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Disposition of land in Czech law and the law of Israel Abstract The main goal of the thesis is to analyse and compare the legal regulation of disposition of land and its protection in the Czech Republic and the State of Israel and answer the question whether the Czech legislation and the State of Israel can benefit from such regulations. Protection of land from degradation is absolutely crucial task that in the light of climate change, accompanied by extreme drought along with social and economic development becomes very actual. The thesis deals with the land and its peculiarities in the legal sense, which together with other factors significantly affect the relationship to land. The introduction to the issue is given by a part of the work devoted to the history and geography of both countries, focusing on the current state and major environmental problems. Emphasis is placed on the legal development over the last hundred years in relation to land-legal relations. Furthermore, the thesis focuses on defining current ownership relations and on the context of land disposition in both countries. Both the private-law structure and the public-law organization of these relations, which are significantly different in both countries, are described in detail. In this respect, much of the attention is focused on the...

Selected drugs are being utilized as models of putative colon carcinogens in a study of the influence of major types of dietary fiber upon drug pharmacokinetics. Adult, male Wistar rats were pretreated with standardized, isocaloric hydrated gelatin diets containing no fiber or 15% (w/w) cellulose, lignin, hemicellulose (metamucil), or pectin for 30 days. An additional group was fed lab chow ad libitum as a reference control. The pharmacokinetics of acetaminophen, FD & C Red No. 2 and mirex were examined following oral administration in three separate experiments. Among fiber types, pectin and hemicellulose (Metamucil) caused higher peak plasma concentrations of acetaminophen and faster rates of absorption. There was no effect of fiber type on the rate of acetaminophen elimination as determined by the interpretation of the plasma data using the computer programs AUTOAN2 and NONLIN69. Minimal quantities of Red No. 2 were absorbed from the rat intestinal tract, but its microbial metabolite, naphtionic acid, was readily taken up. Pectin produced a 5-fold higher peak plasma concentration of naphthionic acid than control animals on fiber free diet. Cellulose feeding lowered peak plasma concentration of naphthionic acid compared to the fiber control animals. Lack of any fiber in the diet produced a prolonged peak plasma concentration of napthionic acid. The metabolism of Red No. 2 to naphtionic acid by rat cecal contents was augmented by pectin feeding, alone among fiber types. Red No. 2 decreased intestinal transit times in all diet groups, including controls, with there being no difference in transit times between fiber-fed and control animals. Hemicellulose and pectin feeding lowered peak plasma concentrations of mirex compared to control and cellulose fed animals. Lignin, however produced higher peak plasma concentrations of mirex and a 4-fold higher rate of mirex elimination when compared to the fiber-free control group. These differential effects of specific fiber types upon the absorption and disposition of acetaminophen, Red No. 2 and mirex were not consistantly related to the chemical binding-capacities of the fibers of their water-holding capacities.

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This dissertation presents an investigation of the impact of Multidrug Resistance-associated Protein 2/ATP-binding cassette superfamily C member 2 (Mrp2/Abcc2) and 3 (Mrp3/Abcc3) on the pharmacokinetics (PKs) of methotrexate (MTX) using gene knockout murine models. MTX is a substrate for numerous human ATP-binding cassette (ABC) efflux transporters, yet the impact of these transporters on the pharmacokinetics of MTX over a large dose range has not been examined. To investigate the effects of two transporters, Abcc2 (Mrp2) and Abcc3 (Mrp3), involved in MTX hepatobiliary disposition in vivo, MTX plasma, urine and feces concentrations were analyzed after 10, 50, and 200 mg/kg intravenous (IV) doses to groups of wild type (WT), Abcc2-/- and Abcc3-/- mice. The absence of Abcc2 caused a decrease in total clearance of MTX relative to WT mice at all dose levels yet was accompanied by compensatory increases in renal excretion and metabolism to 7-hydroxymethotrexate (7OH-MTX). In Abcc3-/- mice total clearance was elevated at the two lower dose levels that was attributed to stimulation of biliary excretion and confirmed by elevated fecal excretion; however at the high 200 mg/kg dose clearance was severely retarded and could be attributed to hepatotoxicity as conversion to 7OH-MTX was diminished. We also sought to characterize the effects of Abcc2 and Abcc3, on the PKs of MTX after oral dosing. Plasma, urine, and fecal concentrations of MTX were measured after 10, 50, and 200 mg/kg oral doses to cohorts of WT, Abcc2-/- and Abcc3-/- mice mouse strains. The absence of Abcc2 caused an approximate 2-fold increase in system exposure and a slight increase in oral bioavailability of MTX relative to WT mice at all dose levels. These elevations were accompanied by compensatory increases in conversion to 7OH-MTX, and based on AUC7OH-MTX/AUCMTX (area under the curve ratio of metabolite and parent drug) that ranged from 3% to 9% in WT mice increased to a range of 16% to 26% in Abcc2-/- mice. Renal excretion of unchanged MTX was unaltered in the Abcc2-/- strain; fraction urinary excretion (fr) ranged from about 4% to 11% in WT mice, whereas in Abcc2-/- mice fr ranged from about 7% to 23%. Abcc3-/- mice exhibited more than a 2-fold decrease in Cmax and significant reductions in AUCMTX when compared to WT mice at all dose levels. There were no compensatory increases in either metabolism or in renal and biliary excretion, which suggests future studies for investigating a potential unknown mechanism. Regardless of the mouse strain, increases in the MTX dose were not accompanied by proportional increases in AUCMTX. The PKs of MTX in different mouse strains was successfully modeled by a nonlinear semi-mechanistic 3-compartmental conditional model incorporating key efflux transporters. The model employed population-based analysis and conditional transport terms to well capture the nonlinear properties of MTX systemic disposition for a wide dose range of 10 - 200 mg/kg in WT and knockout strains. The model correlates the mechanistic nature of the nonlinear phenomenon with the key efflux transporters effects on MTX PKs and provides insight for preclinical therapeutic study design. Overall, the information obtained in this investigation underscores the significance of efflux transporters, Abcc2 and Abcc3, for they significantly influence the pharmacokinetics of MTX and their impact can be reflected by a nonlinear semi-mechanistic 3-compartmental conditional model. The studies also provide implication in the preclinical therapeutic study design and insights on the source of inter-patient variability as well as on the combination drug regimens to maximize drug activity yet without toxicity. / Pharmaceutical Sciences

La présente thèse est basée sur une enquête socio-ethnographique menée sur trois clubs de football de niveaux fédéraux contrastés : l’un est composé d’équipes évoluant à un niveau départemental (District), l’autre à un niveau régional (Ligue) et le dernier à un niveau national (Fédéral). Toutes ces associations sportives sont amateurs, affiliées à la F.F.F. et situées autour d’une ville française moyenne. Ce doctorat s’appuie sur une enquête quantitative, menée par questionnaire, sur les joueurs en formation dans ces trois clubs (de 6 à 18 ans, n=397). Une enquête de type qualitative, composée de 91 entretiens, 71 observations et 18 tests d’aptitudes gestuelles et physiques, complète et pondère les résultats obtenus par le questionnaire. L’objet de la thèse est l’étude de la sociogenèse du goût, des dispositions et des savoir-faire footballistique des joueurs amateurs de ces trois clubs. L’analyse des pratiques, des représentations de ces footballeurs en formation, de leurs éducateurs et de leurs parents, dévoile de quelle manière la socialisation footballistique de ces joueurs se focalise progressivement sur la pratique du club. Le désengagement des joueurs vis-à-vis des autres contextes de pratique s’accompagne d’un investissement intense et durable des joueurs dans la culture et la pratique fédérale, et se traduit par l’acquisition de savoir-faire individuels et collectifs variés quantitativement et qualitativement, produits de cette longue socialisation. / This thesis is based on a socio-ethnographic work conducted on three football clubs of contrasting federal levels: one operates at the county level (District), the second at the regional level (League) and the last at the national level (Federal). All three clubs are amateur sports associations affiliated to the French Football Federation and are situated around a medium town. The study is based on a quantitative survey, conducted by questionnaires, to which responded most players in these three clubs (6 to 18 years, n = 397). A qualitative survey consisting of 91 interviews, 71 observations and 18 aptitude tests and physical gestures, complete and weight the results obtained by questionnaire. The thesis studies the formation of tastes, aptitudes and skills of the amateur players of these three clubs. The analysis of the practices, of the representations of these footballers in training, of their teachers and parents, reveals how the socialization of these football players gradually focuses on the practice of the club. The players’ disengagement from other practice contexts is accompanied by an intense and lasting investment of the players in the federal culture and practice, and results in the acquisition of individual and collective skills diverse in quantity and quality, products of this long socialization.

Texte remanié de: Proefschrift--Utrecht, 2000. / Trad. du néerlandais. Bibliogr. p. 317-332. Index.

Notre thèse de doctorat présente trois études menées en 2011, qui croisent et distinguent le niveau d’apprenance, le sexe et le rapport aux normes du genre de 779 étudiant-e-s en école d’ingénieur-e-s, ceci afin d’évaluer les liens pouvant exister entre ces différentes variables ainsi que leurs effets en contexte d’apprentissage. Sous le postulat que les variations de l’apprenance ne sont pas aléatoires, et qu’existent en dehors des dispositions personnelles, des éléments externes liés aux contextes sociaux et qui ont des effets sur les attitudes des sujets vis-à-vis de l’apprentissage, nous avons décidé d’étendre notre questionnement de départ sur l’apprenance aux liens qu’il pourrait y avoir entre l’apprenance, le sexe d’état civil des sujets et leur rapport aux normes du genre dans des contextes scientifiques d’écoles d’ingénieur-e-s que sont l’Ecole Centrale Paris (ECP), « L’EPF, école d’ingénieurs » anciennement Ecole Polytechnique Féminine (EPF), et Sup’Galilée, qui présentent une spécificité de sexe et un prestige variables. / Our doctoral thesis presents three studies conducted in 2011, which intersect and distinguish the level of learnance, sex and the gender norms of 779 students in engineering school, in order to assess the links that may exist between these variables and their impact on learning environment. Under the assumption that changes in learnance are not random, and that exist outside the personal dispositions, external elements related to social contexts and that affect the attitude of subjects of learning, we decided to extend our initial questioning of learnance to links between learnance, sex and their relation to gender norms in engineer schools that are Ecole Centrale Paris (ECP), "the EPF engineering school" Ecole Polytechnique Feminine formerly (EPF) and Sup'Galilée which have a specific gender variables and prestige.

Une nouvelle théorie du cancer s’est récemment imposée dans la communauté scientifique. Selon cette dernière, les cancers se développeraient à partir d’une sous-population bien particulière de cellules cancéreuses, appelées « cellules souches cancéreuses » (CSC). Les partisans de la théorie des CSC soutiennent que les rechutes seraient causées par ces cellules, plus aptes à échapper aux thérapies classiques. En conséquence, ils soutiennent que l’élimination de toutes les CSC, dans un cancer donné, est nécessaire et suffisante pour guérir le patient. Dans cette thèse, je propose d’examiner cette stratégie thérapeutique de ciblage des CSC et je montre que sa capacité à guérir les cancers dépend de la façon dont on envisage la nature de la propriété souche. En effet, les cellules souches cancéreuses sont définies par la possession de la propriété souche, c’est-à-dire par leur capacité à s’auto-renouveler et à se différencier. Cependant, cette propriété elle-même reste obscure quant à sa nature. S’agit-il d’une propriété catégorique ou d’une disposition ? Une cellule non-souche (cancéreuse ou non) peut-elle acquérir la propriété souche et sous quelle condition ? En me basant sur une analyse de la littérature scientifique, je montre que quatre conceptions distinctes de la nature de la propriété souche sont aujourd’hui possibles et que, si la théorie des CSC est vraie, déterminer la nature exacte de la propriété souche est capital pour le traitement des cancers. / A new theory of cancer has recently gained importance in the scientific community. According to this theory, cancers develop from a particular sub-population of cancer cells, named “cancer stem cells” (CSCs). The proponents of the CSC theory argue that relapses are caused by CSCs because they escape classical therapies. Consequently, they claim that eliminating all the CSCs of a given cancer is a necessary and sufficient condition to cure the patient. In this dissertation, I scrutinize this therapeutic strategy and I argue that its ability to cure cancers will depend on our understanding of the nature of stemness. Indeed, cancer stem cells are characterized by this property, that is, the capacity to self-renew and to differentiate. However, the nature of stemness is rather obscure. Is it a categorical property or a disposition? Can a non-stem cell (cancerous or not) acquire stemness, and under which conditions? On the basis of analysis survey of the scientific literature, I distinguish four possible concepts of the nature of stemness. I contend that if the CSC theory is true, determining the exact nature of stemness is essential for cancers treatments.