A Probabilistic model of meetings that combines words and discourse features

(c) 2008 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other users, including reprinting/ republishing this material for advertising or promotional purposes, creating new collective works for resale or redistribution to servers or lists, or reuse of any copyrighted components of this work in other works.This is the author's accepted version of this article. The final published version can be found here: http://dx.doi.org/10.1109/TASL.2008.92586

Profiling allele-specific gene expression in brains from individuals with autism spectrum disorder reveals preferential minor allele usage.

One fundamental but understudied mechanism of gene regulation in disease is allele-specific expression (ASE), the preferential expression of one allele. We leveraged RNA-sequencing data from human brain to assess ASE in autism spectrum disorder (ASD). When ASE is observed in ASD, the allele with lower population frequency (minor allele) is preferentially more highly expressed than the major allele, opposite to the canonical pattern. Importantly, genes showing ASE in ASD are enriched in those downregulated in ASD postmortem brains and in genes harboring de novo mutations in ASD. Two regions, 14q32 and 15q11, containing all known orphan C/D box small nucleolar RNAs (snoRNAs), are particularly enriched in shifts to higher minor allele expression. We demonstrate that this allele shifting enhances snoRNA-targeted splicing changes in ASD-related target genes in idiopathic ASD and 15q11-q13 duplication syndrome. Together, these results implicate allelic imbalance and dysregulation of orphan C/D box snoRNAs in ASD pathogenesis

Optimizing both catalyst preparation and catalytic behaviour for the oxidative dehydrogenation of ethane of Ni-Sn-O catalysts

[EN] Bulk Ni-Sn-O catalysts have been synthesized, tested in the oxidative dehydrogenation of ethane and characterized by several physicochemical techniques. The catalysts have been prepared by evaporation of the corresponding salts using several additives in the synthesis gel, i.e. ammonium hydroxide, nitric acid, glyoxylic acid or oxalic acid, in the synthesis gel. The catalysts were finally calcined at 500 degrees C in air. Important changes in the catalytic behaviour have been observed depending on the additive. In fact, an important improvement in the catalytic performance is observed especially when some additives, such as glyoxylic or oxalic acid, are used. Thus the productivity to ethylene multiplies by 6 compared to the reference Ni-Sn-O catalyst if appropriate templates are used, and this is the result of an improvement in both the catalytic activity and the selectivity to ethylene. This improved performance has been explained in terms of the decrease of the crystallite size (and the increase in the surface area of catalyst) as well as the modification of the lattice parameter of nickel oxide.The authors would like to acknowledge the DGICYT in Spain (CTQ2015-68951-C3-1-R and CTQ2012-37925-C03-2) for financial support. We also thank the University of Valencia and SCSIE-UV for assistanceSolsona Espriu, BE.; López Nieto, JM.; Agouram, S.; Soriano Rodríguez, MD.; Dejoz, A.; Vázquez, MI.; Concepción Heydorn, P. (2016). Optimizing both catalyst preparation and catalytic behaviour for the oxidative dehydrogenation of ethane of Ni-Sn-O catalysts. Topics in Catalysis. 59(17-18):1564-1572. https://doi.org/10.1007/s11244-016-0674-zS156415725917-18Heracleous E, Lee AF, Wilson K, Lemonidou AA (2005) J Catal 231:159–171Heracleous E, Lemonidou AA (2006) J Catal 237:162–174Savova B, Loridant S, Filkova D, Millet JMM (2010) Appl Catal A 390:148–157Heracleous E, Lemonidou AA (2010) J Catal 270:67–75Solsona B, Nieto JML, Concepcion P, Dejoz A, Ivars F, Vazquez MI (2011) J Catal 280:28–39Skoufa Z, Heracleous E, Lemonidou AA (2012) Catal Today 192:169–176Zhu H, Ould-Chikh S, Anjum DH, Sun M, Biausque G, Basset JM, Caps V (2012) J Catal 285:292–303Skoufa Z, Heracleous E, Lemonidou AA (2012) Chem Eng Sci 84:48–56Zhu H, Rosenfeld DC, Anjum DH, Caps V, Basset JM (2015) ChemSusChem 8:1254–1263Heracleous E, Lemonidou AA (2015) J Catal 322:118–129Solsona B, Concepcion P, Demicol B, Hernandez S, Delgado JJ, Calvino JJ, Nieto JML (2012) J Catal 295:104–114Nieto JML, Solsona B, Grasselli RK, Concepción P (2014) Top Catal 57:1248–1255Popescu I, Skoufa Z, Heracleous E, Lemonidou AA, Marcu IC (2015) PCCP 17:8138–8147Zhang X, Gong Y, Yu G, Xie Y (2002) J Mol Catal A 180:293–298Popescu I, Skoufa Z, Heracleous E, Lemonidou A, Marcu I-C (2015) Phys Chem Chem Phys 17:8138–8147Nakamura KI, Miyake T, Konishi T, Suzuki T (2006) J Mol Catal A 260:144–151Solsona B, Dejoz AM, Vazquez MI, Ivars F, Nieto JML (2009) Top Catal 52:751–757Bortolozzi JP, Gutierrez LB, Ulla MA (2013) Appl Catal A 452:179–188Takeguchi T, Furukawa S, Inoue M (2001) J Catal 202:14–24Richardson JT, Turk B, Twigg MV (1996) Appl Catal 148:97–112Biju V, Khadar MA (2002) J Nanopart Res 4:247–253Van Veenendaal MA, Sawatzky GA (1993) Phys Rev Lett 70:2459–2462Vedrine JC, Hollinger G, Duc TM (1978) J Phys Chem 82:1515–1520Salagre P, Fierro JLG, Medina F, Sueiras JE (1996) J Mol Catal A 106:125–13

Identification of a targetable KRAS-mutant epithelial population in non-small cell lung cancer

Lung cancer is the leading cause of cancer deaths. Tumor heterogeneity, which hampers development of targeted therapies, was herein deconvoluted via single cell RNA sequencingin aggressive human adenocarcinomas (carrying Kras-mutations) and comparable murine model. We identified a tumor-specific, mutant-KRAS-associated subpopulation which is conserved in both human and murine lung cancer. We previously reported a key role for the oncogene BMI-1 in adenocarcinomas. We therefore investigated the effects of in vivo PTC596 treatment, which affects BMI-1 activity, in our murine model. Post-treatment, MRI analysis showed decreased tumor size, while single cell transcriptomics concomitantly detected near complete ablation of the mutant-KRAS-associated subpopulation, signifying the presence of a pharmacologically targetable, tumor-associated subpopulation. Our findings therefore hold promise for the development of a targeted therapy for KRAS-mutant adenocarcinomas

Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number

Elevated basal serum tryptase levels are present in 4-6% of the general population, but the cause and relevance of such increases are unknown. Previously, we described subjects with dominantly inherited elevated basal serum tryptase levels associated with multisystem complaints including cutaneous flushing and pruritus, dysautonomia, functional gastrointestinal symptoms, chronic pain, and connective tissue abnormalities, including joint hypermobility. Here we report the identification of germline duplications and triplications in the TPSAB1 gene encoding α-tryptase that segregate with inherited increases in basal serum tryptase levels in 35 families presenting with associated multisystem complaints. Individuals harboring alleles encoding three copies of α-tryptase had higher basal serum levels of tryptase and were more symptomatic than those with alleles encoding two copies, suggesting a gene-dose effect. Further, we found in two additional cohorts (172 individuals) that elevated basal serum tryptase levels were exclusively associated with duplication of α-tryptase-encoding sequence in TPSAB1, and affected individuals reported symptom complexes seen in our initial familial cohort. Thus, our findings link duplications in TPSAB1 with irritable bowel syndrome, cutaneous complaints, connective tissue abnormalities, and dysautonomia

Meta-analysis of type 2 Diabetes in African Americans Consortium

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR)  = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.Peer reviewe