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We set out to investigate the burden of ultra-rare variants (URVs) in a comprehensive range of ... [more ▼]Background Analyses of few gene-sets in epilepsy showed a potential to unravel key disease associations. We set out to investigate the burden of ultra-rare variants (URVs) in a comprehensive range of biologically informed gene-sets presumed to be implicated in epileptogenesis. Methods The burden of 12 URV types in 92 gene-sets was compared between cases and controls using whole exome sequencing data from individuals of European descent with developmental and epileptic encephalopathies (DEE, n = 1,003), genetic generalized epilepsy (GGE, n = 3,064), or non-acquired focal epilepsy (NAFE, n = 3,522), collected by the Epi25 Collaborative, compared to 3,962 ancestry-matched controls. Findings Missense URVs in highly constrained regions were enriched in neuron-specific and developmental genes, whereas genes not expressed in brain were not affected. GGE featured a higher burden in gene-sets derived from inhibitory vs. excitatory neurons or associated receptors, whereas the opposite was found for NAFE, and DEE featured a burden in both. Top-ranked susceptibility genes from recent genome-wide association studies (GWAS) and gene-sets derived from generalized vs. focal epilepsies revealed specific enrichment patterns of URVs in GGE vs. NAFE. Interpretation Missense URVs affecting highly constrained sites differentially impact genes expressed in inhibitory vs. excitatory pathways in generalized vs. focal epilepsies. The excess of URVs in top-ranked GWAS risk-genes suggests a convergence of rare deleterious and common risk-variants in the pathogenesis of generalized and focal epilepsies. [less ▲]Detailed reference viewed: 88 (0 UL) Distinct involvement of beta3 integrin cytoplasmic domain tyrosine residues 747 and 759 in integrin-mediated cytoskeletal assembly and phosphotyrosine signaling.Schaffner-Reckinger, Elisabeth ; Gouon, V.; Melchior, Chantal et alin The Journal of biological chemistry (1998), 273(20), 12623-32We have investigated the structural requirements of the beta3 integrin subunit cytoplasmic domain necessary for tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin during alphav beta3 ... [more ▼]We have investigated the structural requirements of the beta3 integrin subunit cytoplasmic domain necessary for tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin during alphav beta3-mediated cell spreading. Using CHO cells transfected with various beta3 mutants, we demonstrate a close correlation between alphav beta3-mediated cell spreading and tyrosine phosphorylation of FAK and paxillin, and highlight a distinct involvement of the NPLY747 and NITY759 motifs in these signaling processes. Deletion of the NITY759 motif alone was sufficient to completely prevent alphav beta3-dependent focal contact formation, cell spreading, and FAK/paxillin phosphorylation. The single Y759A substitution induced a strong inhibitory phenotype, while the more conservative, but still phosphorylation-defective, Y759F mutation restored wild type receptor function. Alanine substitution of the highly conserved Tyr747 completely abolished alphav beta3-dependent formation of focal adhesion plaques, cell spreading, and FAK/paxillin phosphorylation, whereas a Y747F substitution only partially restored these events. As none of these mutations affected receptor-ligand interaction, our results suggest that the structural integrity of the NITY759 motif, rather than the phosphorylation status of Tyr759 is important for beta3-mediated cytoskeleton reorganization and tyrosine phosphorylation of FAK and paxillin, while the presence of Tyr at residue 747 within the NPLY747 motif is required for optimal beta3 post-ligand binding events. [less ▲]Detailed reference viewed: 91 (5 UL) Distinct Metabolic States Can Support Self-Renewal and Lipogenesis in Human Pluripotent Stem Cells under Different Culture ConditionsZhang, Hui; Badur, Mehmet G.; Divakaruni, Ajit S. et alin Cell Reports (2016), 16(6), 1536--1547Detailed reference viewed: 92 (1 UL) Distinct metabolomic signature in cerebrospinal fluid in early parkinson's disease: Early Parkinson'S CSF Metabolic SignatureTrezzi, Jean-Pierre ; Galozzi, Sara; Jäger, Christian et alin Movement Disorders (2017)Objective: The purpose of this study was to profile cerebrospinal fluid (CSF) from early-stage PD patients for disease-related metabolic changes and to determine a robust biomarker signature for early ... [more ▼]Objective: The purpose of this study was to profile cerebrospinal fluid (CSF) from early-stage PD patients for disease-related metabolic changes and to determine a robust biomarker signature for early-stage PD diagnosis. Methods: By applying a non-targeted and mass spectrometry-driven approach, we investigated the CSF metabolome of 44 early-stage sporadic PD patients yet without treatment (DeNoPa cohort). We compared all detected metabolite levels with those measured in CSF of 43 age- and gender-matched healthy controls. After this analysis, we validated the results in an independent PD study cohort (T€ubingen cohort). Results: We identified that dehydroascorbic acid levels were significantly lower and fructose, mannose, and threonic acid levels were significantly higher (P <.05) in PD patients when compared with healthy controls. These changes reflect pathological oxidative stress responses, as well as protein glycation/glycosylation reactions in PD. Using a machine learning approach based on logistic regression, we successfully predicted the origin (PD patients vs healthy controls) in a second (n518) as well as in a third and completely independent validation set (n536). The biomarker signature is composed of the three markers—mannose, threonic acid, and fructose—and allows for sample classification with a sensitivity of 0.790 and a specificity of 0.800. Conclusion: We identified PD-specific metabolic changes in CSF that were associated with antioxidative stress response, glycation, and inflammation. Our results disentangle the complexity of the CSF metabolome to unravel metabolome changes related to earlystage PD. The detected biomarkers help understanding PD pathogenesis and can be applied as biomarkers to increase clinical diagnosis accuracy and patient care in early-stage PD. [less ▲]Detailed reference viewed: 67 (11 UL) La distinction entre intentio auditoris et intentio operis et sa mise en oeuvre comme critère d'identité du professeur de musiqueSagrillo, Damien Presentation (2014, December 16)Dans Les Limites de l'interprétation (Paris, 1992) Umberto Ecco distinguait entre la recherche de l’intentio operis et la subordination du texte à l’intentio lectoris. Dans le premier cas, il s’agit d’ « ... [more ▼]Dans Les Limites de l'interprétation (Paris, 1992) Umberto Ecco distinguait entre la recherche de l’intentio operis et la subordination du texte à l’intentio lectoris. Dans le premier cas, il s’agit d’ « in-terprétation », et dans le deuxième, Ecco parle d’ « utilisation des textes ». L’importance de cette thèse pour la pédagogie musicale est que l’intentio lectoris est à l’origine de tout apprentissage de la mu-sique. Transféré à la musique on pourrait parler d’intentio auditoris. Si les apprentis doivent être mo-tivés à changer l’intentio auditoris dans le sens de l’intentio operis, ils doivent profiter de la possibilité de réaliser le lien de leur propre intentionnalité avec la musique, c.à.d. qu’ils doivent tenter de changer l’objet. Ceci est une tâche primordiale qui revient aux professeurs de musique. L'importance des médias électroniques et des nouvelles technologies se situera au centre d’un projet de recherche d’envergure européenne de la FEMP (Forum of European Music Pedagogy, Forum Euro-péen de Pédagogie de Musique, Forum Europäische Musikpädagogik). Il revient à l’identité et au pro-fessionnalisme du professeur de musique de reconnaître la distance entre intentio auditoris et intentio operis (la dernière fut apprise lors de sa propre formation) et d’oeuvrer avec conviction en vue de réduire cette distance. En outre, il devra justifier et remettre en question à tout moment les objectifs de son action pédagogique pour soi-même et pour élèves. L’objectif de notre/nos communication(s) est de retracer l’identité des enseignants de musique sous un angle européen, notamment en distinguant entre les pays orientés plutôt vers la tradition alle-mande (le pédagogue-musicien) d’un côté et des pays préconisant le système d’origine francophone, voire anglo-saxonne (le musicien-enseignant), de l’autre. Repérer des pistes en vue d’un enrichisse-ment réciproque entre les différentes traditions sera un des buts du PR de la FEMP. [less ▲]Detailed reference viewed: 358 (1 UL) Distinctive body perception mechanisms in high versus low symptom reporters: a neurophysiological model for medically-unexplained symptomsSchulz, André ; Rost, Silke; Flasinski, Tabea et alin Journal of Psychosomatic Research (2020), 137(1), 110223OBJECTIVE: The neurophysiological processes involved in the generation of medicallyunexplained symptoms (MUS) remain unclear. This study tested three assumptions of the perception-filter model ... [more ▼]OBJECTIVE: The neurophysiological processes involved in the generation of medicallyunexplained symptoms (MUS) remain unclear. This study tested three assumptions of the perception-filter model contributing to MUS: (I.) increased bodily signal strength (II.) decreased filter function, (III.) increased perception. METHODS: In this cross-sectional, observational study, trait MUS was assessed by a webbased survey (N=486). The upper and lower decile were identified as extreme groups of high (HSR; n=29; 26 women; Mage=26.0 years) and low symptom reporters (LSR; n=29; 21 women; Mage=28.4 years). Mean heart rate (HR) and heart rate variability (HRV), and cortisol awakening response (CAR) were assessed as indicators of bodily signal strength (I.). Heartbeat-evoked potentials (HEPs) were assessed during rest and a heartbeat perception task. HEPs reflect attentional resources allocated towards heartbeats and served as index of filter function (II.). Interoceptive accuracy (IAc) in heartbeat perception was assessed as an indicator of perception (III.). RESULTS: HSR showed higher HR and lower HRV (RMSSD) than LSR (I.), but no differences in CAR. HSR exhibited a stronger increase of HEPs when attention was focused on heartbeats than LSR (II.); there were no group differences in IAc (III.). CONCLUSIONS: The perception-filter model was partially confirmed in that HSR showed altered bodily signals suggesting higher sympathetic activity (I.); higher HEP increases indicated increased filter function for bodily signals (II.). As more attentional resources are mobilized to process heartbeats, but perception accuracy remains unchanged (III.), this overflow could be responsible for detecting minor bodily changes associated with MUS. [less ▲]Detailed reference viewed: 81 (5 UL) Distinguisher and Related-Key Attack on the Full AES-256Biryukov, Alex ; Khovratovich, Dmitry ; Nikolic, Ivica in Advances in Cryptology - CRYPTO (2009)In this paper we construct a chosen-key distinguisher and a related-key attack on the full 256-bit key AES. We define a notion of differential q -multicollision and show that for AES-256 q-multicollisions ... [more ▼]In this paper we construct a chosen-key distinguisher and a related-key attack on the full 256-bit key AES. We define a notion of differential q -multicollision and show that for AES-256 q-multicollisions can be constructed in time q·267 and with negligible memory, while we prove that the same task for an ideal cipher of the same block size would require at least $O(q\cdot 2^{\frac{q-1}{q+1}128})$ time. Using similar approach and with the same complexity we can also construct q-pseudo collisions for AES-256 in Davies-Meyer mode, a scheme which is provably secure in the ideal-cipher model. We have also computed partial q-multicollisions in time q·237 on a PC to verify our results. These results show that AES-256 can not model an ideal cipher in theoretical constructions. Finally we extend our results to find the first publicly known attack on the full 14-round AES-256: a related-key distinguisher which works for one out of every 2^{35} keys with 2^{120} data and time complexity and negligible memory. This distinguisher is translated into a key-recovery attack with total complexity of 2^{131} time and 2^{65} memory. [less ▲]Detailed reference viewed: 189 (1 UL) Distinguishing Propositional and Action Commitment in Agent CommunicationBoella, Guido ; Damiano, R. ; Hulstijn, Joris et alin Proceedings of CMNA'07 (2007)Our goal is to extend agent communication lan- guages for persuasion dialogues. We distinguish action commitments from propositional commit- ments, because both limit future moves, but an action ... [more ▼]Our goal is to extend agent communication lan- guages for persuasion dialogues. We distinguish action commitments from propositional commit- ments, because both limit future moves, but an action commitment is fulfilled when the hearer believes that the action is performed, whereas a propositional commitment is fulfilled only when the hearer concedes to the proposition – where con- cessions are the absence of a belief to the con- trary, and prevent further challenges. Using a com- mon model for both kind of commitments and a role-based semantics of agent communication lan- guages, we show how propositional commitments are related to public beliefs and action commit- ments to public goals [less ▲]Detailed reference viewed: 57 (0 UL) Distinguishing Syntactic Markers From Morphological Markers. A Cross-Linguistic ComparisonWeth, Constanze in Frontiers in Psychology (2020), 11(2082), This brief review summarizes findings about syntactic markers, i.e., graphemic elements that indicate syntactic relations, such as inflection morphemes. Current spelling models subsume inflection with ... [more ▼]This brief review summarizes findings about syntactic markers, i.e., graphemic elements that indicate syntactic relations, such as inflection morphemes. Current spelling models subsume inflection with derivation and stem alternations under “morphological spellings.” They hence consider inflection only in relation to the orthographic word. This paper argues that syntactic markers are a specific category as they are part of the orthographic word but also systematically tied to the presence of syntactic features above the word level. Syntactic spelling refers thus not only to the correct spelling of a syntactic marker but to its correct application within a given syntactical context. In syntactic reading, (proof)readers must notice the marker and interpret it correctly to understand the sentence. Syntactic spelling and reading have hence been found to be highly demanding in many languages. Syntactic information is not decisive for sentence understanding in many cases, since the information can be deduced from the context. In order to focus the definition of syntactic markers, this paper restricts them to those graphemic elements that convey syntactical but no lexical features and are further unrelated to phonology. The paper concludes that syntactic markers and spelling should be distinguished from morphological spelling. Examples are given for English, French, Dutch, and German. [less ▲]Detailed reference viewed: 75 (0 UL) Distraction from pain and executive functioning: an experimental investigation of the role of inhibition, task switching and working memory.Verhoeven, Katrien; Van Damme, Stefaan; Eccleston, Christopher et alin European Journal of Pain (2011), 15(8), 866-73Although many studies have investigated the effectiveness of distraction as a method of pain control, the cognitive processes by which attentional re-direction is achieved, remain unclear. In this study ... [more ▼]Although many studies have investigated the effectiveness of distraction as a method of pain control, the cognitive processes by which attentional re-direction is achieved, remain unclear. In this study the role of executive functioning abilities (inhibition, task switching and working memory) in the effectiveness of distraction is investigated. We hypothesized that the effectiveness of distraction in terms of pain reduction would be larger in participants with better executive functioning abilities. Ninety-one undergraduate students first performed executive functioning tasks, and subsequently participated in a cold pressor task (CPT). Participants were randomly assigned to (1) a distraction group, in which an attention-demanding tone-detection task was performed during the CPT, or (2) a control group, in which no distraction task was performed. Participants in the distraction group reported significantly less pain during the CPT, but the pain experience was not influenced by executive functioning abilities. However, the performance on the distraction task improved with better inhibition abilities, indicating that inhibition abilities might be important in focussing on a task despite the pain. [less ▲]Detailed reference viewed: 109 (2 UL) Distraction from pain: The role of selective attention and pain catastrophizingRischer, Katharina Miriam ; Gonzalez-Roldan, Ana Maria; Montoya, Pedro et alin European Journal of Pain (2020), 24(10), 1880-1891Detailed reference viewed: 72 (5 UL) Distractor inhibition: Evidence from lateralized readiness potentialsPramme, Lisa; Dierolf, Angelika ; Naumann, Ewald et alin Brain and Cognition (2015), 98The present study investigated distractor inhibition on the level of stimulus representation. In a sequential distractor-to-distractor priming task participants had to respond to target letters flanked by ... [more ▼]The present study investigated distractor inhibition on the level of stimulus representation. In a sequential distractor-to-distractor priming task participants had to respond to target letters flanked by distractor digits. Reaction time and stimulus-locked lateralized readiness potentials (S-LRPs) of probe responses were measured. Distractor-target onset asynchrony was varied. For RTs responses to probe targets were faster in the case of prime-distractor repetition compared to distractor changes indicating distractor inhibition. Benefits in RTs and the latency of S-LRP onsets for distractor repetition were also modulated by distractor-target onset asynchrony. For S-LRPs distractor inhibition was only present with a simultaneous onset of distractors and target. The results confirm previous results indicating inhibitory mechanisms of object-based selective attention on the level of distractor representations. [less ▲]Detailed reference viewed: 185 (2 UL) Distributed Adaptive VoIP Load Balancing in Hybrid CloudsCortés-Mendoza, Jorge Mario; Tchernykh, Andrei; Drozdov, Alexander et alScientific Conference (2015, September)Cloud computing as a powerful economic stimulus widely being adopted by many companies. However, the management of cloud infrastructure is a challenging task. Reliability, security, quality of service ... [more ▼]Cloud computing as a powerful economic stimulus widely being adopted by many companies. However, the management of cloud infrastructure is a challenging task. Reliability, security, quality of service, and cost-efficiency are important issues in these systems. They require resource optimization at multiple layers of the infrastructure and applications. The complexity of cloud computing systems makes infeasible the optimal resource allocation, especially in presence of uncertainty of very dynamic and unpredictable environment. Hence, load balancing algorithms are a fundamental part of the research in cloud computing. We formulate the problem of load balancing in distributed computer environments and review several algorithms. The goal is to understand the main characteristics of dynamic load balancing algorithms and how they can be adapted for the domain of VoIP computations on hybrid clouds. We conclude by showing how none of these works directly addresses the problem space of the considered problem, but do provide a valuable basis for our work. [less ▲]Detailed reference viewed: 233 (34 UL) Distributed and anonymous publish-subscribeDaubert, Jörg; Fischer, Mathias; Schiffner, Stefan et alin 7th International Conference (2013, June 03)Detailed reference viewed: 117 (0 UL) Distributed attitude synchronization controlThunberg, Johan ; Montijano, E.; Hu, X.in Proceedings of the 50th IEEE Conference on Decision and Control and European Control Conference (CDC-ECC) (2011)In this paper we consider the problem of constructing feedback control laws for a system of n agents that shall synchronize their attitudes in SO(3). We propose distributed controllers for two ... [more ▼]In this paper we consider the problem of constructing feedback control laws for a system of n agents that shall synchronize their attitudes in SO(3). We propose distributed controllers for two synchronization problems, in which the objective is the same, to synchronize the orientations, but what the agents can perceive or communicate differs. In the first problem the agents can measure their orientation to a common reference object, and either communicate with the neighbors or estimate the relative orientation to their neighbors. In the second problem the agents can, without communication, only measure the relative orientation to the neighbors. For the first problem we present a controller which will lead to synchronization, provided the neighborhood graph is connected. For the second problem we present a controller that will lead to synchronization provided the neighborhood graph is connected and the agents initially are contained within a geodesic ball of radius π/2, which is the maximal convex set in SO(3). [less ▲]Detailed reference viewed: 84 (0 UL) Distributed attitude synchronization control of multi-agent systems with directed topologiesThunberg, Johan ; Song, W.; Hong, Y. et alin the proceedings of the 10th World Congress on Intelligent Control and Automation (2012)In the present paper we consider the problem of attitude synchronization for a system of rigid body agents. We provide distributed kinematic control laws for two different synchronization problems. In the ... [more ▼]In the present paper we consider the problem of attitude synchronization for a system of rigid body agents. We provide distributed kinematic control laws for two different synchronization problems. In the two problems the objective is the same, i.e., to synchronize the orientations of the agents, but what is assumed to be measurable by the agents differs. In problem 1 the agents measure their own orientations in a global reference frame, and obtain the orientations of their neighbors by means of communication. In problem 2 the agents only measure the relative orientations to their neighbors. By using the axis-angle representation of the orientation, we show that simple linear control laws solve both synchronization problems. Moreover we show that our proposed control laws work for directed and connected topologies on almost all SO(3) for problem 1 and on convex balls in SO(3) for problem 2. [less ▲]Detailed reference viewed: 104 (0 UL) Distributed attitude synchronization control of multi-agent systems with switching topologiesThunberg, Johan ; Song, W.; Montijano, E. et alin Automatica (2014), 50(3), 832-840This paper addresses the attitude synchronization problem in multi-agent systems with directed and switching interconnection topologies. Two cases for the synchronization problem are discussed under ... [more ▼]This paper addresses the attitude synchronization problem in multi-agent systems with directed and switching interconnection topologies. Two cases for the synchronization problem are discussed under different assumptions about the measurable information. In the first case the agents can measure their rotations relative to a global reference coordinate frame, whilst in the second case they can only measure the relative rotations between each other. Two intuitive distributed control laws based on the axis–angle representations of the rotations are proposed for the two cases, respectively. The invariance of convex balls in SO(3) is guaranteed. Moreover, attitude synchronization is ensured under the well-known mild switching assumptions, the joint strong connection for the first case and joint quasi-strong connection for the second case. To show the effectiveness of the proposed control schemes, illustrative examples are provided. [less ▲]Detailed reference viewed: 110 (2 UL) Distributed attitude synchronization control of multi-agent systems with time-varying topologiesSong, W.; Thunberg, Johan ; Hong, Y. et alin Proceedings of the 10th World Congress on Intelligent Control and Automation (2012)This paper addresses the attitude synchronization problem of multiple rigid body agents in SO(3) with directed and switching interconnection topologies. Using the axis-angle representation of the ... [more ▼]This paper addresses the attitude synchronization problem of multiple rigid body agents in SO(3) with directed and switching interconnection topologies. Using the axis-angle representation of the orientation, a distributed controller based on differences between the orientations of agents in a global frame is proposed. In the case of the balanced interconnection graph, the attitude synchronization is achieved with the well-known mild assumption (that is, uniform joint strong connection). To demonstrate the effectiveness of the proposed control scheme, an illustrative example is provided. [less ▲]Detailed reference viewed: 85 (0 UL) Distributed attitude synchronization using backstepping and sliding mode controlThunberg, Johan ; Song, W.; Hong, Y. et alin Control Theory and Technology (2014), 12(1), 48-55We consider the problem of attitude synchronization for systems of rigid body agents with directed topologies. Two different scenarios for the rotation matrices of the agents are considered. In the first ... [more ▼]We consider the problem of attitude synchronization for systems of rigid body agents with directed topologies. Two different scenarios for the rotation matrices of the agents are considered. In the first scenario, the rotations are contained in a convex subset of SO(3), which is a ball of radius less than π/2, whereas in the second scenario the agents are contained in a subset of SO(3), which is a ball of radius less than π. Using a control law based on backstepping and sliding mode control, we provide distributed, semi-global, torque control laws for the agents so that the rotations asymptotically synchronize. The control laws for the agents in the first scenario only depend on the relative rotations between neighboring agents, whereas the control laws in the second scenario depend on rotations defined in a global coordinate frame. Illustrative examples are provided where the synchronization is shown for both scenarios. [less ▲]Detailed reference viewed: 168 (0 UL) Distributed Authentication in GRID5000Varrette, Sébastien ; Georget, Sebastien; Montagnat, Johan et alin Proc. of OTM Confederated Int. Workshops on Grid Computing and its Application to Data Analysis (GADA'05) (2005, November)Detailed reference viewed: 140 (0 UL)