelor Thesis, this application can be use not only for a remote control of a motor-generator, but this solution is suitable for other electric devices too, which are out of reach of an attendance for example. In our case a generator with 6kVA power is concerned with rated output voltage 230Vac and rated current 25A. The system of a remote control has the advantage that it is created from standard components (electric instruments, a PLC – programmable automat, a GSM modem, an operating panel and the respective program in the PLC).