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Cell permeabilization by intense electric pulses, called electropermeabilization, is a biological phenomenon involved in recent anticancer therapies. It allows, for example, to increase the efficacy of chemotherapies still reducing their side effects, to improve gene transfer, or to proceed tumor ablation. However, mechanisms of electropermeabilization are not clearly explained yet, and the mostly adopted hypothesis of the formation of pores at the membrane surface is in contradiction with several experimental results.This thesis modeling work is based on a different approach than existing electroporation models. Instead of deriving equations on membranes properties from hypothesis at the molecular scale, we prefer to write ad hoc laws to describe them, based on available experimental data only. Moreover, to be as close as possible to these data, and to ease the forthcoming work of parameter calibration, we added to our model equations of transport and diffusion of molecules in the cell. Another important feature of our model is that we differentiate the conductive state of membranes from their permeable state.Numerical methods, as well as a 3D parallel C++ code were written and validated in order to solve the partial differential equations of our models. The modeling work was validated by showing qualitative match between our simulations and the behaviours that are observed in vitro; La perméabilisation des cellules à l’aide d’impulsions électriques intenses, appelée électroperméabilisation, est un phénomène biologique impliqué dans des thérapies anticancéreuses récentes. Elle permet, par exemple, d’améliorer l’efficacité d’une chimiothérapie en diminuant les effets secondaires, d’effectuer des transferts de gènes, ou encore de procéder à l’ablation de tumeurs. Les mécanismes de l’électroperméabilisation restent cependant encore méconnus, et l’hypothèse majoritairement admise par la communauté de formation de pores à la surface des membranes cellulaires est en contradiction avec certains résultats expérimentaux.Le travail de modélisation proposé dans cette thèse est basé sur une approche différente des modèles d’électroporation existants. Au lieu de proposer des lois sur les propriétés des membranes à partir d’hypothèses à l’échelle moléculaire, nous établissons des lois ad hoc pour les décrire, en se basant uniquement sur les informations expérimentales disponibles. Aussi, afin de rester au plus prèsde ces dernières et faciliter la phase de calibration à venir, nous avons ajouté un modèle de transport et de diffusion de molécules dans la cellule. Une autre spécificité de notre modèle est que nous faisons la distinction entre l’état conducteur et l’état perméable des membranes.Des méthodes numériques spécifiques ainsi qu’un code en 3D et parallèle en C++ ont été écrits et validés pour résoudre les équations aux dérivées partielles de ces différents modèles. Nous validons le travail de modélisation en montrant que les simulations reproduisent qualitativement les comportements observés in vitro.

In this paper, we focus on the behaviour of periodic solutions to a cell- scale electropermeabilization model previously proposed by Kavian et al. (JMB,2012). Since clinical permeabilization protocols mostly submit cancer cells to trains of periodic pulses, we investigate on parameters that modify significantly the resulting permeabilization. Theoretical results of existence and uniqueness of periodic solutions are presented, for two different models of membrane electric conductivity. Numerical simulations were performed to corroborate these results and illustrate the asymptotic convergence to periodic solutions, as well as the dependency on biological parameters such as the cell size and the extracellular conductivity.; Dans ce papier, nous nous intéressons au comportement des solutions périodiques d'un modèle d'électroperméabilisation précédemment proposé par Kavian et al. (JMB,2012). La plupart des protocoles de perméabilisation soumettent les tumeurs à des trains de pulses périodiques, et nous souhaitons déterminer les paramètres qui modifient significativement la perméabilité résultante. Des résultats théoriques d'existence et d'unicité des solutions périodiques sont donnés, pour différents modèles de conductivité. Des simulations numériques ont été effectuées pour appuyer ces résultats et mettre en évidence la convergence asymptotique vers des solutions périodiques, ainsi que la dépendance des paramètres biologiques que sont la taille des cellules et la conductivité extracellulaire.

Publié dans JTB (doi 10.1016/j.jtbi.2014.06.027 ); The aim of this report is to present a new model of in vitro cell electropermeabilization, which describes separately the conducting state and the permeable state of the membrane submitted to high voltage pulses. We first derive the model based on the experimental observations and we present the numerical methods to solve the non-linear partial differential equations. We then present numerical simulations that corroborate qualitatively the experimental data dealing with the uptake of propidium iodide (PI) after millipulses. This tends to justify the validity of our modeling. Forthcoming work will be to calibrate the parameters of the model for quantitative description of the uptake.; Le but de ce rapport est de présenter un nouveau modèle d'électroperméabilisation de cellules in vitro, décrivant séparément les états conducteur et perméable de la membrane soumise à des pulses électriques de fort voltage. Nous construisons d'abord le modèle à partir d'observations expérimentales et nous présentons les méthodes numériques permettant de résoudre les équations aux dérivées partielles. Nous présentons ensuite les simulations corroborant qualitativement les données expérimentales sur l'internalisation d'iodure de propidium après plusieurs millipulses. La validité de notre modèle semble ainsi justifiée. Un travail ultérieur consistera en la calibration des paramètres du modèle pour fournir des résultats quantitatifs.

A fourth metacarpal from Spy is characterized by 8 measurements and compared with five corresponding reference samples: males and females, right and left bones, recent and neolithic populations. As things turned out, this case study raises some problems and suggests a new general strategy in biometrical studies.

Race, sex and hand differences were tested using z -transformation of the means of correlation coefficients between ridge-counts of (a) fingers of right hand among themselves; (b) fingers of left hand among themselves; (c) non-homologous fingers of right and left hands; (d) homologous fingers, for two samples: o (1) individual data for 26 male and 12 female populations; (2) population means for 195 male and 165 female populations. Differences were observed between homologous and non-homologous fingers and between fingers of right and left hands. No significant sexual or racial differences appear from this analysis.

In human palaeontology, samples are generally collections of objects gathered according to morphological criteria and their statistical analysis usually calls for caution because of the relatively small number of objects. Testing normality for such samples is a critical problem. The procedure suggested by Filliben, however, is particularly suitable for small to moderate sample sizes. Moreover, it provides a graphical presentation of the data that permits to locate each object within the distribution range. We briefly review the principle of the method and give a computer program to carry out the necessary computations and plot. Finally, we illustrate the method by studying the distribution of the maximum length and the maximum breadth for a sample of skulls of the Upper Palaeolithic.

SummaryIn order to test if arm folding is a hereditary trait, 319 couples of parents and their 897 children have been examined. The distribution of the two phenotypes, D and G, is different from a O.5-0.5 distribution. No influence of sex nor age is observed. The matings are random and the mean number of children per family is the same for each type of mating.The analysis of family data does not prove the hypothesis of a hereditary transmission of the trait, and important discrepancies are noted between observed values and those expected for genetic mechanisms with two alleles, D and G, of an autosomic or sex-linked gene.

Doctorat en Sciences, info:eu-repo/semantics/nonPublished

A principal components analysis was made on the means of the ten digital ridge-counts, separately for 195 male populations and 165 female populations, using the variance/covariance matrix. The first three components explain respectively 74%, 12% and 4.6% in the male sample and 77.2%, 11.3% and 4.1% in the female sample. The factor scores of the individual samples were computed and scatter diagrams were plotted for the first two components. They show the existence of a geographic distribution. Ellipses of dispersion of the geographic groups show some similarity between male and female samples, although homogeneity is less than in females and less on the right than on the left hand. The structure of the components shows that the first one corresponds to a factor size, the second contrasts the thumb with fingers 2 and 3, third opposes fingers 2 and 3 to fingers 4 and 5. Data from more recent population studies can easily be referred to the suggested scheme. Their position will define more accurately the differentiation between the geographic groups.

For a normally distributed variable, the index of atypicality associated with a measurement of that variable is defined as the probability of finding a result closer to the mean of the reference population than the one actually observed. The method extends straight forwardly to multivariate situations, thus providing a joint interpretation of multiple observations recorded on the same subject. In human palaeontology, atypicality indices allow to analyze and to compare the results obtained from variables closely associated with specific traits of the morphology. We briefly outline the principle of the method and give a computer program to carry out the calculations. Finally, we apply the use of univariate and multivariate atypicality indices to data recorded on 53 Upper Palaeolithic skulls.

In human palaeontology, samples are generally collections of objects gathered according to morphological criteria and their statistical analysis usually calls for caution because of the relatively small number of objects. Testing normality for such samples is a critical problem. The procedure suggested by Filliben, however, is particularly suitable for small to moderate sample sizes. Moreover, it provides a graphical presentation of the data that permits to locate each object within the distribution range. We briefly review the principle of the method and give a computer program to carry out the necessary computations and plot. Finally, we illustrate the method by studying the distribution of the maximum length and the maximum breadth for a sample of skulls of the Upper Palaeolithic.

info:eu-repo/semantics/published

info:eu-repo/semantics/published

COLOUR of skin has always been and still is the most frequently used character in definition of races. The essential reason is that skin colour is considered as an inherited trait for which a hypothetical polygenie mechanism of transmission has been suggested (Davenport, Gates and Stern). It was almost the interracial differences that had caught the eye, but the possibility of using a spectrophotometer1,2 has induced me to explore the inter-individual variability in one population. The essential conclusions of the examination of 143 Belgian male students and 177 female students with an EEL spectrophotometer at nine wave-lengths (430 mµ to 700 mµ) during April 1960 are reported here. Measurements were taken at the forehead and inner arm. Table 1 gives means and standard deviations. More detailed results will be published elsewhere3.