Algunas soluciones aproximadas para diseños split-plot con matrices de covarianza arbitrarias

El presente trabajo revisa con cierto detalle diversos tipos de análisis para diseños split-plot que carecen del mismo número de unidades experimentales dentro de cada grupo y en los que se incumple el supuesto de esfericidad multimuestral. Específicamente, adoptando el enfoque multivariado de aproximar los grados de libertad desarrollado por Johansen (1980) y el procedimiento de aproximación general mejorada corregida basado en Huynh (1980) se muestra cómo obtener análisis robustos y poderosos a la hora de probar los efectos principales y la interacción, así como hipótesis de comparaciones múltiples relacionadas con estos efectos, tanto si se cuenta con una simple variable dependiente asociada con cada una de las medidas repetidas como si se cuenta con más de una

A new non-aggregative splicing isoform of human Tau is decreased in Alzheimer's disease.

Tauopathies, including Alzheimer's disease (AD) and frontotemporal lobar degeneration with Tau pathology (FTLD-tau), are a group of neurodegenerative disorders characterized by Tau hyperphosphorylation. Post-translational modifications of Tau such as phosphorylation and truncation have been demonstrated to be an essential step in the molecular pathogenesis of these tauopathies. In this work, we demonstrate the existence of a new, human-specific truncated form of Tau generated by intron 12 retention in human neuroblastoma cells and, to a higher extent, in human RNA brain samples, using qPCR and further confirming the results on a larger database of human RNA-seq samples. Diminished protein levels of this new Tau isoform are found by Westernblotting in Alzheimer's patients' brains (Braak I n = 3; Braak II n = 6, Braak III n = 3, Braak IV n = 1, and Braak V n = 10, Braak VI n = 8) with respect to non-demented control subjects (n = 9), suggesting that the lack of this truncated isoform may play an important role in the pathology. This new Tau isoform exhibits similar post-transcriptional modifications by phosphorylation and affinity for microtubule binding, but more interestingly, is less prone to aggregate than other Tau isoforms. Finally, we present evidence suggesting this new Tau isoform could be linked to the inhibition of GSK3β, which would mediate intron 12 retention by modulating the serine/arginine rich splicing factor 2 (SRSF2). Our results show the existence of an important new isoform of Tau and suggest that further research on this less aggregation-prone Tau may help to develop future therapies for Alzheimer's disease and other tauopathies.This work was supported by the Ministerio de Ciencia, Innovación y Universidades from Spain (PGC2018-096177-B-00). Institutional grants from the Fundación Ramón Areces and Banco de Santander to CBMSO are also acknowledged. The Asociación Española Contra el Cáncer Scientific Foundation has financed Ricardo Gargini. We would like to acknowledge Daniela Rosiles for her technical support in cloning.S

Contrastación de hipótesis en diseños multivariados split-plot con matrices de dispersión arbitrarias

El presente trabajo examina diversos procedimientos para contrastar hipótesis nulas globales, correspondientes a datos obtenidos mediante diseños multivariados split-plot cuando se incumple el supuesto de homogeneidad de las matrices de dispersión. Un examen de estos procedimientos para un amplio número de variables confirma, por un lado, la robustez del procedimiento multivariado de Welch-James dado por Johansen (1980) para probar el efecto principal de los ensayos y, por otro, la robustez de la generalización multivariada del procedimiento de Brown-Forsythe (1974) para probar la interacción de los grupos x los ensayos. Nuestros resultados también ponen de relieve que las diferencias de potencia eran pequeñas en aquellas condiciones en que tanto el procedimiento de Welch-James como de Brown-Forsythe controlaban las tasas de error de Tipo I

Robust Fuzzy Clustering via Trimming and Constraints

Producción CientíficaA methodology for robust fuzzy clustering is proposed. This methodology can be widely applied in very different statistical problems given that it is based on probability likelihoods. Robustness is achieved by trimming a fixed proportion of “most outlying” observations which are indeed self-determined by the data set at hand. Constraints on the clusters’ scatters are also needed to get mathematically well-defined problems and to avoid the detection of non-interesting spurious clusters. The main lines for computationally feasible algorithms are provided and some simple guidelines about how to choose tuning parameters are briefly outlined. The proposed methodology is illustrated through two applications. The first one is aimed at heterogeneously clustering under multivariate normal assumptions and the second one migh be useful in fuzzy clusterwise linear regression problems.Ministerio de Economía, Industria y Competitividad (MTM2014-56235-C2-1-P)Junta de Castilla y León (programa de apoyo a proyectos de investigación – Ref. VA212U13

New groups of planetary nebulae with peculiar dust chemistry towards the Galactic bulge

We investigate Galactic bulge planetary nebulae without emission-line central stars for which peculiar infrared spectra have been obtained with the Spitzer Space Telescope, including the simultaneous signs of oxygen and carbon based dust. Three separate sub-groups can be defined characterized by the different chemical composition of the dust and the presence of crystalline and amorphous silicates. We find that the classification based on the dust properties is reflected in the more general properties of these planetary nebulae. However, some observed properties are difficult to relate to the common view of planetary nebulae. In particular, it is challenging to interpret the peculiar gas chemical composition of many analyzed objects in the standard picture of the evolution of planetary nebulae progenitors. We confirm that the dual-dust chemistry phenomenon is not limited to planetary nebulae with emission-line central stars.Comment: 17 pages, 13 figure

Study of overall and local electrochemical responses of oxide films grown on CoCr alloy under biological environments

The interaction of the physiological medium and living tissues with the implant surfaces in biological environments is regulated by biopotentials that induce changes in the chemical composition, structure and thickness of the oxide film. In this work, oxide films grown on CoCr alloys at 0.5 V vs Ag/AgCl and 0.7 V vs Ag/AgCl have been characterized through overall and localized electrochemical techniques in a phosphate buffer solution and 0.3% hyaluronic acid. Nanopores of 10–50 nm diameter are homogeneously distributed along the surface in the oxide film formed at 0.7 V vs Ag/AgCl. The distribution of the Constant Phase Element studied by local electrochemical impedance spectroscopy showed a three-dimensional (3D) model on the oxide films grown at 0.5 V vs Ag/AgCl and 0.7 V vs Ag/AgCl. This behaviour is especially noticeable in oxide films grown at 0.7 V vs Ag/AgCl, probably due to surface inhomogeneities, and resistive properties generated by the potentiostatic growth of the oxide film.This work was supported by the Spanish National government [MINECO-MAT2011-29152-C02-01].Peer reviewe

p38 Inhibition Decreases Tau Toxicity in Microglia and Improves Their Phagocytic Function

Alzheimer’s disease (AD) and other tauopathies are histopathologically characterized by tau aggregation, along with a chronic inflammatory response driven by microglia. Over the past few years, the role of microglia in AD has been studied mainly in relation to amyloid-β (Aβ) pathology. Consequently, there is a substantial knowledge gap concerning the molecular mechanisms involved in tau-mediated toxicity and neuroinflammation, thus hindering the development of therapeutic strategies. We previously demonstrated that extracellular soluble tau triggers p38 MAPK activation in microglia. Given the activation of this signaling pathway in AD and its involvement in neuroinflammation processes, here we evaluated the effect of p38 inhibition on primary microglia cultures subjected to tau treatment. Our data showed that the toxic effect driven by tau in microglia was diminished through p38 inhibition. Furthermore, p38 blockade enhanced microglia-mediated tau phagocytosis, as reflected by an increase in the number of lysosomes. In conclusion, these results contribute to our understanding of the functions of p38 in the central nervous system (CNS) beyond tau phosphorylation in neurons and provide further insights into the potential of p38 inhibition as a therapeutic strategy to halt neuroinflammation in tauopathiesOpen Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This research was funded by the Spanish Ministry of Science and Innovation (BES-2015–074405, PGC2018-096177-B-I00) and the Center for Networked Biomedical Research on Neurodegenerative Diseases. Institutional grants from the Fundación Ramón Areces and Banco de Santander are also acknowledged. R. M. M. and M. T. H. are supported by the Helmholtz Association, under the project title “Immunology&Infammation,” project number ZT-002

The GALANTE photometric survey of the northern Galactic plane: Project description and pipeline

The GALANTE optical photometric survey is observing the northern Galactic plane and some adjacent regions using seven narrow- and intermediate-filters, covering a total of 1618 square degrees. The survey has been designed with multiple exposure times and at least two different air masses per field to maximize its photometric dynamic range, comparable to that of Gaia, and ensure the accuracy of its photometric calibration. The goal is to reach at least 1% accuracy and precision in the seven bands for all stars brighter than AB magnitude 17 while detecting fainter stars with lower values of the signal-to-noise ratio.The main purposes of GALANTE are the identification and study of extinguished O+B+WR stars, the derivation of their extinction characteristics, and the cataloguing of F and G stars in the solar neighbourhood. Its data will be also used for a variety of other stellar studies and to generate a high-resolution continuum-free map of the H{\alpha} emission in the Galactic plane. We describe the techniques and the pipeline that are being used to process the data, including the basis of an innovative calibration system based on Gaia DR2 and 2MASS photometry.Comment: 18 pages, accepted for publication in MNRA

New insights on the seismogenic potential of the Eastern Betic Shear Zone (SE Iberia): Quaternary activity and paleoseismicity of the SW segment of the Carrascoy Fault Zone

The Carrascoy Fault (CAF) is one of the main active faults that form part of the Eastern Betic Shear Zone, a 450 km fault system that accommodates most of the convergence between the Eurasian (Iberia) and Nubian plates in the Betic Cordillera, south Spain. Although the CAF represents a major earthquake threat to the nearby City of Murcia, studies on its Quaternary tectonics and seismogenic potential are scarce to date. We present evidence that supports the division of the CAF into two overlapping segments with contrasting tectonic structure, Quaternary activity, and landform control: a SW segment, characterized by a broad fold-and-thrust zone similar to the forebergs defined in the Gobi-Altai region, and a NE segment, characterized by a sharp mountain front controlled by strike-slip tectonics. We attribute the differentiation into these two segments to the stresses associated with topography, which in turn is a consequence of the shortening component, at the middle Pleistocene, after circa 217.4 ka. For the SW segment we infer the occurrence of 9 to 11, Mw 6.7 paleoearthquakes in the last 30.2 kyr, and a slip rate of 0.37 ± 0.08 m/kyr. We date the occurrence of the last surface rupture event after 2750 B.P., and we estimate an average recurrence period of major events of 3.3 ± 0.7 kyrThis work was supported by SISMOGEN (IGME, 2279) and FASEGEO (CGL2009-09726) research projects and a technical assistance of the Civil Protection Service of Murci