Multidimensional Rovella-like attractors

We present a multidimensional flow exhibiting a Rovella-like attractor: a transitive invariant set with a non-Lorenz-like singularity accumulated by regular orbits and a multidimensional non-uniformly expanding invariant direction. Moreover, this attractor has a physical measure with full support but persists along certain0909.1033 submanifolds of the space of vector fields. As in the 3-dimensional Rovella-like attractor, this example is not robust. The construction introduces a class of multidimensional dynamics, whose suspension provides the Rovella-like attractor, which are partially hyperbolic, and whose quotient over stable leaves is a multidimensional endomorphism to which Benedicks-Carleson type arguments are applied to prove non-uniform expansion.Comment: 45 pages, 14 figures; improved introduction with more citations to other relevant related works. To appear in Journal of Differential Equation

Synthetic Conjugates of Ursodeoxycholic Acid Inhibit Cystogenesis in Experimental Models of Polycystic Liver Disease

Altres ajuts: Suported by IKERBASQUE, Basque foundation for Science (M.J. Perugorria and J.M. Banales), Spain; "Junta de Castilla y Leon" (J.J.G. Marin: SA06P17); "Diputación Foral Gipuzkoa" (J.M. Banales: DFG15/010, DFG16/004; M.J. Perugorria: DFG18/114, DFG19/081), BIOEF (Basque Foundation for Innovation and Health Research: EiTB Maratoia BIO15/CA/016/BD to J.M. Banales), Department of Health of the Basque Country (J.M. Banales: 2017111010; M.J. Perugorria: 2019111024), and Euskadi RIS3 (J.M. Banales: 2016222001, 2017222014, and 2018222029; 2019222054); La Caixa Scientific Foundation (J.M. Banales: HR17-00601); "Fundación Científica de la Asociación Española Contra el Cáncer" (AECC Scientific Foundation, to J.M. Banales and J.J.G. Marin); and "Centro Internacional sobre el Envejecimiento", Spain (J.J.G. Marin: OLD-HEPAMARKER, 0348-CIE-6-E). A. Santos-Laso by the Basque Government (PRE_2018_2_0195), and Pui Y. Lee-Law by the European Association for the Study of the Liver (EASL; Sheila Sherlock Award). Basque Government (F.P. Cossío: IT-324-07). I. Rivilla had a postdoctoral contract from the Donostia International Physics Center.Background and Aims: Polycystic liver diseases (PLDs) are genetic disorders characterized by progressive development of symptomatic biliary cysts. Current surgical and pharmacological approaches are ineffective, and liver transplantation represents the only curative option. Ursodeoxycholic acid (UDCA) and histone deacetylase 6 inhibitors (HDAC6is) have arisen as promising therapeutic strategies, but with partial benefits. Approach and Results: Here, we tested an approach based on the design, synthesis, and validation of a family of UDCA synthetic conjugates with selective HDAC6i capacity (UDCA-HDAC6i). Four UDCA-HDAC6i conjugates presented selective HDAC6i activity, UDCA-HDAC6i #1 being the most promising candidate. UDCA orientation within the UDCA-HDAC6i structure was determinant for HDAC6i activity and selectivity. Treatment of polycystic rats with UDCA-HDAC6i #1 reduced their hepatomegaly and cystogenesis, increased UDCA concentration, and inhibited HDAC6 activity in liver. In cystic cholangiocytes UDCA-HDAC6i #1 restored primary cilium length and exhibited potent antiproliferative activity. UDCA-HDAC6i #1 was actively transported into cells through BA and organic cation transporters. Conclusions: These UDCA-HDAC6i conjugates open a therapeutic avenue for PLDs

Evaluación de los costes de mantenimiento y restauración de edificios patrimoniales

En las últimas décadas, no se han adoptado protocolos de mantenimiento adecuados para la conservación y rehabilitación del patrimonio cultural. En España, el mantenimiento de estos edificios tiene, comúnmente, una naturaleza reactiva, estando condicionada por criterios subjetivos y por la existencia de fondos disponibles para la realización de las acciones de rehabilitación. Por tanto, es fundamental que los gestores del patrimonio construido tengan información relevante que ayude a tomar decisiones sobre la prioridad de intervención y las acciones preventivas a realizar en edificios patrimoniales. Existen cada vez más estudios relacionados con la definición de estrategias de mantenimiento adecuadas, que permitan mejorar el estado de conservación del patrimonio construido, con especial foco en la optimización de costos de mantenimiento empleados durante el ciclo de vida de estos edificios. Este trabajo identifica los factores que condicionan la decisión de intervenir en un conjunto de edificios patrimoniales, localizados en el sur de España. Se analizan las acciones de mantenimiento realizadas en un conjunto de 20 iglesias parroquiales y sus costes durante un período de 11 años (entre 2005 y 2015). En este estudio se evalúa la eficacia de las acciones realizadas, identificando los puntos fuertes y débiles de las intervenciones y estrategias adoptadas a lo largo del período de tiempo analizado. Los resultados obtenidos demuestran que las acciones de naturaleza reactiva deben ser minimizadas, para reducir los costes de mantenimiento. El conocimiento adquirido con las estrategias adoptadas en el pasado permite proporcionar información relevante para la planificación adecuada de futuras estrategias de mantenimient

Effects of Trihalomethanes on Liver Mitochondria

Introduction: Trihalomethanes (THMs), namely dibromochloromethane (DBCM) and bromodichloromethane (BDCM), are disinfection byproducts of chlorinated water. This experiment aimed to evaluate the mitochondrial dysfunction induced by THMs at low levels in a mouse model

The exposure of the hybrid detector of the Pierre Auger Observatory

The Pierre Auger Observatory is a detector for ultra-high energy cosmic rays. It consists of a surface array to measure secondary particles at ground level and a fluorescence detector to measure the development of air showers in the atmosphere above the array. The "hybrid" detection mode combines the information from the two subsystems. We describe the determination of the hybrid exposure for events observed by the fluorescence telescopes in coincidence with at least one water-Cherenkov detector of the surface array. A detailed knowledge of the time dependence of the detection operations is crucial for an accurate evaluation of the exposure. We discuss the relevance of monitoring data collected during operations, such as the status of the fluorescence detector, background light and atmospheric conditions, that are used in both simulation and reconstruction.Comment: Paper accepted by Astroparticle Physic

Evidence for a mixed mass composition at the `ankle' in the cosmic-ray spectrum

We report a first measurement for ultra-high energy cosmic rays of the correlation between the depth of shower maximum and the signal in the water Cherenkov stations of air-showers registered simultaneously by the fluorescence and the surface detectors of the Pierre Auger Observatory. Such a correlation measurement is a unique feature of a hybrid air-shower observatory with sensitivity to both the electromagnetic and muonic components. It allows an accurate determination of the spread of primary masses in the cosmic-ray flux. Up till now, constraints on the spread of primary masses have been dominated by systematic uncertainties. The present correlation measurement is not affected by systematics in the measurement of the depth of shower maximum or the signal in the water Cherenkov stations. The analysis relies on general characteristics of air showers and is thus robust also with respect to uncertainties in hadronic event generators. The observed correlation in the energy range around the `ankle' at $\lg(E/{\rm eV})=18.5-19.0$ differs significantly from expectations for pure primary cosmic-ray compositions. A light composition made up of proton and helium only is equally inconsistent with observations. The data are explained well by a mixed composition including nuclei with mass $A > 4$. Scenarios such as the proton dip model, with almost pure compositions, are thus disfavoured as the sole explanation of the ultrahigh-energy cosmic-ray flux at Earth.Comment: Published version. Added journal reference and DOI. Added Report Numbe