We can define Delayed Galaxies as a class of rare galaxies that maintained the bulk of their gas for most of the age of the universe following the initial formation of their disks, with little or no star formation. Invisible galaxies and Malin 1 type low-surface-brightness galaxies qualify as class members. Rare examples among interacting galaxies show that collisions can restart the stalled evolution of such galaxies, and suggest that other members of the Delayed class can be found among interacting systems with vigorous current star formation.

In this thesis we present a model of the interacting agents on the financial market. The agents are represented by a non-Euclidean random graph, where each agent communicate with another with probability p, and the interaction according to the Ising Model. We investigate properties of the model by direct calculations for small graph sizes, and by perfect simulation for larger graph sizes. We also present a model for asset price variation by using the magnetization of the Ising model.

No description available.

We explore the effect of multiscale structure on weakly interacting diffusions through two main projects. In the first, we consider a collection of weakly interacting diffusion processes moving in a two-scale locally periodic environment. We study the large deviations principle of the empirical distribution of the particles' positions in the combined limit as the number of particles grow to infinity and the time-scale separation parameter goes to zero simultaneously. We make use of weak convergence methods providing a convenient representation for the large deviations rate function, which allow us to characterize the effective controlled mean field dynamics. In addition, we obtain equivalent representations for the large deviations rate function of the form of Dawson-G\"artner which hold even in the case where the diffusion matrix depends on the empirical measure and when the particles undergo averaging in addition to the propagation of chaos. In the second, we consider a fully-coupled slow-fast system of McKean-Vlasov SDEs with full dependence on the slow and fast component and on the law of the slow component and derive convergence rates to its homogenized limit. We do not make periodicity assumptions, but we impose conditions on the fast motion to guarantee ergodicity. In the course of the proof we obtain related ergodic theorems and we gain results on the regularity of Poisson type of equations and of the associated Cauchy-Problem on the Wasserstein space that are of independent interest.

Yes / A rigorous model for automatic modulation classification (AMC) in cognitive radio (CR) systems is proposed in this paper. This is achieved by exploiting the Kalman filter (KF) integrated with an adaptive interacting multiple model (IMM) for resilient estimation of the channel state information (CSI). A novel approach is proposed, in adding up the squareroot singular values (SRSV) of the decomposed channel using the singular value decompositions (SVD) algorithm. This new scheme, termed Frobenius eigenmode transmission (FET), is chiefly intended to maintain the total power of all individual effective eigenmodes, as opposed to keeping only the dominant one. The analysis is applied over multiple-input multiple-output (MIMO) antennas in combination with a Rayleigh fading channel using a quasi likelihood ratio test (QLRT) algorithm for AMC. The expectation-maximization (EM) is employed for recursive computation of the underlying estimation and classification algorithms. Novel simulations demonstrate the advantages of the combined IMM-KF structure when compared to the perfectly known channel and maximum likelihood estimate (MLE), in terms of achieving the targeted optimal performance with the desirable benefit of less computational complexity loads.

Innate leukocytes manifest dynamic and distinct inflammatory responses upon challenges with rising dosages of pathogen associated molecular pattern molecules (PAMPs) such as lipopolysaccharide (LPS). To differentiate signal strengths, innate leukocytes may utilize distinct intra-cellular signaling circuitries modulated by adaptor molecules. Toll-interacting protein (Tollip) is one of the critical adaptor molecules in Toll-like receptor 4 (TLR4) signaling and potentially playing key roles in modulating the dynamic adaptation of innate leukocytes to varying dosages of external stimulants. While Tollip may serve as a negative regulator of NFkB signaling pathway in cells challenged with higher dosages of LPS, it acts as a positive regulator for low-grade chronic inflammation in leukocytes programmed by subclinical low-dosages of LPS. We aim to show recent progress in our understanding of complex innate leukocyte dynamics and its relevance in the pathogenesis of resolving versus non-resolving chronic inflammatory diseases. / Ph. D.

This thesis describes the cloning and characterisation of a novel human gene and its protein products, which have been designated SAPK- and Ras-interacting protein (SinRIP). SinRIP shares identity with JC310, a partial human cDNA that was previously identified a candidate Ras-inhibitor (Colicelli et al., 1991, Proc Natl Acad Sci USA 88, p. 2913). In this study, it was shown that SinRIP is a member of an orthologous family of proteins that is conserved from yeast to mammals and contains proteins involved in Ras- and SAPK-mediated signalling pathways. Comparison of this family of proteins showed that human SinRIP contains a potential Ras-binding domain (RBD; residues 279-354), a PH-like domain (PHL; 376-487), and a highly conserved novel region designated the CRIM (134-265). Several other potential targeting sites, such as nuclear localisation signals and target sites for kinases, were identified within the SinRIP sequence. The human SinRIP gene is unusually large (>280 kbp) and is located on chromosome 9 at 9q34. SinRIP mRNA was detected in a wide variety of tissue-types and cell lines by RT-PCR, and the SinRIP sequences in the EST database were derived from an diverse array of tissues, suggesting a widespread or ubiquitous expression. Northern blot analysis revealed the highest levels in skeletal muscle and heart tissue. However, the steady-state levels of SinRIP mRNA vary greatly from cell to cell, and SinRIP expression is likely to be regulated at multiple post-transcriptional levels. It was shown that SinRIP mRNA is likely to be translated inefficiently by the normal cap-scanning mechanism, due to the presence of a GC-rich and structured 5’-UTR, which also contains upstream ORFs. Alternative polyadenylation signals in the SinRIP 3’-UTR can be used, resulting in the expression of short and long SinRIP mRNA isoforms. Several potential A/T-rich regulatory elements were also identified in SinRIP mRNA, which may target specific SinRIP mRNA isoforms for rapid degradation. Importantly, it was shown that SinRIP mRNA is alternatively spliced, resulting in the production of distinct SinRIP protein isoforms. Three isoforms, SinRIP2-4, were definitively identified by RT-PCR and full-length cloning. The SinRIP isoforms contain deletions in conserved regions, and are likely to have biochemical characteristics that are different to full-length SinRIP1. SinRIP2 is C-terminally truncated and lacks the PHL domain and part of the RBD, and relatively high levels of SinRIP2 expression arelikely to occur in kidneys. The RBD is disrupted in SinRIP3, but all other domains are intact, and RT-PCR analyses suggest that SinRIP3 is present in some cells at levels comparable to SinRIP1. A rabbit polyclonal antiserum against SinRIP was generated and detected endogenous SinRIP proteins. Using the anti-SinRIP antibody in immunoblots, multiple SinRIP isoforms were observed in most cell types. SinRIP1 and another endogenous SinRIP protein, likely to be SinRIP3, were detected in most cell lines, and appear to be are the major SinRIP proteins expressed in most cells. The subcellular localisation of both recombinant and endogenous SinRIP proteins was investigated by immunofluorescence assays and biochemical fractionation. Recombinant SinRIP1 protein was found in the cytoplasm and associated with the plasma membrane. In contrast, the SinRIP2 protein was predominantly nuclear, with only low-level cytoplasmic staining observed. The endogenous SinRIP proteins, likely to comprise these and other SinRIP isoforms, were found in both the nucleus and cytoplasm. SinRIP1 interacted with GTP-bound (active) Ras, but not GDP-bound (inactive) Ras, in an in vitro assay, and also co-localised with activated H- and K-Ras in cells. The binding profile observed is typical of Ras-effectors, and SinRIP did not inhibit signalling by the Ras proteins, suggesting that it is not likely to be a Ras-inhibitor. It was also shown that SinRIP1 and SinRIP2 both interact and colocalise with c-Jun NH2- terminal kinase (JNK). Both SinRIP proteins were able to recruit JNK to their respective sub-cellular compartments. These interactions suggest an adaptor role for SinRIP in the Ras and/or JNK pathways. In addition, Sam68 was isolated as a SinRIP-binding protein in a yeast two-hybrid screen. Sam68 was shown to colocalise with SinRIP2 and endogenous SinRIP proteins, but not SinRIP1. Further colocalisation studies showed that endogenous SinRIP proteins localise in nuclear structures that may be associated with pre-mRNA splicing. Likely functions for SinRIP, as indicated by experimental results and studies of the orthologues of SinRIP in other species, are discussed.

Le protéasome est responsable de la dégradation régulée d'une majeure partie des protéines intracellulaires. Cette machinerie multimoléculaire est composée d'un cœur catalytique, le protéasome 20S, qui peut être activé par plusieurs types de protéines régulatrices, en particulier la particule régulatrice 19S ou PA700, les complexes heptamériques formés par les membres de la famille 11S (ou PA28) et PA200. Au cours de ce travail, nous nous sommes focalisés sur PA28gamma, un régulateur nucléaire du protéasome, qui active la dégradation de plusieurs substrats par le protéasome 20S de façon indépendante de l'ubiquitine et de l'ATP. Malgré de multiples études montrant l'implication de PA28gamma dans de nombreux processus cellulaires essentiels tels que le cycle cellulaire, la prolifération, l'apoptose, l'architecture nucléaire, la dynamique de la chromatine, les infections virales et la réponse au stress, ses fonctions exactes ne sont pas encore comprises. De plus, les mécanismes impliqués dans la régulation de l'activité de PA28gamma et de son association avec le protéasome 20S restent mystérieux. Une analyse SILAC des partenaires d'interaction de PA28gamma endogène a révélé l'existence d'un nouveau facteur, non caractérisé, que nous avons appelé PIP30 (PA28gamma Interacting Protein 30 kDa). Le gène PIP30 contient un domaine très conservé chez les Eucaryotes. Nous avons produit et purifié la protéine PIP30 recombinante et montré qu'elle est faiblement structurée, malgré le fait qu'elle puisse se dimériser. Nous avons confirmé, aussi bien in vitro qu'in cellulo, que PIP30 interagit directement et spécifiquement avec PA28gamma. En analysant la co-immunoprécipitation de PA28gamma avec différents mutants tronqués de GFP-PIP30, nous avons pu identifier la séquence de PIP30 responsable de l'interaction avec PA28gamma dans sa partie C-terminale. Nous essayons maintenant d'identifier la séquence de PA28gamma impliquée dans la liaison de PIP30 et de cristalliser le complexe PA28gamma/PIP30. L'élaboration d'un anticorps anti-PIP30 « maison » nous a permis de montrer que PIP30 est une protéine nucléaire stable. Son niveau d'expression diminue en réponse à la déplétion de PA28gamma, ce qui suggère que PIP30 est stabilisée par son interaction avec PA28gamma in cellulo. Nous avons démontré in vitro que PIP30 inhibe partiellement l'activation médiée par PA28gamma des activités de type chymotrypsine et caspase, mais pas trypsine, du protéasome. Cependant, nous avons montré, par une approche ELISA, que PIP30 n'affecte pas la liaison de PA28gamma au protéasome 20S. Par ailleurs, nous avons testé l'effet de PIP30 sur la dégradation de p21 par le complexe PA28gamma/protéasome 20S et observé que PIP30 augmente la vitesse de dégradation de p21 dans ce test. Nos tentatives pour élucider la fonction exacte de PIP30 in cellulo n'ont jusqu'ici pas abouti à une conclusion convaincante. L'ensemble de ces résultats suggère que PIP30 pourrait être impliqué dans le recrutement sélectif des substrats de PA28gamma et/ou dans la modulation de l'activation du protéasome par PA28gamma. / The proteasome is responsible for the regulated degradation of most intracellular proteins. This multi-subunit machinery is composed of a common catalytic core, the 20S proteasome, which can be activated by various types of regulators, notably the 19S regulatory particle or PA700, the heptameric complexes formed by the members of the 11S (or PA28) family and PA200. This work has been focused on PA28gamma, a nuclear regulator of the proteasome, which has been shown to activate degradation of several proteasomal substrates in an ATP- and ubiquitin- independent manner. Despite many evidences revealing the involvement of PA28gamma in many essential cellular processes, such as cell cycle progression, proliferation, apoptosis, nuclear architecture, chromatin dynamics, viral infection and stress response, its exact function(s) remain to be understood. In addition, how PA28gamma activity and association to the 20S proteasome are regulated is completely unclear. A SILAC-based analysis of endogenous PA28gamma interaction partners revealed the existence of a novel, completely uncharacterized protein, which we called PIP30 (PA28gamma Interacting Protein 30 kDa). Evolutionary analysis indicates that PIP30 gene contains a domain highly conserved in Eukaryotes, without any alternative splicing or gene duplication evidences. We produced and purified the recombinant PIP30 protein and showed that it is poorly structured, although it is able to make dimers. We confirmed both in vitro and in cellulo that PIP30 directly and specifically interacts with PA28gamma. By analyzing the co-immunoprecipitation of PA28gamma with various GFP-PIP30 truncation mutants, we identified the sequence of PIP30 responsible for PA28gamma binding in its C-terminal part. Ongoing analyses now focus on the identification of PIP30 binding motif on PA28gamma sequence and the crystallization of the PA28gamma-PIP30 complex. Using homemade anti-PIP30 antibodies, we showed that PIP30 is a stable nuclear protein. Its expression level is decreased in response to PA28gamma depletion, suggesting that it is stabilized by its interaction with PA28gamma in cellulo. We demonstrated in vitro that PIP30 partially inhibits PA28gamma-mediated activation of the chymotrypsin- and caspase-, but not the trypsin-like, activities of the proteasome. However, we showed by an ELISA-based approach that PIP30 does not affect PA28gamma binding to 20S. Considering the limitations of probing proteasome activity with small fluorogenic substrates, we tested the effect of PIP30 on the PA28gamma-dependent proteasomal degradation of in vitro translated p21, a known protein substrate of PA28gamma. We unexpectedly found that PIP30 enhanced the rate of p21 degradation. Our attempts to elucidate the exact functions of PIP30 in cellulo were unsuccessful so far. Altogether, our results suggest that PIP30 could be involved in the selective recruitment of PA28gamma protein substrates and/or modulate PA28gamma-mediated proteasome activation.

Made available in DSpace on 2015-03-26T13:36:45Z (GMT). No. of bitstreams: 1 texto completo.pdf: 2928675 bytes, checksum: b8457e10b48f36e111d09ef311ae3d5a (MD5) Previous issue date: 2010-02-18 / The begomovirus NSP (nuclear shuttle protein) facilitates the transport of viral DNA from the nucleus to the cytoplasm and cooperates with the movement protein MP to promote the translocation of viral DNA to the adjacent, uninfected cells through plasmodesmata. NSP interacts with members of the LRR-RLK ( leucine-rich repeat receptor like kinase ) family, designated NIKs ( NSP-Interacting Kinase ). Binding of NSP to the activation loop of NIK inhibits kinase activity and hence the viral protein suppresses receptor autophosphorylation and defense responses. Mutagenesis assays in the activation loop of NIK have demonstrated that the threonine 474 residue is phosphorylated in vitro and plays a crucial role in the kinase activity that is required for signaling. Replacement of Thr-474 with aspartate produces the T474 mutant, which exhibits constitutive activation, enhanced substrate phosphorylation activity and less inhibitory effect by NSP binding. The goal of this investigation was to analyse the NIK kinase domain in defense responses against begomovirus in tomato. The NIK mutant T474D cDNA was placed under the control of 35S promoter into a binary vector for plant transformation (35S-AtNIK-T474D). Primary transformants were selected by PCR and the expression of the transgene was confirmed by normal and quantitative RT- PCR in independently transformed lines. NIK and NIK-T474D overexpression in tomato plants affected the overall developmental performance of transgenic lines, which display elongated stems and a root system less developed. These phenotypes were consistent with a cross-communication between the NIK-mediated antiviral signaling and developmental signaling pathways. Infectivity assays were carried out in AtNIK- and AtNIK-T474D-overexpressing lines, with the virus ToYSV-[MG-Bi2]. Overexpression of super active AtNIK-T474D altered the infection rate by ToYSV, and interfered in symptom development. As compared to untransformed plants and NIK- overexpressing 35S-AtNIK1-6 transgenic lines, independent transgenic AtNIK-T474D lines displayed lower infection rate and attenuated symptoms. These results confirmed in planta the essential role for phosphorylation of the Thr-474 residue for NIK function and underlined the possibility for the development of more efficient tolerance strategies against geminiviruses. / A proteína NSP de begomovírus facilita o transporte do DNA viral do núcleo para o citoplasma e coopera com a proteína de movimento MP para promover o transporte do DNA viral às células adjacentes não infectadas através dos plasmodesmas. A proteína NSP interage com membros da família LRR-RLK ( leucine- rich repeat receptor like kinase ), designados NIK ( NSP-Interacting Kinase ). A ligação de NSP na alça de ativação de NIK inibe a atividade quinase, e conseqüentemente, a proteína viral inibe a atividade de autofosforilação desses receptores e sua atividade de defesa antiviral. Estudos de mutagênese na alça de ativação de NIK demonstraram que o resíduo Treonina 474 é fosforilado in vitro e exerce uma função crucial para atividade de quinase que é requerida para sinalização antiviral. Mutação no resíduo de Thr-474 para aspartato resulta no mutante T474D que exibe ativação constitutiva, atividade de fosforilaçao do substrato aumentada e menor efeito inibidor de NSP. Este trabalho teve como objetivo caracterizar o domínio quinase de NIK na resposta de defesa antiviral em tomateiros. Tomateiros foram transformados com a construção que codifica para NIK super ativa (35S-AtNIK-T474D). Os transformantes primários foram selecionados por PCR e a expressão do transgene em linhagens independentes foi confirmada por RT-PCR normal e em tempo real. A super expressão da NIK1 e NIK- T474D super ativa em tomateiros promoveu um alongamento de entrenós, mas afetou negativamente o desenvolvimento do sistema radicular, demonstrando uma possível comunicação cruzada entre a via de sinalização antiviral mediada por NIK e vias de sinalização de desenvolvimento. Experimentos de infectividade foram conduzidos em linhagens transgênicas superexpressando AtNIK ou AtNIK-T474D, utilizando o vírus ToYSV-[MG-Bi2]. Super expressão de NIK super ativa alterou a taxa de infecção por ToYSV e interferiu no desenvolvimento dos sintomas. Comparado com as plantas não transformadas e a linhagem transgênica 35S-AtNIK1-6 superexpressando NIK normal, a taxa de infecção foi inferior e os sintomas mais atenuados em linhagens transgênicas independentes superexpressando AtNIK-T474D. Estes resultados confirmam in planta o papel essencial da fosforilação do resíduo de Treonina 474 de NIK e indicam a possibilidade de se desenvolverem estratégias de tolerância a geminivirus mais eficientes.

Le rôle crucial des interfaces solides dans les problèmes de structures dans de nombreux domaines de l'Ingénierie est désormais bien connue et c'est certainement un sujet de grand intérêt scientifique. Aujourd'hui, la modélisation analytique et numérique des interfaces structurelles représentent un défi du fait desphénomènes physiques très complexes qu'il faut prendre en compte (tels que adhésion, contact non-conforme,microfissuration, frottement, contact unilatéral) autant que le besoin d'avoir des méthodes numériques qui soient capables de traiter à la fois la faible épaisseur des zones d'interface et les sauts dans les champs physiques concernés. Cette thèse vise à développer un outil analytique cohérent et général qui soit capable de dépasser les limitations des stratégies existantes et concernant la modélisation des interfaces emph{soft} et emph{hard} caractérisées par une microfissuration évolutive. Une nouvelle approche, appelée emph{Imperfect Interface Approach} (IIA), est proposée. Elle couple de manière cohérente arguments de théorie asymptotique et techniques d'homogénéisation pour les milieux microfissurés dans le cadre de la emph{Non-Interacting Approximation} (NIA). Dans le cadre de l'élasticité linéaire, l'IIA est employée avec succès pour obtenir un ensemble de modèles d'interfaces imparfaites.En généralisant la méthode de développement asymptotique à la théorie élastique des déformations finies, un modèle d'interface soft non-linéaire a été dérivé. Comme une nouvelle application, l'IIA est appliquée afin de formuler un modèle de contact non-conforme à raideurs equivalents. Simulations numériques appliquées à la maçonnerie ont été effectuées. / The crucial role of solid interfaces in structural problems in several engineering fields is well-established and they represent certainly a scientific topic of great interest. Nowadays, analytical and numerical modeling of structural interfaces are challenging tasks, due to the complex physical phenomena to take into account (such as adhesion, non-conforming contact, microcracking, friction, unilateral contact), as well as to the need of numerical methods suitable for treating small thickness of the interface zones and jumps in the physically relevant fields.Present PhD thesis aims to develop a consistent and general analytical tool able to overcome some modeling shortcomings of available modeling strategies accounting for soft and hard interfaces, and characterized by evolving microcracking. A novel approach, referred to as emph{Imperfect Interface Approach} (IIA), is proposed. It consistently couples asymptotic arguments and homogenization techniques for microcracked media in the framework of the Non-Interacting Approximation (NIA). In the context of linear elasticity, the IIA is successfully employed to derive a set of imperfect interface. By generalizing the matched asymptotic expansion method to finite strains, a nonlinear soft interface model has been derived. As a new general application, the IIA is applied to formulate a spring-type model for non-conforming contact. Finally, numerical simulations applying the soft interface models obtained in both linear and nonlinear cases to masonry structures, are carried out, showing effectiveness and soundness of the proposed formulation.