A Estratégia Saúde da Família, caracterizada inicialmente como Projeto QUALIS no município de São Paulo, iniciou as suas atividades em 1996 na zona leste da cidade, através da Casa de Saúde Santa Marcelina. O Programa de Saúde Bucal da estratégia Saúde da Família Santa Marcelina está atuando no território desde 1998, tendo como principal ponto de reivindicações dos gestores a ampliação do número de equipes para garantir a ampliação do acesso à população. Atualmente, a preocupação está focada nos resultados das ações do programa na saúde bucal da população assistida. Porém, avaliar os resultados das ações de saúde de um programa sem conhecer as bases e o contexto em que foi implantado, torna-se uma tarefa muito complicada. O objetivo geral do estudo é avaliar a implantação do Programa de Saúde Bucal da Estratégia Saúde da Família da Casa de Saúde Santa Marcelina/Organização Social Santa Marcelina, na zona leste do município de São Paulo e os objetivos específicos são: verificar o conhecimento dos profissionais do programa sobre as leis, normas e diretrizes estabelecidas para a saúde bucal na Atenção Básica; verificar a adequação dos processos de trabalho às leis, normas e diretrizes propostas pelo Ministério da Saúde e Secretaria Municipal de Saúde; e, verificar se a estrutura estabelecida, nos consultórios odontológicos das unidades de saúde, permite a operacionalização do trabalho de acordo com as leis, normas e diretrizes. Metodologia: Estudo descritivo/analítico através de pesquisa documental e do arcabouço legal que estabelece as bases para a Saúde Bucal na Atenção Básica e de dados primários coletados em instrumento apropriado, aplicado para o levantamento de informações sobre o conhecimento dos profissionais em relação às normas, diretrizes e a legislação específica, e, em relação ao desenvolvimento dos processos de trabalho. O universo de estudo é composto por 14 UBS que desenvolvem a estratégia Saúde da Família na região, assim como todas as ESB habilitadas no Ministério da Saúde pela instituição. A avaliação dos dados foi feita considerando as variáveis em três Eixos de Análises, que correspondem aos objetivos específicos da proposta. Assim foram criados os eixos: 1 Conhecimento dos profissionais; 2 Adequação dos processos de trabalho; e, 3 Estrutura. A hipótese a ser verificada foi, que o Programa de Saúde Bucal está implantado satisfatoriamente considerando os eixos de avaliação propostos. Resultados: o eixo Conhecimento dos profissionais teve um percentual de implantação de 87,7%, o eixo Adequação dos processos de trabalho teve um percentual de implantação de 82,0% e o eixo Estrutura teve um percentual de implantação de 80,5%. Conclusão: O Programa de Saúde Bucal da estratégia Saúde da Família está Satisfatoriamente Implantado (83,4%) na zona leste do município de São Paulo, considerando o conhecimento dos profissionais envolvidos sobre as leis, normas e diretrizes para a Saúde Bucal na Atenção Básica, a adequação do processo de trabalho às leis, normas e diretrizes, e a estrutura oferecida nos consultórios odontológicos para o desenvolvimento das ações. / The Family Healthcare Strategy, characterized initially as Project QUALIS in the municipality of São Paulo, started its activities in 1996 in the eastern area of the city, through the Casa de Saúde Santa Marcelina. The Program of oral healthcare of the Family Health strategy Santa Marcelina is acting in the territory since 1998, the main point of claims of managers the enlargement of the number of teams to ensure the expansion of access to the population. Currently, the concern is focused on the results of the actions of the program in oral health of the population assisted. However, to assess the results of health actions of a program without knowing the bases and the context in which was implemented, becomes a difficult task. The general objective of the study is to assess the implementation of the Program of oral healthcare of the Family Health Strategy of Casa de Saúde Santa Marcelina/Social Organization Santa Marcelina, in the eastern region of the municipality of S Paulo and specific objectives are: to verify the knowledge of professionals of the program about the laws, rules and guidelines established for oral healthcare in primary health; to verify the adequacy of work processes to the laws, rules and guidelines proposed by the Ministry of Health and Municipal Department of Health; and, to verify whether the structure established in dental clinics of public health units allows the structuring of the work in accordance with the laws, rules and guidelines. Methodology: descriptive study/analytical through documental research and the legal framework which lays the foundations for the Oral Health Care in Primary Health and primary data collected in appropriate instrument, applied for setting up information on the knowledge of professionals in relation to standards, guidelines and specific legislation, and, in relation to the development of work processes. The universe of study is composed by 14 public health primary care units which develop the family health strategy in the region as well as all oral health teams empowered in the Health Ministry by the institution. Data evaluation was performed considering the variables in three axles of analyzes, which correspond to specific objectives of the proposal. So were created the axles: 1-Knowledge of professionals; 2- Adequacy of work processes; and, 3- Structure. The hypothesis to be verified was that the Program of Oral healthcare is implemented satisfactorily whereas the axles of evaluation proposed. Results: the axis of knowledge of professionals had a percentage of implementing of 87.7%, the axis Adequacy of the processes of work had a percentage of implementing of 82.0% and the axis Structure had a percentage of implementing of 80.5%. Conclusion: Concerning knowledge of involved professionals about laws, rules and guidelines for the Oral Health in basic care, the adequacy of work processes to the laws, rules and guidelines and structure offered in public dental clinics for clinical procedures it is legitimate that the Program of oral healthcare of the Family Health strategy is satisfactorily implemented (83.4%) in the eastern region of the city of São Paulo.

Hepatitis delta virus (HDV) is the smallest known mammalian RNA virus, containing a genome of ~ 1700 nt. Replication of HDV is extremely dependent on the host transcription machinery. Previous studies indicated that RNA polymerase II (RNAPII) directly binds to and forms an active preinitiation complex on the right terminal stem-loop fragment (R199G) of HDV genomic RNA, and that the polypyrimidine tract-binding protein-associated splicing factor (PSF) directly binds to the same region. Further studies demonstrated that PSF also binds to the carboxyl-terminal domain (CTD) of RNAP II. In my thesis, co-immunoprecipitation assays were performed to show that PSF stimulates the interaction of RNAPII with R199G. Results of co-immunoprecipitation experiments also suggest that both the RNA recognition motif 2 (RRM2) and N-terminal proline-rich region (PRR) of PSF are required for the interaction between PSF and RNAPII, while the two RNA recognition motifs (RRM1 and RRM2) might be required for the interaction of PSF with R199G. Furthermore, in vitro run-off transcription assays suggest that PSF facilitates the HDV RNA transcription from the R199G template. Together, the above experiments suggest that PSF might act as a transcription factor for the RNAPII transcription of HDV RNA by linking the CTD of RNAPII and the HDV RNA promoter. My experiments provide a better understanding of the mechanism of HDV RNA-dependent transcription by RNAP II.

Title: Image Deblurring in Demanding Conditions Author: Jan Kotera Department: Institute of Information Theory and Automation, Czech Academy of Sciences Supervisor: Doc. Ing. Filip Šroubek, Ph.D., DSc., Institute of Information Theory and Automation, Czech Academy of Sciences Abstract: Image deblurring is a computer vision task consisting of removing blur from image, the objective is to recover the sharp image corresponding to the blurred input. If the nature and shape of the blur is unknown and must be estimated from the input image, image deblurring is called blind and naturally presents a more difficult problem. This thesis focuses on two primary topics related to blind image deblurring. In the first part we work with the standard image deblurring based on the common convolution blur model and present a method of increasing robustness of the deblur- ring to phenomena violating the linear acquisition model, such as for example inten- sity clipping caused by sensor saturation in overexposed pixels. If not properly taken care of, these effects significantly decrease accuracy of the blur estimation and visual quality of the restored image. Rather than tailoring the deblurring method explicitly for each particular type of acquisition model violation we present a general approach based on flexible automatic...

La technique de reconstruction de forme par lumière structurée (ou projection de motifs) permet d’acquérir la topographie d’une surface objet avec une précision et un échantillonnage de points dense, de manière strictement non invasive. Pour ces raisons, elle fait depuis plusieurs années l’objet d’un fort intérêt. Les travaux présentés ici ont pour objectif d’adapter cette technique aux conditions sévères des expériences de physique des chocs : aspect monocoup, grande brièveté des phénomènes, diversité des échelles d’observation (de quelques millimètres au décimètre). Pour répondre à ces exigences, nous proposons de réaliser un dispositif autour d’un système d’imagerie rapide par éclairage laser nanoseconde, présentant des performances éprouvées et bien adaptées. La première partie des travaux s’intéresse à analyser les phénomènes prépondérants pour la qualité des images. Nous montrons quels sont les contributeurs principaux à la dégradation des signaux, et une technique efficace de lissage du speckle par fibrage est présentée. La deuxième partie donne une formulation projective de la reconstruction de forme ; celle-ci est rigoureuse, ne nécessitant pas de travailler dans l’approximation de faible perspective, ou de contraindre la géométrie de l’instrument. Un protocole d’étalonnage étendant la technique DLT (Direct Linear Transformation) aux systèmes à lumière structurée est proposé. Le modèle permet aussi, pour une expérience donnée, de prédire les performances de l’instrument par l’évaluation a priori des incertitudes de reconstruction. Nous montrons comment elles dépendent des paramètres du positionnement des sous-ensembles et de la forme-même de l’objet. Une démarche d’optimisation de la configuration de l’instrument pour une reconstruction donnée est introduite. La profondeur de champ limitant le champ objet minimal observable, la troisième partie propose de l’étendre par codage pupillaire : une démarche de conception originale est exposée. L’optimisation des composants est réalisée par algorithme génétique, sur la base de critères et de métriques définis dans l’espace de Fourier. Afin d’illustrer les performances de cette approche, un masque binaire annulaire a été conçu, réalisé et testé expérimentalement. Il corrige des défauts de mise au point très significatifs (Ψ≥±40 radians) sans impératif de filtrage de l’image. Nous montrons aussi que ce procédé donne accès à des composants tolérant des défauts de mise au point extrêmes (Ψ≈±100 radians , après filtrage). La dernière partie présente une validation expérimentale de l’instrument dans différents régimes, et à différentes échelles. Il a notamment été mis en œuvre sur l’installation LULI2000, où il a permis de mesurer dynamiquement la déformation et la fragmentation d’un matériau à base de carbone (champs millimétriques). Nous présentons également les mesures obtenues sous sollicitation pyrotechnique sur un revêtement de cuivre cylindrique de dimensions décimétriques. L’apparition et la croissance rapide de déformations radiales submillimétriques est mesurée à la surface du revêtement. / A Structured Light System (SLS) is an efficient means to measure a surface topography, as it features both high accuracy and dense spatial sampling in a strict non-invasive way. For these reasons, it became in the past years a technique of reference. The aim of the PhD is to bring this technique to the field of shock physics. Experiments involving shocks are indeed very specific: they only allow single-shot acquisition of extremely short phenomena occurring under a large range of spatial extensions (from a few mm to decimeters). In order to address these difficulties, we have envisioned the use of a well-known high-speed technique: pulsed laser illumination. The first part of the work deals with the evaluation of the key-parameters that have to be taken into account if one wants to get sharp acquisitions. The extensive study demonstrates that speckle effect and depth of field limitation are of particular importance. In this part, we provide an effective way to smooth speckle in nanosecond regime, leaving 14% of residual contrast. Second part introduces an original projective formulation for object-points reconstruction. This geometric approach is rigorous; it doesn’t involve any weak-perspective assumptions or geometric constraints (like camera-projector crossing of optical axis in object space). From this formulation, a calibration procedure is derived; we demonstrate that calibrating any structured-light system can be done by extending the Direct Linear Transformation (DLT) photogrammetric approach to SLS. Finally, we demonstrate that reconstruction uncertainties can be derived from the proposed model in an a priori manner; the accuracy of the reconstruction depends both on the configuration of the instrument and on the object shape itself. We finally introduce a procedure for optimizing the configuration of the instrument in order to lower the uncertainties for a given object. Since depth of field puts a limitation on the lowest measurable field extension, the third part focuses on extending it through pupil coding. We present an original way of designing phase components, based on criteria and metrics defined in Fourier space. The design of a binary annular phase mask is exhibited theoretically and experimentally. This one tolerates a defocus as high as Ψ≥±40 radians, without the need for image processing. We also demonstrate that masks designed with our method can restore extremely high defoci (Ψ≈±100 radians) after processing, hence extending depth of focus by amounts unseen yet. Finally, the fourth part exhibits experimental measurements obtained with the setup in different high-speed regimes and for different scales. It was embedded on LULI2000 high energy laser facility, and allowed measurements of the deformation and dynamic fragmentation of a sample of carbon. Finally, sub-millimetric deformations measured in ultra-high speed regime, on a cylinder of copper under pyrotechnic solicitation are presented.

O ganho crescen te de desempenho nos computadores modernos tem impulsionado os trabalhos científicos nas áreas de simulação computacional. Muitos autores utilizam em suas pesquisas ferramentas comerciais que limitam seus trabalhos ao esconder os algoritmos internos destas ferramentas e dificultam a adição de dados in-vivo nestes trabalhos. Este trabalho explora esta lacuna deixada por aqueles autores. Elaboramos um arcabouço computacional capaz de reproduzir os fenômenos óticos e fisiológicos do sistema visual. Construímos com superfícies quádricas os modelos esquemáticos do olho humano e propomos um algoritmo de traçado de raio realístico. Então realizamos um estudo nos modelos esquemáticos e a partir deles mais a adição de dados in-vivo obtidos de um topógrafo de córnea extraímos informações óticas destes modelos. Calculamos os coeficientes e Zernike dos modelos para tamanhos diversos de pupila e obtivemos medidas de aberração do olho humano. Os resultados encontrados estão de acordo com os trabalhos relacionados e as simulações com dados in-vivo estão consoantes com as produzidas por um aparelho de frente de onda comerciais. Este trabalho é um esforço em aproveitar as informações adquiridas pelos equipamentos modernos de oftalmologia, além de auxiliar o entendimento de sistemas visuais biológicos acabam também em auxiliar a elaboração de sistemas de visão artificial e os projetistas de sistemas óticos / The increase in performance of the modern computers has driven scientific work in the areas of computer simulation. Many authors use in their research commercial tools that use embedding algorithms, which sources are not provided, and it makes harder and sometimes impossible, the development of novel theories or experiments. This work explores this gap left for those authors. We present a computational framework capable to reproduce the optical and physiological phenomena of the human visual system. We construct schematical models of the human eye from quadrics surfaces and consider an algorithm of realistic ray tracing. Afterward, we performed a study on schematics models and in addition we introduce, in these models, in-vivo data obtained from corneal topography machine and extract optical information. We calculate the Zernike coefficients in the models for different sizes of pupil and measures of aberration of the human eye. The results are in agreement with related work and simulations with in-vivo data are according with the produced by a commercial wave-front device. This work is an effort in using to advantage the information acquired for the modern equipment of ophthalmology, besides assisting the understanding of biological visual systems, it also helps the development of artificial vision systems and the designing of optical systems

Effective knowledge sharing within project teams is critical to knowledge-intensive professional service firms. Prior research studies indicate a positive association between trust, social-cognitive factors, and effective knowledge sharing among co-workers. The conceptual framework proposed here builds on these studies, and draws from theoretical foundations from the organizational behavior, psychology, information studies, sociology, and management literature on organizational trust and knowledge sharing, and identifies the most significant factors found to influence organizational knowledge sharing directly and indirectly through trust. The study makes methodological contributions in the form of conceptualizations for knowledge sharing behavior, trust, and tie strength. Also, it provides a more nuanced and focused analysis, by factoring for knowledge type and co-worker working relationship. Data were collected from 275 knowledge workers (‘legal professionals’ and paralegals) engaged in shared legal project work, at one of Canada’s largest multijurisdictional law firms. The nature of their work required a significant reliance on co-workers, for both explicit and tacit knowledge. Multiple regression analysis, among other statistical techniques, was used to test the hypotheses and determine significant relationships. Of the factors examined in the study, the three found to have the strongest effect on respondents’ trust in their co-workers were shared vision, shared language, and tie strength. Furthermore, the two factors found to have the strongest effect on organizational knowledge sharing behavior were trust and shared vision. Overall trust was also found to have a mediating effect between shared vision and knowledge sharing behavior, and between shared language and knowledge sharing behavior. A significant implication for practitioners is that effective knowledge sharing among co-workers requires a nurturing manager to work on developing co-worker trust and shared vision. Furthermore, a manager wanting to promote trust between co-workers must nurture shared language and shared vision.

Ma thèse se situe à la jonction de trois domaines : l'étude des noyaux actifs de galax- ies (AGN), l'optique adaptative (OA) et l'optimisation des méthodes de traitement de données associées. Elle porte sur le développement d'outils permettant d'obtenir la meilleure qualité d'image en terme de résolution et de contraste et ainsi de max- imiser le retour scientifique notamment pour l'étude des AGN. L'optique adaptative permet de compenser les effets de la turbulence atmosphérique sur le front d'onde et ainsi de s'approcher de la limite théorique de résolution d'un télescope optique. La correction apportée est cependant partielle et des résidus de correction limitent le contraste dans l'image. Afin de maximiser celui-ci, il est possible d'utiliser des méthodes de déconvolution, mais il est nécessaire pour les appliquer de connaître précisément la fonction d'étalement de point (FEP) durant l'observation. J'ai étudié le noyau actif de la galaxie NGC 1068 à l'aide de NACO, une caméra proche infrarouge munie d'une optique adaptative sur le VLT. J'ai pu déterminer que le jet, détecté en radio, est la source d'excitation probable des raies coronales observées dans les régions proches (30-60 pc), au nord du noyau, ayant une struc- turation très particulière en vagues régulièrement espacées et disposées le long du jet. J'ai aussi mis en évidence la présence de super amas d'étoiles dans ces mêmes régions. L'étude a été limitée par la perte de contraste dans certaines images qui aurait pu être restaurée à l'aide d'une déconvolution. La seconde partie de ma thèse est alors dédiée à la reconstruction de la FEP afin de déconvoluer les images. Après le développement d'un outil utilisant une estimation au sens des moindres-carrés (MC) pour reconstruire la FEP à partir des données de l'OA, j'ai développé une nouvelle méthode basée sur une approche de type maximum de vraisemblance (MV) qui utilise également les données de boucle. J'ai montré sur simulation numérique (sur un système de type Canary) que la méthode MV et MC permettent toutes deux une estimation précise de la FEP dans les cas où le système d'optique adaptative fonctionne à fréquence élevée. À basse fréquence, où la méthode MC atteint ses limites, la méthode MV reste robuste et permet une estimation précise de la FEP. Sur la base des résultats préliminaires que j'ai obtenus, la méthode MV semble très prometteuse et pourra être à terme appliquée dans le cadre des ELT.

Effective knowledge sharing within project teams is critical to knowledge-intensive professional service firms. Prior research studies indicate a positive association between trust, social-cognitive factors, and effective knowledge sharing among co-workers. The conceptual framework proposed here builds on these studies, and draws from theoretical foundations from the organizational behavior, psychology, information studies, sociology, and management literature on organizational trust and knowledge sharing, and identifies the most significant factors found to influence organizational knowledge sharing directly and indirectly through trust. The study makes methodological contributions in the form of conceptualizations for knowledge sharing behavior, trust, and tie strength. Also, it provides a more nuanced and focused analysis, by factoring for knowledge type and co-worker working relationship. Data were collected from 275 knowledge workers (‘legal professionals’ and paralegals) engaged in shared legal project work, at one of Canada’s largest multijurisdictional law firms. The nature of their work required a significant reliance on co-workers, for both explicit and tacit knowledge. Multiple regression analysis, among other statistical techniques, was used to test the hypotheses and determine significant relationships. Of the factors examined in the study, the three found to have the strongest effect on respondents’ trust in their co-workers were shared vision, shared language, and tie strength. Furthermore, the two factors found to have the strongest effect on organizational knowledge sharing behavior were trust and shared vision. Overall trust was also found to have a mediating effect between shared vision and knowledge sharing behavior, and between shared language and knowledge sharing behavior. A significant implication for practitioners is that effective knowledge sharing among co-workers requires a nurturing manager to work on developing co-worker trust and shared vision. Furthermore, a manager wanting to promote trust between co-workers must nurture shared language and shared vision.

p53 is a nodal tumor suppressor protein that acts as a major defense against cancers. Approximately 50% of human tumours have mutations in p53 gene. Among its myriad features, the most distinctive is the ability to elicit both apoptotic death and cell cycle arrest. p53 has several isoforms. Most of them are produced by either internal promoter activity of the gene or alternate splicing of the pre-mRNA. Apart from these mechanisms, p53 mRNA has also been shown to be translated into two isoforms, the full-length p53 (FL-p53) and a truncated isoform ΔN-p53, which acts as a dominant-negative inhibitor of FL-p53. Under conditions of cellular stress, the canonical mode of translation initiation is compromised. To maintain the synthesis of proteins important for cell survival and cell-fate decisions, a subset of cellular mRNAs utilizes a non-canonical mode of translation initiation. The 5’ untranslated region of these mRNAs are highly structured and function as Internal Ribosome Entry Site (IRES). Previously, from our laboratory it has been shown that translation of p53 and its N-terminally truncated isoform ΔN-p53 can be initiated by IRES mediated mechanism. IRES mediated translation of ΔNp53 was maximum at G1-S phase but that of FL-p53 was maximum at the G2-M phase. Interestingly in case of a human genetic disorder X-linked dyskeratosis congenita (X-DC), aberrant IRES mediated p53 translation has been reported. It has also been reported that during oncogenic induced senescence (OIS) a switch between cap-dependent to IRES meditated translation occurs in p53 mRNA. From our laboratory, we have also demonstrated that polypyrimidine tract binding protein (PTB) positively regulates the IRES activities of both the p53 isoforms by shuttling from nucleus to the cytoplasm during genotoxic stress conditions. It is very important to understand how these two isoforms are regulated and in turn control the cellular functions. In the first part of the thesis, to investigate the importance of the structural integrity of the cis acting elements within p53 RNA, we have compared the secondary structure of the wild-type RNA with cancer-derived silent mutant p53 RNAs having mutations in the IRES elements such as L22L (CTA to CTG) a natural cancer mutation and Triple Silent Mutation (mutations were present at the wobble position of codon 17, 18, 19). These mutations result in the conformational alterations of p53 IRES RNA that abrogates the IRES function ex vivo significantly. It appears that these mutant RNAs failed to bind some trans-acting factors (p37, p41/44 etc) which might be critical for the IRES function. By super-shift assay using anti hnRNPC1/C2 antibody, we have demonstrated that the TSM mutant showed reduced binding to this protein factor. Partial knockdown of hnRNP C1/C2 showed significant decrease in p53 IRES activity and reduced synthesis of ΔN-p53. Also we have showed that introducing compensatory mutations in TSM mutant RNA rescued the secondary structure as well as function of p53 IRES. Further, the role of another silent point mutation in the coding sequence of p53 was investigated. Silent mutation (CCG to CCA) at codon 36 (P36P) showed decreased IRES activity. The mutation also resulted in differential binding of cellular proteins. Taken together, our observations suggest pivotal role of some specific trans acting factors in regulating the p53-IRES function, which in turn influences the synthesis of different p53 isoforms. In the second part of the thesis, p53 IRES RNA interacting proteins were identified using RNA affinity approach. Annexin A2 and PTB associated Splicing Factor (PSF/SFPQ) were identified and their interaction with p53 IRES RNA in vitro and ex vivo was studied. Interestingly, in the presence of Ca2+ ions Annexin A2 showed increased binding with p53 IRES. By competition UV crosslinking we have showed Annexin A2 and PSF interact specifically with p53 IRES. Toe printing assay results showed the putative contact points of Annexin A2 and PSF proteins on p53 IRES RNA. Interestingly, both proteins showed extensive toe-prints in the neighbourhood of the initiator AUG region of p53. Further, competition UV-crosslinking reveals the interplay of these two proteins. Annexin A2 and PSF appear to compete each other for binding with p53 IRES. PSF is known to interact with PTB protein. Since PTB also interacts with p53 IRES and positively regulates the translation, we wanted to study the interplay between PTB and PSF proteins binding with p53 IRES. To address this, we have performed competition UV crosslinking experiment and showed that increasing concentrations of PTB decreases PSF and p53 IRES interaction. However, increasing concentrations of PSF does not decrease or increase in PTB p53 IRES interaction. Results suggest that both Annexin A2 and PSF proteins play important role in regulation of p53 IRES activity. To address the physiological role of Annexin A2 and PSF proteins on p53 IRES activity, these proteins were partially knocked down in cellulo. This in turn showed decrease in p53 IRES activity in dual luciferase assays as well as in the steady state levels of both the p53 isoforms in transient transfection experiments. Heightened or continued expression of p53 protein is very important under stress where IRES-dependent translation supersedes normal cap-dependent translation. Results showed that expression of Annexin A2 under doxorubicin and thapsigargin induced stress are important for maintenance of both p53 IRES activity and steady state levels of p53 isoforms. Earlier from our laboratory we have showed that the IRES responsible for ∆N-p53 translation is active at G1/S phase while the IRES responsible for full length p53 translation is active at G2/M phase. Subcellular localization of the trans-acting factors plays a pivotal role in regulation of IRES activity of cellular mRNA. In this context we wanted to study the nuclear and cytoplasm localization of Annexin A2 under different cell cycle stages. We have seen Annexin A2 protein is dispersed in nucleus and cytoplasm at G1/S boundary, but post-G2 phase it moved from nucleus to cytoplasm. Further we wanted to investigate the effect of Annexin A2 and PSF on expression of p53 transactivated genes. Partial knock down of Annexin A2 and PSF proteins showed decrease in p21 luciferase activity. By real-time PCR analysis, we have also showed decrease in expression of different p53 targets upon silencing of Annexin A2 protein. Taken together, our observations suggest pivotal role of cis acting and trans-acting factors in regulating the p53-IRES function, which in turn influences the synthesis of p53 isoforms.

O ganho crescen te de desempenho nos computadores modernos tem impulsionado os trabalhos científicos nas áreas de simulação computacional. Muitos autores utilizam em suas pesquisas ferramentas comerciais que limitam seus trabalhos ao esconder os algoritmos internos destas ferramentas e dificultam a adição de dados in-vivo nestes trabalhos. Este trabalho explora esta lacuna deixada por aqueles autores. Elaboramos um arcabouço computacional capaz de reproduzir os fenômenos óticos e fisiológicos do sistema visual. Construímos com superfícies quádricas os modelos esquemáticos do olho humano e propomos um algoritmo de traçado de raio realístico. Então realizamos um estudo nos modelos esquemáticos e a partir deles mais a adição de dados in-vivo obtidos de um topógrafo de córnea extraímos informações óticas destes modelos. Calculamos os coeficientes e Zernike dos modelos para tamanhos diversos de pupila e obtivemos medidas de aberração do olho humano. Os resultados encontrados estão de acordo com os trabalhos relacionados e as simulações com dados in-vivo estão consoantes com as produzidas por um aparelho de frente de onda comerciais. Este trabalho é um esforço em aproveitar as informações adquiridas pelos equipamentos modernos de oftalmologia, além de auxiliar o entendimento de sistemas visuais biológicos acabam também em auxiliar a elaboração de sistemas de visão artificial e os projetistas de sistemas óticos / The increase in performance of the modern computers has driven scientific work in the areas of computer simulation. Many authors use in their research commercial tools that use embedding algorithms, which sources are not provided, and it makes harder and sometimes impossible, the development of novel theories or experiments. This work explores this gap left for those authors. We present a computational framework capable to reproduce the optical and physiological phenomena of the human visual system. We construct schematical models of the human eye from quadrics surfaces and consider an algorithm of realistic ray tracing. Afterward, we performed a study on schematics models and in addition we introduce, in these models, in-vivo data obtained from corneal topography machine and extract optical information. We calculate the Zernike coefficients in the models for different sizes of pupil and measures of aberration of the human eye. The results are in agreement with related work and simulations with in-vivo data are according with the produced by a commercial wave-front device. This work is an effort in using to advantage the information acquired for the modern equipment of ophthalmology, besides assisting the understanding of biological visual systems, it also helps the development of artificial vision systems and the designing of optical systems