A Diels–Alder Reaction Triggered by a [4 + 3] Metallacycloaddition

The TpMe2Ir(III) complex 1-OH2 (TpMe2 = hydrotris(3,5-dimethylpyrazolyl)borate), which contains a labile molecule of water and an iridium-bonded alkenyl moiety (−C(R)═C(R)–(R=CO2Me)) as part of a benzo-annulated five-membered iridacycle, reacts readily with the conjugated dienes butadiene and 2,3-dimethylbutadiene to afford the corresponding Diels–Alder products. Experimental and DFT studies are in accordance with an initial [4 + 3] cyclometalation reaction between the diene and the five-coordinated 16-electron organometallic fragment 1 (generated from 1-OH2 by facile water dissociation). The reaction can be extended to a related TpIr(III) complex (Tp = hydrotris(pyrazolyl)borate) that also features a labile ligand (i.e., 2-THF).Ministerio de Economía y Competitividad CTQ2014- 51912-REDCJunta de Andalucía FQM-119, P09-FQM-483

Reactivity of TpMe2-containing hydride-iridafurans with alkenes, alkynes, and H2

The TpMe2-containing hydride-iridafurans 2a,b (TpMe2 = hydrotris(3,5-dimethylpyrazolyl)borate) cleanly reacted with ethylene to give the bicyclic derivatives 6a,b. Formation of the latter complexes is a reversible process, and it is proposed to occur by an electrocyclic ring closure that takes place between C2H4 and the 16e unsaturated intermediates A, resulting from hydride migration to the α carbon of the metallacycle. Similar reactions were observed with a variety of alkynes RC≡CR (R = H, Ph, CO2Me) and R′C≡CH (R′= CO2Me, Ph, CMe3), with the regioselectivity observed for the latter substrates depending on the nature of R′. In the case of Me3SiC≡CH the structure of an unexpected byproduct indicates that an alkyne–vinylidene rearrangement has taken place on the metal coordination sphere during the reaction, and this observation suggests that in the mechanism of all these coupling processes the corresponding π adducts are active intermediates. Finally, complexes 2a,b reacted with H2 to give products derived from the hydrogenation of their alkenyl arms.Ministerio de Ciencia e Innovación CTQ2010-17476. Consolider Ingenio 2010 CSD 2007-0006Junta de Andalucía FQM-119, P09-FQM-483

Transcription, indexing and automatic analysis of judicial declarations from phonetic representations and techniques of forensic linguistics

Recientes avances tecnológicos han permitido mejorar los procesos judiciales para la búsqueda de información en los expedientes judiciales asociados a un caso. Sin embargo, cuando técnicos y peritos deben revisar pruebas almacenadas en vídeos y fragmentos de audio, se ven obligados a realizar una búsqueda manual en el documento multimedia para localizar la parte que desean revisar, lo cual es una tarea tediosa y que consume bastante tiempo. Para poder facilitar el desempeño de los técnicos, el presente proyecto consiste en un sistema que permite la transcripción e indexación automática de contenido multimedia basado en tecnologías de deep-learning en entornos de ruido y con múltiples interlocutores, así como la posibilidad de realizar análisis de lingüística forense sobre los datos para ayudar a los peritos a analizar los testimonios de modo que se aporten evidencias sobre la veracidad del mismo.Recent technological advances have made it possible to improve the search for information in the judicial files of the Ministry of Justice associated with a trial. However, when judicial experts examine evidence in multimedia files, such as videos or audio fragments, they must manually search the document to locate the fragment at issue, which is a tedious and time-consuming task. In order to ease this task, we propose a system that allows automatic transcription and indexing of multimedia content based on deep-learning technologies in noise environments and with multiple speakers, as well as the possibility of applying forensic linguistics techniques to enable the analysis of witness statements so that evidence on its veracity is provided.Este proyecto ha sido financiado por el Instituto de Fomento de la Región de Murcia con fondos FEDER dentro del proyecto con referencia 2018.08.ID+I.0025

Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks : The GR@ACE project

Introduction: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. Methods: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. Results: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. Discussion: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Escritura de elevación a público con la composición de cargos del Comité Nacional

Escritura de elevación a público del nuevo Comité Nacional de PA

Formation of β-Metallanaphthalenes by the Coupling of a Benzo-Iridacyclopentadiene with Olefins

We have synthesized a new type of metallaaromatic complexes, namely the hydride-β-iridanaphthalenes TpMe2tiebar above startr(H)[C(CH2R′)-C6H4-o-C(R)═tiebar above endC(R)] (benzo-3-H,CH2R′), by reaction of the benzo-iridacyclopentadiene TpMe2tiebar above startr[C6H4-o-C(R)═tiebar above endC(R)](OH2) (benzo-1-OH2) (TpMe2 = hydrotris(3,5-dimethylpyrazolyl)borate, R = CO2Me) with olefins of the type CH2═CHR′ (R′ = H, Me, C6H4-p-Me, OPh). These reactions are proposed to take place with the initial coordination of the olefin and isomerization to a carbene form and subsequent insertion into the Ir–C(phenylic) bond and a final α-H elimination. The reaction with ethoxyethylene does not afford the corresponding derivative but rather gives a mixture of three, isolable, compounds, which are proposed to derive from three different types of insertion of the olefin, one of them a typical 1,2-insertion and the other two as (different) carbenes. The related reactions of the iridacyclopentadiene TpMe2tiebar above startr[C(R)═C(R)-C(R)═tiebar above endC(R)](OH2) (1-OH2) are also discussed. For different combinations of precursor and olefin, we have observed differences in the regio- and stereochemistry of the insertions.Peer reviewe

A Diels–Alder Reaction Triggered by a [4 + 3] Metallacycloaddition

The TpMe2Ir(III) complex 1-OH2 (TpMe2 = hydrotris(3,5-dimethylpyrazolyl)borate), which contains a labile molecule of water and an iridium-bonded alkenyl moiety (−C(R)═C(R)–(R=CO2Me)) as part of a benzo-annulated five-membered iridacycle, reacts readily with the conjugated dienes butadiene and 2,3-dimethylbutadiene to afford the corresponding Diels–Alder products. Experimental and DFT studies are in accordance with an initial [4 + 3] cyclometalation reaction between the diene and the five-coordinated 16-electron organometallic fragment 1 (generated from 1-OH2 by facile water dissociation). The reaction can be extended to a related TpIr(III) complex (Tp = hydrotris(pyrazolyl)borate) that also features a labile ligand (i.e., 2-THF).Peer reviewe