443 research outputs found

    A Conductor\u27s Guide to Alec Roth\u27s A Time to Dance

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    The purpose of this monograph is to provide a comprehensive analysis and conductor’s guide for Alec Roth’s masterwork, A Time to Dance. This study will explore the origins of this work, provide rehearsal and performance considerations, and bring greater attention to its composer, Alec Roth. Compared to his English contemporaries, Alec Roth’s (b.1948) music is lesser-known within the British tradition. Roth composes for choir, orchestra, and musical theatre and is also well-known for his contributions to both the guitar and gamelan repertory. His music spans a variety of languages, voicings, orchestrations, and levels of difficulty, as he is also noted for his work with children’s choirs. Roth’s music has been performed by the choirs of St. Paul’s Cathedral, Westminster Abbey, The Sixteen, and Ex Cathedra with whom he premiered A Time to Dance in 2012.[1] A Time to Dance demonstrates a diverse poetic and musical landscape, celebrating the “times and seasons of human existence.”[2]This study will focus on textual and musical analyses of the work as well as performance consideration for the prospective conductor. It will also provide additional information on the life of the composer and the creation of the work. This paper will, in turn, inform future conductors and build a platform for Alec Roth and his music. [1]“Biography,” Biography, Alec Roth, accessed June 16, 2018,http://www.alecroth.com/about/ [2]John Quinn, “Birmingham Dances to Alec Roth’s tune,” Seen and Heard International,September 15, 2012, accessed June 16, 2018. http://seenandheard-international.com/2012/10/birmingham-dances-to-alec-roths-tune

    Sweepouts of amalgamated 3-manifolds

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    We show that if two 3-manifolds with toroidal boundary are glued via a `sufficiently complicated' map then every Heegaard splitting of the resulting 3-manifold is weakly reducible. Additionally, if Z is a manifold obtained by gluing X and Y, two connected small manifolds with incompressible boundary, along a closed surface F. Then the genus g(Z) of Z is greater than or equal to 1/2(g(X)+g(Y)-2g(F)). Both results follow from a new technique to simplify the intersection between an incompressible surface and a strongly irreducible Heegaard splitting.Comment: This is the version published by Algebraic & Geometric Topology on 24 February 200

    Dopaminergic innervation at the central nucleus of the amygdala reveals distinct topographically segregated regions

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    The central nucleus of the amygdala (CeA) is involved in the expression of fear and anxiety disorders. Anatomically, it is divided into medial (CeM), lateral (CeL), and capsular (CeC) divisions. The CeA is densely innervated by dopaminergic projections that originate in the ventral periaqueductal gray/dorsal raphe (vPAG/DR) and the ventral tegmental area (VTA). However, whether dopamine (DA) exerts a homogenous control over the CeA or differentially regulates the various CeA subdivisions is still unknown. Here, we performed a neuroanatomical analysis of the mouse CeA and found that DAergic innervations from the PAG/DR and VTA constitute distinct, non-overlapping, pathways differing also in the relative expression of the dopamine transporter. By quantifying the distribution of DAergic fibers and the origin of DA inputs we identified two distinct regions in the CeL: a frontal region innervated by the VTA and vPAG/DR, a caudal region innervated only by the vPAG/DR, and three distinct regions in the CeC: fronto-dorsal innervated only by the VTA, fronto-ventral with sparse DAergic innervation, and a caudal region with low innervation from the vPAG/DR. In addition, we found that each region displays a distinct pattern of c-Fos activation following the administration of various DAeric drugs such as cocaine, SKF 38,393, quinpirole or haloperidol. In summary, we revealed unique properties of the DAergic pathways innervating the CeA, distinguishing six topographically segregated and functionally distinct regions. This unanticipated level of heterogeneity calls for more precise neuroanatomical specificity in future functional studies of the CeA.Fil: Casey, Eric. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Avale, Maria Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Kravitz, Alexxai. Washington University in St. Louis; Estados UnidosFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentin

    Epitopia: a web-server for predicting B-cell epitopes

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    <p>Abstract</p> <p>Background</p> <p>Detecting candidate B-cell epitopes in a protein is a basic and fundamental step in many immunological applications. Due to the impracticality of experimental approaches to systematically scan the entire protein, a computational tool that predicts the most probable epitope regions is desirable.</p> <p>Results</p> <p>The Epitopia server is a web-based tool that aims to predict immunogenic regions in either a protein three-dimensional structure or a linear sequence. Epitopia implements a machine-learning algorithm that was trained to discern antigenic features within a given protein. The Epitopia algorithm has been compared to other available epitope prediction tools and was found to have higher predictive power. A special emphasis was put on the development of a user-friendly graphical interface for displaying the results.</p> <p>Conclusion</p> <p>Epitopia is a user-friendly web-server that predicts immunogenic regions for both a protein structure and a protein sequence. Its accuracy and functionality make it a highly useful tool. Epitopia is available at <url>http://epitopia.tau.ac.il</url> and includes extensive explanations and example predictions.</p

    Practical algorithms and experimentally validated incentives for equilibrium-based fair division (A-CEEI)

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    Approximate Competitive Equilibrium from Equal Incomes (A-CEEI) is an equilibrium-based solution concept for fair division of discrete items to agents with combinatorial demands. In theory, it is known that in asymptotically large markets: 1. For incentives, the A-CEEI mechanism is Envy-Free-but-for-Tie-Breaking (EF-TB), which implies that it is Strategyproof-in-the-Large (SP-L). 2. From a computational perspective, computing the equilibrium solution is unfortunately a computationally intractable problem (in the worst-case, assuming PPAD≠FP\textsf{PPAD}\ne \textsf{FP}). We develop a new heuristic algorithm that outperforms the previous state-of-the-art by multiple orders of magnitude. This new, faster algorithm lets us perform experiments on real-world inputs for the first time. We discover that with real-world preferences, even in a realistic implementation that satisfies the EF-TB and SP-L properties, agents may have surprisingly simple and plausible deviations from truthful reporting of preferences. To this end, we propose a novel strengthening of EF-TB, which dramatically reduces the potential for strategic deviations from truthful reporting in our experiments. A (variant of) our algorithm is now in production: on real course allocation problems it is much faster, has zero clearing error, and has stronger incentive properties than the prior state-of-the-art implementation.Comment: To appear in EC 202

    Régulation de la métalloprotéase ADAM10/Kuzbanian par les tétraspanines à 8 cystéines et conséquences sur l'activation de la voie Notch chez les mammifères et la Drosophile

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    L importance des activités protéolytiques associées à la membrane plasmique dans divers processus biologiques fondamentaux est de mieux en mieux définie. Les protéases de la famille ADAM (A Disintegrin and Metalloprotease), et ADAM10 en particulier, ont suscité un intérêt tout particulier du fait de l importance de leurs substrats (récepteur de l EGF, TNFa, Notch, APP ). Néanmoins, peu d études se sont intéressées aux mécanismes régulant le trafic d ADAM10.Les tétraspanines sont une super-famille de protéines de surface impliquées dans de nombreux processus biologiques fondamentaux parmi lesquels la migration, les interactions intercellulaires, la réponse immunitaire, la fusion des gamètes L une des caractéristiques majeure des tétraspanines est leur capacité à organiser un réseau d interactions moléculaires appelé le tetraspanin web . De précédentes études menées dans le laboratoire ont montré qu ADAM10 est associé au tetraspanin web . Néanmoins, la tétraspanine en interaction directe avec ADAM10 permettant son association au réseau n est pas encore connue. Dans cette étude nous nous sommes intéressés à la régulation d ADAM10 par les tétraspanines. Nous avons ainsi pu identifier une sous-famille de tétraspanines à 8 cystéines, les TspanC8 (Tspan5, Tspan10, Tspan14, Tspan15, Tspan17 et Tspan33), comme étant capables d interagir directement avec ADAM10 et de réguler sa sortie du réticulum endoplasmique. Nous avons montré que Tspan5, Tspan14, Tspan15 et Tspan33 sont capables de réguler l expression de surface d ADAM10 et que Tspan10 et Tspan17 entrainent l accumulation d ADAM10 dans un compartiment endosomal tardif. Les TspanC8 pourraient également contribuer à la régulation de la spécificité de substrat d ADAM10 puisque nous avons montré que l expression des TspanC8 humaines Tspan5 et Tspan14 augmente l activation de la voie Notch alors que Tspan15 n a pas d effet. Par ailleurs, les TspanC8 de Drosophile sont capables d interagir directement avec Kuzbanian (l orthologue d ADAM10), permettent son accumulation à la surface cellulaire et régulent l activation de la voie Notch dans différents contextes développementaux. Nous proposons que les TspanC8 soient une nouvelle famille de protéines ayant une fonction très conservée dans la régulation de l activité et du trafic d ADAM10, capables de réguler l activation de la voie Notch.Increasing evidence suggests a critical implication of membrane-associated protease activities in numerous biological processes. ADAM (A Disintegrin and Metalloprotease) proteases, and especially ADAM10, are of particular interest because of the importance of their substrates (EGF receptor, TNF a, Notch, APP ). However, few studies focus on the mechanisms of ADAM10 trafficking. Tetraspanins are a super-family of proteins implicated in numerous biological processes including migration, intercellular interactions, immune response, gamete fusion One of the most striking features of tetraspanins is their ability to organise multi-molecular complexes called Tetraspanin Web . Previous studies in the laboratory have shown that ADAM10 is associated to the Tetraspanin Web . Nevertheless, the tetraspanin in direct interaction with ADAM10 that drives its association to the web is not known. In this study, we focused on ADAM10 regulation by tetraspanins. We identified a subfamily of tetraspanins with 8 cysteines in their large extracellular domain that we called TspanC8 (Tspan5, Tspan10, Tspan14, Tspan15, Tspan17 and Tspan33) that can directly interact with ADAM10 and regulate its egress from the endoplasmic reticulum. We have shown that Tspan5, Tspan14, Tspan15 and Tspan33 regulate the surface expression of ADAM10 and that Tspan10 and Tspan17 accumulate ADAM10 in a late endosomal compartment. TspanC8 could also contribute to substrate specificity since Tspan5 and Tspan14 can increase Notch activation when Tspan15 cannot. Drosophila TspanC8 directly interact with the Drosophila ADAM10 ortholog Kuzbanian, increase its accumulation at the cell surface and modulate Notch activation in several developmental contexts. We propose that TspanC8 constitute a new family of Notch regulators with conserved functions in the regulation of ADAM10 trafficking and activity.PARIS11-SCD-Bib. électronique (914719901) / SudocSudocFranceF

    Differential stability of tetraspanin/tetraspanin interactions: role of palmitoylation

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    AbstractThe tetraspanins associate with various surface molecules and with each other to build a network of molecular interactions, the tetraspanin web. The interaction of tetraspanins with each other seems to be central for the assembly of the tetraspanin web. All tetraspanins studied, CD9, CD37, CD53, CD63, CD81, CD82 and CD151, were found to incorporate [3H]palmitate. By site-directed mutagenesis, CD9 was found to be palmitoylated at any of the four internal juxtamembrane regions. The palmitoylation of CD9 did not influence the partition in detergent-resistant membranes but contributed to the interaction with CD81 and CD53. In particular, the resistance of the CD9/CD81 interaction to EDTA, which disrupts other tetraspanin/tetraspanin interactions, was entirely dependent on palmitoylation
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