Paediatric high grade glioma (HGG), including diffuse intrinsic pontine glioma (DIPG) are highly aggressive tumours with no effective cures. Lack of understanding of the molecular biology of these tumours, in part due to lack of well-characterised pre-clinical models, is a great challenge in the development of novel therapies. Analysis of paired cell culture/biopsy samples in this study revealed that paediatric HGG short-term cell cultures retain many of the tumour characteristics in vivo. Using a genome-wide approach, copy number, gene and miRNA expression, and methylation changes were characterised in 17 paediatric HGG-derived short-term cell cultures including 3 from DIPG. The majority of the genomic changes were unique from those arising in adult HGG. Approximately 65% (11/17) of paediatric HGG short-term cell cultures had balanced genetic profiles resembling normal karyotypes. The most frequent copy number gain and loss were detected at 14q11.2 (94%) and 8p11.23-p11.22 (59%), respectively. H3F3A (K27M) mutation was present in 2/17 (12%) cases and concurrent loss of CDKN2A and BRAFV600E in 1/17 (6%) case. Genes involved in reelin/PI3K signaling (DAB1), RTK signaling (PTPRE), and arginine biosynthesis (ASS1 and ASL) were frequently deregulated by methylation in these tumours. The anti-growth and anti-migratory properties of DAB1 and PTPRE were demonstrated in vitro. Preliminary investigations validated the therapeutic potential of ADI-PEG20 (arginine depletion), and PI-103 (PI3K/mTOR inhibition) in a subset of paediatric HGG short-term cell cultures. This study has identified novel genetic and epigenetic changes in paediatric HGG that may, following further validation, be translated into potential biomarkers and/or therapeutic targets.

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Submitted by Mariana Dornelles Vargas (marianadv) on 2015-05-14T18:09:24Z No. of bitstreams: 1 revitalizacao_coisa.pdf: 971660 bytes, checksum: 79b2bb366d78ea930d46b5e84577719c (MD5) / Made available in DSpace on 2015-05-14T18:09:24Z (GMT). No. of bitstreams: 1 revitalizacao_coisa.pdf: 971660 bytes, checksum: 79b2bb366d78ea930d46b5e84577719c (MD5) Previous issue date: 2011-06 / Nenhuma / A temática a ser abordada traz inicialmente a observação do instituto da coisa julgada e seus principais cotejos, requisitos, efeitos e demais relevâncias. Nesta linha, ainda no primeiro capítulo, observar-se-á a crise de diversos institutos como do Estado, da Constituição e do Poder Judiciário. Seguidamente, será observado o controle de constitucionalidade, passando por suas bases introdutórias e a fixação do guardião da Constituição para depois efetivamente ser estudado o processo objetivo de controle de constitucionalidade (ADI, ADC e ADPF), tanto compreendendo os seus requisitos, efeitos e demais pontuações relevantes. Por fim, será observada a relativização da coisa julgada no processo subjetivo de controle de constitucionalidade como base para o processo objetivo de controle de constitucionalidade. Depois dessa abordagem será feito um levantamento da temática, sendo perceptível que a coisa julgada pode ser relativizada no processo objetivo de controle de constitucionalidade, ocorrendo especificamente em relação à declaração de inconstitucionalidade de uma norma (lei ou ato normativo) que tenha sido anteriormente já declarada constitucional, sendo essa uma decorrência das novas tendências sociais e das mutações dessa sociedade volátil. Os casos da referida relativização são bem fechados, pois só se darão em relação à ADC procedente ou ADI improcedente que tenham declarado constitucionais leis ou atos normativos que poderão posteriormente, frente à evolução constante da sociedade, ser declarados inconstitucionais, podendo ocorrer nos casos de mudança da realidade fática observada, alteração legal ou até a mudança de interpretação do próprio Supremo Tribunal Federal sobre a temática. / La temática a ser abordada tras inicialmente la observación del instituto da la cosa juzgada y sus principales puntos, requisitos, efectos y demás relevancias. En esta observación no primer capítulo será observada la crises de los diversos institutos como el Estado, la Constitución y del Poder Judiciario. En un secundo momento será observado lo control de constitucionalidad, estudiando sus bases introductorias y la fijación del guardián de la Constitución para después efectivamente ser estudiado lo proceso objetivo del control de constitucionalidad (ADI, ADC e ADPF), tanto comprendiendo los sus requisitos, efectos y demás aspectos relevantes. Por fin, será observada la relativización de la cosa juzgada no proceso subjetivo de control de constitucionalidad como bases para lo proceso objetivo de control de constitucionalidad. Después de la referida abordaje será hecho un levantamiento de la temática siendo perceptible que la cosa juzgada pode ser relativizada en el proceso objetivo del control de constitucionalidad, ocurriendo específicamente en relación a la declaración de inconstitucionalidad de una norma (ley o acto normativo) que tenga sido anteriormente ya declarada constitucional, siendo esa una consecuencia de las nuevas tendencias sociales y de las mutaciones de la sociedad volátil.Los casos de la referida relativización san bien cerrados, donde solo ocurrirán en relación a la ADC procedente o la ADI improcedente que tengan declarado constitucionales las leyes o los actos normativos que podrán posteriormente, frente a la evolución constante da la sociedad, ser declarados inconstitucionales, pudiendo ocurrir en los casos de mudanza de la realidad fática observada, alteración legal o até la mudanza de interpretación de lo proprio Supremo Tribunal Federal sobre la temática. Palavras-chave: Cosa juzgada. Relativización de la cosa juzgada. Control de constitucionalidad. Relativización de la cosa juzgada en la ADI, ADC e ADPF.

This dissertation concerns the model reduction of linear periodic descriptor systems both in continuous and discrete-time case. In this dissertation, mainly the projection based approaches are considered for model order reduction of linear periodic time varying descriptor systems. Krylov based projection method is used for large continuous-time periodic descriptor systems and balancing based projection technique is applied to large sparse discrete-time periodic descriptor systems to generate the reduce systems. For very large dimensional state space systems, both the techniques produce large dimensional solutions. Hence, a recycling technique is used in Krylov based projection methods which helps to compute low rank solutions of the state space systems and also accelerate the computational convergence. The outline of the proposed model order reduction procedure is given with more details. The accuracy and suitability of the proposed method is demonstrated through different examples of different orders. Model reduction techniques based on balance truncation require to solve matrix equations. For periodic time-varying descriptor systems, these matrix equations are projected generalized periodic Lyapunov equations and the solutions are also time-varying. The cyclic lifted representation of the periodic time-varying descriptor systems is considered in this dissertation and the resulting lifted projected Lyapunov equations are solved to achieve the periodic reachability and observability Gramians of the original periodic systems. The main advantage of this solution technique is that the cyclic structures of projected Lyapunov equations can handle the time-varying dimensions as well as the singularity of the period matrix pairs very easily. One can also exploit the theory of time-invariant systems for the control of periodic ones, provided that the results achieved can be easily re-interpreted in the periodic framework. Since the dimension of cyclic lifted system becomes very high for large dimensional periodic systems, one needs to solve the very large scale periodic Lyapunov equations which also generate very large dimensional solutions. Hence iterative techniques, which are the generalization and modification of alternating directions implicit (ADI) method and generalized Smith method, are implemented to obtain low rank Cholesky factors of the solutions of the periodic Lyapunov equations. Also the application of the solvers in balancing-based model reduction of discrete-time periodic descriptor systems is discussed. Numerical results are given to illustrate the effciency and accuracy of the proposed methods.

Today in the scientific and technological world, physical and artificial processes are often described by mathematical models which can be used for simulation, optimization or control. As the mathematical models get more detailed and different coupling effects are required to include, usually the dimension of these models become very large. Such large-scale systems lead to large memory requirements and computational complexity. To handle these large models efficiently in simulation, control or optimization model order reduction (MOR) is essential. The fundamental idea of model order reduction is to approximate a large-scale model by a reduced model of lower state space dimension that has the same (to the largest possible extent) input-output behavior as the original system. Recently, the system-theoretic method Balanced Truncation (BT) which was believed to be applicable only to moderately sized problems, has been adapted to really large-scale problems. Moreover, it also has been extended to so-called descriptor systems, i.e., systems whose dynamics obey differential-algebraic equations. In this thesis, a BT algorithm is developed for MOR of index-1 descriptor systems based on several papers from the literature. It is then applied to the setting of a piezo-mechanical system. The algorithm is verified by real-world data describing micro-mechanical piezo-actuators. The whole algorithm works for sparse descriptor form of the system. The piezo-mechanical original system is a second order index-1 descriptor system, where mass, damping, stiffness, input and output matrices are highly sparse. Several techniques are introduced to reduce the system into a first order index-1 descriptor system by preserving the sparsity pattern of the original models. Several numerical experiments are used to illustrate the efficiency of the algorithm.

The aim of this dissertation work is the evaluation of the influence of nickel alloying on the structure and mechanical properties, both monotonic and dynamic, of nodular cast iron with ferritic and bainitic matrix. Two chock melts with 0.5 and 2.7 % Ni were used to study the nickel influence. The quantitative evaluation of structure of these melts using image analysis was done and basic tensile mechanical properties were determined. Subsequently, the time optimization of two-stage ferritic annealing and isothermal austempered heat treatment at 375 °C was performed with the aim to obtain optimal ferritic and bainitic structures with best static and dynamic mechanical properties. After ferritic annealing the nickel alloying contributes to substitution hardening of ferritic matrix which positively affects its strength and other mechanical properties. The higher nickel content in the bainitic structure causes the shift of phase transformation times to longer times which results in restricted production of small carbides and in bigger volume of retained austenite. These features were confirmed by observation in transmission electron microscope. Precise tensile and low cycle fatigue tests at temperatures 23 and – 45 °C were performed on the optimized structures of both nodular cast irons. As a result of the notch effect of graphite nodules, microplastic deformation of both nodular cast irons was observed at stresses which were lower than the yield stress. The Hollomon's equation very well describes the individual parts of tensile curves for both nodular cast irons including their mutual comparison. From the low cycle fatigue tests, the cyclic hardening/softening curves, the evolution of elastic modulus and hysteresis loop shape parameters, cyclic stress-strain curves and fatigue life curves were obtained for both temperatures and materials. Moreover, the decrease of retained austenite volume was measured by neutron diffraction and the evolution of surface relief was characterized during cyclic straining for both austempered nodular cast irons at both temperatures. On the basis of these results both cyclic plasticity and fatigue degradation mechanisms in relation to the cyclic strain localization were described for both nodular cast irons.

Title: Analysis of didactic interaction of group skiing tuition at primary schools Objectives: Goal of this research is to compare didactic interaction of the teacher and group of pupils while skiing tuition at primary schools Methodos: As a basic method in this research has been used the M ADI method (Modified analysis of didactic interaction) which is a categorical observational system. With this analysis it is possible to get data that describe didactic interaction between teacher ( instructor) and his pupils, particularly forms of teachers behavior, didactic content of his tuition, didactic situations and approach activity.Questionnaire was another used method. Results: Results of this research have confirmed that the didactic interaction structure is highly influenced by skiing abilities of the pupils. Changes in quality of didactic interaction were not found in both groups. Results of both the analysis and questionnaire provide feedback to the instructor. Keywords: Analysis, didactic interaction, M ADI, skiing, skiing course, school middle age

Title of the thesis: Interaction between a teacher and a student compared group and individual teaching skiing. Objectives: The aim of this work was to find, what differences are in the didactic interaction in comparison of group and individual ski lessons. Methods: In this work we used the method of observation, data collection was realized using a video camera and the subsequent recording was evaluated using the MADI method (modified analysis of didactic interaction). Results: From the results we found that the greatest difference was in the expression factual purportwhich in individual lessons grow avarage by 20%. Furthermore, in the individual lesson form grow education activity above organizational by on avarage10% and in the type of attitude activity integration has increased on avrage 7%. The results also showed that in the individual form of teaching did not appear activity without direct control. Key words: Individual and group skiing lessons, ski school, analysis of didactic interaction, ADI, MADI

Gerade in Hinblick auf die Kombination aus hervorragender Festigkeit, relativ guter Zähigkeit und Dauerfestigkeit sowie beachtlicher Verschleißbeständigkeit macht bainitisches Gusseisen mit Kugelgrafit und dabei besonders das ADI (Austempered Duktile Iron) durch sein ausferritisches Gefüge seine Vorteile gegenüber Gusseisenwerkstoffen insbesondere Gusseisen mit Kugelgraphit und auch Stahlguss deutlich. Die konventionelle Herstellung von ADI erfolgt über ein Austenitisieren und ein anschließendes Abschrecken und Halten im Salzbad. Die Salzbadbehandlung stellt einen technologisch und ökologisch problematischen Prozess dar. Im Rahmen dieser Arbeit wurde im Labormaßstab eine neue Technologie, die auf dem Einfluss des Nickels auf die Martensitstarttemperatur des Gusseisens und auf seinen zahlreichen positiven Wirkungen basiert, zur alternativen Herstellung von ausferritischem Gusseisen mit Kugelgraphit erforscht. Des Weiteren wurde der Einfluss von erhöhten Nickelzusätzen auf die mechanischen Eigenschaften des nach konventioneller Wärmebehandlung im Salzbad hergestellten bainitischen Gusseisens mit Kugelgraphit untersucht. Als Ergebnis ergibt sich eine deutliche Reduzierung der Ms-Temperatur bis unter 100°C und damit die Möglichkeit einfacher, wirtschaftlicher und ökologischer Fertigung. Jedoch zeigte sich auch ein Einfluss des Nickels auf die erreichbaren Eigenschaften, der ggf. für die Anwendung berücksichtigt werden muss.