Gradient Scan Gibbs Sampler: an efficient algorithm for high-dimensional Gaussian distributions

This paper deals with Gibbs samplers that include high dimensional conditional Gaussian distributions. It proposes an efficient algorithm that avoids the high dimensional Gaussian sampling and relies on a random excursion along a small set of directions. The algorithm is proved to converge, i.e. the drawn samples are asymptotically distributed according to the target distribution. Our main motivation is in inverse problems related to general linear observation models and their solution in a hierarchical Bayesian framework implemented through sampling algorithms. It finds direct applications in semi-blind/unsupervised methods as well as in some non-Gaussian methods. The paper provides an illustration focused on the unsupervised estimation for super-resolution methods.Comment: 18 page

Sampling high-dimensional Gaussian distributions for general linear inverse problems

International audienceThis paper is devoted to the problem of sampling Gaussian distributions in high dimension. Solutions exist for two specific structures of inverse covariance: sparse and circulant. The proposed algorithm is valid in a more general case especially as it emerges in linear inverse problems as well as in some hierarchical or latent Gaussian models. It relies on a perturbation-optimization principle: adequate stochastic perturbation of a criterion and optimization of the perturbed criterion. It is proved that the criterion optimizer is a sample of the target distribution. The main motivation is in inverse problems related to general (non-convolutive) linear observation models and their solution in a Bayesian framework implemented through sampling algorithms when existing samplers are infeasible. It finds a direct application in myopic,unsupervised inversion methods as well as in some non-Gaussian inversion methods. An illustration focused on hyperparameter estimation for super-resolution method shows the interest and the feasibility of the proposed algorithm

Seguindo os rastros da música espectral: análise genética dos modelos compositivos em Périodes, de Gérard Grisey

Traduction en Portugais par Michelle Agnes Magalhães de l'article: "Sur les traces de la musique spectrale : analyse génétique des modèles compositionnels dans Périodes (1974) de Gérard Grisey", Revue de musicologie, vol. 96 no. 2, 2010, pp. 411-443.International audienceFirst developed in the mid-1970s, spectral music represents one of the main currents of contemporary French music. In Périodes (1974) for 7 instruments,Gérard Grisey (1946-1998) sets the foundations of this new approach to musical composition, which explores both the acoustical properties of sound and specific features of the auditory system. The Gérard Grisey archives at the Paul Sacher Foundation in Basel contain, amongst other things, musical manuscripts (sketches, autograph notes, drawings, etc.) of each of the composer’s works, as well as manuscripts of his writings, lesson notes, and books from his library. The examination of these documents, in addition to information gained from interviews with some of the composer’s close friends, allow us to better understand how Grisey imagined, developed, and brought to fruition his spectral approach to composition. In this paper, we begin by describing the composer’s education and explore his private investigation of musical acoustics from 1972 and 1974 by studying the work of Émile Leipp and Fritz Winckel. We then look closely at the two models (the respiratory cycle and the harmonic spectrum built on E1 fundamental) that lie at the heart of the piece and underscore both their structural and auditory influence. Finally, after offering a close analysis of the last section of the piece in which Grisey uses instruments to recreate a sound’s spectrum, we challenge the existence of a trombone’s spectrogram that the composer himself claims to have used as a model. Through this genetic study of Périodes, we seek more generally to document the construction of the cycle entitled Les espaces acoustiques (1974-1985), which is considered emblematic of the spectral aesthetic.La musique spectrale représente l’un des principaux courants de la création musicale contemporaine en France depuis le milieu des années 1970. Dans Périodes (1974) pour 7 instruments, Gérard Grisey (1946-1998) pose les fondements de cette nouvelle approche de la composition qui tire profit des propriétés acoustiques du son et des modalités remarquables de l’audition. La collection Gérard Grisey de la Fondation Paul Sacher à Bâle comprend, entre autres, les avant-textes (esquisses, notes manuscrites, schémas…) relatifs à chaque œuvre du compositeur, les manuscrits de ses écrits, ses notes de cours et une partie de sa bibliothèque. L’étude de ces documents et les informations recueillies au cours des quelques entretiens réalisés avec les proches du compositeur a permis d’appréhender la manière dont Grisey a imaginé, développé et concrétisé musicalement son approche spectrale de la composition. Dans cet article, nous revenons tout d’abord sur les années de formation du compositeur et montrons que celui-ci s’est familiarisé de manière autodidacte avec l’acoustique musicale entre 1972 et 1974 en lisant des ouvrages scientifiques d’Émile Leipp et de Fritz Winckel. Nous nous intéressons alors à la mise en place des deux modèles (le cycle respiratoire et le spectre harmonique de fondamentale mi 0) qui sont au cœur de l’œuvre en soulignant leur impact tant du point du vue structurel que sonore. Enfin, après avoir proposé une analyse détaillée de la dernière section de l’œuvre dans laquelle Grisey restitue instrumentalement le spectre d’un son, nous remettons en question l’existence du sonagramme de son de trombone qui, selon le compositeur, aurait servi de modèle. À travers cette étude génétique de Périodes, nous documentons plus généralement l’élaboration du cycle Les espaces acoustiques (1974-1985) considéré comme l’un des emblèmes de l’esthétique spectrale.Elaborada inicialmente na metade dos anos 1970, a música espectral representa uma das principais correntes da música francesa. Em Périodes (1974), para 7 instrumentos, Gérard Grisey (1946-1998) define as bases desta nova abordagem da composição musical que explora tanto as propriedades acústicas do som, quanto as características específicas do sistema auditivo. Os arquivos Gérard Grisey da fundação Paul Sacher, situados na Basileia, contém, entre outros documentos, manuscritos musicais (rascunhos, notas autografas, desenhos etc.) de cada uma das obras do compositor, assim como manuscritos de seus escritos, notas de aula e livros da sua biblioteca. O exame destes documentos, além da informação coletada por meio de entrevistas de amigos próximos do compositor, permite-nos compreender como Grisey imaginou, desenvolveu e concretizou sua abordagem espectral da composição. Neste artigo, iniciamos por descrever a formação do compositor e explorar sua pesquisa particular da acústica a partir de 1972 e 1974, por meio do estudo da obra de Émile Leipp e Fritz Winckel. Em seguida, analisamos de perto estes dois modelos (o ciclo respiratório e o espectro harmônico construído a partir da fundamental Mi1), que se encontram no coração da obra e marcam tanto sua influência estrutural quanto auditiva. Finalmente, depois de fazemos uma análise detalhada da última seção da peça, na qual Grisey utiliza instrumentos para recriar o espectro sonoro, questionamos a existência do espectrograma de trombone, que o próprio compositor alega ter utilizado como modelo. Por meio deste estudo genético de Périodes, buscamos, de maneira mais geral, documentar a construção do ciclo intitulado Les espaces acoustiques (1974-1985), que é considerado emblemático da estética espectral

Vitamin D interacts with Esr1 and Igf1 to regulate molecular pathways relevant to Alzheimer’s disease

International audienceAbstractBackgroundIncreasing evidence suggests a potential therapeutic benefit of vitamin D supplementation against Alzheimer’s disease (AD). Although studies have shown improvements in cognitive performance and decreases in markers of the pathology after chronic treatment, the mechanisms by which vitamin D acts on brain cells are multiple and remain to be thoroughly studied. We analyzed the molecular changes observed after 5 months of vitamin D3 supplementation in the brains of transgenic 5xFAD (Tg) mice, a recognized mouse model of AD, and their wild type (Wt) littermates. We first performed a kinematic behavioural examination at 4, 6 and 8 months of age (M4, M6 and M8) followed by a histologic assessment of AD markers. We then performed a comparative transcriptomic analysis of mRNA regulation in the neocortex and hippocampus of 9 months old (M9) female mice.ResultsTranscriptomic analysis of the hippocampus and neocortex of both Wt and Tg mice at M9, following 5 months of vitamin D3 treatment, reveals a large panel of dysregulated pathways related to i) immune and inflammatory response, ii) neurotransmitter activity, iii) endothelial and vascular processes and iv) hormonal alterations. The differentially expressed genes are not all direct targets of the vitamin D-VDR pathway and it appears that vitamin D action engages in the crosstalk with estrogen and insulin signaling. The misexpression of the large number of genes observed in this study translates into improved learning and memory performance and a decrease in amyloid plaques and astrogliosis in Tg animals.ConclusionsThis study underlies the multiplicity of action of this potent neurosteroid in an aging and AD-like brain. The classical and non-classical actions of vitamin D3 can act in an additive and possibly synergistic manner to induce neuroprotective activities in a context-specific way

Temporal gene profiling of the 5XFAD transgenic mouse model highlights the importance of microglial activation in Alzheimer’s disease

International audienceBackground: The 5XFAD early onset mouse model of Alzheimer's disease (AD) is gaining momentum. Behavioral, electrophysiological and anatomical studies have identified age-dependent alterations that can be reminiscent of human AD. However, transcriptional changes during disease progression have not yet been investigated. To this end, we carried out a transcriptomic analysis on RNAs from the neocortex and the hippocampus of 5XFAD female mice at the ages of one, four, six and nine months (M1, M4, M6, M9). Results: Our results show a clear shift in gene expression patterns between M1 and M4. At M1, 5XFAD animals exhibit region-specific variations in gene expression patterns whereas M4 to M9 mice share a larger proportion of differentially expressed genes (DEGs) that are common to both regions. Analysis of DEGs from M4 to M9 underlines the predominance of inflammatory and immune processes in this AD mouse model. The rise in inflammation, sustained by the overexpression of genes from the complement and integrin families, is accompanied by an increased expression of transcripts involved in the NADPH oxidase complex, phagocytic processes and IFN-γ related pathways. Conclusions: Overall, our data suggest that, from M4 to M9, sustained microglial activation becomes the predominant feature and point out that both detrimental and neuroprotective mechanisms appear to be at play in this model. Furthermore, our study identifies a number of genes already known to be altered in human AD, thus confirming the use of the 5XFAD strain as a valid model for understanding AD pathogenesis and for screening potential therapeutic molecules

Fibroblast and Lymphoblast Gene Expression Profiles in Schizophrenia: Are Non-Neural Cells Informative?

Lymphoblastoid cell lines (LCLs) and fibroblasts provide conveniently derived non-neuronal samples in which to investigate the aetiology of schizophrenia (SZ) using gene expression profiling. This assumes that heritable mechanisms associated with risk of SZ have systemic effects and result in changes to gene expression in all tissues. The broad aim of this and other similar studies is that comparison of the transcriptomes of non-neuronal tissues from SZ patients and healthy controls may identify gene/pathway dysregulation underpinning the neurobiological defects associated with SZ. Using microarrays consisting of 18,664 probes we compared gene expression profiles of LCLs from SZ cases and healthy controls. To identify robust associations with SZ that were not patient or tissue specific, we also examined fibroblasts from an independent series of SZ cases and controls using the same microarrays. In both tissue types ANOVA analysis returned approximately the number of differentially expressed genes expected by chance. No genes were significantly differentially expressed in either tissue when corrected for multiple testing. Even using relaxed parameters (p≤0.05, without multiple testing correction) there were still no differentially expressed genes that also displayed ≥2-fold change between the groups of SZ cases and controls common to both LCLs and fibroblasts. We conclude that despite encouraging data from previous microarray studies assessing non-neural tissues, the lack of a convergent set of differentially expressed genes associated with SZ using fibroblasts and LCLs indicates the utility of non-neuronal tissues for detection of gene expression differences and/or pathways associated with SZ remains to be demonstrated

Olfactory Stem Cells, a New Cellular Model for Studying Molecular Mechanisms Underlying Familial Dysautonomia

International audienceBackground: Familial dysautonomia (FD) is a hereditary neuropathy caused by mutations in the IKBKAP gene, the most common of which results in variable tissue-specific mRNA splicing with skipping of exon 20. Defective splicing is especially severe in nervous tissue, leading to incomplete development and progressive degeneration of sensory and autonomic neurons. The specificity of neuron loss in FD is poorly understood due to the lack of an appropriate model system. To better understand and modelize the molecular mechanisms of IKBKAP mRNA splicing, we collected human olfactory ecto-mesenchymal stem cells (hOE-MSC) from FD patients. hOE-MSCs have a pluripotent ability to differentiate into various cell lineages, including neurons and glial cells.Methodology/Principal Findings: We confirmed IKBKAP mRNA alternative splicing in FD hOE-MSCs and identified 2 novel spliced isoforms also present in control cells. We observed a significant lower expression of both IKBKAP transcript and IKAP/hELP1 protein in FD cells resulting from the degradation of the transcript isoform skipping exon 20. We localized IKAP/hELP1 in different cell compartments, including the nucleus, which supports multiple roles for that protein. We also investigated cellular pathways altered in FD, at the genome-wide level, and confirmed that cell migration and cytoskeleton reorganization were among the processes altered in FD. Indeed, FD hOE-MSCs exhibit impaired migration compared to control cells. Moreover, we showed that kinetin improved exon 20 inclusion and restores a normal level of IKAP/hELP1 in FD hOE-MSCs. Furthermore, we were able to modify the IKBKAP splicing ratio in FD hOE-MSCs, increasing or reducing the WT (exon 20 inclusion):MU (exon 20 skipping) ratio respectively, either by producing free-floating spheres, or by inducing cells into neural differentiation.Conclusions/Significance: hOE-MSCs isolated from FD patients represent a new approach for modeling FD to better understand genetic expression and possible therapeutic approaches. This model could also be applied to other neurological genetic diseases

Ecclesiastes et Psychosoma (2015) : deux manuscrits inédits de John Zorn

International audienceCourte introduction à deux manuscrits de John Zorn écrits à l'attention du groupe Simulacru