Oralidade, leitura e escrita no domínio do sistema da escrita alfabética

Orientadora: Profª Drª Veronica BrancoDissertação (mestrado) - Universidade Federal do Paraná, Setor de Educação, Programa de Pós-Graduação em Educação : Teoria e Prática de Ensino. Defesa: Curitiba, 20/07/2015Inclui referências : f. 127-130Resumo: Este estudo relata pesquisa-ação realizada com alunos da rede municipal de Curitiba. O trabalho considerou os estudos voltados à alfabetização com embasamento teórico nas áreas da Psicologia da Educação e da Línguística. Os principais teóricos utilizados foram: Ferreiro (2001), Ferreiro e Teberosky (1999), Teberosky (1995), Teberosky e Colomer (2003) Halliday (1998), Morais (2012), Cagliari (1994; 1998). O principal objetivo foi estudar os níveis de escrita dos alunos de uma turma de 1º ano de ensino fundamental em aplicação de atividades sequenciadas de oralidade, leitura e escrita. Realizou-se uma microanálise das condições iniciais dos alunos, bem como um acompanhamento da evolução dos níveis de conhecimento após a intervenção. O trabalho apresenta, também, análises das atividades propostas as quais podem auxiliar professores alfabetizadores na escolha de metodologias e no acompanhamento dos avanços dos alunos no processo de aquisição do sistema de escrita alfabética. Palavras-chave: Alfabetização. Oralidade. Leitura e Escrita.Abstract: This study reports an action-research conducted with students from public elementary schools of Curitiba. The studies about literacy with theoretical background in the fiels of Educational Psychology and Linguistics were considered in this research. The main theoretical references are: Ferreiro (2001), Ferreiro and Teberosky (1999), Teberosky (1995), Teberosky and Colomer (2003) Halliday (1998), Morais (2012), Cagliari (1994; 1998). The action-research main goal was to study the levels of writing of first grade students from Primary Education during the application of orality, reading and writing sequenced activities. A microanalysis of the initial conditions of the students was held, as well as monitoring the improvement in levels of knowledge after the intervention. It also presents analysis of proposed activities that can help literacy teachers in the process of choosing methodologies and in monitoring the progress of students in the alphabetic writing system process acquisition. Keywords: Literacy; Orality; Reading and Writin

Mathematical modeling of differential effects of neo-adjuvant Sunitinib on primary tumor and metastatic growth

International audienceSunitinib is a drug with anti-angiogenic activity used in the treatment of patients with metastases from renal cell carcinoma or gastrointestinal tumors. However, despite clear efficacy in reducing established tumor growth, recent preclinical studies have shown limited, or even opposing, efficacies in preventing metastatic spread [1, 2]. In this work, we evaluated a previously validated mechanistic mathematical model of metastasis [3] to describe primary tumor and metastatic dynamics in response to neoadjuvant anti-angiogenic treatment in clinically relevant mouse models of spontaneous metastatic breast and kidney cancers that develop after surgical removal of orthotopically implanted primary tumors. The data of more than 380 mice receiving either vehicle or sunitinib in the neoadjuvant (presurgical) setting according to different schedules was analyzed. The experimental datasets comprise measurements of primary tumor and metastatic burden kinetics as well as pre-surgical molecular and cellular biomarkers, including vascular cell Ki67 and CD31 expression, circulating tumor cells (CTCs) and myeloid derived suppressor cell counts (MDSCs). Estimation of the mathematical model's parameters was performed using a mixed-effects population approach. Population fits obtained modeling the effect of treatment only on primary tumor growth described well the experimental data of all the treated groups considered, suggesting a negligible effect of the neo-adjuvant treatment on early metastatic spread and growth. When inserting in the model the available biomarkers as covariates, measurements of Ki67+/CD31+, CTCs and granulocytic MDSCs were found significantly correlated with a specific model parameter expressing the metastatic aggressiveness of the tumor. Together, our mathematical model confirms a differential effect of sunitinib on primary (localized) tumors compared to secondary (metastatic) disease. Our results suggest that CTCs and MDSCs might help in predicting metastatic potential and provide a biologically-based computational model integrating these biomarkers into personalized predictions of metastatic benefit of pre-operative treatments. [1] Ebos, J. M. L., Lee, C. R., Cruz-Munoz, W., Bjarnason, G. A., Christensen, J. G., and Kerbel, R. S. (2009). Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell, 15(3):232-239

Modeling Spontaneous Metastasis following Surgery: An In Vivo-In Silico Approach

International audienceRapid improvements in the detection and tracking of early-stage tumor progression aim to guide decisions regarding cancer treatments as well as predict metastatic recurrence in patients following surgery. Mathematical models may have the potential to further assist in estimating metastatic risk, particularly when paired with in vivo tumor data that faithfully represent all stages of disease progression. Herein we describe mathematical analysis that uses data from mouse models of spontaneous metastasis developing after surgical removal of orthotopically implanted primary tumors. Both presurgical (primary tumor) and postsurgical (metastatic) growth was quantified using bioluminescence and was then used to generate a mathematical formalism based on general laws of the disease (i.e. dissemination and growth). The model was able to fit and predict pre-/post-surgical data at the level of the individual as well as the population. Our approach also enabled retrospective analysis of clinical data describing the probability of metastatic relapse as a function of primary tumor size. In these data-based models, inter-individual variability was quantified by a key parameter of intrinsic metastatic potential. Critically, our analysis identified a highly nonlinear relationship between primary tumor size and postsurgical survival, suggesting possible threshold limits for the utility of tumor size as a predictor of metastatic recurrence. These findings represent a novel use of clinically relevant models to assess the impact of surgery on metastatic potential and may guide optimal timing of treatments in neoadjuvant (presurgical) and adjuvant (postsurgical) settings to maximize patient benefit

STAT3/LKB1 controls metastatic prostate cancer by regulating mTORC1/CREB pathway

Prostate cancer (PCa) is a common and fatal type of cancer in men. Metastatic PCa (mPCa) is a major factor contributing to its lethality, although the mechanisms remain poorly understood. PTEN is one of the most frequently deleted genes in mPCa. Here we show a frequent genomic co-deletion of PTEN and STAT3 in liquid biopsies of patients with mPCa. Loss of Stat3 in a Pten-null mouse prostate model leads to a reduction of LKB1/pAMPK with simultaneous activation of mTOR/CREB, resulting in metastatic disease. However, constitutive activation of Stat3 led to high LKB1/pAMPK levels and suppressed mTORC1/CREB pathway, preventing mPCa development. Metformin, one of the most widely prescribed therapeutics against type 2 diabetes, inhibits mTORC1 in liver and requires LKB1 to mediate glucose homeostasis. We find that metformin treatment of STAT3/AR-expressing PCa xenografts resulted in significantly reduced tumor growth accompanied by diminished mTORC1/CREB, AR and PSA levels. PCa xenografts with deletion of STAT3/AR nearly completely abrogated mTORC1/CREB inhibition mediated by metformin. Moreover, metformin treatment of PCa patients with high Gleason grade and type 2 diabetes resulted in undetectable mTORC1 levels and upregulated STAT3 expression. Furthermore, PCa patients with high CREB expression have worse clinical outcomes and a significantly increased risk of PCa relapse and metastatic recurrence. In summary, we have shown that STAT3 controls mPCa via LKB1/pAMPK/mTORC1/CREB signaling, which we have identified as a promising novel downstream target for the treatment of lethal mPCa

Oralidade, leitura e escrita no domínio do sistema da escrita alfabética

Orientadora: Profª Drª Veronica BrancoDissertação (mestrado) - Universidade Federal do Paraná, Setor de Educação, Programa de Pós-Graduação em Educação : Teoria e Prática de Ensino. Defesa: Curitiba, 20/07/2015Inclui referências : f. 127-130Resumo: Este estudo relata pesquisa-ação realizada com alunos da rede municipal de Curitiba. O trabalho considerou os estudos voltados à alfabetização com embasamento teórico nas áreas da Psicologia da Educação e da Línguística. Os principais teóricos utilizados foram: Ferreiro (2001), Ferreiro e Teberosky (1999), Teberosky (1995), Teberosky e Colomer (2003) Halliday (1998), Morais (2012), Cagliari (1994; 1998). O principal objetivo foi estudar os níveis de escrita dos alunos de uma turma de 1º ano de ensino fundamental em aplicação de atividades sequenciadas de oralidade, leitura e escrita. Realizou-se uma microanálise das condições iniciais dos alunos, bem como um acompanhamento da evolução dos níveis de conhecimento após a intervenção. O trabalho apresenta, também, análises das atividades propostas as quais podem auxiliar professores alfabetizadores na escolha de metodologias e no acompanhamento dos avanços dos alunos no processo de aquisição do sistema de escrita alfabética. Palavras-chave: Alfabetização. Oralidade. Leitura e Escrita.Abstract: This study reports an action-research conducted with students from public elementary schools of Curitiba. The studies about literacy with theoretical background in the fiels of Educational Psychology and Linguistics were considered in this research. The main theoretical references are: Ferreiro (2001), Ferreiro and Teberosky (1999), Teberosky (1995), Teberosky and Colomer (2003) Halliday (1998), Morais (2012), Cagliari (1994; 1998). The action-research main goal was to study the levels of writing of first grade students from Primary Education during the application of orality, reading and writing sequenced activities. A microanalysis of the initial conditions of the students was held, as well as monitoring the improvement in levels of knowledge after the intervention. It also presents analysis of proposed activities that can help literacy teachers in the process of choosing methodologies and in monitoring the progress of students in the alphabetic writing system process acquisition. Keywords: Literacy; Orality; Reading and Writin

O perfil político-pedagógico do professor e a qualidade de sua relação com o aluno

Orientador: Maria Célia Barbosa AiresMonografia (especialização) - Universidade Federal do Paraná, Especialização em Organização do Trabalho PedagógicoInclui referênciasResumo: Este trabalho apresenta uma pesquisa realizada na tarefa de conclusão do curso de Especialização de Organização do Trabalho Pedagógico: A Relação entre Escola Pública e Educação Popular. Propôs-se a analisar o perfil político-pedagógico do professor e a qualidade de sua relação com o aluno. Defende que o melhor perfil de um professor, objetivando a qualidade da relação professor-aluno, e a aprendizagem significativa, é o profissional que se identifica com a profissão, compreende a especificidade da escola, participa ativamente das ações pedagógicas do âmbito escolar, busca ter bom relacionamento com seus alunos e tem compromisso e envolvimento com o processo de ensino-aprendizagem. O objeto de estudo foi delimitado a partir da inquietação e dificuldades encontradas na prática pedagógica pela pesquisadora e colegas de trabalho. A pesquisa de caráter exploratório mostrou que há uma grande necessidade por parte dos professores, de se comprometerem no sentido de implementar convicções pedagógicas que, muitas vezes não se efetivam na prática cotidiana da sala de aula de alguns dos docentes, por diversos motivos, ou ocorrem de maneira insuficiente, o que, certamente, acaba por comprometer o êxito escolar dos alunos, presentes na escola pública. Assim, a questão central da pesquisa consistiu em verificar o posicionamento e traços do perfil que os professores se atribuem como educadores na escola e, considerando as respostas que os mesmos situaram em categorias de 0 a 10, analisar os seguintes aspectos: a qualidade da formação acadêmica; importância da formação continuada; qualidade da relação com os alunos; compromisso como profissional da educação; identificação com a profissão; relação com os demais professores da escola; compreensão da especificidade do papel ou função social da escola; inserção na dinâmica da organização da escola; nível de participação na formulação do Projeto- Político-Pedagógico da escola; qualidade do aproveitamento das permanências para planejamento de aulas; nível de envolvimento emocional com os alunos; nível de autoridade em sala de aula; e o grau de importância atribuído à qualidade da relação professor-aluno para o processo de ensino-aprendizagem e ao envolvimento com o êxito do processo de ensino-aprendizagem. A metodologia do estudo caracterizou-se por uma pesquisa de abordagem qualitativa, envolvendo o estudo teórico e o conhecimento da realidade, por meio das técnicas de análise documental (foi analisado o Projeto Político- Pedagógico da escola) e do questionário (realizada a pesquisa com os professores). A pesquisa enfatizou, a partir do perfil político-pedagógico, a busca em saber e compreender o nível de participação e envolvimento dos professores com a escola, a busca por uma boa relação com seus alunos e consequentemente, o envolvimento com a qualidade do processo de ensino-aprendizagem que interessa às classes populare

Classical Mathematical Models for Description and Forecast of Experimental Tumor Growth

Despite internal complexity, tumor growth kinetics follow relatively simple laws that can be expressed as mathematical models. To explore this further, quantitative and discriminant analyses were performed for the purpose of comparing alternative models for their abilities to describe and predict tumor growth. The models were assessed against data from two in vivo experimental systems: an ectopic syngeneic tumor (Lewis lung carcinoma) and an orthotopically xenografted human breast carcinoma. The models included in the study comprised the exponential (with or without free initial volume), exponential-linear, power law, Gompertz, logistic, generalized logistic and von Bertalanffy models, as well as a model with dynamic carrying capacity. For the breast data, the observed linear dynamics were best captured by the Gompertz and exponential-linear models. The latter also exhibited the highest predictive power for this data set, with excellent prediction scores (≥80%) extending out as far as 12 days in the future. For the lung data, the Gompertz and power law models provided the most parsimonious and parametrically identifiable description. In contrast to the breast data, not one of the models was able to achieve a substantial prediction rate (≥70%) beyond the next day lung data point. In this context, adjunction of a priori information on the parameter distribution led to considerable improvement of predictions. For instance, forecast success rates went from 14.9% to 62.7% when using the power law model to predict the full future tumor growth curves, using just three data points. These results not only have important implications for biological theories of tumor growth and the use of mathematical modeling in preclinical anti-cancer drug investigations, but also may assist in defining how mathematical models could serve as potential prognostic tools in the clinic

Enhanced efficacy of sitravatinib in metastatic models of antiangiogenic therapy resistance.

Tyrosine kinase inhibitors (TKIs) that primarily target angiogenesis are approved to treat several cancers in the metastatic setting; however, resistance is common. Sequential treatment or 'switching' from one TKI to another following failure can be effective, but predicting which drugs will have cross-over sensitivity remains a challenge. Here we examined sitravatinib (MGCD516), a spectrum-selective TKI able to block MET, TAM (TYRO3, AXL, MerTK) and multiple receptor families (including PDGFRs, VEGFRs, and Ephs). Transcriptomic analysis of several mouse and human cell lines revealed diverse molecular changes after resistance to two TKIs (sunitinib and axitinib) with multiple sitravatinib targets found to be upregulated. Sitravatinib treatment in vitro resulted in enhanced anti-proliferative effects in resistant cells and was improved compared to TKIs with similar target profiles. In vivo, primary tumor growth inhibition after sitravatinib treatment in mice was enhanced in resistant tumors and metastasis suppression improved when tumors were surgically removed. Together, these results suggest that the diverse and often inconsistent compensatory signaling mechanisms found to contribute to TKI resistance may paradoxically improve the tumor-inhibiting effects of broad-spectrum TKIs such as sitravatinib that are able to block multiple signaling pathways. Sitravatinib in the second-line setting following antiangiogenic TKI treatment may have enhanced inhibitory effects in local and disseminated disease, and improve outcomes in patients with refractory disease