MAG: A Multilingual, Knowledge-base Agnostic and Deterministic Entity Linking Approach

Entity linking has recently been the subject of a significant body of research. Currently, the best performing approaches rely on trained mono-lingual models. Porting these approaches to other languages is consequently a difficult endeavor as it requires corresponding training data and retraining of the models. We address this drawback by presenting a novel multilingual, knowledge-based agnostic and deterministic approach to entity linking, dubbed MAG. MAG is based on a combination of context-based retrieval on structured knowledge bases and graph algorithms. We evaluate MAG on 23 data sets and in 7 languages. Our results show that the best approach trained on English datasets (PBOH) achieves a micro F-measure that is up to 4 times worse on datasets in other languages. MAG, on the other hand, achieves state-of-the-art performance on English datasets and reaches a micro F-measure that is up to 0.6 higher than that of PBOH on non-English languages.Comment: Accepted in K-CAP 2017: Knowledge Capture Conferenc

Insights from Super-Metal-Rich Stars: Is the Milky Way bar young?

Super-metal-rich (SMR) stars, currently in the solar neighbourhood, are expected to originate only in the inner Galaxy and have definitely migrated. We aim at studying a large sample of SMR stars to provide constraints on the epoch of the bar formation and its impact on the MW disc stellar populations. We investigate a sample of 169,701 MSTO and SGB stars with 6D phase space information and high-quality stellar parameters coming from the hybrid-CNN analysis of the Gaia-DR3 RVS stars. We compute distances and ages using the StarHorse code with a mean precision of 1% and 11%, respectively. From these, 11,848 stars have metallicity ([Fe/H]) above 0.15 dex. We report a metallicity dependence of spatial distribution of stellar orbits shown by the bimodal distribution in the guiding radius at 6.9 and 7.9 kpc, first appearing at [Fe/H]~0.1 dex, becoming very pronounced at larger [Fe/H]. In addition, we've observed a trend where the most metal-rich stars, with [Fe/H]~0.4 dex, are predominantly old (9-12 Gyrs) but show a gradual decline in [Fe/H] with age, reaching around 0.25 dex at about 4 Gyrs ago, followed by a sharp drop around 3 Gyrs ago. Furthermore, our full dataset reveals a clear peak in the age-metallicity relationship during the same period, indicating a SF burst around 3-4 Gyrs ago with slightly sub-solar [Fe/H] and enhanced [$\alpha$/Fe]. We show the SMR stars are good tracers of the bar activity. We interpret the steep decrease in number of SMR stars at around 3 Gyr as the end of the bar formation epoch. In this scenario, the peak of bar activity also coincides with a peak in the SF activity in the disc. Although the SF burst around 3 Gyr ago has been reported previously, its origin was unclear. Here, we suggest the SF burst to have been triggered by the high bar activity, 3-4 Gyr ago. According to these results and interpretation, the MW bar could be young.Comment: Accepted for publication on A&A Letter

Role of histone modifications and early termination in pervasive transcription and antisense-mediated gene silencing in yeast

Most genomes, including yeast Saccharomyces cerevisiae, are pervasively transcribed producing numerous non-coding RNAs, many of which are unstable and eliminated by nuclear or cytoplasmic surveillance pathways. We previously showed that accumulation of PHO84 antisense RNA (asRNA), in cells lacking the nuclear exosome component Rrp6, is paralleled by repression of sense transcription in a process dependent on the Hda1 histone deacetylase (HDAC) and the H3K4 histone methyl transferase Set1. Here we investigate this process genome-wide and measure the whole transcriptome of various histone modification mutants in a Δrrp6 strain using tiling arrays. We confirm widespread occurrence of potentially antisense-dependent gene regulation and identify three functionally distinct classes of genes that accumulate asRNAs in the absence of Rrp6. These classes differ in whether the genes are silenced by the asRNA and whether the silencing is HDACs and histone methyl transferase-dependent. Among the distinguishing features of asRNAs with regulatory potential, we identify weak early termination by Nrd1/Nab3/Sen1, extension of the asRNA into the open reading frame promoter and dependence of the silencing capacity on Set1 and the HDACs Hda1 and Rpd3 particularly at promoters undergoing extensive chromatin remodelling. Finally, depending on the efficiency of Nrd1/Nab3/Sen1 early termination, asRNA levels are modulated and their capability of silencing is change

DNA Delivery by Virus-Like Nanocarriers in Plant Cells

Tobacco mild green mosaic virus (TMGMV)-like nanocarriers were designed for gene delivery to plant cells. High aspect ratio TMGMVs were coated with a polycationic biopolymer, poly(allylamine) hydrochloride (PAH), to generate highly charged nanomaterials (TMGMV-PAH; 56.20 ± 4.7 mV) that efficiently load (1:6 TMGMV:DNA mass ratio) and deliver single-stranded and plasmid DNA to plant cells. The TMGMV-PAH were taken up through energy-independent mechanisms in Arabidopsis protoplasts. TMGMV-PAH delivered a plasmid DNA encoding a green fluorescent protein (GFP) to the protoplast nucleus (70% viability), as evidenced by GFP expression using confocal microscopy and Western blot analysis. TMGMV-PAH were inactivated (iTMGMV-PAH) using UV cross-linking to prevent systemic infection in intact plants. Inactivated iTMGMV-PAH-mediated pDNA delivery and gene expression of GFP in vivo was determined using confocal microscopy and RT-qPCR. Virus-like nanocarrier-mediated gene delivery can act as a facile and biocompatible tool for advancing genetic engineering in plants

Perceived uneasiness due to labor instability and psychological well-being in salaried and freelancer workers from Córdoba and Catamarca

Se analizó el malestar percibido por inestabilidad laboral y el bienestar psicológico en trabajadores en relación de dependencia (RDEP) y autónomos (AUT), de Córdoba y Catamarca, a fin de conocer características comunes y específicas e indagar relaciones entre esas variables. Se administraron el Inventario de Malestar Percibido en la Inestabilidad Laboral (IMPIL) y la Escala de Bienestar Psicológico para Adultos (BIEPS-A). La muestra fue de 140 sujetos. No hubo diferencias significativas en el malestar percibido por inestabilidad laboral según tipo de relación laboral o provincia, pero el bienestar psicológico fue mayor en participantes de Catamarca. La categoría problemas interpersonales del IMPIL se asoció inversamente con el bienestar psicológico en la muestra total y en AUT, pero no en RDEP. Contrario a lo que señala la literatura, no se hallaron asociaciones con otras categorías del IMPIL. Se discuten las implicancias de lo hallado.The perceived uneasiness due to labor instability and psychological well-being in salaried workers (RDEP) and freelancers (AUT), from Córdoba and Catamarca, were analyzed in order to know common and specific features and to test relationships among these variables. The Inventory of Perceived Uneasiness in an Unstable Work Setting (IMPIL) and the Scale of Psychological Well-Being for Adults (BIEPS-A) were administered. The sample consisted of 140 participants. There were no significant differences in the perceived uneasiness due to labor instability according to type of labor relationship or province, but psychological well-being was higher in participants from Catamarca. The interpersonal problems category of IMPIL was inversely associated with psychological well-being in the whole sample and in AUT, but not in RDEP. Contrary to what literature indicates, no associations were found with other IMPIL categories. The implications of these findings are discussed.Fil: López Steinmetz, Lorena Cecilia. Universidad Nacional de Córdoba. Instituto de Investigaciones Psicológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Psicológicas; Argentina. Universidad Empresarial Siglo XXI; ArgentinaFil: Hill, Andrea Melissa. Universidad Empresarial Siglo XXI; ArgentinaFil: Rivas Ruzo, Sofía Belén. Universidad Empresarial Siglo XXI; ArgentinaFil: Caracciolo, Giuliana. Universidad Empresarial Siglo XXI; Argentin

A fluorescence anisotropy assay to discover and characterize ligands targeting the maytansine site of tubulin.

Microtubule-targeting agents (MTAs) like taxol and vinblastine are among the most successful chemotherapeutic drugs against cancer. Here, we describe a fluorescence anisotropy-based assay that specifically probes for ligands targeting the recently discovered maytansine site of tubulin. Using this assay, we have determined the dissociation constants of known maytansine site ligands, including the pharmacologically active degradation product of the clinical antibody-drug conjugate trastuzumab emtansine. In addition, we discovered that the two natural products spongistatin-1 and disorazole Z with established cellular potency bind to the maytansine site on β-tubulin. The high-resolution crystal structures of spongistatin-1 and disorazole Z in complex with tubulin allowed the definition of an additional sub-site adjacent to the pocket shared by all maytansine-site ligands, which could be exploitable as a distinct, separate target site for small molecules. Our study provides a basis for the discovery and development of next-generation MTAs for the treatment of cancer

Protein-ligand complex for structure-based design: impact on the affinity and antitumor activity of new tubulin ligands

Resumen del trabajo presentado en el XVIII Congreso de la Sociedad Española de Química Terapéutica, celebrado en Salamanca (España), del 23 al 26 de enero de 2018Microtubules, made of ¿ß¿tubulin heterodimers, are the key components of the cytoskeleton and play a crucial role in many cellular processes, such as cell motility, morphogenesis and mitosis.[1] Interference with microtubule dynamics induces cell cycle arrest during mitosis and triggers cell death. Compounds that interact with tubulin, especially those binding at the colchicine domain, have been deeply investigated as anticancer drugs due to their dual mechanism of action as antimitotics and as vascular disrupting agents.[2,3] Our research group has recently described a new family of colchicine¿domain binders, based on a cyclohexanedione skeleton, with potent antiproliferative activity against tumor and endothelial cells.[4] Moreover, to gain insight into the binding mode of these cyclohexanediones, we have determined the crystal structure of ¿ß¿tubulin in complex with our hit compound (TUB075). Based on this detailed information and by applying the affinity maps program cGRILL, a structurebased synthesis of new cyclohexanedione derivatives has been accomplished with the objective of improving their affinity for tubulin and their antitumor activity. Following this approach, we have obtained new compounds with potent antiproliferative activity against tumor and endothelial cells (IC50=8¿31 nM) and with the highest Kb value reported for compounds binding at the colchicine site in tubulin. Additional studies have shown that they arrest cell cycle at G2/M and disrupt a network of endothelial cells. Moreover they keep antiproliferative activity against cell lines overexpressing P¿gp, further supporting the potential of these compounds.The financial support of the Spanish MINECO (SAF2012‐39760‐C02‐01 and SAF 2015‐64629‐C2‐1‐R), Comunidad de Madrid (BIPEDD2; ref P2010/BMD‐2457) and the COST action CM1407 (to M J. P.P., S.L., M.O.S. and J.F.D.) is sincerely acknowledge