Synthesis of xanthone-1,2,3-triazole dyads

Xanthones and 1,2,3-triazoles are known to exhibit several biological, pharmacological and biocidal properties[1]. The potential applications of these two classes of heterocycles led us to develop new strategies to synthesize xanthone-1,2,3-triazole dyads, aiming to get potentially improved therapeutic agents[2]. With this rational in mind we designed and synthesized novel chromone derivatives 1a-d to be used as building motifs and to explore the reactivity of the two unsaturated systems (the diene and the alkyne). In the present communication we will present a new synthetic route towards the synthesis of xanthone-1,2,3-triazole dyads 7a-d using consecutively the azide-alkyne Huisgen 1,3-dipolar cycloaddition and Diels-Alder reaction. Our approach involves the synthesis chromone-triazole derivatives 2a-d using the reaction of 1a-d with sodium azide, followed by the methylation of the NH of the triazole moiety. The methylation afforded three isomers 3a-d, 4a-d and 5a-d, as expected. The major isomers 3a-d were used in the Diels-Alder reaction with N-methylmaleimide, and the adducts obtained 6a-d were oxidized to afford the xanthone-1,2,3-triazole dyads 7a-d. All the synthetic details as well as the structural characterization (by 1D and 2D NMR studies) of the new synthesised compounds will be presented and discussed.

Genetic association of CD247 (CD3ζ) with SLE in a large-scale multiethnic study

A classic T-cell phenotype in systemic lupus erythematosus (SLE) is the downregulation and replacement of the CD3ζ chain that alters T-cell receptor signaling. However, genetic associations with SLE in the human CD247 locus that encodes CD3ζ are not well established and require replication in independent cohorts. Our aim was therefore to examine, localize and validate CD247-SLE association in a large multiethnic population. We typed 44 contiguous CD247 single-nucleotide polymorphisms (SNPs) in 8922 SLE patients and 8077 controls from four ethnically distinct populations. The strongest associations were found in the Asian population (11 SNPs in intron 1, 4.99 × 10(-4) < P < 4.15 × 10(-2)), where we further identified a five-marker haplotype (rs12141731-rs2949655-rs16859085-rs12144621-rs858554; G-G-A-G-A; P(hap) = 2.12 × 10(-5)) that exceeded the most associated single SNP rs858554 (minor allele frequency in controls = 13%; P = 4.99 × 10(-4), odds ratio = 1.32) in significance. Imputation and subsequent association analysis showed evidence of association (P < 0.05) at 27 additional SNPs within intron 1. Cross-ethnic meta-analysis, assuming an additive genetic model adjusted for population proportions, showed five SNPs with significant P-values (1.40 × 10(-3) < P< 3.97 × 10(-2)), with one (rs704848) remaining significant after Bonferroni correction (P(meta) = 2.66 × 10(-2)). Our study independently confirms and extends the association of SLE with CD247, which is shared by various autoimmune disorders and supports a common T-cell-mediated mechanism.

Les caractères musicaux au sein d'une démarche artistique dramatique : exploration des indices acoustiques jouant un rôle dans l'évocation des états affectifs en musique.

Cette thèse de doctorat en composition comprend deux projets de nature différente et complémentaire : (1) un projet de recherche théorique sur la communication des caractères musicaux; (2) un projet artistique s'articulant autour de la composition de trois pièces : L'homme à deux têtes - opéra de chambre, Un instant dans l'esprit de Lovecraft - pour clarinette solo, orchestre à cordes et percussions, et Balade ornithologique - pour orchestre à vents. La conception de la musique comme un moyen de communication est à l'origine de cette recherche théorique qui est motivée par un désir de compréhension des stratégies d'expressions des émotions en musique, à partir du point de vue du compositeur. Cette thèse aborde les modèles de communication, le concept de personnage virtuel et la théorie de la contagion des humeurs. Par la suite, nous détaillerons les indices acoustiques menant à la perception des caractères musicaux. Toutes ces notions sont illustrées et explorées par la composition de miniature ayant un caractère bien ciblé. Finalement, nous proposons un système d'analyse musical des caractères et des émotions qui est appliqué à l'analyse de sections des pièces composées au cours de ce projet de doctorat. Ce dernier chapitre met en lumière les stratégies utilisées pour créer un discours dramatique tout en exposant l'évocation de différents caractères musicaux.

Stable isotope and Mg/Ca ratio of sediment core GeoB12610-2

To reconstruct the still poorly understood thermocline fluctuations in the western tropical Indian Ocean, a sediment core located off Tanzania (GeoB12610-2; 04°49.00'S, 39°25.42'E, 399?m water depth) covering the last 35 ka was analysed. Mg/Ca-derived temperatures from the planktonic foraminifera Globigerinoides ruber (white) and Neogloboquadrina dutertrei indicate that the last glacial was ~2.5 °C colder in the surface waters and ~3.5 °C colder in the thermocline compared with the present day. The depth of the thermocline and thus the stratification of the water column were shallower during glacial periods and deepened during the deglaciation and Holocene. The increased inflow of Southern Ocean Intermediate Waters via 'ocean tunnels' appears to cool the thermocline from below, leading to a similarity between the thermocline record of GeoB12610-2 with the Antarctic EDML temperature curve during the glacial. With rising sea level and the corresponding greater inflow of Red Sea Waters and Indonesian Intermediate Waters, the proportion of Southern Ocean Intermediate Water within the South Equatorial Current is reduced and, by Holocene time, the correlation to Antarctica is barely traceable. Comparison with the eastern Indian Ocean reveals that the thermocline depth reverses from the last glacial to present.

Retinal ganglion cell layer change in patients treated with anti-VEGF for neovascular age related macular degeneration.

PURPOSE To evaluate macular retinal ganglion cell thickness in patients with neovascular age-related macular degeneration (AMD) and intravitreal anti-vascular endothelial growth factor (VEGF) therapy. DESIGN Retrospective case series with fellow-eye comparison METHODS: Patients with continuous unilateral anti-VEGF treatment for sub- and juxtafoveal neovascular AMD and a minimum follow-up of 24 months were included. The retinal nerve fiber (RNFL) and retinal ganglion cell layer (RGCL) in the macula were segmented using an ETDRS grid. RNFL and RGCL thickness of the outer ring of the ETDRS grid were quantified at baseline and after repeated anti-VEGF injections, and compared to the patients' untreated fellow eye. Furthermore, best-corrected visual acuity (BCVA), age, and retinal pigment epithelium (RPE) atrophy were recorded and correlated with RNFL and RGCL. RESULTS Sixty eight eyes of 34 patients (23 female and 11 male; mean age 76.7 (SD±8.2) with a mean number of 31.5 (SD ±9.8) anti-VEGF injections and a mean follow-up period of 45.3 months (SD±10.5) were included. Whereas the RGCL thickness decreased significantly compared to the non-injected fellow eye (p=0.01) the decrease of the RNFL was not significant. Visual acuity gain was significantly correlated with RGCL thickness (r=0.52, p<0.05) at follow-up and negatively correlated (r=-0.41, p<0.05) with age. Presence of RPE atrophy correlated negatively with the RGCL thickness at follow-up (r= -0.37, p=0.03). CONCLUSION During the course of long term anti-VEGF therapy there is a significant decrease of the RGCL in patients with neovascular AMD to the fellow (untreated) eye.

Première rhapsodie pour orchestre avec clarinette principale en si♭.

Mode of access: Internet.

Concert-allegro : op. 46 /

Mode of access: Internet.

Troisième sextuor (ut) pour deux violons, deux altos et violoncelles. Op. 11.

Pl. no. 2639.

Für das Totenfest: O wie selig seid ihr doch, ihr Frommen;

On cover: Choralkantaten ... No. 2; on p. [1]: Choralkantate Nr. 3.

Trio in G dur für 2 Violinen, Violoncell und Pianoforte /

Mode of access: Internet.

Trio in B dur für 2 Violinen, Violoncell und Pianoforte /

Mode of access: Internet.

La Steinquerque, sonate en si♭ pour 2 violons et piano avec violoncelle non obligé.

"Éditée d'après le manuscrit de Bibl. Nat. La réalisation de la basse et les nuances ont été ajoutées."

[Sonata a tre] Op. 3, No. 5, D dur (da chiesa) für 2 Violinen, Violoncell und Pianoforte /

Mode of access: Internet.

Trio in F dur für 2 Violinen und Violoncello (B[asso] c[ontinuo] /

Possibly based on Ms.2423,Q7, of the Dresden Staatsbibliothek.

Trio in G-dur, Op. 3, No. 1, für 2 Violinen (Flöten), Violoncell und Pianoforte /

Mode of access: Internet.