998 resultados para Core Domain
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Presented at Work in Progress Session, The 28th GI/ITG International Conference on Architecture of Computing Systems (ARCS 2015). 24 to 27, Mar, 2015. Porto, Portugal.
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The Smart Drug Search is publicly accessible at http://sing.ei.uvigo.es/sds/. The BIOMedical Search Engine Framework is freely available for non-commercial use at https://github.com/agjacome/biomsef
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Polyphosphate (polyP) occurs ubiquitously in cells, but its functions are poorly understood and its synthesis has only been characterized in bacteria. Using x-ray crystallography, we identified a eukaryotic polyphosphate polymerase within the membrane-integral vacuolar transporter chaperone (VTC) complex. A 2.6 angstrom crystal structure of the catalytic domain grown in the presence of adenosine triphosphate (ATP) reveals polyP winding through a tunnel-shaped pocket. Nucleotide- and phosphate-bound structures suggest that the enzyme functions by metal-assisted cleavage of the ATP gamma-phosphate, which is then in-line transferred to an acceptor phosphate to form polyP chains. Mutational analysis of the transmembrane domain indicates that VTC may integrate cytoplasmic polymer synthesis with polyP membrane translocation. Identification of the polyP-synthesizing enzyme opens the way to determine the functions of polyP in lower eukaryotes.
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The brain-spliced isoform of Myosin Va (BR-MyoVa) plays an important role in the transport of dense core secretory granules (SGs) to the plasma membrane in hormone and neuropeptide-producing cells. The molecular composition of the protein complex that recruits BR-MyoVa to SGs and regulates its function has not been identified to date. We have identified interaction between SG-associated proteins granuphilin-a/b (Gran-a/b), BR-MyoVa and Rab27a, a member of the Rab family of GTPases. Gran-a/b-BR-MyoVa interaction is direct, involves regions downstream of the Rab27-binding domain, and the C-terminal part of Gran-a determines exon specificity. MyoVa and Gran-a/b are partially colocalised on SGs and disruption of Gran-a/b-BR-MyoVa binding results in a perinuclear accumulation of SGs which augments nutrient-stimulated hormone secretion in pancreatic beta-cells. These results indicate the existence of at least another binding partner of BR-MyoVa that was identified as rabphilin-3A (Rph-3A). BR-MyoVa-Rph-3A interaction is also direct and enhanced when secretion is activated. The BR-MyoVa-Rph-3A and BR-MyoVa-Gran-a/b complexes are linked to a different subset of SGs, and simultaneous inhibition of these complexes nearly completely blocks stimulated hormone release. This study demonstrates that multiple binding partners of BR-MyoVa regulate SG transport, and this molecular mechanism is universally used by neuronal, endocrine and neuroendocrine cells.
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Comprend : Canzonetta / Bernado Pasquini, comp. ; Aria / Antonio Caldara, comp.
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This paper provides an axiomatic framework to compare the D-core (the set of undominatedimputations) and the core of a cooperative game with transferable utility. Theorem1 states that the D-core is the only solution satisfying projection consistency, reasonableness (from above), (*)-antimonotonicity, and modularity. Theorem 2 characterizes the core replacing (*)-antimonotonicity by antimonotonicity. Moreover, these axioms alsocharacterize the core on the domain of convex games, totally balanced games, balancedgames, and superadditive games
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In this paper we present a new method to track bonemovements in stereoscopic X-ray image series of the kneejoint. The method is based on two different X-ray imagesets: a rotational series of acquisitions of the stillsubject knee that will allow the tomographicreconstruction of the three-dimensional volume (model),and a stereoscopic image series of orthogonal projectionsas the subject performs movements. Tracking the movementsof bones throughout the stereoscopic image series meansto determine, for each frame, the best pose of everymoving element (bone) previously identified in the 3Dreconstructed model. The quality of a pose is reflectedin the similarity between its simulated projections andthe actual radiographs. We use direct Fourierreconstruction to approximate the three-dimensionalvolume of the knee joint. Then, to avoid the expensivecomputation of digitally rendered radiographs (DRR) forpose recovery, we reformulate the tracking problem in theFourier domain. Under the hypothesis of parallel X-raybeams, we use the central-slice-projection theorem toreplace the heavy 2D-to-3D registration of projections inthe signal domain by efficient slice-to-volumeregistration in the Fourier domain. Focusing onrotational movements, the translation-relevant phaseinformation can be discarded and we only consider scalarFourier amplitudes. The core of our motion trackingalgorithm can be implemented as a classical frame-wiseslice-to-volume registration task. Preliminary results onboth synthetic and real images confirm the validity ofour approach.
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This paper provides an axiomatic framework to compare the D-core (the set of undominatedimputations) and the core of a cooperative game with transferable utility. Theorem1 states that the D-core is the only solution satisfying projection consistency, reasonableness (from above), (*)-antimonotonicity, and modularity. Theorem 2 characterizes the core replacing (*)-antimonotonicity by antimonotonicity. Moreover, these axioms alsocharacterize the core on the domain of convex games, totally balanced games, balancedgames, and superadditive games
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SUMMARY BACKGROUND: P-selectin glycoprotein ligand 1 (PSGL-1) is a major selectin ligand, mediating leukocyte rolling along inflamed vascular wall. It is a mucin-like homodimer composed of a N-terminal domain which binds selectins, followed by 14-16 decameric repeats (DR), a transmembrane domain and a cytoplasmic tail, which may be involved in regulating leukocyte rolling and in generating intracellular signals, through its binding to moesin and Syk. P- and L-selectin binding is dependent on core-2 O-glycosylation and tyrosine sulfation of PSGL-1 N-terminus. However, a minor part of E-selectin-mediated rolling is dependent on N-terminal O-glycans; additional binding sites may thus be involved. In this project, we studied whether (1) PSGL-1 DR and (2) PSGL-1 cytoplasmic residues which bind moesin, were also involved in the regulation of selectin-dependent rolling. METHODS: Several mutated cDNAs were obtained: (1) PSGL-1 DR were either deleted, or substituted by platelet GPlba macroglycopeptide, (2) Ser-336, -348, Lys-337 and Arg-338 were mutated to alanine; moreover, truncation mutants retaining only 6 or 2 cytoplasmic residues were also generated. Transfected CHO expressing mutant PSGL-1 were tested for their ability to bind soluble selectin chimeras and to support selectin-dependent rolling under flow conditions. RESULTS: (1) Deletion of the DR had a dramatic effect on P- and L-selectin-dependent cell recruitment and rolling stability, which could only partially be compensated for, by GPlba substitution. In addition, we observed that DR create a binding site for E-selectin and thus support PSGL-1-dependent rolling. (2) Flow assays revealed that the moesin-binding site, in particular Ser-336, plays a crucial role in regulating the recruitment, velocity and rolling stability of PSGL-1-expressing cells on P- and L-selectin. CONCLUSIONS: Data presented here highlight the structure -function relationship of PSGL-1 DR. Moreover, they reveal a crucial role for the moesin-binding residues in regulating P-and L-selectin-dependent rolling. RÉSUMÉ CONTEXTE: PSGL-1 (P-selectin glycoprotein ligand 1) est un ligand majeur des sélectines permettant le roulement des leucocytes le long de la paroi vasculaire enflammée. C'est un homodimère de type mucine, composé d'un domaine N-terminal liant les sélectines, suivi de 14-16 répétitions décamèriques (RD), d'un domaine transmembranaire et d'une queue cytoplasmique qui pourrait être impliquée dans la régulation du roulement leucocytaire et la génération de signaux intracellulaires, via sa liaison à la moésine et à Syk. La liaison à la Pet à la L-sélectine dépend de la présentation par le N-terminus de PSGL-1 de O-glycans sur des structures core-2 et de tyrosines sulfatées. Cependant, une fraction mineure du roulement médié par la E-sélectine dépend des O-glycans N-terminaux; des sites de liaisons supplémentaires pourraient donc être impliqués. Dans ce projet, nous avons étudié si (1) les RD de PSGL-1 ainsi que (2) les résidus cytoplasmiques liant la moésine, étaient impliqués dans la régulation du roulement dépendant des sélectines. MÉTHODES: Plusieurs ADN codant des formes mutées de PSGL-1 ont été obtenus: (1) Les RD de PSGL-1 ont été soit ôtées, soit remplacées par le macroglycopeptide de la GPlba plaquettaire, (2) les Ser-336, -348, la Lys-337 et l'Arg-338 ont été mutées en alanine; par ailleurs, des mutants tronqués ne retenant plus que 6 ou 2 résidus cytoplasmiques ont également été générés. Des CHO transfectées exprimant PSGL-1 muté ont été testées pour leur capacité à lier des sélectines chimériques solubles et à soutenir un roulement dépendant des sélectines dans des conditions de flux. RÉSULTATS: (1) La perte des RD a eu un effet dramatique sur le recrutement cellulaire et la stabilité de roulement dépendant des P- et L-sélectine, qui n'a pu être que partiellement compensé par la substitution par la GPlba. De plus, nous avons observé que les RD forment un site de liaison pour la E-sélectine et soutiennent ainsi le roulement dépendant de PSGL-1. (2) Les tests de flux ont révélé que le site de liaison à la moésine, notamment la Ser-336, joue un rôle crucial dans la régulation du recrutement, de la vitesse et de la stabilité du roulement des cellules exprimant PSGL-1 sur les P- et L-sélectine. CONCLUSIONS; Les données présentées ici ont permis d'éclaircir la relation structure -fonction des RD de PSGL-1. Par ailleurs, elles révèlent un rôle crucial pour les résidus liant la moésine dans le roulement dépendant des P- et L-sélectine. RÉSUMÉ DESTINÉ À UN LARGE PUBLIC Pour accomplir ses fonctions, le sang circule sur un réseau de 96'000 kilomètres; ainsi, il approvisionne les cellules de l'organisme en énergie, il transporte diverses substances, il assure la défense contre les pathogènes et il participe à la régulation de la température corporelle. Le sang contient plusieurs types de cellules: la grande majorité sont les globules rouges, auxquels il faut ajouter les plaquettes (dont le rôle est de colmater les lésions vasculaires) et les globules blancs (leucocytes) qui, bien que présents en très faible quantité (moins de 0.01 %), jouent un rôle crucial en cas d'infection ou d'inflammation. Une attaque par un pathogène provoque plusieurs changements (rougeur, chaleur, gonflement, douleur), qui sont des manifestations de l'inflammation. Pour atteindre l'agent infectieux, des globules blancs spécialisés (les granulocytes) doivent quitter la circulation sanguine. Afin de faciliter leur capture, les vaisseaux sanguins vont exprimer des protéines telles que les sélectines, qui sont reconnues par une protéine leucocytaire appelée PSGL-1 (P-selectin glycoprotein ligand 7). L'interaction des sélectines avec PSGL-1 soutient le roulement du globule blanc le long de la paroi vasculaire, à une vitesse très inférieure à celle du flux sanguin. Ce roulement conduit à l'activation du globule blanc par des molécules de l'inflammation, permettant son adhésion ferme, puis son arrêt. Finalement, le granulocyte va migrer à travers la paroi du vaisseau pour atteindre et éliminer les causes de l'inflammation. L'adhésion est un processus intéressant à caractériser, car outre l'inflammation, il est également impliqué dans l'artériosclérose, l'infarctus, la métastatisation et la thrombose. Dans ce travail, nous nous sommes intéressés à définir les rôles des différents domaines de PSGL-1 dans la régulation de son interaction avec les sélectines. En effet, en plus de son extrémité extracellulaire de haute affinité pour les sélectines, PSGL-1 est composé de plusieurs séquences répétées hautement glycosylées et d'une courte région intracellulaire, dont les fonctions n'avaient pas été étudiées auparavant. En créant des formes mutées de PSGL-1, nous avons pu montrer qu'un roulement efficace des leucocytes nécessite la présence des régions répétitives et du domaine intracellulaire au complet.
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The transcription factors TFIIB, Brf1, and Brf2 share related N-terminal zinc ribbon and core domains. TFIIB bridges RNA polymerase II (Pol II) with the promoter-bound preinitiation complex, whereas Brf1 and Brf2 are involved, as part of activities also containing TBP and Bdp1 and referred to here as Brf1-TFIIIB and Brf2-TFIIIB, in the recruitment of Pol III. Brf1-TFIIIB recruits Pol III to type 1 and 2 promoters and Brf2-TFIIIB to type 3 promoters such as the human U6 promoter. Brf1 and Brf2 both have a C-terminal extension absent in TFIIB, but their C-terminal extensions are unrelated. In yeast Brf1, the C-terminal extension interacts with the TBP/TATA box complex and contributes to the recruitment of Bdp1. Here we have tested truncated Brf2, as well as Brf2/TFIIB chimeric proteins for U6 transcription and for assembly of U6 preinitiation complexes. Our results characterize functions of various human Brf2 domains and reveal that the C-terminal domain is required for efficient association of the protein with U6 promoter-bound TBP and SNAP(c), a type 3 promoter-specific transcription factor, and for efficient recruitment of Bdp1. This in turn suggests that the C-terminal extensions in Brf1 and Brf2 are crucial to specific recruitment of Pol III over Pol II.
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Diplomityö käsittelee IPSec-protokollan (IP Security Protocol) implementointia UMTS:n (Universal Mobile Telecommunications System) pakettikytkentäiseen verkkoon. Runkoverkkoa käytetään mobiilikäyttäjän datan siirtämiseen sekä verkkoelementtien väliseen ohjausinformaation välitykseen. Koska UMTS:n runkoverkot ovat IP-pakettikytkentäisiä verkkoja, IPSec-protokollaa voidaan käyttää lähetettyjen IP-datasähkeiden suojaamiseen. IPSec- ja IKE-protokollien (Internet Key Exchange) käyttö on koettu monimutkaiseksi kiinteissä verkoissa. Tämän saman ongelman edessä tulevat olemaan myös operaattorit, kun he alkavat rakentaa UMTS-verkkojaan. On kuitenkin muistettava se, että tulevaisuudessa lähes kaikki data mukaanlukien ääni ja video on tarkoitus siirtää IP-protokollan avulla. IP-teknologiaan perustuva tiedonsiirron kasvu lisää IPSec-protokollan merkitystä ei ainoastaan runkoverkossa mutta myös radioliityntäverkoissa sekä SS7-merkinantoverkoissa (Signaling System No. 7). Diplomityö on tehty osaksi diplomi-insinöörin tutkintoa Lappeenrannan teknillisessä yliopistossa. Työ on tehty Nokia Networksin palveluksessa Helsingissä, vuosien 2002 ja 2003 välisenä aikana.
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[cat] En aquest treball es demostra que en el domini dels jocs d’assignació equilibrats multisectorials (Quint, 1991), el core és l’única solució no buida que satisfà derived consistency i projection consistency. També es caracteritza el core en tota la classe dels jocs d’assignació multisectorials amb els axiomes de singleness best, individual antimonotonicity i derived consistency. Com a casos particulars, s’obtenen dues noves axiomàtiques del core per als jocs d’assignació bilaterals (Shapley and Shubik, 1972).
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[cat] En aquest treball es demostra que en el domini dels jocs d’assignació equilibrats multisectorials (Quint, 1991), el core és l’única solució no buida que satisfà derived consistency i projection consistency. També es caracteritza el core en tota la classe dels jocs d’assignació multisectorials amb els axiomes de singleness best, individual antimonotonicity i derived consistency. Com a casos particulars, s’obtenen dues noves axiomàtiques del core per als jocs d’assignació bilaterals (Shapley and Shubik, 1972).
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In my doctoral thesis I evaluate strategies designed to cope with the multicultural nature of four European nations: Great Britain, The Netherlands, Sweden, and Denmark. I also analyse and clarify the question of the place of religion in present-day Europe. The empirical material analysed in the study consists of politicians’ statements and policy documents dealing with immigration policy and religious and values education in the four countries. In addition, I analyse statements issued by the Council of Europe regarding religious education, along with all cases relevant to religious education brought before the United Nations Human Rights Committee or the European Court of Human Rights. The theoretical framework is formed by the scholarly debate – among philosophers, sociologists and scholars of religion in education – concerning the question of a just society. Special emphasis is given to philosophical theories that are in favour of granting special group rights to religious minorities in the name of equal treatment. With regard to the question of the appropriate place of religion, I apply Kim Knott’s methodological model for locating religion in secular contexts, and Émile Durkheim’s theory as to the significance of religion and collective sentiments in uniting adherents or members of a group into a single moral community. The study shows that even when the positive side of immigration, as a potential force for the enrichment of the public culture, is acknowledged, there is anxiety as to the successful integration of immigrants. The premises and goals of immigration policies have also been questioned. One central problem is the incommensurability between the values upheld by Western liberal democracies and certain religious traditions, above all those of Islam. Great Britain, The Netherlands, Sweden, and Denmark have tightened control over their citizens’ ethical attitudes and want to regulate these as well. In coping with cultural diversity, the significance of education, especially religious education, plays a significant role; as future citizens, pupils are expected to internalise the society’s core values as well as gaining an understanding of different cultures and ways of life. It is also worth noting that both the Council of Europe and the European Court of Human Rights have recently expressed the view that one important goal of religious education is to enable pupils to be critical and autonomous with regard to different religions and moral positions. The study shows that religion is not seen as purely a personal matter. Religion is closely linked to individual and national identity, and religious traditions thus have a place in the public domain. It should be noted, however, that a religious tradition – more precisely, an interpretation of religious tradition – qualifies as a legitimate partner in the democratic decision-making process only if it shares similar values with Western European nations.