Tunable coupled surface acoustic cavities

We demonstrate the electric tuning of the acoustic field in acoustic microcavities(MCs) defined by a periodic arrangement of metal stripes within a surface acoustic delay line on LiNbO3 substrate. Interferometric measurements show the enhancement of the acoustic field distribution within a single MC, the presence of a"bonding" and"anti-bonding" modes for two strongly coupled MCs, as well as the positive dispersion of the"mini-bands" formed by five coupled MCs. The frequency and amplitude of the resonances can be controlled by the potential applied to the metal stripes

Multimodal Interactive Parsing

The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-642-38628-2_57Probabilistic parsing is a fundamental problem in Computational Linguistics, whose goal is obtaining a syntactic structure associated to a sentence according to a probabilistic grammatical model. Recently, an interactive framework for probabilistic parsing has been introduced, in which the user and the system cooperate to generate error-free parse trees. In an early prototype developed according to this interactive parsing technology, user feedback was provided by means of mouse actions and keyboard strokes. Here we augment the interaction style with support for (non-deterministic) natural handwritten recognition, and provide confidence measures as a visual aid to ease the correction process. Handwriting input seems to be a modality specially suitable for parsing, since the vocabulary size involved in the recognition of syntactic labels is fairly limited and thus intuitively errors should be small. However, errors may increase as handwriting quality (i.e., calligraphy) degrades. To solve this problem, we introduce a late fusion approach that leverages both on-line and off-line information, corresponding to pen strokes and contextual information from the parse trees. We demonstrate that late fusion can effectively help to disambiguate user intention and improve system accuracy.This research has received funding from the EC’s 7th Framework Programme (FP7/2007-13) under grant agreement No.287576- CasMaCat; from the Spanish MEC under the STraDA project (TIN2012-37475- C02-01) and the MITTRAL project (TIN2009-14633-C03-01); from the GV under the Prometeo project; and from the Universidad del Cauca (Colombia)Benedí Ruiz, JM.; Sánchez Peiró, JA.; Leiva, LA.; Sánchez Sáez, R.; Maca, M. (2013). Multimodal Interactive Parsing. En Pattern Recognition and Image Analysis. Springer. 484-491. https://doi.org/10.1007/978-3-642-38628-2_57S484491Afonso, S., Bick, E., Haber, R., Santos, D.: Floresta sintá(c)tica: a treebank for portuguese. In: Proc. LREC, pp. 1698–1703 (2002)Brants, T., Plaehn, O.: Interactive corpus annotation. In: Proc. LREC (2000)Guyon, I., Schomaker, L., Plamondon, R., Liberman, M., Janet, S.: UNIPEN project of on-line data exchange and recognizer benchmarks. In: Proc. ICPR, pp. 29–33 (1994)Lease, M., Charniak, E., Johnson, M., McClosky, D.: A look at parsing and its applications. In: Proc. AAAI, pp. 1642–1645 (2006)Marcus, M.P., Santorini, B., Marcinkiewicz, M.A.: Building a large annotated corpus of English: the Penn Treebank. Computational Linguistics 19(2), 313–330 (1993)Ortiz, D., Leiva, L.A., Alabau, V., Casacuberta, F.: Interactive machine translation using a web-based architecture. In: Proc. IUI, pp. 423–425 (2010)Romero, V., Leiva, L.A., Toselli, A.H., Vidal, E.: Interactive multimodal transcription of text images using a web-based demo system. In: Proc. IUI, pp. 477–478 (2009)Sánchez-Sáez, R., Leiva, L.A., Sánchez, J.A., Benedí, J.M.: Interactive predictive parsing using a web-based architecture. In: Proc. NAACL-HLT, pp. 37–40 (2010)Sánchez-Sáez, R., Sánchez, J.A., Benedí, J.M.: Interactive predictive parsing. In: Proc. IWPT, pp. 222–225 (2009)Sánchez-Sáez, R., Sánchez, J.A., Benedí, J.M.: Confidence measures for error discrimination in an interactive predictive parsing framework. In: Proc. COLING, pp. 1220–1228 (2010

Whole exome sequencing of Rett syndrome-like patients reveals the mutational diversity of the clinical phenotype

Classical Rett syndrome (RTT) is a neurodevelopmental disorder where most of cases carry MECP2 mutations. Atypical RTT variants involve mutations in CDKL5 and FOXG1. However, a subset of RTT patients remains that do not carry any mutation in the described genes. Whole exome sequencing was carried out in a cohort of 21 female probands with clinical features overlapping with those of RTT, but without mutations in the customarily studied genes. Candidates were functionally validated by assessing the appearance of a neurological phenotype in Caenorhabditis elegans upon disruption of the corresponding ortholog gene. We detected pathogenic variants that accounted for the RTT-like phenotype in 14 (66.6 %) patients. Five patients were carriers of mutations in genes already known to be associated with other syndromic neurodevelopmental disorders. We determined that the other patients harbored mutations in genes that have not previously been linked to RTT or other neurodevelopmental syndromes, such as the ankyrin repeat containing protein ANKRD31 or the neuronal acetylcholine receptor subunit alpha-5 (CHRNA5). Furthermore, worm assays demonstrated that mutations in the studied candidate genes caused locomotion defects. Our findings indicate that mutations in a variety of genes contribute to the development of RTT-like phenotypes

Inhibition of Gsk3b Reduces Nfkb1 Signaling and Rescues Synaptic Activity to Improve the Rett Syndrome Phenotype in Mecp2-Knockout Mice

Rett syndrome (RTT) is the second leading cause of mental impairment in girls and is currently untreatable. RTT is caused, in more than 95% of cases, by loss-of-function mutations in the methyl CpG- binding protein 2 gene (MeCP2). We propose here a molecular target involved in RTT: the glycogen synthase kinase-3b (Gsk3b) pathway. Gsk3b activity is deregulated in Mecp2-knockout (KO) mice models, and SB216763, a specific inhibitor, is able to alleviate the clinical symptoms with consequences at the molecular and cellular levels. In vivo, inhibition of Gsk3b prolongs the lifespan of Mecp2-KO mice and reduces motor deficits. At the molecular level, SB216763 rescues dendritic networks and spine density, while inducing changes in the properties of excitatory synapses. Gsk3b inhibition can also decrease the nuclear activity of the Nfkb1 pathway and neuroinflammation. Altogether, our findings indicate that Mecp2 deficiency in the RTT mouse model is partially rescued following treatment with SB216763

Mutations in JMJD1C are involved in Rett syndrome and intellectual disability

PURPOSE: Autism spectrum disorders are associated with defects in social response and communication that often occur in the context of intellectual disability. Rett syndrome is one example in which epilepsy, motor impairment, and motor disturbance may co-occur. Mutations in histone demethylases are known to occur in several of these syndromes. Herein, we aimed to identify whether mutations in the candidate histone demethylase JMJD1C (jumonji domain containing 1C) are implicated in these disorders. METHODS: We performed the mutational and functional analysis of JMJD1C in 215 cases of autism spectrum disorders, intellectual disability, and Rett syndrome without a known genetic defect. RESULTS: We found seven JMJD1C variants that were not present in any control sample ( 6,000) and caused an amino acid change involving a different functional group. From these, two de novo JMJD1C germline mutations were identified in a case of Rett syndrome and in a patient with intellectual disability. The functional study of the JMJD1C mutant Rett syndrome patient demonstrated that the altered protein had abnormal subcellular localization, diminished activity to demethylate the DNA damage-response protein MDC1, and reduced binding to MECP2. We confirmed that JMJD1C protein is widely expressed in brain regions and that its depletion compromises dendritic activity. CONCLUSIONS: Our findings indicate that mutations in JMJD1C contribute to the development of Rett syndrome and intellectual disability.Genet Med 18 1, 378-385.This study was supported by the European Community’s Seventh Framework Program (FP7/2007–2013) under grant agreement PITN-GA-2012–316758 of the EPITRAIN project and PITN-GA-2009–238242 of DISCHROM; ERC grant agreement 268626 of the EPINORC project; the E-RARE EuroRETT network (Carlos III Health Institute project PI071327); the Fondation Lejeune (France); MINECO projects SAF2011-22803 and CSD2006-00049; the Cellex Foundation; the Botín Foundation; the Catalan Association for Rett Syndrome; Fundación Alicia Koplowitz 2011 Grant AKOPLOWITZ11_006; the FIS project PI1002512; Grants PI10/01422, PI13/00285, CA10/01474, RD06/0020/1050, RD12/0036/008, and 2009-SGR293; and the Health and Science Departments of the Catalan government (Generalitat de Catalunya). K.S. and P.P. are EPITRAIN Research Fellows. M.E. is an ICREA Research Professor

Defective body-weight regulation, motor control and abnormal social interactions in Mecp2 hypomorphic mice

MeCP2 is an abundant protein that binds to methylated cytosine residues in DNA and regulates transcription. Mutations in MECP2 cause Rett syndrome, a severe neurological disorder that affects approximately 1:10 000 females. Mice lacking MeCP2 have been generated and constitute important models of Rett syndrome. However, it is yet unclear whether certain physiological events are sensitive to a decrease, rather than a complete lack of MeCP2. Here we report that a Mecp2 floxed allele (Mecp2 lox ) that was generated to allow conditional mutagenesis behaves as a hypomorph and the corresponding mutant mice exhibit phenotypical alterations including body weight gain, motor abnormalities and altered social behavior. Our data reinforce the view that the central nervous system is extremely sensitive to MeCP2 expression levels and suggest that the 3′-UTR of Mecp2 might contain important elements that contribute to the regulation of its stability or processing

Opening of pannexin- and connexin-based channels increases the excitability of nodose ganglion sensory neurons

Satellite glial cells (SGCs) are the main glia in sensory ganglia. They surround neuronal bodies and form a cap that prevents the formation of chemical or electrical synapses between neighboring neurons. SGCs have been suggested to establish bidirectional paracrine communication with sensory neurons. However, the molecular mechanism involved in this cellular communication is unknown. In the central nervous system (CNS), astrocytes present connexin43 (Cx43) hemichannels and pannexin1 (Panx1) channels, and the opening of these channels allows the release of signal molecules, such as ATP and glutamate. We propose that these channels could play a role in glia-neuron communication in sensory ganglia. Therefore, we studied the expression and function of Cx43 and Panx1 in rat and mouse nodose-petrosal-jugular complexes (NPJcs) using confocal immunofluorescence, molecular and electrophysiological techniques. Cx43 and Panx1 were detected in SGCs and in sensory neurons, respectively. In the rat and mouse, the electrical activity of vagal nerve increased significantly after nodose neurons were exposed to a Ca(2+)/Mg(2+)-free solution, a condition that increases the open probability of Cx hemichannels. This response was partially mimicked by a cell-permeable peptide corresponding to the last 10 amino acids of Cx43 (TAT-Cx43CT). Enhanced neuronal activity was reduced by Cx hemichannel, Panx1 channel and P2X7 receptor blockers. Moreover, the role of Panx1 was confirmed in NPJc, because in those from Panx1 knockout mice showed a reduced increase of neuronal activity induced by Ca(2+)/Mg(2+)-free extracellular conditions. The data suggest that Cx hemichannels and Panx channels serve as paracrine communication pathways between SGCs and neurons by modulating the excitability of sensory neurons.status: publishe

Multimodal Interactive Parsing

Abstract. Probabilistic parsing is a fundamental problem in Computational Linguistics, whose goal is obtaining a syntactic structure associated to a sentence according to a probabilistic grammatical model. Recently, an interactive framework for probabilistic parsing has been introduced, in which the user and the system cooperate to generate error-free parse trees. In an early prototype developed according to this interactive parsing technology, user feedback was provided by means of mouse actions and keyboard strokes. Here we augment the interaction style with support for (non-deterministic) natural handwritten recognition, and provide confidence measures as a visual aid to ease the correction process. Handwriting input seems to be a modality specially suitable for parsing, since the vocabulary size involved in the recognition of syntactic labels is fairly limited and thus intuitively errors should be small. However, errors may increase as handwriting quality (i.e., calligraphy) degrades. To solve this problem, we introduce a late fusion approach that leverages both on-line and off-line information, corresponding to pen strokes and contextual information from the parse trees. We demonstrate that late fusion can effectively help to disambiguate user intention and improve system accuracy