Aquaporin-4-dependent K(+) and water transport modeled in brain extracellular space following neuroexcitation.

Potassium (K(+)) ions released into brain extracellular space (ECS) during neuroexcitation are efficiently taken up by astrocytes. Deletion of astrocyte water channel aquaporin-4 (AQP4) in mice alters neuroexcitation by reducing ECS [K(+)] accumulation and slowing K(+) reuptake. These effects could involve AQP4-dependent: (a) K(+) permeability, (b) resting ECS volume, (c) ECS contraction during K(+) reuptake, and (d) diffusion-limited water/K(+) transport coupling. To investigate the role of these mechanisms, we compared experimental data to predictions of a model of K(+) and water uptake into astrocytes after neuronal release of K(+) into the ECS. The model computed the kinetics of ECS [K(+)] and volume, with input parameters including initial ECS volume, astrocyte K(+) conductance and water permeability, and diffusion in astrocyte cytoplasm. Numerical methods were developed to compute transport and diffusion for a nonstationary astrocyte-ECS interface. The modeling showed that mechanisms b-d, together, can predict experimentally observed impairment in K(+) reuptake from the ECS in AQP4 deficiency, as well as altered K(+) accumulation in the ECS after neuroexcitation, provided that astrocyte water permeability is sufficiently reduced in AQP4 deficiency and that solute diffusion in astrocyte cytoplasm is sufficiently low. The modeling thus provides a potential explanation for AQP4-dependent K(+)/water coupling in the ECS without requiring AQP4-dependent astrocyte K(+) permeability. Our model links the physical and ion/water transport properties of brain cells with the dynamics of neuroexcitation, and supports the conclusion that reduced AQP4-dependent water transport is responsible for defective neuroexcitation in AQP4 deficiency

Continuous variable entanglement measurement without phase locking

A new simple entanglement measurement method is proposed for the bright EPR beams generated from a non-degenerate optical parametric amplifier operating at deamplification. Due to the output signal and idler modes are frequency degenerate and in phase, the needed phase shift of interference for the measurement of the correlated phase quadratures and anti-correlated amplitude quadratures can be accomplished by a quarter-wave plate and a half wave plate without separating the signal and idler beam. Therefore, phase locking and local oscillators are avoided.Comment: 8 pages,3 figure

Greatly attenuated experimental autoimmune encephalomyelitis in aquaporin-4 knockout mice

<p>Abstract</p> <p>Background</p> <p>The involvement of astrocyte water channel aquaporin-4 (AQP4) in autoimmune diseases of the central nervous system has been suggested following the identification of AQP4 autoantibodies in neuromyelitis optica, an inflammatory demyelinating disease.</p> <p>Results</p> <p>We investigated the involvement of AQP4 in disease severity in an established mouse model of experimental autoimmune encephalomyelitis (EAE) produced by immunization with myelin oligodendrocyte glycoprotein (MOG_35–55) peptide. EAE was remarkably attenuated in AQP4 null mice compared to identically treated wildtype mice. Whereas most wildtype mice developed progressive tail and hindlimb paralysis, clinical signs were virtually absent in AQP4 null mice. Brain and spinal cords from AQP1 null mice showed greatly reduced mononuclear cell infiltration compared to wildtype mice, with relatively little myelin loss and axonal degeneration.</p> <p>Conclusion</p> <p>The reduced severity of autoimmune encephalomyelitis in AQP4 deficiency suggests AQP4 as a novel determinant in autoimmune inflammatory diseases of the central nervous system and hence a potential drug target.</p

Density-Matrix Algorithm for Phonon Hilbert Space Reduction in the Numerical Diagonalization of Quantum Many-Body Systems

Combining density-matrix and Lanczos algorithms we propose a new optimized phonon approach for finite-cluster diagonalizations of interacting electron-phonon systems. To illustrate the efficiency and reliability of our method, we investigate the problem of bipolaron band formation in the extended Holstein Hubbard model.Comment: 14 pages, 6 figures, Workshop on High Performance Computing in Science and Engineering, Stuttgart 200

Nonlinear Rheology of Unentangled Polymer Melts Reinforced with High Concentration of Rigid Nanoparticles

A scaling model is presented to analyze the nonlinear rheology of unentangled polymer melts filled with high concentration of small spherical particles. Assuming the majority of chains to be reversibly adsorbed to the surface of the particles, we show that the emergence of nonlinearity in the viscoelastic response of the composite system subjected to a 2D shear flow results from stretching of the adsorbed chains and increasing desorption rate of the adsorbed segments due to the imposed deformation. The steady-state shear viscosity of the mixture in nonlinear shear thinning regime follows the power lawwhereis the applied shear rate. At large strain amplitude γ 0, the storage and loss moduli in strain sweep tests scale asandrespectively

Corticomuscular coherence analysis on the static and dynamic tasks of hand movement

The synchronization between cortical motor and muscular activity can be revealed by corticomuscular coherence (CMC). This paper designed two neuromuscular activity paradigms of hand movement, i.e. static gripping task and dynamic finger moving task. The electroencephalography (EEG) from C3 and C4 channels and the surface electromyography (sEMG) from the flexor digitorum superficialis were collected simultaneously from 4 male and 4 female right-handed healthy young subjects. For the static griping task, CMCs during low-level forces under 4%, 8%, and 16% MVC (Maximal Voluntary Contraction) were investigated by using magnitude squared coherence calculated from EEGs and sEMGs. For the dynamic finger moving task, the time-frequency domain analysis was used to process dynamic data of temporary action in a period of 2 seconds and get the latency of the maximum CMC. The results of this study indicated that the force increasing within the low-level range in static task is associated with the enhanced CMC. The maximum amplitude of CMC occurred about 0.3–0.5s after the onset of hand movement. Subjects showed significant CMC performance both in static and dynamic task of hand movement.published_or_final_versio

Neuromyelitis optica IgG and natural killer cells produce NMO lesions in mice without myelin loss.

The pathogenesis of neuromyelitis optica (NMO) involves targeting of NMO-immunoglobulin G (NMO-IgG) to aquaporin-4 (AQP4) on astrocytes in the central nervous system. Prior work provided evidence for complement-dependent cytotoxicity (CDC) in NMO lesion development. Here, we show that antibody-dependent cellular cytotoxicity (ADCC), in the absence of complement, can also produce NMO-like lesions. Antibody-dependent cellular cytotoxicity was produced in vitro by incubation of mouse astrocyte cultures with human recombinant monoclonal NMO-IgG and human natural killer cells (NK-cells). Injection of NMO-IgG and NK-cells in mouse brain caused loss of AQP4 and GFAP, two characteristic features of NMO lesions, but little myelin loss. Lesions were minimal or absent following injection of: (1) control (non-NMO) IgG with NK-cells; (2) NMO-IgG and NK-cells in AQP4-deficient mice; or (3) NMO-IgG and NK-cells in wild-type mice together with an excess of mutated NMO-IgG lacking ADCC effector function. NK-cells greatly exacerbated NMO lesions produced by NMO-IgG and complement in an ex vivo spinal cord slice model of NMO, causing marked myelin loss. NMO-IgG can thus produce astrocyte injury by ADCC in a complement-independent and dependent manner, suggesting the potential involvement of ADCC in NMO pathogenesis

Acute respiratory distress syndrome: new definition, current and future therapeutic options.

Since acute respiratory distress syndrome (ARDS) was first described in 1967 there has been large number of studies addressing its pathogenesis and therapies. Despite this intense research activity, there are very few effective therapies for ARDS other than the use of lung protection strategies. This lack of therapeutic modalities is not only related to the complex pathogenesis of this syndrome but also the insensitive and nonspecific diagnostic criteria to diagnose ARDS. This review article will summarize the key features of the new definition of ARDS, and provide a brief overview of innovative therapeutic options that are being assessed in the management of ARDS

Reliability and time-to-failure bounds for discrete-time constrained Markov jump linear systems

[EN] This paper presents a methodology to obtain a guaranteed-reliability controller for constrained linear sys- tems, which switch between different modes according to a Markov chain (Markov jump linear systems). Inside the classical maximal robust controllable set, there is 100% guarantee of never violating constraints at future time. However, outside such set, some sequences might make hitting constraints unavoidable for some disturbance realisations. A guaranteed-reliability controller based on a greedy heuristic approach was proposed in an earlier work for disturbance-free, robustly stabilisable Markov jump linear systems. Here, extensions are presented by, &#64257;rst, considering bounded disturbances and, second, presenting an iterative algorithm based on dynamic programming. In non-stabilisable systems, reliability is zero; therefore, prior results cannot be applied; in this case, optimisation of a mean-time-to-failure bound is proposed, via minor algorithm modi&#64257;cations. Optimality can be proved in the disturbance-free, &#64257;nitely generated case.The authors gratefully acknowledge the financial support of Spanish MINECO (DPI2011-27845-C02-01, FPU12/02107) and Generalitat Valenciana (PrometeoII/2013/004).Hernandez-Mejias, MA.; Sala, A. (2017). Reliability and time-to-failure bounds for discrete-time constrained Markov jump linear systems. International Journal of Robust and Nonlinear Control. 27:1773-1791. https://doi.org/10.1002/rnc.3635S177317912