Analysis of Antidepressant-like Effects and Action Mechanisms of GSB-106, a Small Molecule,Affecting the TrkB Signaling

Induction of BDNF-TrkB signaling is associated with the action mechanisms of conventional and fast-acting antidepressants. GSB-106, developed as a small dimeric dipeptide mimetic of BDNF, was previously shown to produce antidepressant-like effects in the mouse Porsolt test, tail suspension test, Nomura water wheel test, in the chronic social defeat stress model and in the inflammation-induced model of depression. In the present study, we evaluated the effect of chronic per os administration of GSB-106 to Balb/c mice under unpredictable chronic mild stress (UCMS). It was observed for the first time that long term GSB-106 treatment (1 mg/kg, 26 days) during ongoing UCMS procedure ameliorated the depressive-like behaviors in mice as indicated by the Porsolt test. In addition, chronic per os administration of GSB-106 resulted in an increase in BDNF levels, which were found to be decreased in the prefrontal cortex and hippocampus of mice after UCMS. Furthermore, prolonged GSB-106 treatment was accompanied by an increase in the content of pTrkB^706/707 in the prefrontal cortex and by a pronounced increase in the level of pTrkB⁸¹⁶ in both studied brain structures of mice subjected to UCMS procedure. In summary, the present data show that chronic GSB-106 treatment produces an antidepressant-like effect in the unpredictable chronic mild stress model, which is likely to be associated with the regulation of the BDNF-TrkB signaling.     

Single-Dose P2 X4R Single-Chain Fragment Variable Antibody Permanently Reverses Chronic Pain in Male Mice

Non-opioid single-chain variable fragment (scFv) small antibodies were generated as pain-reducing block of P2X4R receptor (P2X4R). A panel of scFvs targeting an extracellular peptide sequence of P2X4R was generated followed by cell-free ribosome display for recombinant antibody selection. After three rounds of bio-panning, a panel of recombinant antibodies was isolated and characterized by ELISA, cross-reactivity analysis, and immunoblotting/immunostaining. Generated scFv antibodies feature binding activity similar to monoclonal antibodies but with stronger affinity and increased tissue penetrability due to their ~30% smaller size. Two anti-P2X4R scFv clones (95, 12) with high specificity and affinity binding were selected for in vivo testing in male and female mice with trigeminal nerve chronic neuropathic pain (FRICT-ION model) persisting for several months in untreated BALBc mice. A single dose of P2X4R scFv (4 mg/kg, i.p.) successfully, completely, and permanently reversed chronic neuropathic pain-like measures in male mice only, providing retention of baseline behaviors indefinitely. Untreated mice retained hypersensitivity, and developed anxiety- and depression-like behaviors within 5 weeks. In vitro P2X4R scFv 95 treatment significantly increased the rheobase of larger-diameter (>25 µm) trigeminal ganglia (TG) neurons from FRICT-ION mice compared to controls. The data support use of engineered scFv antibodies as non-opioid biotherapeutic interventions for chronic pain.     

Gas-Transport Characteristics of PdCu–Nb–PdCu Membranes Modified with Nanostructured Palladium Coating

A method for obtaining composite gas-diffusion PdCu–Nb–PdCu membranes modified with a nanostructured crystalline coating was developed to increase the performance of Nb-based membranes. A modifying functional layer with a controlled size and composition was synthesized by electrochemical deposition, which made it possible to determine a certain geometric shape for palladium nanocrystallites. Developed PdCu–Nb–PdCu membranes have demonstrated flux values up to 0.232 mmol s⁻¹ m⁻² in the processes of diffusion purification of hydrogen at 400 °C. A very significant difference in the hydrogen fluxes through the modified and non-modified composite PdCu–Nb–PdCu membranes reached 1.73 times at the lower threshold temperature of 300 °C. Cu doping of protective layer did not affect the selective properties of the membranes, which was confirmed by the obtained high selectivity values up to 1323, and made it possible to reduce the noble metal content. The research data indicate that the modification of the membrane surface significantly accelerates the hydrogen transfer process at sufficiently low temperatures due to the acceleration of dissociative–associative processes on the surface. The reported approach demonstrates new possibilities for creating productive and cost-efficient membranes based on niobium.     

Cubic spline approximation based on half-step discretization for 2D quasilinear elliptic equations

Abstract

We report a new cubic spline approximation based on half-step discretization of order 2 in y- and order 4 in x-directions, for 2D quasi-linear elliptic PDEs. We use only two extra half-step points in x-direction and a central point. The cubic spline method is directly obtained from the continuity of first derivative terms and is applicable to elliptic problems irrespective of coordinates, which is the main advantage of our work. The error analysis of a model problem is discussed in details. Some benchmark problems are solved in order to test the numerical stability and accuracy of the method.     

A typology of course of motion in simulated environments based on Bézier curve analysis

This paper proposes a novel method of analysing trajectories followed by people while they perform navigational tasks. The results indicate that modelling trajectories with Bézier curves provides a basis for the diagnosis of navigational patterns. The method offers five indicators: goodness of fit, average curvature, number of inflexion points, lengths of straight line segments, and area covered. Study results, obtained in a virtual environment show that these indicators carry important information about user performance, specifically spatial knowledge acquisition. Corina Sas is a Lecturer in the field of human–computer interaction in the Computing Department at Lancaster University. She holds bachelor degrees in Computer Science and Psychology and an M.A. in Industrial Psychology from Romania. She received her Ph.D. degree in Computer Science from University College Dublin in 2004. Her research interests include user modelling, adaptive systems, data mining, spatial cognition, user studies and individual differences. She has published in various journals and international conferences in these areas. Nikita Schmidt is a Postdoctoral Research Fellow at University College Dublin (UCD). He received his Ph.D. degree from UCD in 2004 and M.Sc. from St-Petersburg State University, Russia in 1994. His research interests include pervasive, ubiquitous and location-aware computing, embedded systems, hardware-close software development and tree-structured data. His work experience is a mix of industry and academia.     

An approach to surface retouching and mesh smoothing

In this paper, we discuss a novel, fast, practical algorithm for surface modification of geometric objects. A space-mapping technique is used to transform a given or damaged part of a surface into a different shape in a continuous manner. The proposed approach is used for surface-retouching and mesh-smoothing problems. The technique, in fact, is based on a local processing of polygonal data that can be applied to the fairing of 3D meshes. We consider shape transformation as a general type of operation for surface modification and attempt to approach the problem from a single point of view, namely, that of the space-mapping technique based on the implementation of radial-basis functions. Experimental results are included to demonstrate the functionality of our mesh-modeling tool.     

Study of the coupling between human head and cellular phone helical antennas

The interaction between normal-mode helical antennas and human head models is analyzed, using both a novel accurate semi-analytical method and finite-difference time-domain (FDTD) simulations. The semi-analytical method is based on the combination of Green's functions theory with the method of moments (Green/MoM) and is able to model arbitrarily shaped wire antennas radiating in the close proximity of layered lossy dielectric spheres representing simplified models of the human head. The purpose of the development of the Green/MoM technique is to provide a reliable tool for preliminary (worst case) estimation of human head exposure to the field generated by different antenna configurations with emphasis on the helical antenna, representing the most diffused antenna type used in modern cellular handsets. Furthermore, the accurate semi-analytical character of the Green/MoM technique permits the accuracy assessment of purely numerical techniques, such as the FDTD, which is currently the most widely used computational method in mobile communication dosimetric problems, since it allows modeling of anatomically based head models. After appropriate benchmarking, FDTD simulations are used to study the interaction between a heterogeneous anatomically correct model of the human head exposed to a normal-mode helix monopole operating at 1710 MHz mounted on the top of a metal box representing a realistic mobile communication terminal. The study of both canonical and realistic exposure problems includes computations of specific absorption rates (SARs) inside the human head, total power absorbed by the head and assessment of antenna performance. Emphasis is placed on the comparative dosimetric assessment between adults and children head models.     

Design and performance of asymmetric supported membranes for oxygen and hydrogen separation

Producing syngas and hydrogen from biofuels is a promising technology in the modern energy. In this work results of authors’ research aimed at design of supported membranes for oxygen and hydrogen separation are reviewed. Nanocomposites were deposited as thin layers on Ni–Al foam substrates. Oxygen separation membranes were tested in CH₄ selective oxidation/oxi-dry reforming. The hydrogen separation membranes were tested in C₂H₅OH steam reforming. High oxygen/hydrogen fluxes were demonstrated. For oxygen separation membranes syngas yield and methane conversion increase with temperature and contact time. For reactor with hydrogen separation membrane a good performance in ethanol steam reforming was obtained. Hydrogen permeation increases with ethanol inlet concentration, then a slight decrease is observed. The results of tests demonstrated the oxygen/hydrogen permeability promising for the practical application, high catalytic performance and a good thermochemical stability.