FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgico / In this dissertation we present complexity results related to the hull number and the convexity number for P3 convexity. We show that the hull number and the convexity number are NP-hard even for bipartite graphs. Inspired by our research in convexity based on paths, we introduce a new convexity, where we defined as convexity of induced paths of order three or P∗ 3 . We show a relation between the geodetic convexity and the P∗ 3 convexity when the graph is a join of a Km with a non-complete graph. We did research in geometric convexity and from that we characterized graph classes under some convexities such as the star florest in P3 convexity, chordal cographs in P∗ 3 convexity, and the florests in TP convexity. We also demonstrated convexities that are geometric only in specific graph classes such as cographs in P4+-free convexity, F free graphs in F-free convexity and others. Finally, we demonstrated some results of geodesic convexity and P∗ 3 in graphs with few P4âs. / In this dissertation we present complexity results related to the hull number and the convexity number for P3 convexity. We show that the hull number and the convexity number are NP-hard even for bipartite graphs. Inspired by our research in convexity based on paths, we introduce a new convexity, where we defined as convexity of induced paths of order three or P∗ 3 . We show a relation between the geodetic convexity and the P∗ 3 convexity when the graph is a join of a Km with a non-complete graph. We did research in geometric convexity and from that we characterized graph classes under some convexities such as the star florest in P3 convexity, chordal cographs in P∗ 3 convexity, and the florests in TP convexity. We also demonstrated convexities that are geometric only in specific graph classes such as cographs in P4+-free convexity, F free graphs in F-free convexity and others. Finally, we demonstrated some results of geodesic convexity and P∗ 3 in graphs with few P4âs.

Le métabolisme des phosphoinositides est constitué d’un réseau complexe d’enzymes et de seconds messagers phospholipidiques et solubles cruciaux pour de nombreux processus cellulaires. Le phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3), second messager très important dans la cellule est contrôlé par plusieurs phosphatases. La phosphatase PTEN, fréquemment mutée dans de nombreux cancers humains (glioblastome, cancer de la prostate, cancer du sein, …), le déphosphoryle en position 3 pour donner du phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). Les cellules de mammifères possèdent également une activité « inositol 5-phosphatase » pour de nombreux dérivés du myo-inositol. C’est la protéine SHIP2 (SH2-containing Inositol 5-phosphatase 2), une lipide phosphatase membre de la famille des phosphatidylinositol polyphosphate 5-phosphatases qui est, entre autres, responsable de cette activité. <p>Le but de ce travail de thèse a été de mettre en évidence un rôle potentiel de SHIP2 et/ou PTEN dans un modèle murin de tumeurs stromales gastro-intestinales (GIST) ;ce modèle exprime une forme constitutivement active du récepteur tyrosine kinase Kit muté sur l’acide aminé 641. Les souris qui ont été générées par le groupe du Dr Brian Rubin (Lerner Research Institute and Taussig Cancer Center, Cleveland) sont dénommées, les souris KitK641E.<p>La caractérisation des souris KitK641E nous a permis de montrer que SHIP2 et PTEN étaient exprimés dans les cellules Kit positives, les cellules de Cajal et qu’ils semblaient régulés de façons différentes.<p>En effet, nous avons pu mettre en évidence une augmentation de l’expression de PTEN dans l’antre gastrique des souris KitK641E homozygotes. Cette augmentation d’expression a également été observée dans l’antre gastrique de souris double transgéniques KitK641E x PTEN+/- alors que l’expression de PTEN dans le foie, un tissu n’exprimant pas de cellules Kit positives, était bien diminuée. Des expériences de PCR quantitative ont également permis de montrer que cette augmentation d’expression de PTEN ne provenait pas d’une augmentation du taux d’ARNm mais qu’elle se situait plutôt au niveau post-traductionnel. Ces données nous permettent de conclure que l’augmentation d’expression de PTEN dans les cellules Kit positives des souris KitK641E homozygotes est influencée par l’activation constitutive du récepteur Kit. <p>A l’inverse, l’expression de SHIP2 dans les cellules Kit positives n’a pu être mise en évidence qu’après activation constitutive du récepteur Kit. En parallèle, l’étude des voies de signalisation dépendantes du récepteur Kit nous ont permis de montrer que la phosphorylation de PKB ne semblait pas être affectée et que ce serait plutôt la voie des MAPK kinases qui interviendrait dans ce modèle. <p>Nous avons également observé la localisation subcellulaire de SHIP2 et de PTEN en utilisant un modèle cellulaire de cellules GIST882 (cellules dérivées d’un GIST humain portant la mutation correspondante à notre modèle murin). Dans ce modèle, PTEN est principalement localisé dans le noyau alors que SHIP2 est localisé à la fois au sein du noyau et du cytoplasme. Ce modèle nous a également permis de montrer que la forme phosphorylée sur tyrosine de SHIP2 (Y1135) était localisée dans le noyau et qu’elle était modulée en fonction du cycle cellulaire.<p>En conclusion, ces travaux ont permis de montrer que dans le modèle de souris KitK641E, SHIP2 et PTEN étaient localisés au sein des cellules Kit positives et qu’ils étaient modulés par des mécanismes différents. L’augmentation d’expression de PTEN observée dans les souris KitK641E homozygotes pourrait constituer un mécanisme de rétrocontrôle négatif afin de modifier l’impact de voies de signalisation en aval du récepteur Kit dans ce modèle oncogénique.<p> / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished

This research, with the main focus on HIV/AIDS, tuberculosis and malaria, was based on data from the literature, and on questionnaire and interview surveys with the main stakeholders: authorities, drug-developers and NGOs/foundations. It revealed the following determinants, which contributed to the occurrence of drug pricing conflicts in Brazil, Thailand and South Africa: governmental constitutional commitments to supply medicines to poor people, the existence of a local pharmaceutical industry capable of producing generic versions of patented medicines and long histories of disease treatment programmes. The research documented the preferred approaches to increase global access to life-saving medicines for the next decade, which were found to be: public-private-partnerships, prevention measures, dedication of >0.5% of GNP to poor countries, and improvement of national healthcare/insurance systems. Those approaches were integrated into a conceptual framework, which could enable country-level organizations to move beyond the conflict mentality via a ¿Public-Private-Partnership for gradual Self-Sufficiency and Sustainability Model,¿ (P3S3). Within this framework, rich countries should invest >0.5% of their GNP to help to alleviate poverty in poor countries. With these funds, national governments should implement programmes to expand implementation of disease prevention measures and improve national - 4 - healthcare/insurance systems and the quality of the medicines involved. Public-private-partnerships should act as ¿steering-and-controlling¿ organizations to guide the process and to minimise corruption. As a positive message to all who currently lack access to these medicines, the thesis author¿s conclusion is that the use of this model could help to turn the current unsustainable development policies into sustainable ones, and as a consequence, it would contribute to improvements in the quality of life of millions of people in poor countries. / Tibotec-Virco BVBA

Acute sleep loss may lead to elevated fatigue, decreased energy, and diminished cognitive performance. Traditionally, sleep extension is used to restore mood and cognitive function to baseline levels following insufficient sleep, yet this method may not be feasible or preferred. Acute exercise may serve as an affordable and relatively safe intervention to reduce detriments to daytime functioning following sleep loss. The primary purpose of this study was to examine the effects of moderate-intensity aerobic exercise on neurocognitive function following acute sleep restriction. A secondary aim was to examine the effects of exercise in subjective reports of fatigue, energy, and sleepiness following acute sleep restriction. Fifty-six participants, matched by sex, age, and chronotype, were randomly assigned to either an exercise (EX) or seated control (SC) condition. Following a 4-hour sleep restriction protocol, participants completed the oddball paradigm before and after 20 minutes of exercise or stationary sitting. P3 amplitude and latency, arousal, sleepiness, energy, and fatigue were assessed during the experiment. After controlling for pre-test differences, P3 latency was significantly faster following exercise relative to the control group. No significant P3 amplitude differences were observed between conditions. The EX group displayed significant improvements in arousal, sleepiness, energy, and fatigue compared to the SC group. Findings suggest that 20 minutes of moderate-intensity aerobic exercise following acute sleep restriction may improve cognitive processing speeds, as well as improve arousal, sleepiness, energy, and fatigue.

Den här kandidatuppsatsen handlar om hur ett radioprogram bör agera utifrån ett tidskritiskt perspektiv på sociala medier, med bakgrund i den ökade användningen av podcasts och annan medieanvändning on demand. Studien i den här uppsatsen har syftet att identifiera vilka tidskritiska styrkor och svagheter tre olika svenska morgonradioprogram – Morgonpasset i P3, Rix MorronZoo och Gry & Anders med vänner, besitter för att på olika sätt interagera med dess följare på Facebook. Studiens huvudsakliga empiri är insamlad genom en innehållsanalys, inom kategorierna interaktion, marknadsföring och koherens, över tre olika morgonradioprogams Facebookinlägg under en avgränsad tidsperiod. Vidare har studiens empiri kompletterats med en fokusgrupp på sex deltagare som är experter på områdena radio, podcast och sociala medier. Studiens resultat visar att de olika radioprogrammen skiljer sig åt i användningen av Facebook när det på olika sätt interagerar med sina följare. Slutsatsen pekar på Morgonpasset i P3 är det radioprogram som har den lämpligaste strategin sett ur ett tidskritiskt perspektiv, följt av Gry & Anders med vänner vars strategi både är lämplig och olämplig ur ett tidskritiskt perspektiv. Vidare är den strategi som Rix MorronZoo tillämpar på Facebook den mest olämpliga utifrån ett tidskritiskt perspektiv. / This bachelor thesis examines how a terrestrial radio program should act upon a time-critical perspective within social media, with a background in the increasing use of podcasts and other media use on demand. The study in this paper has the purpose to identify what time-critical strengths and weaknesses three different Swedish morning radio shows posses when it comes to interact with their followers on Facebook. The study's primary empirical data is collected through a content analysis who built upon the categories; interaction, marketing and coherence, where the three radio shows Facebook post’s where analyzed during a limited time. Furthermore, a focus group of six participants who are experts in the fields of radio, podcasts and social media was also conducted. The results show that the various radio shows differ in the use of Facebook in different ways to interact with their followers. The conclusion points out that Morgonpasset i P3 have the most appropriate strategy from a time-critical perspective, followed by Gry & Anders med vänner, whose strategy is both appropriate and inappropriate from a time-critical perspective, and the radio show Rix MorronZoo have the most inappropriate strategy from a time-critical perspective.

This research, with the main focus on HIV/AIDS, tuberculosis and malaria, was based on data from the literature, and on questionnaire and interview surveys with the main stakeholders: authorities, drug-developers and NGOs/foundations. It revealed the following determinants, which contributed to the occurrence of drug pricing conflicts in Brazil, Thailand and South Africa: governmental constitutional commitments to supply medicines to poor people, the existence of a local pharmaceutical industry capable of producing generic versions of patented medicines and long histories of disease treatment programmes. The research documented the preferred approaches to increase global access to life-saving medicines for the next decade, which were found to be: public-private-partnerships, prevention measures, dedication of >0.5% of GNP to poor countries, and improvement of national healthcare/insurance systems. Those approaches were integrated into a conceptual framework, which could enable country-level organizations to move beyond the conflict mentality via a 'Public-Private-Partnership for gradual Self-Sufficiency and Sustainability Model,' (P3S3). Within this framework, rich countries should invest >0.5% of their GNP to help to alleviate poverty in poor countries. With these funds, national governments should implement programmes to expand implementation of disease prevention measures and improve national - 4 - healthcare/insurance systems and the quality of the medicines involved. Public-private-partnerships should act as 'steering-and-controlling' organizations to guide the process and to minimise corruption. As a positive message to all who currently lack access to these medicines, the thesis author's conclusion is that the use of this model could help to turn the current unsustainable development policies into sustainable ones, and as a consequence, it would contribute to improvements in the quality of life of millions of people in poor countries.

Afin de comprendre pourquoi tous les nouveaux projets de tramways en cours de développement au Canada sont réalisés en mode partenariat public-privé (PPP) plutôt que grâce au mode traditionnel (gestion publique) utilisé par le passé, cette recherche porte sur trois projets de tramways présentement en cours de réalisation (Edmonton, Ottawa et Toronto). À l’aide de trois études de cas, nous explorons l’argumentaire entourant chacune des décisions menant au choix du mode de gouvernance PPP ainsi que la forme prise par ce PPP. Nous démontrons que dans tous les cas, il est possible d’observer les mécanismes du transfert de politique, tant volontaire que coercitif. Nous croyons que le transfert de politique peut donc fournir un élément de réponse à notre question. De plus, l’argumentaire utilisé par les acteurs locaux pour justifier le choix du mode PPP, bien que semblable sur plusieurs points, comporte tout de même une combinaison de justifications unique à chacun des cas, ce qui nous laisse croire que le PPP est un instrument de politique polyvalent. Ces constats démontrent l’intérêt de prendre en considération les transferts de politique au niveau municipal et non seulement les transferts qui prennent place entre les États nationaux. To understand why all new light rail projects under development in Canada are carried out in public-private partnership (P3) rather than through the traditional mode (public administration) that prevailed in the past, this research explores three light rail projects currently underway in Edmonton, Ottawa and Toronto. We study the arguments surrounding each decision leading to the choice of P3 governance. We show that in all cases, it is possible to observe the mechanisms of policy transfer, whether voluntary or coercive. Moreover, the argument used by local actors to justify the choice of P3, although similar in several respects, still forms a unique combination of justifications for each case, which leads us to believe that P3s are a versatile policy instrument. These findings demonstrate the importance of taking into account policy transfer at the municipal level and not only transfers that take place between national states.

The control of phosphatidylinositol 3, 4, 5-trisphosphate [PtdIns(3,4,5)P3] level depends on the activities of both PI kinase and PtdIns(3,4,5)P3 phosphatases: 5-phosphatase like SHIP1 and SHIP2, and 3-phosphatase like PTEN. The ubiquitous SH2 domain containing inositol 5-phosphatase SHIP2 contains both a series of protein interacting domains and the ability to dephosphorylate PtdIns(3,4,5)P3. Previous reports obtained in SHIP2 deficient mice have shown that SHIP2 is involved in the control of insulin sensitivity and reducing weight gain on fatty diet. <p><p>Since SHIP2 is a lipid phosphatase as well as a docking protein, the initial aim that emerged in the lab was to measure the inositol lipid levels in SHIP2 +/+ and deficient cells and compare the levels of 3-phosphoinositides PtdIns(3,4,5)P3 and PtdIns(3,4)P2. At first, we developed mouse embryonic fibroblasts (MEF) as a cellular model. Amongst various stimuli tested, surprisingly, only serum showed an obvious difference in terms of PtdIns(3,4,5)P3 level. This lipid was significantly up regulated in SHIP2 -/- cells but only after short-term (i.e. 5-10 min) incubation with serum. The difference in PtdIns(3,4,5)P3 levels in heterozygous fibroblast cells was intermediate between the +/+ and -/- cells. Serum stimulated PI3K activity appeared to be comparable between +/+ and -/- cells. Moreover, PKB, but not MAP kinase activity, was also potentiated in SHIP2 deficient cells stimulated by serum. The up regulation of PKB activity in serum stimulated cells was totally reversed in the presence of the PI3K inhibitor LY-294002, in both +/+ and -/- cells.<p><p>Reactive oxygen species (ROS) have emerged as physiological mediators of many cellular responses. H2O2 mimics some effects of insulin in a number of cell culture systems. It also inactivates tyrosine phosphatase activities including PTEN. In addition, in Swiss 3T3 fibroblasts, Gray et al reported that exposure of the cells to H2O2 resulted a huge increase in PtdIns(3,4)P2 level. The authors suspected that the effect was attributed to a inositol 5-phosphatase activity. We thus exposed our cells to H2O2 in order to address the question of the role of SHIP2 in response to oxidative stress.<p><p>We worked on the same SHIP2 MEF model, stimulated by H2O2: at 15 min, PtdIns(3,4,5)P3 was markedly increased in SHIP2 -/- cells as compared to +/+ cells. In contrast, no significant increase in PtdIns(3,4)P2 could be detected at 15 or 120 min incubation of the cells with H2O2 (0.6 mM). PKB activity was upregulated in SHIP2 -/- cells in response to H2O2 and therefore follows the regulation of PtdIns(3,4,5)P3. As for serum, the PI3K activity appeared to be comparable between +/+ and -/- cells. The levels of PTEN and type I 4-phosphatase [an enzyme that acts on PtdIns(3,4)P2] remained unchanged between the two types of cells. SHIP2 add back experiments in SHIP2 -/- cells confirm its critical role in the control of PtdIns(3,4,5)P3 level in response to H2O2: the decrease in PtdIns(3,4,5)P3, observed in SHIP2 expressing cells, was no longer seen in cells infected with a catalytic mutant of this enzyme. <p> / Doctorat en sciences biomédicales / info:eu-repo/semantics/nonPublished

Afin de comprendre pourquoi tous les nouveaux projets de tramways en cours de développement au Canada sont réalisés en mode partenariat public-privé (PPP) plutôt que grâce au mode traditionnel (gestion publique) utilisé par le passé, cette recherche porte sur trois projets de tramways présentement en cours de réalisation (Edmonton, Ottawa et Toronto). À l’aide de trois études de cas, nous explorons l’argumentaire entourant chacune des décisions menant au choix du mode de gouvernance PPP ainsi que la forme prise par ce PPP. Nous démontrons que dans tous les cas, il est possible d’observer les mécanismes du transfert de politique, tant volontaire que coercitif. Nous croyons que le transfert de politique peut donc fournir un élément de réponse à notre question. De plus, l’argumentaire utilisé par les acteurs locaux pour justifier le choix du mode PPP, bien que semblable sur plusieurs points, comporte tout de même une combinaison de justifications unique à chacun des cas, ce qui nous laisse croire que le PPP est un instrument de politique polyvalent. Ces constats démontrent l’intérêt de prendre en considération les transferts de politique au niveau municipal et non seulement les transferts qui prennent place entre les États nationaux. To understand why all new light rail projects under development in Canada are carried out in public-private partnership (P3) rather than through the traditional mode (public administration) that prevailed in the past, this research explores three light rail projects currently underway in Edmonton, Ottawa and Toronto. We study the arguments surrounding each decision leading to the choice of P3 governance. We show that in all cases, it is possible to observe the mechanisms of policy transfer, whether voluntary or coercive. Moreover, the argument used by local actors to justify the choice of P3, although similar in several respects, still forms a unique combination of justifications for each case, which leads us to believe that P3s are a versatile policy instrument. These findings demonstrate the importance of taking into account policy transfer at the municipal level and not only transfers that take place between national states.

This dissertation investigates the advantages of procuring capital-intensive infrastructure services via Public-Private Partnerships (P3s or PPPs) – cost and time savings and; innovation and high levels of efficiency – accounting for these advantages by reference to the underlying legal provisions and principles that facilitate them; and in this process highlights two significant directions in which Canadian P3 law, policy and practice has evolved – the enactment of P3 legislation and/or the formulation of non-statutory P3-related policy; as well as the establishment of legal institutions that promote and/or facilitate P3 procurements. The dissertation also addresses key arguments raised against P3s, by reference to aspects of Canadian law, policy and P3 practice. The research methodology comprises a detailed review of legal and non-legal sources. The implication of the research findings is that, given the foregoing developments in Canadian P3 law, policy and practice, the key arguments canvassed against P3s are overstated and lacking in merit.