Modelagem (matemática) e modelagem na educação: reflexos na e da formação continuada

This article reports an experience of the development of a task of Modeling (Mathematics) and its projection to the classroom from the reflexes in and the continued formation. From the reflections in the training, the task triggered new research activities and favored the insertion of Modeling in the classroom to explore two main concepts of Mathematics: reason and proportionality through the concept of density.The results indicate the positive evaluation regarding the task developed and projection of the insertion of new practices of Modeling (Mathematics) by the teachers to the teaching action, thus increasing the use of Modeling in Education in the teacher's doing.However, they indicate concern about the fulfillment of the prescriptions, among them, the programmatic contents that are included in the Mathematics curriculum matrix. In relation to the students who experienced the task implemented by one of the teachers, they (re) organized the representations initially textualized and signified the concept of density by verbally expressing the mathematical model. They did so to perform their calculation and to use the concept to make arguments during the development of the task.Este artículo relata una experiencia del desarrollo de una tarea de Modelación (Matemática) y su proyección para el aula a partir de los reflejos en y de la formación continuada. A partir de las reflexiones en la formación, la tarea desencadenó nuevas actividades investigativas y favoreció la inserción del Modelaje en el aula para explorar dos conceptos destaques de la Matemática: razón y proporcionalidad por medio del concepto de densidad. Los resultados indican la evaluación positiva referente a la tarea desarrollada y proyección de inserción de nuevas prácticas de Modelado (Matemática) por los docentes a la acción docente, ampliando así la utilización de Modelado en la Educación en el hacer del profesor. Sin embargo, señalan preocupación por el cumplimiento de las prescripciones, entre ellas, los contenidos de la matriz curricular de Matemáticas. En cuanto a los estudiantes que vivenciaron la tarea hecha por una de las profesoras, éstos (re) organizaron las representaciones iniciales y significaron el concepto de densidad al expresar, verbalmente, el modelo matemático. Lo hicieron para ejecutar su cálculo y al usar el concepto para hacer argumentaciones en el momento del desarrollo de latarea.Este artigo relata a experiência do desenvolvimento de uma tarefa de Modelagem (Matemática) realizada com um grupo de professores de Matemática e sua projeção para a sala de aula a partir dos reflexos na e da formação continuada. Decorrente das reflexões na formação, a tarefa desencadeou novas atividades investigativas e favoreceu a inserção da Modelagem na sala de aula para explorar dois conceitos destaques da Matemática: razão e proporcionalidade por meio do conceito de densidade. Os resultados indicam a avaliação positiva referente à tarefa desenvolvida e projeção de inserção de novas práticas de Modelagem (Matemática) pelos docentes à ação docente, ampliando assim a utilização da Modelagem na Educação no fazer do professor. No entanto, assinalam preocupação com o cumprimento das prescrições, dentre essas, os conteúdos programáticos que constam na matriz curricular de Matemática. Em relação aos estudantes que vivenciaram a tarefa implementada por uma das professoras, estes (re)organizaram as representações textualizadas inicialmente e significaram o conceito de densidade ao expressarem, verbalmente, o modelo matemático. O fizeram para realizar seu cálculo e ao utilizar o conceito para realizar argumentações durante o desenvolvimento da tarefa

Cross talk between Wnt/β-catenin and Irf8 in leukemia progression and drug resistance

Progression and disease relapse of chronic myeloid leukemia (CML) depends on leukemia-initiating cells (LIC) that resist treatment. Using mouse genetics and a BCR-ABL model of CML, we observed cross talk between Wnt/β-catenin signaling and the interferon-regulatory factor 8 (Irf8). In normal hematopoiesis, activation of β-catenin results in up-regulation of Irf8, which in turn limits oncogenic β-catenin functions. Self-renewal and myeloproliferation become dependent on β-catenin in Irf8-deficient animals that develop a CML-like disease. Combined Irf8 deletion and constitutive β-catenin activation result in progression of CML into fatal blast crisis, elevated leukemic potential of BCR-ABL–induced LICs, and Imatinib resistance. Interestingly, activated β-catenin enhances a preexisting Irf8-deficient gene signature, identifying β-catenin as an amplifier of progression-specific gene regulation in the shift of CML to blast crisis. Collectively, our data uncover Irf8 as a roadblock for β-catenin–driven leukemia and imply both factors as targets in combinatorial therapy

Detection of motor changes in huntington's disease using dynamic causal modeling

Deficits in motor functioning are one of the hallmarks of Huntington's disease (HD), a genetically caused neurodegenerative disorder. We applied functional magnetic resonance imaging (fMRI) and dynamic causal modeling (DCM) to assess changes that occur with disease progression in the neural circuitry of key areas associated with executive and cognitive aspects of motor control. Seventy-seven healthy controls, 62 pre-symptomatic HD gene carriers (preHD), and 16 patients with manifest HD symptoms (earlyHD) performed a motor finger-tapping fMRI task with systematically varying speed and complexity. DCM was used to assess the causal interactions among seven pre-defined regions of interest, comprising primary motor cortex, supplementary motor area (SMA), dorsal premotor cortex, and superior parietal cortex. To capture heterogeneity among HD gene carriers, DCM parameters were entered into a hierarchical cluster analysis using Ward's method and squared Euclidian distance as a measure of similarity. After applying Bonferroni correction for the number of tests, DCM analysis revealed a group difference that was not present in the conventional fMRI analysis. We found an inhibitory effect of complexity on the connection from parietal to premotor areas in preHD, which became excitatory in earlyHD and correlated with putamen atrophy. While speed of finger movements did not modulate the connection from caudal to pre-SMA in controls and preHD, this connection became strongly negative in earlyHD. This second effect did not survive correction for multiple comparisons. Hierarchical clustering separated the gene mutation carriers into three clusters that also differed significantly between these two connections and thereby confirmed their relevance. DCM proved useful in identifying group differences that would have remained undetected by standard analyses and may aid in the investigation of between-subject heterogeneity

BET-inhibition by JQ1 promotes proliferation and self-renewal capacity of hematopoietic stem cells

Although inhibitors of bromodomain and extra terminal domain (BET) proteins show promising clinical activity in different hematologic malignancies, a systematic analysis of the consequences of pharmacological BET inhibition on healthy hematopoietic (stem) cells is urgently needed. We found that JQ1 treatment decreases the numbers of pre-, immature and mature B cells while numbers of early pro-B cells remain constant. In addition, JQ1 treatment increases apoptosis in T cells, all together leading to reduced cellularity in thymus, bone marrow and spleen. Furthermore, JQ1 induces proliferation of long-term hematopoietic stem cells, thereby increasing stem cell numbers. Due to increased numbers, JQ1-treated hematopoietic stem cells engrafted better after stem cell transplantation and repopulated the hematopoietic system significantly faster after sublethal myeloablation. As quantity and functionality of hematopoietic stem cells determine the duration of life-threatening myelosuppression, BET inhibition might benefit patients in myelosuppressive conditions

German Contributions to the 15th International Congress of Slavists, Minsk 2013

Der Sammelband enthält die 39 Beiträge der deutschen Teilnehmerinnen und Teilnehmer am 15. Internationalen Slavistenkongress, der vom 20.-27. August 2013 in Minsk stattfand.Beitr. teilw. dt., teilw. engl., teilw. franz., teilw. in kyrill. Schr., russ., teilw. in kyrill. Schr., weißruss.German Contributions to the 15th International Congress of Slavists, Minsk 2013. Comprises all 39 German papers (linguistics 31, literature 8). Published on behalf of the German Association of Slavists (Deutscher Slavistenverband)

AML1-ETO inhibits maturation of multiple lymphohematopoietic lineages and induces myeloblast transformation in synergy with ICSBP deficiency

The translocation (8;21), generating the AML1-ETO fusion protein, is one of the most frequent chromosomal abnormalities associated with acute myelogenous leukemia (AML). To elucidate its role in oncogenesis, bone marrow (BM) cells were infected with a retroviral vector carrying AML1-ETO and transplanted into mice. In contrast to previous transgenic mouse models, we show that AML1-ETO directly stimulates granulopoiesis, suppresses erythropoiesis, and impairs the maturation of myeloid, B, and T lymphoid cells in vivo. To determine the significance of earlier findings that expression of the tumor suppressor ICSBP is often downregulated in AML myeloblasts, AML1-ETO was introduced into BM cells derived from mice lacking the interferon regulatory factor ICSBP. Our findings demonstrate that AML1-ETO synergizes with an ICSBP deficiency to induce myeloblastic transformation in the BM, reminiscent of AML. Key words: leukemia • translocation (genetics) • IFN regulatory factor • B cell differentiation