Halévy and his Contribution to the Evolution of the Orchestra in the Mid-Nineteenth Century

In the history of French orchestration in the 19th century, Meyerbeer and Berlioz are usually considered the most important innovators. Halévy was, nevertheless, also highly regarded for his innovations. This study examines Halévy's use of new and rare instruments in operas (1838-1851), particularly in ballet music, but also as accompaniment to choruses during marches and other solemn occasions, and finally, if only rarely, as accompaniment to arias. In the first category (ballet), the mélophone and the valve trombone, both used in Guido in Ginévra, reflect a taste for strange and unheard sonorities that was characteristic of French music in the 1840s. In the second one (accompaniment) are the families of saxhorns and saxophones, recently invented by Adolphe Sax, which were used in Le juif errant, and revived techniques of consort writing that had been used in the 17th century. The last part of the essay examines new orchestration procedures with traditional instruments, such as the division of strings, the mixture of woodwind instruments, and the simultaneous use of valve and natural horns.Dans l'histoire de l'orchestration en France au XIXème siècle, Meyerbeer et Berlioz sont généralement considérés comme les novateurs les plus importants. Halévy était cependant admiré pour ses innovations. Cette étude examiné l'emploi d'instruments rares ou nouveaux par Halévy dans ses opéras, de 1838 à 1851, en particulier dans les musiques de ballet, mais aussi dans les fonctions d'accompagnement de chœurs, de marches et autres pièces solennelles, et enfin l'accompagnement des arias. Dans la première catégorie (ballet), le mélophone et le trombone à pistons, employés dans Guido et Ginévra, traduisent un goût pour les sonorités étranges ou inouïes, qui était typique de la musique française des années 1840. Dans la seconde (accompagnement) se distinguent les catégories des saxhorns et saxophones, récemment inventées par Adolphe Sax, qui furent employées dans Le juif errant, et permirent le recours à l'orchestration par familles instrumentales entières (écriture en consort), typiques du XVIIème siècle. La dernière partie de l'étude examines de nouvelles techniques d'orchestration appliquées à des instruments traditionnels, comme la division des cordes, les doublures des bois et l'emploi simultané de cors naturels et à piston

Loss of Melanopsin Photoreception and Antagonism of the Histamine H3 Receptor by Ciproxifan Inhibit Light-Induced Sleep in Mice

Light has direct effects on sleep and wakefulness causing arousal in diurnal animals and sleep in nocturnal animals. In the present study, we assessed the modulation of light-induced sleep by melanopsin and the histaminergic system by exposing mice to millisecond light flashes and continuous light respectively. First, we show that the induction of sleep by millisecond light flashes is dose dependent as a function of light flash number. We found that exposure to 60 flashes of light occurring once every 60 seconds for 1-h (120-ms of total light over an hour) induced a similar amount of sleep as a continuous bright light pulse. Secondly, the induction of sleep by millisecond light flashes was attenuated in the absence of melanopsin when animals were presented with flashes occurring every 60 seconds over a 3-h period beginning at ZT13. Lastly, the acute administration of a histamine H3 autoreceptor antagonist, ciproxifan, blocked the induction of sleep by a 1-h continuous light pulse during the dark period. Ciproxifan caused a decrease in NREMS delta power and an increase in theta activity during both sleep and wake periods respectively. The data suggest that some form of temporal integration occurs in response to millisecond light flashes, and that this process requires melanopsin photoreception. Furthermore, the pharmacological data suggest that the increase of histaminergic neurotransmission is sufficient to attenuate the light-induced sleep response during the dark period.Down Syndrome Research and Treatment FoundationResearch Down Syndrome Organizatio

Regional age-related changes in neuronal nitric oxide synthase (nNOS), messenger RNA levels and activity in SAMP8 brain

BACKGROUND: Nitric oxide (NO) is a multifunctional molecule synthesized by three isozymes of the NO synthase (NOSs) acting as a messenger/modulator and/or a potential neurotoxin. In rodents, the role of NOSs in sleep processes and throughout aging is now well established. For example, sleep parameters are highly deteriorated in senescence accelerated-prone 8 (SAMP8) mice, a useful animal model to study aging or age-associated disorders, while the inducible form of NOS (iNOS) is down-regulated within the cortex and the sleep-structures of the brainstem. Evidence is now increasing for a role of iNOS and resulting oxidative stress but not for the constitutive expressed isozyme (nNOS). To better understand the role of nNOS in the behavioural impairments observed in SAMP8 versus SAMR1 (control) animals, we evaluated age-related variations occurring in the nNOS expression and activity and nitrites/nitrates (NOx(-)) levels, in three brain areas (n = 7 animals in each group). Calibrated reverse transcriptase (RT) and real-time polymerase chain reaction (PCR) and biochemical procedures were used. RESULTS: We found that the levels of nNOS mRNA decreased in the cortex and the hippocampus of 8- vs 2-month-old animals followed by an increase in 12-vs 8-month-old animals in both strains. In the brainstem, levels of nNOS mRNA decreased in an age-dependent manner in SAMP8, but not in SAMR1. Regional age-related changes were also observed in nNOS activity. Moreover, nNOS activity in hippocampus was found lower in 8-month-old SAMP8 than in SAMR1, while in the cortex and the brainstem, nNOS activities increased at 8 months and afterward decreased with age in SAMP8 and SAMR1. NOx(- )levels showed profiles similar to nNOS activities in the cortex and the brainstem but were undetectable in the hippocampus of SAMP8 and SAMR1. Finally, NOx(- )levels were higher in the cortex of 8 month-old SAMP8 than in age-matched SAMR1. CONCLUSION: Concomitant variations occurring in NO levels derived from nNOS and iNOS at an early age constitute a major factor of risk for sleep and/or memory impairments in SAMP8

Pumilio-2 Function in the Mouse Nervous System

Coordinated mRNA translation at the synapse is increasingly recognized as a critical mechanism for neuronal regulation. Pumilio, a translational regulator, is known to be involved in neuronal homeostasis and memory formation in Drosophila. Most recently, the mammalian Pumilio homolog Pumilio-2 (Pum2) has been found to play a role in the mammalian nervous system, in particular in regulating morphology, arborization and excitability of neuronal dendrites, in vitro. However, the role of Pum2 in vivo remains unclear. Here, we report our investigation of the functional and molecular consequences of Pum2 disruption in vivo using an array of neurophysiology, behavioral and gene expression profiling techniques. We used Pum2-deficient mice to monitor in vivo brain activity using EEG and to study behavior traits, including memory, locomotor activity and nesting capacities. Because of the suspected role of Pum2 in neuronal excitability, we also examined the susceptibility to seizure induction. Finally, we used a quantitative gene expression profiling assay to identify key molecular partners of Pum2. We found that Pum2-deficient mice have abnormal behavioral strategies in spatial and object memory test. Additionally, Pum2 deficiency is associated with increased locomotor activity and decreased body weight. We also observed environmentally-induced impairment in nesting behavior. Most importantly, Pum2-deficient mice showed spontaneous EEG abnormalities and had lower seizure thresholds using a convulsing dosage of pentylenetetrazole. Finally, some genes, including neuronal ion channels, were differentially expressed in the hippocampus of Pum2-deficient mice. These findings demonstrate that Pum2 serves key functions in the adult mammalian central nervous system encompassing neuronal excitability and behavioral response to environmental challenges

Safety, Tolerability, Pharmacokinetics and Initial Pharmacodynamics of a Subcommissural Organ-Spondin-Derived Peptide:A Randomized, Placebo-Controlled, Double-Blind, Single Ascending Dose First-in-Human Study

Introduction This randomized, double-blind, placebo-controlled study in healthy volunteers assessed the safety, tolerability, and pharmacokinetics of single ascending doses of intravenously administered NX210-a linear peptide derived from subcommissural organ-spondin-and explored the effects on blood/urine biomarkers and cerebral activity. Methods Participants in five cohorts (n = 8 each) were randomized to receive a single intravenous dose of NX210 (n = 6 each) (0.4, 1.25, 2.5, 5, and 10 mg/kg) or placebo (n = 2 each); in total, 10 and 29 participants received placebo and NX210, respectively. Blood samples were collected for pharmacokinetics within 180 min post dosing. Plasma and urine were collected from participants (cohorts: 2.5, 5, and 10 mg/kg) for biomarker analysis and electroencephalography (EEG) recordings within 48 h post dosing. Safety/tolerability and pharmacokinetic data were assessed before ascending to the next dose. Results The study included 39 participants. All dosages were safe and well tolerated. All treatment-emergent adverse events (n = 17) were of mild severity and resolved spontaneously (except one with unknown outcome). Twelve treatment-emergent adverse events (70.6%) were deemed drug related; seven of those (58.3%) concerned nervous system disorders (dizziness, headache, and somnolence). The pharmacokinetic analysis indicated a short half-life in plasma (6-20 min), high apparent volume of distribution (1870-4120 L), and rapid clearance (7440-16,400 L/h). In plasma, tryptophan and homocysteine showed dose-related increase and decrease, respectively. No drug dose effect was found for the glutamate or glutamine plasma biomarkers. Nevertheless, decreased blood glutamate and increased glutamine were observed in participants treated with NX210 versus placebo. EEG showed a statistically significant decrease in beta and gamma bands and a dose-dependent increasing trend in alpha bands. Pharmacodynamics effects were sustained for several hours (plasma) or 48 h (urine and EEG). Conclusion NX210 is safe and well tolerated and may exert beneficial effects on the central nervous system, particularly in terms of cognitive processing

Melanopsin as a Sleep Modulator: Circadian Gating of the Direct Effects of Light on Sleep and Altered Sleep Homeostasis in Opn4−/− Mice

Analyses in mice deficient for the blue-light-sensitive photopigment melanopsin show that direct effects of light on behavior and EEG depend on the time of day. The data further suggest an unexpected role for melanopsin in sleep homeostasis

Synaptic vesicle recycling is unaffected in the Ts65Dn mouse model of Down syndrome

Down syndrome (DS) is the most common genetic cause of intellectual disability, and arises from trisomy of human chromosome 21. Accumulating evidence from studies of both DS patient tissue and mouse models has suggested that synaptic dysfunction is a key factor in the disorder. The presence of several genes within the DS trisomy that are either directly or indirectly linked to synaptic vesicle (SV) endocytosis suggested that presynaptic dysfunction could underlie some of these synaptic defects. Therefore we determined whether SV recycling was altered in neurons from the Ts65Dn mouse, the best characterised model of DS to date. We found that SV exocytosis, the size of the SV recycling pool, clathrin-mediated endocytosis, activity-dependent bulk endocytosis and SV generation from bulk endosomes were all unaffected by the presence of the Ts65Dn trisomy. These results were obtained using battery of complementary assays employing genetically-encoded fluorescent reporters of SV cargo trafficking, and fluorescent and morphological assays of fluid-phase uptake in primary neuronal culture. The absence of presynaptic dysfunction in central nerve terminals of the Ts65Dn mouse suggests that future research should focus on the established alterations in excitatory / inhibitory balance as a potential route for future pharmacotherapy

Opéra italien et français au XIXe siècle. Études de philologie et de dramaturgie musicale

Après une formation en biochimie, puis en musicologie, j'ai commencé la recherche au début des années 1990, tout en enseignant l'histoire de la musique à l'Université Paris-IV, et je suis entré au CNRS en 1995. Mes travaux portent sur l'opéra du XIXe siècle, et plus particulièrement sur l'opéra italien et français. Ils s'inscrivent aujourd'hui dans quatre directions : – la philologie musicale, en particulier l'analyse de la mélodie, sa grammaire, sa génétique, – l'histoire de l'orchestre et de l'orchestration d'opéra, – les échanges culturels franco-italiens, – la dramaturgie musicale. 1. Pendant ma thèse de doctorat, à partir de 1990, je me suis penché sur les matériels d'exécution des compositeurs italiens de la première moitié du XIXe siècle conservés à Paris, afin d'y collecter les annotations des chanteurs relatives au travail de variation et d'ornementation de leurs parties. Cette recherche, conduite sous la direction de Jean-Michel Vaccaro (CESR, Université François-Rabelais) et de Philip Gossett (University of Chicago), m'a permis d'acquérir des compétences quant à l'état des sources, la notation de la musique de cette époque, sa performance practice et sa grammaire. 2. Lors de mon affectation au Centre d'études franco-italiennes (CNRS, Chambéry) en 1995, j'ai été invité à donner en DEA des séminaires de recherche sur les échanges culturels franco-italiens. Cette approche interdisciplinaire m'a amené, dans le domaine de l'opéra, à me tourner vers les principales tensions entre les systèmes poétiques en vigueur sur les scènes italienne et française, du XVIIe au XIXe siècle. 3. Un programme européen de recherches sur les orchestres d'opéra aux XVIIIe et XIXe siècles a été constitué en 1998, sous l'égide de l'European Science Foundation, dans le cadre du projet Musical life in Europe (1600-1900). J'y ai été chargé de diriger la recherche sur les orchestres parisiens. Les investigations ont porté autant sur les aspects institutionnels du fonctionnement des orchestres que sur les aspects artistiques (répétitions, évolution de la constitution et de l'organologie, orchestration et réorchestrations). 4. Dans le cadre de la convention passée entre mon laboratoire actuel, l'IRPMF (UMR 200) et le département de musique et musicologie de l'Université François-Rabelais (Tours), j'enseigne depuis 2003 un cours d'initiation aux écrits de Carl Dahlhaus sur la dramaturgie musicale. Ces écrits, qui constituent le socle de la formation des étudiants en matière d'opéra dans les universités européennes, restent peu étudiés en France, sans doute en raison du rôle central qu'a joué la littérature comparée dans ce domaine. Ces quatre directions se rattachent toutes à mon objet premier d'étude, les matériels d'exécution d'opéra, et c'est à l'occasion d'enseignements universitaires et de participations à des programmes de recherches internationaux que j'ai été amené à diversifier mon activité de recherche. Les deux parties de la synthèse, bilan et perspectives, sont constituées de travaux réalisés dans les quatre domaines présentés ici, au cours des années 1997-2009. La partie « bilan » (pp. 1-530) contient les études déjà publiées : 1.1. Analyse de la mélodie dans sa composante ornementale Melody and ornamentation (2004) Revisioni delle parti vocali di Bellini (2004) Colas, Di Profio ⋅ Rondò de Sarti et variations de Sarti (2009) 1.2. Analyse de la mélodie dans sa composante prosodique Alexandrin dans Les vêpres siciliennes (2000) Prosodie et mélodie dans Dom Sébastien (2000) 2. Échanges culturels franco-italiens Le duc d'Albe und Les vêpres siciliennes (2001) Terminologia dei critici francesi (2002) Victor Hugo e l'estetica del melodramma (2003) Duetto e dialogo in Bellini (2004) Heldenportraits in den französischen Opern von Verdi (2006) Théophile Gautier critique au Théâtre italien (2007) Perspectives (D'une scène à l'aute, vol. II, 2009) 3. Orchestres d'opéra Audéon, Colas, Di Profio ⋅ Orchestras of the Paris opera theatres (2007) Halévy and the orchestra (2007) 4. Dramaturgie musicale Roman de Tatiana (2002) Immagini infernali in Berlioz (2009) La partie « perspectives » (pp. 531-751) contient les travaux en cours et sous presse : 1. Édition critique du Comte Ory 2. Rossini et les critiques musicaux français 2. Isouard et le modèle italien 4. Berlioz et l'imitatio

Multiscale approach of aging and cyclic behaviour of tantalum

La conception de structures complexes requiert une connaissance exhaustive des matériaux utilisés à la fois au niveau macroscopique et au niveau microscopique. Dans le cas du tantale, peu d'études ont été menées pour des sollicitations cycliques et pour l'influence du vieillissement (au sens de la diffusion des atomes interstitiels vers les dislocations) sur le comportement macroscopique et sur les champs locaux de déformation. Afin de mieux comprendre les mécanismes microstructuraux régissant la déformation, cette étude mène de front des essais avec un suivi de déformation à l'échelle locale couplés à une modélisation adaptée, autorisant la prise en compte explicite de la microstructure.Dans un premier volet, une étude macroscopique du vieillissement et du comportement cyclique du tantale est présentée. Plusieurs techniques expérimentales ont été utilisées, mettant en évidence la propagation d'une bande de localisation de la déformation lors de l'entrée en plasticité. En parallèle, un modèle phénoménologique EKMC (de Estrin, Kubin et McCormick) rendant compte du comportement macroscopique (notamment du pic de traction dû au vieillissement statique) a été identifié ; permettant ensuite des investigations numériques sur les manifestations de la localisation de la déformation.Ensuite, l'étude a été poursuivie à l'échelle locale à la fois expérimentalement et numériquement. Pour ce faire, des matrices micrométriques de plots en nickel ont été déposées à la surface d'un échantillon. Les images sucessives autorisent le calcul des cartes de déformation expérimentales lors d'un essai de traction interrompu. La modélisation explicite de la microstructure a été rendue possible par la génération d'agrégats polycristallins spécifiques avec des conditions de surface libre. L'étude de l'influence de la prise en compte du vieillissement sur l'hétérogénéité des champs locaux de déformation a permis de confronter ces derniers avec les champs expérimentaux.Enfin, une étude multi-échelles du comportement en fatigue a été effectuée. Un essai de fatigue interrompu avec observations microscopiques et construction de cartes de déformation a été réalisé. L'hétérogénéité de déformation locale a ainsi été identifiée et quantifiée, jusqu'à l'amorçage de fissures. Une simulation d'une sollicitation équivalente a été réalisée sur un agrégat polycristallin, permettant la comparaison directe des champs locaux de surface. Des investigations approfondies ont été menées sur l'agrégat pour mettre en place un critère d'amorçage basé sur des grandeurs physiques en accord avec l'expérience.Designing complex structures requires an exhaustive knowledge of the materials used at both macroscopical and microscopical scales. In the case of tantalum, only few studies have been focused on the cyclic behaviour and on static strain aging's (aging in the sense of atoms diffusion to dislocations) influence on macroscopical behaviour and on the local strain fields. In order to extend the comprehension of microstructural mechanisms driving deformation, this study deals with experiments following the local strain fields evolution and with an appropriate modelling, taking into account microstructure explicitly.In a first step, a macroscopical study of aging and cyclic behaviour is presented. Several experimental techniques have been used in order to highlight a strain localisation band propagation associated to the anomalous yield point phenomenon. In parallel, a phenomenological EKMC (from Estrin, Kubin and McCormick) macroscopic model has been adopted, capturing the macroscopic behaviour (especially the anomalous yield point associated to static strain aging) ; and then used for several numerical investigations about the strain localisation occurence.Then, the study has been continued at the microscale in both numerical and experimental matters. Thus, several micrometrical matrixes of nickel dots have been led on the sample's surface. The have then been used for the experimental strain maps computation during an interrupted tensile test. The explicit computation of the microstructure through a specific generation of polycrystalline aggregates using free surface conditions has permitted to study the influence of aging on the local strain fields heterogeneity and to compare them with the experimental ones.Finally, a multi-scale study of the cyclic behaviour has been carried out. An interrupted fatigue test with microscopic observations and strain maps computations has been carried out, permitting the identification and quantification of the local strain heterogeneity up to the crack initiation. A computation of an equivalent loading has been done on a polycrystalline aggregate in order to set up a fatigue criterion based on physical quantities in agreement with experimental datas