Hhex transcription factor is expressed in multiple endoderm-derived tissues, like the liver, where it is essential for proper development. The pleiotropic effect of Hhex in the embryo and its dual role as a transcriptional repressor/activator suggest the presence of different interaction partners capable of modulating its activity and function. In the current study we identified two new Hhex protein interactors: SOX13 and c-Myc. We show that Hhex interacts directly with SOX13. By doing so, Hhex sequesters SOX13 from the SOX13•TCF1 complex, overturning SOX13-dependent repression of the Wnt pathway. On the other hand, Hhex induces proliferation of non-tumorigenic human fibroblast through a Myc-dependent mechanism. Hhex and c-Myc interact directly upregulating Cyclin D1, a c-Myc target gene involved in cell cycle progression and proliferation. Elevation of Cyclin D1 might be the final effector of Hhex capacity to regulate cell proliferation.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / When the controller s performance is reduced along the time and the control efficiency is no longer satisfactory, then it is necessary to develop certain techniques for continuously monitor control systems such as it can keep track of process changes maintaining the characteristics of efficiency of the original controller design. The divergences between controlled variables and the desired setpoint can be quantified by a single number that is known as performance index. In the present work, a novel way of evaluating the control process performance is introduced and applied as a new measure of performance for a control structure. For doing that, the knowledge of the invariants of the process under feedback and factorization tools of linear local models were applied for designing a new reference model. The proposed techniques were used as a reference of what can or cannot be achieved by a particular system operating under the action of a feedback control law: minimum variance control (MVC), proportional-integral (PI), and model predictive control (MPC). Hence, the proposed performance indexes are the tools for the evaluation of the behavior of the control system during regular industrial operation, not only based upon the physical point of view, in which the reference is treated as a realizable system, but also from a theoretical point of view, in which the model factorization procedure takes place, and therefore allowing the extraction of the invariant part of a system, changing the system to its easiest controlled form description, and then serving as a reference model for the calculation of the performance index, with a low computing cost and preserving the importance of interactions and high frequency effects for balancing the reference behavior. In this work was investigated, with success, the effect of coupling, interactions and quality degradation of the control for SISO (Single-Input and Signle-Output) and MIMO (Multiple-Input and Multiple-Output) processes. The results show that the proposed technique are effective and a viable tool for process monitoring and controlled systems performance evaluation. / Quando o desempenho de um controlador se reduz ao longo do tempo e a eficiência de controle já não é mais satisfatória, tem-se que o controle em vigor ficou obsoleto devido às mudanças ocorridas no processo. Dessa forma, surge a necessidade de se desenvolver técnicas de monitoramento contínuo de sistemas de controle para que o mesmo possa acompanhar as mudanças ocorridas no processo, mantendo as características de eficiência do projeto original do controlador. As divergências entre variáveis controladas e os valores desejados (setpoint) podem ser quantificadas por um número que ´e conhecido como ´índice de desempenho. Neste trabalho, investiga-se o desempenho de sistemas de controle através de novas medidas de desempenho para estruturas de controle. As medidas propostas utilizam o conhecimento dos invariantes do processo obtidos através de ferramentas de fatoração de modelos locais lineares e da definição de um padrão de referencia `a ação possível de controle para plantas operando com controladores feedback para casos de controladores com variância mínima (MVC), proporcional-integral (PI) e controlador preditivo baseado em modelos (MPC). Desta forma, a técnica proposta neste trabalho serve como uma ferramenta para a avaliação do comportamento do sistema de controle durante a operação industrial, pois, tanto do ponto de vista físico, por se tratar de uma referencia realizável, quanto do ponto de vista teórico, que ao realizar a fatoração, as informações dos invariantes dos modelos são extraídos, fazendo com que os mesmos se tornem mais fáceis de serem controlados, então, servindo como referencia para o cálculo do ´índice de desempenho para o sistema. As técnicas propostas possuem baixo custo computacional e preservam a importância de interações e efeitos de elevadas freqüências no compromisso entre a atenuação da sensibilidade das perturbações e a velocidade de resposta da malha de controle avaliada. Investigou-se então, com sucesso, o efeito de acoplamentos, interações e degradação da qualidade do controle para processos com uma entrada e uma saída (SISO) e sistemas com múltiplas entradas e múltiplas saídas (MIMO), comprovando então a eficácia da técnica proposta como uma ferramenta viável para o monitoramento e avaliação de sistemas de controle. / Mestre em Engenharia Química

No description available.

La plupart des virus ont développé des mécanismes de résistance ou de suppression du système immunitaire pour parvenir à infecter durablement leur hôte. Ces mécanismes demeurent encore imparfaitement connus. Un domaine immunosuppresseur (IS) a été identifié au niveau de la région transmembranaire des protéines d’enveloppe des rétrovirus endogènes ou infectieux. Ce domaine hautement conservé a été décrit par exemple comme inhibant l’activation lymphocytaire. Dans le laboratoire, il a été caractérisé en particulier via des expériences de rejet de cellules tumorales in vivo, ce qui a permis de définir des mutations inactivatrices. Afin de mieux comprendre les mécanismes de résistance des rétrovirus au système immunitaire, mes travaux de thèse ont porté sur l’identification de la ou des protéines capables d’interagir avec le domaine IS. Plusieurs approches cellulaires et moléculaires ont été développées, basées pour la plupart sur l’utilisation de sondes fluorescentes obtenues par synthèse chimique, constituées des domaines IS provenant de différents rétrovirus. Dans un premier temps, les cellules du système immunitaire qui lient les protéines virales ont été identifiées : les lymphocytes B et les cellules myéloïdes (monocytes, cellules dendritiques et macrophages). Dans un second temps, des expériences de co-immunoprécipitation et de chromatographie d’affinité couplées à la spectrométrie de masse ont été réalisées dans le but d’identifier sur ces cellules les protéines membranaires responsables de ces liaisons. Plusieurs agents de couplages chimiques ont été utilisés afin de maintenir les liaisons domaine IS - protéine de faibles affinités. En raison de résultats non-reproductibles obtenus au cours de ces expériences, des tests de liaison du domaine IS sur des cellules transfectées avec des banques d’ADNc, ou lors d’expériences de double hybride ont été réalisées. Ces deux approches ont permis d’identifier des protéines membranaires potentiellement impliquées dans la liaison du domaine IS : les protéines X1 et X2. Les co-transfections de vecteurs d’expression du domaine IS et de X2 ont mis en évidence des interactions protéiques au cours d’expériences de co-immunoprécipitation et de microscopie confocale, en particulier avec le domaine IS du rétrovirus HIV-1. Concernant X1, sa transfection induit la liaison cellulaire des domaines IS de HERV-W et MLV. En revanche, aucune interaction directe entre X1 et le domaine IS n’a pu être démontrée, notamment dans des expériences de co-immunoprécipitation et de microscopie confocale.La découverte des protéines membranaires qui interagissent avec le domaine IS demeure un enjeu critique pour la compréhension des voies de signalisation et de transcription qui permettent aux rétrovirus d’exercer leur effet sur le système immunitaire, l’objectif de ces travaux étant d’identifier à terme des nouvelles cibles thérapeutiques.En conclusion, même si des travaux complémentaires demeurent nécessaires, les protéines X1 et X2 pourraient contribuer à l’immunosuppression rétrovirale. / Most viruses have developed mechanisms of resistance or suppression of the immune system to achieve lasting infection of their host. These mechanisms are still imperfectly known. An immunosuppressive (IS) domain has been identified in the transmembrane region of envelope proteins of endogenous or infectious retroviruses. This highly conserved domain has been described, for example, as inhibiting lymphocyte activation. In the laboratory, it has been characterized by tumor cell rejection experiments in vivo, which has made it possible to define inactivating mutations. In order to better understand the mechanisms of resistance of retroviruses to the immune system, my thesis focused on the identification of the protein(s) interacting with the IS domain. Several cellular and molecular approaches have been developed, based for the most part on the use of fluorescent probes obtained by chemical synthesis, consisting of IS domains from different retroviruses. At first, immune system cells that bind viral proteins have been identified: B cells and myeloid cells (monocytes, dendritic cells and macrophages). In a second step, co-immunoprecipitation and affinity chromatography coupled to mass spectrometry were performed to identify on these cells the membrane proteins responsible for these bonds. Several chemical coupling agents have been used to prevent detachment of low affinity binding between proteins and the IS domain. Due to non-reproducible results obtained during these experiments, IS domain binding assays on cells transfected with cDNA libraries, or in double hybrid experiments were performed. These two approaches made it possible to identify membrane proteins potentially involved in the binding of the IS domain: the X1 and X2 proteins. Co-transfections of IS domain and X2 expression vectors demonstrated protein interactions in co-immunoprecipitation and confocal microscopy experiments, particularly with the IS domain of the HIV-1 retrovirus. Concerning X1, its transfection induces binding of the IS domains of HERV-W and MLV on cells membrane. On the other hand, no direct interaction between X1 and the IS domain could be demonstrated, especially in co-immunoprecipitation and confocal microscopy experiments.The discovery of membrane proteins that interact with the IS domain remains a critical issue for understanding the signaling and transcription pathways that allow retroviruses to exert their effect on the immune system, the aim of this work being to identify new therapeutic targets.In conclusion, although further work is still needed, the X1 and X2 proteins may contribute to retroviral immunosuppression.

This report studies the possibility of integrating Transport Management Services (TMS) in a low-cost platform called Communicator 200 (C200). The platform is developed by Scania and is a black box that manages vehicle data, positioning, and wireless communication. The C200’s main purpose is to connect a hauler’s vehicles to their office system via wireless links and Internet. The thesis describes the design and implements a prototype of a service called Messaging that is used to send text messages between truck and office. The prototype is evaluated and tested with different web browsers in various hand-held terminals with different screen sizes. The main conclusion is that it is technically possible to integrate TMS in the C200 without altering the platform architecture too much. / Denna rapport undersöker möjligheten att integrera transportledningstjänster i en billig platform kallad Communicator 200 (C200). Platformen är utvecklad av Scania och är en svart låda som hanterar fordonsdata, positionering och trådlös kommunikation. C200 huvudsyfte är att sammankoppla ett åkeris fordon med deras kontorssystem via trådlösa förbindelser och Internet. Rapporten beskriver designen och implementerar en prototyp av en tjänst kallad Messaging som används för att skicka textmeddelanden mellan lastbil och kontor. Prototypen utvärderas och testas mot webbläsare i olika handhållna terminaler med olika skärmstorlekar. Huvudslutsatsen är att det är möjligt att integrera transportledningstjänster i C200 utan att ändra plattformens arkitektur alltför mycket.

In 2018, there were 3.6 billion mobile internet users worldwide, which shows that digital designers have to tackle navigational patterns and menu anchor interactors for smartphone-sized screens early in their projects. As user satisfaction is crucial for the success of a website, and as successful navigation through a menu system is imperative to user satisfaction, the menu system is a key component in the UI. This study concerned three types of menu anchor interactors in smartphone UIs (Transient, Top persistent, and Navigation hub), on three website types (Single service, Brand, and Service directory). The goal was to investigate what influence the website type has on the user’s preferences of menu anchor itneractors. The theoretical base is previous research on menu systems in graphical UIs. The study was done by a questionnaire where the participants were presented images of three different menu anchor interactors on three different website types, and asked to score the assumed helpfulness of the menu anchor interactor from one to seven on a Likert scale. In addition, they were asked to clarify their scoring in a qualitative response. The key findings are that users prefer menu anchor interactors that display several navigation links, and that there are indications that the Top persistent menu anchor interactor works best on the Service directory website type, while Single service and Brand website types seem to benefit from a Navigation hub. However, the results also show the importance of studying UI components in their full UI context, as the whole UI affects the perceived usability of the menu anchor interactor. / 2018 fanns det 3,6 miljarder mobila internetanvändare i världen, vilket visar att digitala designers måste tackla navigationsmöster och menyinteraktörer till smarta telefoner och små skärmar tidigt i sina projekt. Då användarnöjdhet är avgörande för en webbsidas framgång, och då en lyckad navigationsprocess genom ett menysystem är nödvändig för användarnöjdheten, är menysystemet en nyckelkomponent i gränssnittet. Den här studien avser tre typer av menyinteraktörer (obeständig dold meny, beständig toppmeny och navigationshub), på tre typer av webbsidor (enskild tjänsteleverantör, varumärkessajt och tjänsteregister). Målet var att undersöka hur webbsidans typ påverkar användarens inställning till menyinteraktörer. Den teoretiska basen utgörs av tidigare forskning på menysystem i grafiska användargränssnitt. Studien genomfördes med hjälp av ett frågeformulär där bilder av tre olika menyinteraktörer på tre olika typer av webbsidor presenterades för deltagarna. De ombads att på en Likertskala från ett till sju bedöma hur hjälpsam den enskilda menyinteraktören uppfattas. Därtill ombads de att förtydliga sitt omdöme i ett kvalitativt svar. De viktigaste resultaten från studien visar att användare föredrar menyinteraktörer som visar flera navigationslänkar och det finns indikationer på att den beständiga toppmenyinteraktören fungerar bäst för webbsidor av typen tjänsteregister, medan sidor av typen enskild tjänsteleverantör och varumärkessajt gynnas av en navigationshub. Resultaten visar emellertid också vikten av att studera användargränssnittskomponenter i deras fullständiga gränssnittskontext, eftersom helheten påverkar den uppfattade användbarheten hon menyinteraktören.

Submitted by Clebson Anjos (clebson.leandro54@gmail.com) on 2016-02-17T18:27:46Z No. of bitstreams: 1 arquivototal.pdf: 3132190 bytes, checksum: 7e00b90467562b4503c163aaa492c1e3 (MD5) / Made available in DSpace on 2016-02-17T18:27:46Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 3132190 bytes, checksum: 7e00b90467562b4503c163aaa492c1e3 (MD5) Previous issue date: 2013-06-21 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / From orality to mediation, narratives are surrounded by reconfiguration. The popularization of the use of computers and their post-mass functions has enhanced the ways of telling stories, bringing a communication system apparently horizontal when stories are told in environments that elevate the status of spectator to interactor. In a convergence era, these stories leave behind the narrative in a single media and become counted in a transmedia system, creating a fictional and immersive universe for viewers to interact. On one side you can see behind the scenes, the other side is the public. In the middle, a mirror that blurs fact from fiction. This text intends to resume atheoretical discussionof empirical situations on the concept of transmedia instituted by Henry Jenkins between 2000 and 2011. This discussion appears relevant from the time that new aspects of the concept become popular, and especially while new objects bring strange situations to the phenomenon, such as the national series Alice, produced and aired by HBO Latin America. Alice brings the discussion to production transmedia in Brazil, but highlights a peculiarity: the characters do not only exist on television and in social networks (Orkut, Twitter, Facebook), but also began to inhabit the everyday, the urban space, going to events and creating situations that functioned as unfolding of the events of the episodes, bringing new aspects to the concept of transmedia that Max Giovagnolli (2011) shall call "urban actions”. We question the television as this “mirror”, within this new narrative system and communication functions, and try to understand what new in bringing viewers to the center of this media. / Da oralidade à mediação, as narrativas passaram por momentos de reconfiguração constante. A popularização do uso dos computadores e de suas funções pós-massivas tem possibilitado novas instâncias às formas de se contar histórias, colocando em prática um sistema de comunicação aparentemente horizontal quando histórias são contadas em ambientes que elevam o status de espectador a interator. Em uma situação de convergência, estas histórias deixam para trás a narrativa em uma única mídia e passam a ser contadas de forma transmidiática, criando um universo fictício e imersivo para os espectadores interagirem. De um lado, os bastidores, do outro lado, o público. No meio, um espelho que não permite distinguir realidade de ficção. Este texto pretende retomar uma reflexão teórica através de situações empíricas sobre o conceito que promove estes embaralhamentos, o de narrativa transmidiática, instituído por Henry Jenkins entre 2000 e 2011. Esta discussão se mostra pertinente a partir do momento que novas vertentes do conceito se popularizam e, principalmente, novo objetos trazem situações ainda estranhas ao fenômeno, como a série nacional Alice, produzida e exibida pelo canal HBO Latin America. Alice traz a discussão para a produção nacional transmidiática e destaca uma particularidade: os personagens não só existiam na televisão e nas redes sociais (Orkut, Twitter, Facebook), como também “atravessaram o espelho” e passaram a habitar o cotidiano, indo a eventos e criando situações que funcionavam como desdobramentos dos acontecimentos dos episódios, trazendo novas situações para o conceito de transmídia, que Max Giovagnolli (2011) passa a chamar de “ações urbanas”. Questionamos então a televisão no lugar deste “espelho”, dentro deste novo sistema narrativo e comunicacional e tentamos entender quais funções o novo local de espectadores dentro desta mídia traz para a comunicação.

<p>Uvod: Nespecifičnost kliničke slike sepse, velike individualne razlike u odgovoru organizma na infekciju kao i neophodnost adekvatne inicijalne procene težine kliničke slike, toka i ishoda bolesti, čine istraživanja biomarkera koji bi doprineli pravovremenom postavljanju dijagnoze i adekvatnoj prognozi bolesti izuzetno značajnim. Do sada je ispitivano preko 200 biomarkera od kojih ni jedan nije pokazao zadovoljavajuću senzitivnost i specifičnost. Uloga B limfocita u patogenezi sepse pri tome je nedovoljno istražena. Članovi superfamilije tumor-nekrozis faktora alfa: A proliferation inducing ligand (APRIL), Bcell activating factor (BAFF) i solubilni transmembrane activator and calcium modulator cyclophilin ligand interactor (sTACI) su citokini koji imaju ključnu ulogu u homeostazi B limfocita. Cilj istraživanja bio je da se ispita dijagnostički i prognostički značaj citokina članova superfamilije tumor nekrozis faktora alfa (APRIL, BAFF, sTACI) za procenu težine kliničke slike, razvoja multiorganske disfunkcije (MODS) u prvih 48h hospitalizacije i letalnog ishoda sepse. Ispitanici i metode: Istraživanjem je obuhvaćeno 150 obolelih od sepse lečenih na Klinici za infektivne bolesti i Odeljenju anestezije i reanimacije Kliničkog centra Vojvodine i 30 zdravih dobrovljnih davalaca krvi. Kod svih bolesnika evidentirani su demografski i ostali podaci iz istorije bolesti kao i laboratorijske analize u okviru rutinske dijagnostike sepse. Iz dodatnih 5ml venske krvi svim ispitanicima određene su koncentracije APRIL-a, BAFF-a, sTACI-ja ELISA metodom komercijalnim testovima proizvođača R&amp;D Systems. Rezultati pokazuju da su koncentracije sva tri citokina (APRIL, BAFF i sTACI) statistički značajno povi&scaron;ene kod obolelih od sepse u odnosu na zdravu populaciju (p&lt;0.001), pri čemu APRIL pokazuje najveću senzitinvost (99%) i specifičnost (97%). Najveći dijagnostički značaj BAFF-a ogleda se u sposobnosti distinkcije između sepsi uzrokovanih Gram pozitivnim i Gram negativnim bakterijama (p=0,03). U predikciji razvoja MODS-a i letalnog ishoda sepse multivarijantnom regresionom analizom kao nezavisni prediktori pokazali su se jedino antiinflamatorni biomarker sTACI receptor i klinička procena pacijenta iskazana kroz APACHE II i SOFA skor. Senzitivnost i specifilnost sTACI receptora u predikciji razvoja MODS-a i letalnog ishoda daleko nadma&scaron;uje do sada rutinski kori&scaron;ćen prokalcitonin. Zaključak: Dobijeni rezultati ukazuju na to da su citokini koji učestvuju u regulaciji funkcije B limfocita značajni dijagnostički i prognostički parametri u sepsi. Predominacija antiinflamatornog odgovora na koju ukazuju povi&scaron;ene koncentracije sTACI receptora pokazala se pored APACHE II i SOFA skora kao jedini nezavisni prediktor razvoja MODS-a i letalnog ishoda septičnih bolesnika. Neophodna su dalja istraživanja u pravcu određivanja momenta kada u imunskom odgovoru organizam prelazi iz stanja dominacije proniflamatornog u dominaciju antiinflamatornog odgovora radi pravovremenog reagovanja imunomodulatornom terapijom.</p> / <p>Introduction: The nonspecific clinical presentation of sepsis and great individual response variations, as well as huge significance of adequate early prognosis of its clinical course and outcome made sepsis biomarkers research extremely significant. The properties of more than 200 biomarkers have been evaluated for prognostic value, but none have adequate specificity and sensitivity. The role of the B cells in sepsis pathogenesis also remains unclear. Tumor necrosis factor alpha (TNF-&alpha;) superfamily members: A proliferation inducing ligand (APRIL), Bcell activating factor (BAFF) and soluble transmembrane activator and calcium modulator cyclophilin ligand interactor (sTACI) are key factors in B cell biology. The aim of the study was to evaluate the diagnostic and prognostic significance of determining the concentrations of tumor necrosis factor alpha superfamily members for the prediction of MODS development in the first 48h of hospitalization as well as outcome prediction.<br />Subjects and methods: The study included 150 patients suffering from sepsis treated at the Clinic for infectious diseases and Department for anesthesiology and reanimatology of the Clinical center of Vojvodina, and 30 healthy volunteer blood donors. The demographic and other data regarding routine blood analysis performed during sepsis treatment of the patients has been acquired from their hospitalization documentation. Additional 5 ml of venous blood was taken from the patients and the concentrations of APRIL, BAFF and sTACI have been determined using the ELISA method by using R&amp;D Systems commercial kit&rsquo;s. Results: There is a statistically significant difference in concentrations of APRIL, BAFF and sTACI between healthy blood donors and septic patients (p&lt;0.001). APRIL showed the highest sensitivity (99%) and specificity (97%) in distinguishing sepsis from healthy subjects. BAFF showed statistically significant higher concentrations in Gram positive than in Gram negative sepsis (p=0,03). In the multivariate logistic regression analysis, only anti-inflammatory cytokine sTACI and APACHE II or SOFA score remained significant predictors of MODS and lethal outcome. sTACI showed greater sensitivity and specificity for MODS and outcome prediction then the widely used procalcitonin.&nbsp; Conclusions: The concentrations of TNF superfamily members, the main regulators of B cell function, have a significant diagnostic and prognostic value in predicting sepsis course and outcome. The predomination of the anti-inflammatory response, as being pointed out by elevated concentrations of sTACI receptors, has proved to be the only independent predictor, besides APACHE II and SOFA score, in MODS and lethal outcome development in sepsis. Further research is needed in order to accurately determine the exact moment when the immunological response shifts from the predominance of the pro-inflammatory response to the predominance of the anti-inflammatory response, so as to ensure the timely application of therapy that modulates the immunological response.</p>

No description available.

No description available.