Renal cell carcinoma (RCC) accounts for 85% of kidney cancer incidence in the US. Since 1950 there has been a 126% increase in kidney cancer incidence in the US. Thirty percent of new patients present with a localized easily treatable carcinoma while 30% of patients present with a high-grade metastatic carcinoma. Five-year survival rates for metastatic RCC is 6-12 months (Lipworth et al, 2006). Current disease treatment options for metastasis include chemotherapy and radiation (8% response rate), immunotherapy (15-30% response rate) and newly developed angiogenesis inhibitors which are in phase III trials (Staehler et el, 2005). In RCC cells, it has been shown that PPARγ agonists inhibit cell proliferation, induce apoptosis, and induce anti-angiogenic effects in vitro. Unlike most tumor types, PPARγ is downregulated in tissue samples from 47 RCC patients. However, in cell culture studies PPARγ expression does not correlate with growth inhibitory or apoptotic effects of PPARγ agonists in renal cell lines indicating that PPARγ independent responses may play a large role in actions associated with the PPARγ agonists (Yuan et al, 2006). 1,1-Bis(3'-indolyl)-1-(p-substitutedphenyl)methanes containing p-trifluoromethyl, p-t-butyl and p-phenyl substituents activate peroxisome proliferator-activated receptor (PPAR) and inhibit growth of ACHN and 786-0 renal cell carcinoma cell lines. PPAR is overexpressed in ACHN cells and barely detectable in 786-0 cells, and treatment with the t-butyl analog (DIM-C-pPhtBu) induces cell cyle inhibition. DIM-C-pPhtBu also induced several common PPAR-independent proapoptotic responses in ACHN and 786-0 cells, including increased expression of nonsteroidal antiimflammatory drug-activated gene-1 (NAG-1) and endoplasmic reticulum stress which activates death receptor 5 and the extrinsic pathway of apoptosis. In addition, DIM-C-pPhtbu (40 mg/kg/d) also inhibited tumor growth in an orthotopic mouse model for renal carcinogenesis, and this was accompanied by induction of apoptosis in renal tumors treated with DIM-C-pPhtBu but not in tumors treated with the corn oil vehicle (control). Thus, DIM-C-pPhtBu and related compounds represent a novel class of mechanism-based drugs that have potential for treatment of renal adenocarcinoma for which there are currently limited options for successful chemotherapy.

Renal cell carcinoma (RCC) accounts for 85% of kidney cancer incidence in the US. Since 1950 there has been a 126% increase in kidney cancer incidence in the US. Thirty percent of new patients present with a localized easily treatable carcinoma while 30% of patients present with a high-grade metastatic carcinoma. Five-year survival rates for metastatic RCC is 6-12 months (Lipworth et al, 2006). Current disease treatment options for metastasis include chemotherapy and radiation (8% response rate), immunotherapy (15-30% response rate) and newly developed angiogenesis inhibitors which are in phase III trials (Staehler et el, 2005). In RCC cells, it has been shown that PPARγ agonists inhibit cell proliferation, induce apoptosis, and induce anti-angiogenic effects in vitro. Unlike most tumor types, PPARγ is downregulated in tissue samples from 47 RCC patients. However, in cell culture studies PPARγ expression does not correlate with growth inhibitory or apoptotic effects of PPARγ agonists in renal cell lines indicating that PPARγ independent responses may play a large role in actions associated with the PPARγ agonists (Yuan et al, 2006). 1,1-Bis(3'-indolyl)-1-(p-substitutedphenyl)methanes containing p-trifluoromethyl, p-t-butyl and p-phenyl substituents activate peroxisome proliferator-activated receptor (PPAR) and inhibit growth of ACHN and 786-0 renal cell carcinoma cell lines. PPAR is overexpressed in ACHN cells and barely detectable in 786-0 cells, and treatment with the t-butyl analog (DIM-C-pPhtBu) induces cell cyle inhibition. DIM-C-pPhtBu also induced several common PPAR-independent proapoptotic responses in ACHN and 786-0 cells, including increased expression of nonsteroidal antiimflammatory drug-activated gene-1 (NAG-1) and endoplasmic reticulum stress which activates death receptor 5 and the extrinsic pathway of apoptosis. In addition, DIM-C-pPhtbu (40 mg/kg/d) also inhibited tumor growth in an orthotopic mouse model for renal carcinogenesis, and this was accompanied by induction of apoptosis in renal tumors treated with DIM-C-pPhtBu but not in tumors treated with the corn oil vehicle (control). Thus, DIM-C-pPhtBu and related compounds represent a novel class of mechanism-based drugs that have potential for treatment of renal adenocarcinoma for which there are currently limited options for successful chemotherapy.

Large-scale networked environments, such as the Internet, possess the characteristics of distributed data, distributed access and distributed control; this gives the user a powerful mechanism for building and integrating large repositories of distributed information from diverse resource sets. However, few support tools have been developed to allow the user to take advantage of the distributed nature of their information. Distributed information management is the process by which users can create, disseminate, discover and manage information that is spread across distributed resources. Distributed open hypermedia systems have shown how distributed information, such as documents and hypermedia links, can be managed and handled within an environment that integrates smoothly between the user's desktop and the network. However, such systems are now looking at addressing the problem of interoperability across hypermedia systems, so that documents and links can be shared between users on heterogeneous integrating technologies. This thesis proposes that the distributed information management provided by open hypermedia systems needs to be extended so that it is more interoperable, extensible and pervasive and that this can be achieved by integrating the principles of open hypermedia with the technology of mobile agents. Mobile agents present a new development mechanism for designing and building distributed applications which are well suited to the dynamic environment of large-scale networks. This thesis describes the development of a mobile agent architecture within which distributed information management tasks can be built and executed. Mobile agents present an important abstraction mechanism when designing distributed environments and also allow the user to manage distributed information indirectly through their mobile agents. A number of prototype agents are described that have been developed to illustrate distributed information management tasks within the architecture and to show how abstractionism and indirect management can be achieved.

In this master thesis the advanced design methodology is presented by which information systems requirements represented with precise UML models are transformed to project. The first section describes a research of five existing MDA tools comparison according to evaluation criteria. This criteria covers model to model and model to code transformations approach, platform of generated code and integration with UML CASE tools abilities. For requirements model transformation to design, plug-in for CASE tool MagicDraw is created according MDA standards. Model transformation plug-in takes system requirement model as input and generates design model. In this way it is possible to implement design methods that have explicit design rules. Created plug-in requirements, functional specification and architecture described in Project section. The investigation section describes investigation of the developed plug-in. In this section were investigate the working efficiency of designer increasing and the quality of design models ensuring with create MagicDraw plug-in.

Notre laboratoire s'intéresse aux mécanismes impliqués dans la régulation de l'expression génique et plus particulièrement au rôle de la chromatine dans cette régulation. En effet, chez les eucaryotes l'ADN est compactée autour de protéines appelées histones créant ainsi des nucléosomes lesquels forment une structure plus complexe, la chromatine. Cette dernière est une barrière aux processus cellulaires touchant l'ADN dont la transcription. La compréhension de la régulation de la structure de la chromatine est essentielle pour saisir les variations de l'expression génique. Mon projet de doctorat a porté sur l'étude de la régulation des gènes cibles du récepteur aryl hydrocarbone (AhR), CYP1A1 et CYP1B1, et plus particulièrement sur le rôle du variant d'histone H2A.Z dans l'expression de ces gènes. AhR est un senseur moléculaire auquel va [i.e. vont] se lier de nombreux polluants appartenant principalement à ces deux grandes familles : les hydrocarbones aromatiques halogènes (HAH) et les hydrocarbones aromatiques polycycliques (PAH). En réponse à la liaison de ces polluants, AhR va induire l'expression de ses gènes cibles. CYP1A1 et CYP1B1 sont impliquées dans le métabolisme de l'estradiol (E2) en 2hydroxyestradiol et 4-hydroxyestradiol respectivement. Il a été proposé qu'une diminution du ratio CYP1A1/CYP1B1 soit importante pour l'initiation du cancer du sein. Au cours de mon doctorat, j'ai pu mettre en évidence un rôle du variant H2A.Z dans la régulation de l'expression de CYP1A1 et CYP1B1. J'ai aussi pu montrer que le statut de ER[alpha] déterminait l'importance de H2A.Z lors de l'induction de CYP1A1. De plus, nous avons observé que la déplétion de H2A.Z induit une augmentation de la méthylation de l'ADN au promoteur de CYP1A1. En parallèle, nous avons confirmé que ER[alpha] réprime spécifiquement l'induction de CYP1A1 sans affecter celle de CYP1B1. Nos résultats montrent qu'en présence de TCDD et d'E2, ER[alpha] et DNMT3B sont recrutés au promoteur de CYP1A1, ce qui conduit à une augmentation de la méthylation du promoteur de CYP1A1 et conséquemment à une diminution de son induction. AhR possède de nombreux ligands d'origine très variée qui peuvent être aussi bien toxiques que bénéfiques. Nous avons choisi de comparer deux de ces ligands : le TCDD et le DIM. Au cours de ces travaux, nous avons montré que le DIM utilisé à forte concentration (>50[mu]M) induit les gènes cibles de AhR (CYP1A1 et CYP1B1) mais aussi un arrêt de la croissance et la mort des cellules. À l'opposé, le traitement avec des concentrations plus faible [i.e. faibles] de DIM (10[mu]M) induit principalement les gènes cibles de ER[alpha] (TFF1 et GREB1) et la prolifération des cellules. Nous avons aussi montré que l'activation de ER[alpha] par le DIM est due à l'action de la protéine kinase A (PKA). En effet, l'inhibition de la PKA ainsi que la déplétion de ER[alpha] abolissent les effets du DIM sur l'expression de GREB1 et CYPIA1 ainsi que sur la prolifération cellulaire. En conclusion, nous avons dans un premier temps mis en évidence le rôle de deux protéines, DNMT3B et H2A.Z, dans la régulation de CYP1A1 dans les cellules MCF7. Nous avons ainsi découvert un nouveau corépresseur partenaire de ER[alpha] en DNMT3B et nous avons proposé une nouvelle façon pour ER[alpha] de promouvoir la carcinogenèse en dérégulant le ratio CYP1A1/CYP1B1. Dans un deuxième temps, nous avons montré que la concentration de DIM utilisée dans les expériences peut conduire à des résultats diamétralement opposés sur la croissance cellulaire.

Portfolio strategies focusing on following the trend, so called momentum based strategies, have been popular for a long time among investors and have had many academic studies, however with varying results. This study sets out to investigate different momentum trading signals as well as combining them in ensemble models such as Random Forest and the unique Dim Switch portfolio and then compare them to set benchmarks. Only one of the benchmarks, the 100% equity portfolio, is found to have better returns than the constructed momentum based strategies, however the momentum based strategies show a lot of potential with high risk-adjusted returns and good performance with regards to Expected Shortfall, Value at Risk and Maximum Drawdown. The most common momentum trading signal, the momentum rule with 9 months lookback, was found to have the highest risk-adjusted returns compared to both the benchmarks and the ensemble models, but it was also found to have slightly heavier left tail than the ensemble models. / Portföljstrategier som baserar sig på att följa trenden, så kallade momentumstrategier, har varit populära länge bland investerare. Många akademiska studier har gjorts om ämnet med varierande resultat. Denna studie utreder olika trendsignaler och kombinerar dem för att forma så kallade ensemble modeller, mer specifikt Random Forest och den unika "Dim Switch"-approachen, för att sedan jämföra dessa strategier mot benchmark portföljer. Endast en av benchmark portföljerna, 100% aktier i en ''buy and hold''-portfölj hade bättre avkastning än de momentumbaserade ensemble modellerna i studien. Däremot har momentumbaserade ensemble modellerna högre riskjusterad avkastning, Expected Shortfall, Value at Risk och Maximum drawdown. Den mest återkommande trendsignalen ''Momentum rule'' med nio månaders lookback hade extremt hög riskjusterad avkastning jämfört med benchmarks och ensemble modellerna, men det kom med kostnaden av högre risker i svansen.

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Η Θεωρία Διαστάσεων είναι από τους παλαιότερους κλάδους της Γενικής Τοπολογίας και μελετά, εκτός των άλλων, τη μικρή επαγωγική διάσταση ind, τη μεγάλη διάσταση Ind και την επονομαζόμενη διάσταση της κάλυψης dim. Οι πρώτοι που έδωσαν αποτελέσματα στη θεωρία διαστάσεων είναι οι Poincare, Brouwer και Lebesgue. Κατά την κατασκευή από τον Ρeano, μιας συνεχούς απεικόνισης από ένα τμήμα επί ενός τετραγώνου, προέκυψε το πρόβλημα: «το κατά πόσον ένα τμήμα και ένα τετράγωνο είναι ομοιόμορφα» και γενικότερα «εάν ο n- κύβος I^n είναι ομοιόμορφος με τον m-κύβο I^m για n διφορετικό του m». Το πρόβλημα αυτό λύθηκε από τον Brouwer [1911] αποδεικνύοντας ότι αν n διαφορετικό του m τότε οι I^n και I^m δεν είναι ομοιόμορφοι. Οι Urysohn [1922, 1925, 1926] και Menger [1923,1924] απέδειξαν με τις εργασίες τους, ότι η θεωρία διαστάσεων είναι μία ανεξάρτητη περιοχή της Γενικής Τοπολογίας. Αυτοί ανέπτυξαν και διατύπωσαν ανεξάρτητα τη θεωρία της μικρής επαγωγικής διάστασης ind για την κλάση των συμπαγών μετρικών χώρων. Αυτή η θεωρία αργότερα επεκτάθηκε για την κλάση των διαχωρίσιμων μετρικών χώρων από τους Tumarkin [1925, 1926] και Hurewicz [1927]. Σήμερα, οι διαστάσεις ορίζονται για οποιονδήποτε τοπολογικό χώρο. Σημειώνουμε ότι, στην κλάση των διαχωρίσιμων μετρικών χώρων, οι τρείς διαστάσεις συμπίπτουν. Δηλαδή: ind(X)=Ind(X)=dim(X), όπου X διαχωρίσιμος μετρικός χώρος. Σε μεγαλύτερη κλάση τοπολογικών χώρων αυτό δεν ισχύει, δηλαδή οι τρείς διαστάσεις διαφέρουν. Στην κλάση των μετρικών χώρων οι διαστάσεις Ind και dim συμπίπτουν. Δηλαδή, αν X μετρικός χώρος: Ind(X)=dim(X). Στην εργασία αυτή δίνουμε τον ορισμό της διάστασης κάλυψης dim, ισοδύναμες εκφράσεις των ορισμών των διαστάσεων και θεωρήματα υποχώρου – αθροίσματος και γινομένου, που αφορούν τη διάσταση αυτή. / The theory of Dimensions is one of the oldest branch of General Topology and studies, among the other, the small inductive dimension ind, the large inductive dimension Ind and the covering dimension dim. Poincare, Brouwer and Lebesgue were the first who gave results in the theory of dimensions. Peano, trying to make a continuous function from a line segment on a square, became the problem: “if a line segment and a square must be uniform” and more generally “if the n- cube I^n can be uniform with the m-cube I^m for n different of m”. Brouwer [1911] gave an answer to this problem by proving that if n different of m then I^n and I^m can not be uniform. Urysohn [1922, 1925, 1926] and Menger [1923,1924] proved that the theory of dimensions is a independent region of General Topology. These developed and formulated independent the theory of the small inductive dimension ind for the class of compact metric spaces. Later, Tumarkin [1925, 1926] and Hurewicz [1927], extended this theory for the class of separable metric spaces. Today, the dimensions are fixed for any topological space. We mention that the three dimensions coincide, in the class of separable metric spaces, that is: ind(X) =Ind (X) =dim (X), where X is a separable metric space. In a bigger class of topological spaces this is not true, that is the three dimensions are different. In the class of metric spaces the dimensions Ind and dim coincide. That is, if X is a metric space then: Ind (X) =dim (X). In this work we give the definition of covering dimension dim, equivalence expressions of the definition of dimensions and also theorems of subspace, addition and product theorems that concern the covering dimension dim.

Cyrba algerina is a salticid (Salticidae) spider that lives on the undersides of stones. Two populations were studied, Sintra and Algarve (Portugal), and shown to have similar phenology but different dominant prey. Life cycle in the laboratory was similar for the two populations, but Sintra matured at larger size than Algarve individuals, with these differences potentially having a genetic basis. Sintra individuals used prey-specific prey-capture behaviour against allopatric (Oecobius amboseli) and sympatric (O. machadoi, Trachyzelotes bardiae) spider and insect (bristletails) species. In contrast, Algarve C. algerina only adopted specialised capture behaviour against bristletails. Sintra, but not Algarve, individuals responded to the odour of O. machadoi and T. bardiae, and showed preference for T. bardiae over O. machadoi. Interpopulation variation in the use of specific prey-capture behaviour and in sensitivity to odour cues from prey is directly related to the prey available to individuals from each population, suggesting local adaptation to local prey. Preference for oecobiids seems to be controlled by an experiencetriggered developmental switch. The optics and histology of C. algerina’s principal eye suggest that living in a microhabitat with dim ambient light has favoured sensitivity at the expense of spatial acuity. Short focal length, reduced power of the eye’s diverging lens, and wide, contiguous rhabdomeres, seem to minimise the visual constraints imposed by the low light levels in C. algerina’s microhabitat. While relying solely on vision, C. algerina can detect, identify and capture prey in dim-light conditions under which other salticids perform poorly. C. algerina’s behaviour suggest use of temporal summation to improve its visual performance in dim light.

This thesis examines the performance of some dim target detection algorithms in low-SNR imaging scenarios. In the past research, there have been numerous attempts for detection and tracking barely visible targets for military surveillance applications with infrared sensors. In this work, two of these algorithms are analyzed via extensive simulations. In one of these approaches, dynamic programming is exploited to coherently integrate the visible energy of dim targets over possible relative directions, whereas the other method is a Bayesian formulation for which the target likelihood is updated along time to be able to detect a target moving in any direction. Extensive experiments are conducted for these methods by using synthetic image sequences, as well as some real test data. The simulation results indicate that it is possible to detect dim targets in quite low-SNR conditions. Moreover, the performance might further increase, in case of incorporating any a priori information about the target trajectory.