Les modèles de mutations décrivent le processus d’apparitions rares et aléatoires de mutations au cours de lacroissance d’une population de cellules. Les échantillons obtenus sont constitués de nombres finaux de cellules mutantes,qui peuvent être couplés avec des nombres totaux de cellules ou un nombre moyen de cellules en fin d’expérience.La loi du nombre final de mutantes est une loi à queue lourde : de grands décomptes, appelés “jackpots”,apparaissent fréquemment dans les données.Une construction générale des modèles se décompose en troisniveaux. Le premier niveau est l’apparition de mutations aléatoires au cours d’un processus de croissance de population.En pratique, les divisions cellulaires sont très nombreuses, et la probabilité qu’une de ces divisions conduise à une mutation est faible,ce qui justifie une approximation poissonnienne pour le nombre de mutations survenant pendant un temps d’observation donné.Le second niveau est celui des durées de développement des clones issus de cellules mutantes. Du fait de la croissance exponentielle,la majeure partie des mutations ont lieu à la fin du processus, et les durées de développement sont alors indépendanteset exponentiellement distribuées. Le troisième niveau concerne le nombre decellules qu’un clone issu d’une cellule mutante atteint pendant une durée de développement donnée.La loi de ce nombre dépend principalement de la loi des instants de division des mutantes.Le modèle classique, dit de Luria-Delbrück, suppose que les développements cellulaires des cellules normales aussi bien que mutantess’effectue selon un processus de Yule. On peut dans ce cas calculer expliciter la loi du nombre final de mutantes.Elle dépend de deux paramètres, qui sont le nombre moyen de mutations et le paramètre de fitness (ratio des taux de croissance des deux types de cellules).Le problème statistique consiste à estimer ces deux paramètres au vu d’un échantillon denombres finaux de mutantes. Il peut être résolu par maximisation de la vraisemblance,ou bien par une méthode basée sur la fonction génératrice. Diviser l'estimation du nombre moyen de mutations par le nombre total de cellulespermet alors d'estimer la probabilité d’apparition d’une mutation au cours d’une division cellulaire.L’estimation de cette probabilité est d’une importancecruciale dans plusieurs domaines de la médecine et debiologie: rechute de cancer, résistance aux antibiotiques de Mycobacterium Tuberculosis, etc.La difficulté provient de ce que les hypothèses de modélisation sous lesquelles la distribution du nombre final de mutants est explicitesont irréalistes.Or estimer les paramètres d’un modèle quand la réalité en suit un autre conduit nécessairement à un biais d’estimation.Il est donc nécessaire de disposer de méthodes d’estimation robustes pour lesquelles le biais, en particulier sur la probabilité de mutation,reste le moins sensible possible aux hypothèses de modélisation.Cette thèse contient une étude probabiliste et statistique de modèles de mutations prenant en compte les sources de biais suivantes : durées de vie non exponentielles, morts cellulaires,variabilité du nombre final de cellules, durées de vie non-exponentielles et non-identiquement distribuées, dilution de la population initiale.Des études par simulation des méthodes considérées sont effectuées afin de proposer, selon les caractéristiques du modèle,l’estimation la plus fiable possible. Ces méthodes ont également été appliquées à desjeux de données réelles, afin de comparer les résultats avec les estimations obtenues avec les modèles classiques.Un package R a été implémenté en collaboration avec Rémy Drouilhet et Stéphane Despréaux et est disponible sur le CRAN.Ce package est constitué des différents résultats obtenus au cours de ce travail. Il contient des fonctions dédiées aux modèles de mutations,ainsi qu'à l'estimation des paramètres. Les applications ont été développées pour le Labex TOUCAN (Toulouse Cancer). / Mutation models are probabilistic descriptions of the growth of a population of cells, where mutationsoccur randomly during the process. Data are samples of integers, interpreted as final numbers ofmutant cells. These numbers may be coupled with final numbers of cells (mutant and non mutant) or a mean final number of cells.The frequent appearance in the data of very large mutant counts, usually called “jackpots”, evidencesheavy-tailed probability distributions.Any mutation model can be interpreted as the result of three ingredients. The first ingredient is about the number of mutations occuring with small probabilityamong a large number of cell divisions. Due to the law of small numbers, the number of mutations approximately follows aPoisson distribution. The second ingredient models the developing duration of the clone stemming from each mutation. Due to exponentialgrowth, most mutations occur close to the end of the experiment. Thus the developing time of arandom clone has exponential distribution. The last ingredients represents the number of mutant cells that any clone developing for a given time will produce. Thedistribution of this number depends mainly on the distribution of division times of mutants.One of the most used mutation model is the Luria-Delbrück model.In these model, division times of mutant cells were supposed to be exponentially distributed.Thus a clone develops according to a Yule process and its size at any given time follows a geometric distribution.This approach leads to a family of probability distributions which depend on the expected number of mutations and the relative fitness, which is the ratio between the growth rate of normal cells to that of mutants.The statistic purpose of these models is the estimation of these parameters. The probability for amutant cell to appear upon any given cell division is estimated dividing the mean number of mutations by the mean final number of cells.Given samples of final mutant counts, it is possible to build estimators maximizing the likelihood, or usingprobability generating function.Computing robust estimates is of crucial importance in medical applications, like cancer tumor relapse or multidrug resistance of Mycobacterium Tuberculosis for instance.The problem with classical mutation models, is that they are based on quite unrealistic assumptions: constant final number of cells,no cell deaths, exponential distribution of lifetimes, or time homogeneity. Using a model for estimation, when thedata have been generated by another one, necessarily induces a bias on estimates.Several sources of bias has been partially dealed until now: non-exponential lifetimes, cell deaths, fluctuations of the final count of cells,dependence of the lifetimes, plating efficiency. The time homogeneity remains untreated.This thesis contains probabilistic and statistic study of mutation models taking into account the following bias sources:non-exponential and non-identical lifetimes, cell deaths, fluctuations of the final count of cells, plating efficiency.Simulation studies has been performed in order to propose robust estimation methods, whatever the modeling assumptions.The methods have also been applied to real data sets, to compare the results with the estimates obtained under classical models.An R package based on the different results obtained in this work has been implemented (joint work with Rémy Drouilhetand Stéphane Despréaux) and is available on the CRAN. It includes functions dedicated to the mutation models and parameter estimation.The applications have been developed for the Labex TOUCAN (Toulouse Cancer).

This research report attempts to establish the cognitive consequences of the disruption of schooling. Specifically the report investigates Vygotsky and Luna’s claim that formal schooling necessarily produces scientific concepts in learners, by examining the performance of learners who had been subjected to disrupted schooling. On the basis of empirical research conducted, the report challenges Vygotsky and Luria's claim about the cognitive consequences of schooling.

Modes of information processing were examined for 91 subjects aged between 5 years 7 months and 6 years 3 months, using A.R. Luria's model of brain function as the theoretical basis of the study. A factor analysis of the results of six psychometric tests administered to all subjects indicated the presence of two distinct factors. These were hypothesised to represent the separate contributions of simultaneous and successive synthesis. Further separate factor analyses, of the six psychometric tests and tests of M-Space (derived from the work of R. Case) and tests of standard school assessment tasks (that were also administered to the subjects), were performed. The results indicated that although both modes of synthesis are available to children of this age, simultaneous synthesis is not a potent factor in school learning. A further exploratory study was carried out using the same 91 subjects. Subjects were given a series of verbal subtraction problems requiring understanding of mathematical relationships, and randomly assigned to two presentation groups. One group received pictorial information in addition to the verbal presentation. The other group received concrete materials. A multiple regression analysis was performed on the whole group using factor scores for simultaneous and successive syntheses (derived from the factor analysis of the six psychometric tests) as independent variables and criterion test scores for the verbal subtraction problems as the dependent variable. The analysis indicated that although neither aptitude for successive synthesis nor aptitude for simultaneous synthesis had predictive value for this kind of probelm solving, simultaneous synthesis was possibly the predominant mode of information processing. Further multiple regression analyses performed on each of the presentation groups indicated an interaction between successive synthesis and the modes of presentation of information. Due to the small numbers of subjects in each presentation group this result was inconclusive.

This study addresses the criticism leveled at A.C.T. Mathematics teachers with regard to their failure to use any other method of teaching than chalk-and-talk. By considering the changed needs of society for mathematics and the changed perceptions by society of education, the criticism is placed in context. The importance of spatial ability for mathematics is examined in the context of theories of cognitive abilities and its current under utilization within the classroom. On the basis of the increased need to utilize more talent the study was designed to operationalise in the classroom the constructs of simultaneous and successive synthesis, derived from Luria's model of brain functioning. The question of gender differences in mathematics achievment and spatial ability is addressed. The possible role of the maturation of language in determining differences in the acquistion of ability to form simultaneous synthesis is briefly discussed. The study was designed to utilize and enhance simultaneous synthesis. By demonstrating an Aptitude-Treatment Interaction it was intended to confirm that students, who function at a high level in simultaneous synthesis but at a low level in successive synthesis, would achieve more with experience with spatial activates than in a more traditional chalk-and-talk classroom. Gender differences in achievement were not found. Gender differences in successive/simultaneous profiles were found in accordance with theory predictions. The need for the duration of longer treatment periods is briefly discussed in the context of funding and the appearance of greater efficiency of traditional teaching methods when the students are functioning at the highest level of symbolic thought.

Texte remanié de: Diss. Ph. D.--Philosophy--Jerusalem--Hebrew university of Jerusalem, 1991. / Mention parallèle de titre ou de responsabilité : Myth and metaphor : Abraham Cohen Herrera's philosophic interpretation of Lurianic Kabbalah / Nissim Yosha. Table des matières trad. en anglais. Contient un résumé en anglais. Bibliogr. p. 375-398. Index.

Alexandria Luria's approach to neuropsychological assessment and his theory of brain functioning have been exploited in order to develop a neuropsychological evaluation procedure for children which incorporates a conceptualization of brain-behaviour development. Luria's Neuropsychological Investigation for adults was administered to intact children aged eight to 14 years in order to ascertain which tasks were beyond their capabilities. These were then adapted or deleted. The adapted version of the protocol was then administered to a second group of intact children to determine that the proposed adaptations were appropriate. This process was guided by the results of a statistical analysis which revealed significant findings with respect to age, socioeconomic status, and task performance. A model of brain-behaviour development and interpretive protocol were devised. Together these provide a conceptual and interpretive framework for the battery. Developmental trends which emerged whilst developing Luria's Neuropsychological Investigation for Children (LNI-C) were consistent with the progressive development of successively more complex forms of information processing as depicted in this model. They were also in keeping with prominent developmental theories such as those of Piaget and Vygotsky. These trends revealed that children made most mistakes on adult LNI tasks involving abstract reasoning, the simultaneous synthesis of data, and complex goal-directed behaviour - all of which apparently reflect tertiary cortical zone functioning. Fewer mistakes were related to a lack of training and inability to process the same quantity of information as adults - difficulties which seemed related to secondary zone functioning. None of the mistakes made appeared to reflect subcortical or primary zone functioning. The LNI-C was applied to brain-damaged children who had had a CT scan in order to demonstrate its application and the hypothetico-deductive process of interpreting findings using the concepts of syndrome analysis and double dissociation. The LNI-C findings were consistent with the general pattern of symptoms Luria described for different brain disorders and lesion localities in children, although additional insight into the nature of the sequelae present was gained in each case. In early brain damage, the most frequent disturbances were a disruption in the role played by executive functions and the ability to process data simultaneously - both of which are associated with the tertiary zones of the brain. Furthermore, these disturbances appeared to be important factors underlying disturbances to language and educationally acquired skills. The qualitative, process-orientated nature of the LNI-C proved effective for identifying the factors underlying disturbances described in paramedical reports. These seemed to be the linchpins on which retraining should focus. It was argued that the CT scan was limited in its ability to identify the type of diffuse and/or multifocal brain pathology frequently found in children. The usefulness of the model of brain-behaviour ontogeny and interpretive protocol for diagnosis, understanding and predicting the developmental consequences of childhood brain pathology was demonstrated on the basis of nine brain disorders. Finally, areas of future research were highlighted by the study. / Thesis (Ph.D.)-University of Natal, Durban, 1989.

Orientador: Dione Lucchesi de Carvalho / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Educação / Made available in DSpace on 2018-08-04T04:21:59Z (GMT). No. of bitstreams: 1 Franco_IzabelCristinadeAraujo_M.pdf: 317084 bytes, checksum: ffb84823c4bcc2dfb6b164c6c52395ab (MD5) Previous issue date: 2004 / Resumo: O objetivo central deste estudo refere-se a investigar os procedimentos matemáticos expressos oralmente pelos alunos na resolução de um problema de multiplicação, quando se busca o registro desses procedimentos pela escrita matemática aceita escolar e socialmente. Para abordar a questão investigativa: como acontece a passagem dos procedimentos de cálculo mental à escrita matemática, passando pela expressão oral, evidenciados na resolução de um problema referente a multiplicação na alfabetização de jovens e adultos? optamos por uma análise qualitativa dos dados produzidos.O trabalho de campo foi realizado com alunos de uma classe de alfabetização de jovens e adultos. O estudo apresenta a descrição dos encontros ocorridos no desenvolvimento das atividades do trabalho de campo, os diálogos em sala de aula e as produções dos alunos. O material alvo de análise consistiu dos registros do diário de campo da pesquisadora e dos registros produzidos pelos alunos, sendo analisado em três categorias: ¿ Procedimentos aditivos e procedimentos multiplicativos; ¿ A expressão oral de procedimentos e a produção de conhecimento matemático; ¿ A valorização do algoritmo escolar da multiplicação. Com as análises surgiram considerações que destacamos: a busca pela apropriação do algoritmo escolar da multiplicação por esses jovens e adultos como ato emancipador e conquista de autonomia; o papel da linguagem na apropriação desse conhecimento e o exercício da capacidade humana de ir além da experiência sensorial dando o salto rumo ao conhecimento racional / Abstract: The main objective of this study refers to investigate the mathematical procedure verbally expressed by the pupils in the resolution of a multiplication problem, when the register of theses procedures for the mathematical writing are accepted pertaining to school and socially. To approach the investigative question: how the pass of the procedures of mental calculate to mathematical writing happens, passing by the verbal expression, evidenced in a resolution of a problem referring to multiplication in the education of a young and adult people? We opt to nake a qualitative analysis of carried through with pupils of a young and adults education classroom. The study shows the description of the meetings accured during the activities of the work field, the dialogues in the classroom and the productions of the pupils. The material of analysis consisted of the registers of field of the researcher and the registers produced by the pupils, being analyzed in three categories: ¿ Aditives and multiplicatives procedures; ¿ The verbal expression of procedures and the production of mathematical knowledge; ¿ The valuation of school algorithm of multiplication. With the analyses, considerations had appeared we want to detach: the search for the school algorithm of multiplication appropriation by these youngs and adults as emancipate act and autonomy conquest; the language importance in the appropriation of this knowledge and the exercise of human capacity being to go beyond the sensorial experience giving the jump joing to the rational knowledge / Mestrado / Educação Matematica / Mestre em Educação

American Reform Judaism currently associates the Kabalistic term, tikkun olam, with one of its core principles, social justice. This association is relatively new, dating roughly to the 1950s. The appropriation of a Kabbalistic term by American Reform Judaism is unusual given the historical animosity of American Reform Judaism toward the Kabbalah. The purpose of this thesis to explain this appropriation by contextualizing the use of tikkun olam within American Reform Judaism. The method through which this will be accomplished is the analysis of official documents, journal articles and theological discussions found within the American Reform movement. The thesis concludes that American Reform Judaism chose to appropriate tikkun olam and associate it with social justice in order to locate social justice in a historically Jewish context. This reworking of the concept of social justice to place it within a specifically Jewish frame work reflects the theological shift which occurs in reaction to the Holocaust, fears over Jewish assimilation and other social factors taking place during the 1940s and 1950s.

American Reform Judaism currently associates the Kabalistic term, tikkun olam, with one of its core principles, social justice. This association is relatively new, dating roughly to the 1950s. The appropriation of a Kabbalistic term by American Reform Judaism is unusual given the historical animosity of American Reform Judaism toward the Kabbalah. The purpose of this thesis to explain this appropriation by contextualizing the use of tikkun olam within American Reform Judaism. The method through which this will be accomplished is the analysis of official documents, journal articles and theological discussions found within the American Reform movement. The thesis concludes that American Reform Judaism chose to appropriate tikkun olam and associate it with social justice in order to locate social justice in a historically Jewish context. This reworking of the concept of social justice to place it within a specifically Jewish frame work reflects the theological shift which occurs in reaction to the Holocaust, fears over Jewish assimilation and other social factors taking place during the 1940s and 1950s.

American Reform Judaism currently associates the Kabalistic term, tikkun olam, with one of its core principles, social justice. This association is relatively new, dating roughly to the 1950s. The appropriation of a Kabbalistic term by American Reform Judaism is unusual given the historical animosity of American Reform Judaism toward the Kabbalah. The purpose of this thesis to explain this appropriation by contextualizing the use of tikkun olam within American Reform Judaism. The method through which this will be accomplished is the analysis of official documents, journal articles and theological discussions found within the American Reform movement. The thesis concludes that American Reform Judaism chose to appropriate tikkun olam and associate it with social justice in order to locate social justice in a historically Jewish context. This reworking of the concept of social justice to place it within a specifically Jewish frame work reflects the theological shift which occurs in reaction to the Holocaust, fears over Jewish assimilation and other social factors taking place during the 1940s and 1950s.