Time-dependent Mechanics and Lagrangian submanifolds of Dirac manifolds

A description of time-dependent Mechanics in terms of Lagrangian submanifolds of Dirac manifolds (in particular, presymplectic and Poisson manifolds) is presented. Two new Tulczyjew triples are discussed. The first one is adapted to the restricted Hamiltonian formalism and the second one is adapted to the extended Hamiltonian formalism

HI tomographic imaging of the Cosmic Dawn and Epoch of Reionization with SKA

We provide an overview of 21cm tomography of the Cosmic Dawn and Epoch of Reionization as possible with SKA-Low. We show why tomography is essential for studying CD/EoR and present the scales which can be imaged at different frequencies for the different phases of SKA- Low. Next we discuss the different ways in which tomographic data can be analyzed. We end with an overview of science questions which can only be answered by tomography, ranging from the characterization of individual objects to understanding the global processes shaping the Universe during the CD/EoRComment: 14 pages, 3 figures. Accepted for publication in the SKA Science Book 'Advancing Astrophysics with the Square Kilometre Array', to appear in 2015. PoS(AASKA14)01

In vitro modeling of dysfunctional glial cells in neurodegenerative diseases using human pluripotent stem cells

Most neurodegenerative diseases are characterized by a complex and mostly still unresolved pathology. This fact, together with the lack of reliable models, have precluded the development of effective therapies counteracting the disease progression. In the past few years, several studies have evidenced that lack of proper functionality of glial cells (astrocytes, microglia and oligodendrocytes) has a key role in the pathology of several neurodegenerative conditions including Alzheimer´s disease, amyotrophic lateral sclerosis and multiple sclerosis among others. However, this glial dysfunction is poorly modelled by available animal models, and we hypothesize that patientderived cells can serve as a better platform where to study this glial dysfunction. In this sense, human pluripotent stem cells (hPSCs) has revolutionized the field allowing the generation of disease-relevant neural cell types that can be used for disease modelling, drug screening and, possibly, cell transplantation purposes. In the case of the generation of oligodendrocytes (OLs) from hPSCs, we have developed a fast and robust protocol to generate surface antigen O4-positive (O4+) and myelin basic protein-positive OLs from hPSCs in only 22 days, including from patients with multiple sclerosis or amyotrophic lateral sclerosis. The generated cells resemble primary human OLs at the transcriptome level and can myelinate neurons in vivo. Using in vitro OLneuron co-cultures, effective myelination of neurons can also be demonstrated. This platform is being translated as well to the generation of the other glial cell types, allowing the derivation of patient-specific glial cells where to model disease-specific dysfunction. This methodology can be used for elucidating pathogenic pathways associated with neurodegeneration and to identify therapeutic targets susceptible of drug modulation, contributing to the development of novel and effective drugs for these devastating disorders.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Supported by PI18/01557 (to AG) and P18/1556 (to JV) grants from ISCiii of Spain co-financed by FEDER funds from European Union, and PI-0276-2018 grant (to JAGL) from Consejeria de Salud of Junta de Andalucia. JAGL held a postdoctoral contract from the I Research Plan Propio of the University of Malaga. CV and KE were supported by IWT-SBO-150031-iPSCAF and the Thierry Lathran Foundation grant – ALS-OL, and KN by FWO1166518

On the Hamilton-Jacobi Theory for Singular Lagrangian Systems

We develop a Hamilton-Jacobi theory for singular lagrangian systems using the Gotay-Nester-Hinds constraint algorithm. The procedure works even if the system has secondary constraints.Comment: 36 page

Current account sustainability in the US: What do we really know about its?

We revisit the debate on the sustainability of the current account dynamics in the US. Using the concept of sustainability as the ability to meet the long run intertemporal budget constraint, we test for unit roots in the US current account for the 1960-2004 period. We argue that there are several reasons to believe that the current account may follow a non-linear behaviour under the null of stationarity. This is confirmed by a set of non-linearity tests. We then fit an ESTAR model to the current account dynamics and reject the null of non-stationarity. Hence, we conclude in favour of sustainability. Furthermore, our results reveal that only for the period 1974-1992 we can find significant deviations of the current account from equilibrium and a slower speed of mean reversion

A revised distance to IRAS 16293−-2422 from VLBA astrometry of associated water masers

IRAS 16293-2422 is a very well studied young stellar system seen in projection towards the L1689N cloud in the Ophiuchus complex. However, its distance is still uncertain with a range of values from 120 pc to 180 pc. Our goal is to measure the trigonometric parallax of this young star by means of H$_2$O maser emission. We use archival data from 15 epochs of VLBA observations of the 22.2 GHz water maser line. By modeling the displacement on the sky of the H$_2$O maser spots, we derived a trigonometric parallax of $7.1\pm1.3$ mas, corresponding to a distance of $141_{-21}^{+30}$ pc. This new distance is in good agreement with recent values obtained for other magnetically active young stars in the L1689 cloud. We relate the kinematics of these masers with the outflows and the recent ejections powered by source A in the system.Comment: 14 pages, 6 tables, 8 figures. Accepted to be published in Astronomy \& Astrophysic

Optimized magnesium force field parameters for biomolecular simulations with accurate solvation, ion-binding, and water-exchange properties

Magnesium ions play an essential role in many vital processes. To correctly describe their interactions in molecular dynamics simulations, an accurate parametrization is crucial. Despite the importance and considerable scientific effort, current force fields based on the commonly used 12-6 Lennard-Jones interaction potential fail to reproduce a variety of experimental solution properties. In particular, no parametrization exists so far that simultaneously reproduces the solvation free energy and the distance to the water oxygens in the first hydration shell. Moreover, current Mg2+ force fields significantly underestimate the rate of water exchange leading to unrealistically slow exchange kinetics. In order to make progress in the development of improved models, we systematically optimize the Mg2+ parameters in combination with the TIP3P water model in a much larger parameter space than previously done. The results show that a long-ranged interaction potential and modified Lorentz-Berthelot combination rules allow us to accurately reproduce multiple experimental properties including the solvation free energy, the distances to the oxygens of the first hydration shell, the hydration number, the activity coefficient derivative in MgCl2 solutions, the self-diffusion coefficient, and the binding affinity to the phosphate oxygen of RNA. Matching this broad range of thermodynamic properties, we present two sets of optimal parameters: MicroMg yields water exchange on the microsecond timescale in agreement with experiments. NanoMg yields water exchange on the nanosecond timescale facilitating the direct observation of ion-binding events. As shown for the example of the add A-riboswitch, the optimized parameters correctly reproduce the structure of specifically bound ions and permit the de novo prediction of Mg2+-binding sites in biomolecular simulations