In this study, I introduce the alternative-dependent focal Luce model (ADFLM), a random choice model generalizing the well-known Luce model (1959). In the ADFLM, focal alternatives are chosen more frequently relative to their utilities. I identify utilities, focal sets, and the magnitude of focal biases from choice data. Additionally, I axiomatically characterize the ADFLM by weakening the independence of irrelevant alternatives (IIA) axiom. This model can explain the well-known behavioral phenomena, the attraction and compromise effects. Furthermore, I also study the seller's profit maximization problem in the ADFLM. I also study an asymmetric dynamic patent race with a deadline under complete information. In my model, two firms decide whether to invest in RandD. The patent arrives randomly according to a Poisson process, and the large firm has a higher hazard rate than the small firm. I find the unique sub-game perfect Nash equilibrium strategy for this game. At the equilibrium, the large firm will stay longer in the race, while the small firm will quit earlier. The large firm's optimal stopping time is not affected by the competition, while the small firm's stopping time is reduced. Additionally, I find that companies will remain longer in the race if the investigation cost is lower, the winning premium is higher, the deadline is extended further, and the hazard rate is more prominent. Moreover, the market becomes more efficient with the competition since the patent is easier to realize. / Doctor of Philosophy / In this research, I study the consumer's behavior when individuals have limited cannot or do not give the same attention to each alternative available to them. In my study, I characterize the alternative-dependent focal Luce model (ADFLM), a consumer behavior model. Moreover, I solve the seller's profit maximization problem when the consumer's behavior follows the ADFLM. Meanwhile, I also study a dynamic patent race problem that occurs when firms compete for a patent with a deadline. If no firms achieve the patent, the stopping time (when the firm quits the patent race) of the large firm's (with a higher success rate every period) is not affected by the introduction of the small firm. However, the small firm quits earlier when the large firm is introduced. The competition between the two companies increases the overall probability of receiving a patent.

International Telemetering Conference Proceedings / October 27-30, 1997 / Riviera Hotel and Convention Center, Las Vegas, Nevada / This paper will investigate the areas which must be addressed to implement a truly integrated Range instrumentation system on a GPS-based Range, using a patented L-Band commanding scheme. Hardware issues will be highlighted as well the issues to be addressed in changing from an audio tone-frequency modulated command system to a digital system incorporating encryption and spread spectrum. Some thoughts addressing costs and schedule to incorporate this approach into the architecture of the U. S. Air Force Range Standardization and Automation (RSA) architecture, as a candidate GPS-based Range are also presented, as well as a discussion of the benefits to be accrued over the existing system, if this approach were adopted.

Human response to ionising radiation (IR) shows a wide variation. This is most clearly seen in the radiation-response of cells as measured by frequencies of chromosomal aberrations. Different frequencies of IR-induced aberrations can be conveniently observed in phytohaemagglutin-stimulated peripheral blood T-lymphocytes from both normal individuals and sporadic cancer cases, in either metaphase chromosomes or as micronuclei in the following cell cycle. Metaphase cells show frequent chromatid breaks, defined as chromatid discontinuities or terminal deletions, if irradiated in the G 2 -phase of the cell cycle. It has been shown that the frequency of chromatid breaks in cells from approximately 40% of sporadic breast cancer patients, are significantly higher than in groups of normal individuals. This suggests that elevated radiation-induced chromatid break frequency may be linked with susceptibility to breast cancer. It is known that chromatid breaks are initiated by a double strand break (DSB), but it appears that the two are linked only indirectly as repair kinetics for DSBs and chromatid breaks do not match. Therefore, the underlying causes of the wide variation in frequencies of chromatid breaks in irradiated T-lymphocytes from different normal individuals and from sporadic breast cancer cases are still unclear but it is unlikely to be linked directly to DSB rejoining. My research has focused on the mechanism through which chromatid breaks are formed from initial DSBs. The lack of a direct association suggested that a signalling process might be involved, connecting the initial DSB and resulting chromatid break. The signal model, suggested that the initial DSB is located within a chromatin loop that leads to an intra- or interchromatid rearrangement resulting in incomplete mis-joining of chromatin ends during the decatenation of chromatids during G 2 . It was therefore proposed that topoisomerase II alpha (topo IIα) might be involved, mainly because of its ability to incise DNA and its role in sister chromatid decatenation. During my PhD research I have used a strategy of altering topo II activity or expression and studying whether this alters IR-induced chromatid break frequency. The first approach involved cell lines that varied in topo IIα expression. The frequency of IR-induced chromatid breaks was found to correlate positively with topo IIα expression level, as measured in three different cell lines by immunoblotting, i.e. two cell lines with lower topo IIα expression exhibited lower chromatid break frequency. Topo II activity in these three cell lines was also estimated indirectly by the ability of a topo IIα poison to activate the G 2 /M checkpoint, and this related well with topo IIα expression. A second approach involved ‘knocking down’ topo IIα protein expression by silencing RNA (siRNA). Lowered topo IIα expression was confirmed by immunoblotting and polymerase chain reaction. SiRNA-lowered topo IIα expression correlated with a decreased IR-induced chromatid break frequency. In a third series of experiments cells were treated with ICRF-193, a topo IIα catalytic inhibitor. It was shown that inhibition of topo IIα also significantly reduced IR-induced chromatid breaks. I also showed that lowered chromatid break frequency was not due to cells with high chromatid break frequencies being blocked in G 2 as the mitotic index was not altered significantly in cells with lowered topo IIα expression or activity. These experiments show that topo IIα is involved in IR-induced chromatid break formation. The final experiments reported here attempted to show how topo II might be recruited in the process of forming IR-induced chromatid breaks. Hydrogen peroxide was used as a source of reactive oxygen species (reported to poison topo IIα) and it was shown that topo IIα under these conditions is involved in the entanglement of metaphase chromosomes and formation of chromatin ‘dots’ as well as chromatid breaks. Experiments using atomic force microscopy attempted to confirm these dots as excised chromatin loops. The possible role of topo IIα in both radiation- and hydrogen peroxide-induced primary DNA damage was also tested. It was shown that topo IIα does not affect radiation-induced DSBs, even though it does affect chromatid break frequency. Also, topo IIα does not affect hydrogen peroxide-induced DNA damage at low doses. The results support the idea that topo IIα is involved in the conversion of DSBs to chromatid breaks after both irradiation and treatment with hydrogen peroxide at a low concentrations. I have demonstrated that topo IIα is involved in forming IR-induced chromatid breaks, most likely by converting the initial DSBs into chromosomal aberrations as suggested by the signal model.

Les eicosanoïdes sont des médiateurs importants qui encadrent et régulent les fonctions osseuses. Leur production est sous la tutelle des phospholipases A[indice inférieur 2] qui permettent la relâche d’acide arachidonique et de lysophospholipides puis de leur métabolisme subséquent des membranes cellulaires. Les PLA[indice inférieur 2] sécrétées ont également comme particularité de pouvoir exercer leurs effets directement via leurs récepteurs membranaires comme ligand. Malgré l’implication connue des prostaglandines sur les fonctions ostéoclastiques et dans plusieurs processus pathologiques résultants en érosion osseuse, les phospholipases A[indice inférieur 2] ostéoclastiques restent inconnues et leurs rôles, spéculatifs. Les études présentées démontrent la présence de la cPLA[indice inférieur 2]-α et de la sPLA[indice inférieur 2] IIA chez les ostéoclastes humains. Par contre, leur expression semble différer selon l’état de l’os. En effet, la cPLA[indice inférieur 2]-α semble exprimée ubiquitairement, mais la sPLA[indice inférieur 2] IIA n’est détectable que dans l’os fœtal ou atteint de la maladie de Paget et n’est pas exprimée dans l’os sain, ostéoporotique ou arthrosique. La sPLA[indice inférieur 2] IIA semble donc exprimée en condition de fort remodelage osseux. Dans notre modèle, la cPLA[indice inférieur 2]-α revêt un rôle anti-ostéoclastogénique. En effet, la cPLA[indice inférieur 2]- α produit des écosanoïdes qui inhibent l’ostéoclastogenèse. Ces derniers sensibilisent les ostéoclastes à l’apoptose. En revanche, un certain degré d’activation de la cPLA[indice inférieur 2]-α est requis pour la résorption osseuse, car son inhibition bloque la résorption osseuse en désorganisant les anneaux d’actine requis pour la résorption, et ce, de façon dépendante de la production d’acide arachidonique. En ce qui a trait à la sPLA[indice inférieur 2] IIA, elle stimule l’ostéoclastogenèse indépendamment de son activité catalytique, probablement via l’un de ses récepteurs membranaires. D’autre part, elle confère une résistance à l’apoptose autant chez les ostéoclastes matures que chez leurs précurseurs CD14+. Par contre, l’inhibition de la sPLA[indice inférieur 2] IIA bloque la résorption osseuse indépendamment du remodelage du cytosquelette d’actine, probablement via leur apoptose. Les résultats inclus dans cette thèse semblent donc démontrer la présence de deux PLA[indice inférieur 2]s chez les ostéoclastes humains ainsi que leur attribuer des rôles en physiologie et pathologie osseuse. Ces évidences pourraient faire des PLA[indice inférieur 2] de nouvelles cibles thérapeutiques pour le traitement de pathologies ostéo-articulaires, dont la maladie osseuse de Paget. // Abstract : Eicosanoïds are important mediators of bone biology. The first regulated enzymes in the biosynthetic pathway of eicosanoids are the PLA[subscript 2]s, which release arachidonic acid and lysophospholipids from membrane phospholipids. Further metabolism of arachidonic acid will lead, among other things, to the synthesis of prostaglandins, which deeply influence bone metabolism. Secreted PLA[subscript 2]s (sPL[subscript 2]) may also act independently of their catalytic activity, as a ligand to their membrane bound receptors. Even though PLA[subscript 2]s have been associated with joint and bone pathologies, their presence and functions were never investigated in osteoclasts (OCs), the principal cell responsible for bone destruction. Our study established the presence of cPLA[subscript 2] and sPLA[subscript 2] in human OCs, but demonstrated a contrast in their expression. cPLA[subscript 2] seems to be expressed ubiquitously, contrary to sPLA[subscript 2] whose expression is restricted to OCs from foetal bone and bone suffering from Paget disease. There is no trace of sPLA[subscript 2] in healthy bone or bone suffering from osteoarthrosis or osteoporosis, thus sPLA[subscript 2] seems tightly linked to high bone turnover. In our model, cPLA[subscript 2] exerted an anti-osteoclastogenic effect. Indeed, cPLA[subscript 2] produces eicosanoïds that inhibit osteoclastogenesis and sensitize OCs to apoptosis. Nevertheless, a minimum cPLA[subscript 2] activity is required since complete cPLA[subscript 2] inhibition blocks osteoclast mediated bone resorption. Its inhibition leads to disorganization of the OC cytoskeleton and inhibits the actin ring formation required for bone resorption in an arachidonic acid dependent fashion. On the other hand, sPLA[subscript 2] stimulates osteoclastogenesis independently of its catalytic activity; probably via interaction with one of its membrane bound receptors. sPLA[subscript 2] decreases OC and their CD14+ precursors’ sensibility to apoptosis. Moreover, sPLA[subscript 2] inhibition inhibits bone resorption independently of actin cytoskeleton remodeling, probably by inducing mature OC apoptosis. Together, these results demonstrate the presence of two PLA[subscript 2]s in human OCs and highlight their important roles in bone physiology and pathophysiology. Highlighting those functions could eventually lead to the elaboration of new strategies to control hyperosteoclastic states by targeting PL[subscript 2]s.

Les récepteurs nucléaires de l’acide rétinoïque (AR) appelés RAR, se comportent comme des facteurs de transcription inductibles par le ligand. La transcription des gènes cibles induite par l’AR, nécessite la fixation des RAR au niveau de séquences spécifiques des promoteurs et met en jeu des changements conformationnels des récepteurs qui contrôlent l’association/dissociation de toute une panoplie de corégulateurs. Cependant, en plus de ce modèle génomique et nucléaire bien établi, l’équipe du Dr Cécile Rochette-Egly a montré récemment que l’AR a aussi des effets non-génomiques et induit rapidement la voie de signalisation p38MAPK/MSK1 qui ensuite cible les RAR pour des cascades de phosphorylations et module la transcription des gènes cibles. Pendant mon travail de thèse, j’ai mis en exergue trois nouveaux concepts originaux du mécanisme d’action du sous-type RARα. J’ai montré qu’une sous-population de RARα est présente dans des microdomaines membranaires, les radeaux lipiques ou “lipid rafts”où elle interagit avec les protéines Gαq. Cette interaction est le signal des effets non génomiques de l’AR, l’activation de la voie de la p38MAPK. Ces effets ont été corrélés à l’activité des gènes cibles de l’AR, prouvant ainsi leur nécessité. J’ai identifié un nouveau partenaire de RARα, la profiline IIA. J’ai analysé le mécanisme moléculaire de l’interaction et démontré qu’elle a lieu dans le noyau. La profiline IIA s’est révélée être un régulateur des effects génomiques de RARα et est recrutée avec RARα au niveau des promoteurs des gènes cibles. Finalement j’ai mis en évidence une nouvelle fonction de RARα dans le contrôle de l’adhésion et de l’étalement des cellules. D’où l’hypothèse de nouveaux effets génomiques de RARα avec la profiline IIA dans le contrôle de l‘expression des protéines d’adhésion. Cependant, de manière inattendue, j ‘ai identifié une nouvelle population de RARα dans le cytoplasme de ces cellules. D’où l’hypothèse de nouveaux effets non génomiques dans le cytoplasme, via l’interaction de RARα avec des protéines d’adhésion. / Nuclear retinoic acid (RA) receptors (RARs) are ligand-dependent regulators of transcription. Their transcriptional activity relies mainly on their recruitment to specific DNA response elements and on their interactions with several coregulators at the ligand-binding domain. In addition to these classical genomic effects, the team of C. Rochette-Egly demonstrated that RA also induces the rapid activation of the p38MAPK/MSK1 pathway with characteristic downstream consequences on thephosphorylation of RARs and the expression of their target genes. Here I highlighted three novel paradigms in the field of the RARα subtype. I found that a fraction of the cellular RARα pool is present in membrane lipid rafts, where it interacts with G protein alpha Q in response to RA. This interaction is the signal for nongenomic effects, i.e. the activation of p38MAPK and of the downstream kinase MSK1. These effects have been correlated to the activation of RA-target genes, highlighting its physiological relevance. I identified a new binding partner of RARα, profilin IIA. I deciphered the mechanism of the interaction and found that it occurs in nuclei. Remarkably, profilin IIA modulates positively the genomic effects of RARα and is recruited with RARα to target genes promoters. Finally, in an attempt to decipher the relevance of the RARα interaction with profilin IIA, I found that RARα controls cell adhesion and spreading. This might suggest a novel genomic functionof RARα and profiling in the control of the expression of genes involved in adhesion. However, preliminary experiments indicate that a pool of RARα is present in the cytosol, suggesting also novel nongenomic effects. Whether RARα controls adhesion via its interaction in the cytosol proteins involved in adhesion will require further investigations.

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he title above comprises elements of the strategic studies concept 'foundations of military force'. Military force has been the final arbiter between the political entities of mankind throughout all ages. The prevalence of this social scourge has left a footprint in every dispensation of man's efforts at civilisation. Regrettably, warfare was and remains one of the core characteristics of human nature. The artefacts of antiquity are catalogued in archaeological periods. In nearly every instance each layer of human settlement is separated by the effects of warfare. Rather than a sub-discipline on the periphery it is demonstrated herein that military archaeology, refined with the post-World War Two scientific discipline of polemology, can and ought to be moved onto the centre stage of archaeology. The application of core polemological concepts to IA IIa accurately describes the unfolding of the United Monarchy's capacity to pursue political goals commensurate with its evolutionary war potential. / Religious Studies & Arabic / M.A. (Biblical Studies)

In dieser Arbeit wird ein simultanes Quell-, Ziel-, Verkehrsmittel- und Routenwahlmodell (Modell EVA-U) entwickelt, welches ein stochastisches Nutzergleichgewicht erreicht. Die Routenwahlmodelle der Verkehrsarten sind nicht mehr Teil der Umlegungsalgorithmen, sondern in das Nachfragemodell integriert. Dadurch ist eine konsistente Bewertung aller Alternativen (der Verkehrsarten) möglich. Das Simultanmodell EVA-U stellt eine Weiterentwicklung des Simultanmodells EVA von LOHSE dar. Das EVA-U-Modell ist den universalen Logit-Modellen zuzuordnen. Die Randsummenbedingungen der Verkehrsverteilung werden beachtet. Die Bewertung der Alternativen erfolgt mittels Generalisierter Kosten. Die Abhängigkeit von Routen wird berücksichtigt, ebenso die Tagesganglinie der Verkehrsnachfrage und die Fahrpläne des ÖV-Systems. Das Modell EVA-U erlaubt auch die Berücksichtigung von Routen intermodaler Verkehrsarten (z.B. P+R). Darüber hinaus ist die Integration eines Modells des ruhenden Verkehrs möglich. / In this thesis a simultaneous Trip Generation-, Distribution-, Modal-Split and Route Choice Model (modell EVA-U) is elaborated. The model tends to reach a stochastic user equilibrium. The route choice algorithms are not longer part of an assignment procedure but part of the demand model. A consistent assessment of properties of all transport systems is possible. The simultaneous model EVA-U is an advancement of the EVA-Model by Lohse. The model EVA-U is to be assigned to the generalised logit-models. All matrix constrains are taken into account. The assessment is effected by generalised costs. The dependence of routes is taken into account. Moreover, the integration of day time and the schedules of private transport lines is possible. Furthermore, it is possible to integrate a model of parked cars and circuits of inter-modal traffic forms (park and ride) in the Model EVA-U.

he title above comprises elements of the strategic studies concept 'foundations of military force'. Military force has been the final arbiter between the political entities of mankind throughout all ages. The prevalence of this social scourge has left a footprint in every dispensation of man's efforts at civilisation. Regrettably, warfare was and remains one of the core characteristics of human nature. The artefacts of antiquity are catalogued in archaeological periods. In nearly every instance each layer of human settlement is separated by the effects of warfare. Rather than a sub-discipline on the periphery it is demonstrated herein that military archaeology, refined with the post-World War Two scientific discipline of polemology, can and ought to be moved onto the centre stage of archaeology. The application of core polemological concepts to IA IIa accurately describes the unfolding of the United Monarchy's capacity to pursue political goals commensurate with its evolutionary war potential. / Religious Studies and Arabic / M.A. (Biblical Studies)

Since the late 20th century there has been an increase migration in of people due to the development of new technologies, easier ways of travel and the opening of national borders. People travel abroad for jobs, studies, or exploring new countries. During these travels some of them find life partners abroad, settle down there, conclude marriages and establish families. It often happens that such marriages end in divorce. If children are born in such a wedlock questions arise as to who will take care of them, who will pay maintenance etc. In some cases a parent decides to solve a conflict situation in such a way that he/she moves with the child without consent of the other parent to another place within the country or he/she decides to move to another country, usually to the country of his/her origin. He/she wants to settle there with the child and to legalize staying there. Such removal where national borders are crossed is considered to be international child abduction. The basic document dealing with the issue of international child abductions is the Hague Convention on the Civil Aspects of International Child Abduction (hereinafter the Hague Convention) adopted on 25 October 1980 and currently acceded to by 87 states. The Hague Convention establishes rules according to which cases of...