GABAB receptor ligands for the treatment of alcohol use disorder: preclinical and clinical evidence.

The present paper summarizes the preclinical and clinical studies conducted to define the "anti-alcohol" pharmacological profile of the prototypic GABAB receptor agonist, baclofen, and its therapeutic potential for treatment of alcohol use disorder (AUD). Numerous studies have reported baclofen-induced suppression of alcohol drinking (including relapse- and binge-like drinking) and alcohol reinforcing, motivational, stimulating, and rewarding properties in rodents and monkeys. The majority of clinical surveys conducted to date-including case reports, retrospective chart reviews, and randomized placebo-controlled studies-suggest the ability of baclofen to suppress alcohol consumption, craving for alcohol, and alcohol withdrawal symptomatology in alcohol-dependent patients. The recent identification of a positive allosteric modulatory binding site, together with the synthesis of in vivo effective ligands, represents a novel, and likely more favorable, option for pharmacological manipulations of the GABAB receptor. Accordingly, data collected to date suggest that positive allosteric modulators of the GABAB receptor reproduce several "anti-alcohol" effects of baclofen and display a higher therapeutic index (with larger separation-in terms of doses-between "anti-alcohol" effects and sedation)

Thermal transport in nanocrystalline graphene investigated by approach-to-equilibrium molecular dynamics simulations

Approach-to-equilibrium molecular dynamics simulations have been used to study thermal transport in nanocrystalline graphene sheets. Nanostructured graphene has been created using an iterative process for grain growth from initial seeds with random crystallographic orientations. The resulting cells have been characterized by the grain size distribution based on the radius of gyration, by the number of atoms in each grain and by the number of atoms in the grain boundary. Introduction of nanograins with a radius of gyration of 1 nm has led to a significant reduction in the thermal conductivity to 3% of the value in single crystalline graphene. Analysis of the vibrational density of states has revealed a general reduction of the vibrational intensities and broadening of the peaks when nanograins are introduced which can be attributed to phonon scattering in the boundary layer. The thermal conductivity has been evaluated as a function of the grain size with increasing size up to 14 nm and it has been shown to follow an inverse rational function. The grain size dependent thermal conductivity could be approximated well by a function where transport is described by a connection in series of conducting elements and resistances (at boundaries).Comment: 9 pages, 9 figure

Regular Moebius transformations of the space of quaternions

Let H be the real algebra of quaternions. The notion of regular function of a quaternionic variable recently presented by G. Gentili and D. C. Struppa developed into a quite rich theory. Several properties of regular quaternionic functions are analogous to those of holomorphic functions of one complex variable, although the diversity of the quaternionic setting introduces new phenomena. This paper studies regular quaternionic transformations. We first find a quaternionic analog to the Casorati-Weierstrass theorem and prove that all regular injective functions from H to itself are affine. In particular, the group Aut(H) of biregular functions on H coincides with the group of regular affine transformations. Inspired by the classical quaternionic linear fractional transformations, we define the regular fractional transformations. We then show that each regular injective function from the Alexandroff compactification of H to itself is a regular fractional transformation. Finally, we study regular Moebius transformations, which map the unit ball B onto itself. All regular bijections from B to itself prove to be regular Moebius transformations.Comment: 12 page

Advanced microbial check valve development

A flight certified assembly identified as a Microbial Check Valve (MCV) was developed and tested. The MCV is a canister packed with an iodinated anionic exchange resin. The device is used to destroy organisms in a water stream as the water passes through the device. The device is equally effective for fluid flow in either direction and its primary method of organism removal is killing rather than filtering. The MCV was successfully developed for the space shuttle to: disinfect fuel cell water; and prevent back contamination of the stored potable water supply. One version of the device consists of a high residual iodinated resin bed that imparts approximately 2 ppm of iodine to the fuel cell water as it flows to the potable water tanks. A second version of the device consists of a low residual iodinated resin bed. One of these low residual beds is located at each use port in the potable water system for the dual purpose of removing some iodine from the potable water as it is dispensed and also to prevent back contamination of the potable supply

Schur functions and their realizations in the slice hyperholomorphic setting

we start the study of Schur analysis in the quaternionic setting using the theory of slice hyperholomorphic functions. The novelty of our approach is that slice hyperholomorphic functions allows to write realizations in terms of a suitable resolvent, the so called S-resolvent operator and to extend several results that hold in the complex case to the quaternionic case. We discuss reproducing kernels, positive definite functions in this setting and we show how they can be obtained in our setting using the extension operator and the slice regular product. We define Schur multipliers, and find their co-isometric realization in terms of the associated de Branges-Rovnyak space

Carlhintzeite, Ca2AlF7•H2O, from the Gigante granitic pegmatite, Córdoba province, Argentina: Description and crystal structure

Carlhintzeite, Ca2AlF7•H2O, has been found at the Gigante pegmatite, Punilla Department, Córdoba Province, Argentina. It occurs as colourless prismatic crystals up to 0.8 mm long, ubiquitously twinned on {001}. Electron microprobe analyses provided the empirical formula Ca1.98Al1.02F6.24(OH) 0.76•H1.62O. A crystal fragment used for the collection of structure data provided the triclinic, C1 cell: a = 9.4227(4), b = 6.9670(5), c = 9.2671(7) Å, α = 90.974(6), β = 104.802(5), γ = 90.026(6)°, V = 558.08(7) Å3 and Z = 4. The crystal structure, solved by direct methods and refined to R 1 = 0.0322 for 723 Fo > 4σF reflections, is made up of linkages of AlF6 octahedra, CaF8 polyhedra and CaF 6(H2O)2 polyhedra. The AlF6 octahedra are isolated from one another, but share polyhedral elements with Ca polyhedra. Most notably, the Al1 octahedron shares trans faces with two CaF 8 polyhedra and the Al2 octahedron shares trans edges with two CaF6(H2O)2 polyhedra. The linkage of the Ca polyhedra alone can be described as a framework in which edge-sharing chains along b are cross-linked by edge-sharing. Edge-sharing chains of Ca polyhedra along b in the carlhintzeite structure are similar to those along c in the structures of gearksutite, CaAlF4(OH)•(H2O), and prosopite, CaAl2F4(OH)4. © 2010 Mineralogical Society.Fil: Kampf, A. R.. Natural History Museum of Los Angeles County; Estados UnidosFil: Colombo, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Ciencias de la Tierra. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones en Ciencias de la Tierra; ArgentinaFil: González Del Tánago, J.. Universidad Complutense de Madrid; Españ

Discrete Approximations of a Controlled Sweeping Process

The paper is devoted to the study of a new class of optimal control problems governed by the classical Moreau sweeping process with the new feature that the polyhe- dral moving set is not fixed while controlled by time-dependent functions. The dynamics of such problems is described by dissipative non-Lipschitzian differential inclusions with state constraints of equality and inequality types. It makes challenging and difficult their anal- ysis and optimization. In this paper we establish some existence results for the sweeping process under consideration and develop the method of discrete approximations that allows us to strongly approximate, in the W^{1,2} topology, optimal solutions of the continuous-type sweeping process by their discrete counterparts