DDT - Drug Discovery Tool: a fast and intuitive graphics user interface for Docking and Molecular Dynamics analysis.

Abstract Motivation The ligand/protein binding interaction is typically investigated by docking and molecular dynamics (MD) simulations. In particular, docking-based virtual screening (VS) is used to select the best ligands from database of thousands of compounds, while MD calculations assess the energy stability of the ligand/protein binding complexes. Considering the broad use of these techniques, it is of great demand to have one single software that allows a combined and fast analysis of VS and MD results. With this in mind, we have developed the Drug Discovery Tool (DDT) that is an intuitive graphics user interface able to provide structural data and physico-chemical information on the ligand/protein interaction. Results DDT is designed as a plugin for the Visual Molecular Dynamics (VMD) software and is able to manage a large number of ligand/protein complexes obtained from AutoDock4 (AD4) docking calculations and MD simulations. DDT delivers four main outcomes: i) ligands ranking based on an energy score; ii) ligand ranking based on a ligands' conformation cluster analysis; iii) identification of the aminoacids forming the most occurrent interactions with the ligands; iv) plot of the ligands' center-of-mass coordinates in the Cartesian space. The flexibility of the software allows saving the best ligand/protein complexes using a number of user-defined options. Availability and implementation DDT_site_1 (alternative DDT_site_2); the DDT tutorial movie is available here. Supplementary information Supplementary data are available at Bioinformatics online

Going beyond diffServ in IP traffic classification

Quality of Service (QoS) management in IP networks today relies on static configuration of classes of service definitions and related forwarding priorities. Packets are actually classified according to the DiffServ architecture based on the RFC 4594, typically thanks to static configuration or filters matching packet features, at network access equipment. In this paper, we propose a dynamic classification procedure, referred to as Learning-powered DiffServ (L-DiffServ), able to detect the distinctive characteristics of traffic and to dynamically assign service classes to IP packets. The idea is to apply semi-unsupervised Machine Learning techniques, such as Linear Discriminant Analysis (LDA) and K-Means, with a proper customization to take into account the issues related to packet-level analysis, i.e. unbalanced distribution of traffic among classes and selection of proper IP header related features. The performance evaluation highlights that L-DiffServ is able to change dynamically the classification outcome, providing an higher number of classes than DiffServ. This last result represents the first step toward a more granular differentiation of IP traffic

A Methodology to Characterize Power Control Systems for Limiting Exposure to Electromagnetic Fields Generated by Massive MIMO Antennas

The fifth-generation (5G) New Radio (NR) cellular network has been launched recently. The assignment of new spectrum bands and the widespread use of Massive MIMO (MaMIMO) and beamforming techniques for better radio coverage are two major features of the new architecture. They imply both opportunities and challenges, one of the most daring one among the latter ones is the research for methods to assess human exposure to electromagnetic fields radiated by the base stations. The long-term time-varying behavior and spatial multiplexing feature of the MaMIMO antennas, along with the radio resource utilization and adoption of Time-Division Duplexing (TDD), requires that the assessment of exposure to electromagnetic fields radiated by 5G systems is based on a statistical approach that relies on the space and time distribution of the radiated power. That, in turn, is determined through simulations based on the actual maximum transmitted power - defined as the 95 th percentile of the empirical distribution obtained from historical data of radiated power - rather than on the nominal one. To ensure that exposure limits are never exceeded, a monitoring and control system (usually referred to as Power Lock (PL)) that limits the transmitted power can be used. In this paper we propose a methodology, independent from the specific technical solution implemented by the manufacturer, to characterize such control systems and determine their capability to limit the average power transmitted over a given time interval to a value that keeps the corresponding average exposure to electromagnetic fields below a specified value. Experimental results show the effectiveness of the methodology and that it can also be used to identify when the PL interacts with the higher levels of the MaMIMO system architecture

The earliest evidence for mechanically delivered projectile weapons in Europe

Microscopic analysis of backed lithic pieces from the Uluzzian technocomplex (45\u201340 thousand yr ago) at Grotta del Cavallo (southern Italy) reveals their use as mechanically delivered projectile weapons, attributed to anatomically modern humans. Use-wear and residue analyses indicate that the lithics were hunting armatures hafted with complex adhesives, while experimental and ethnographic comparisons support their use as projectiles. The use of projectiles conferred a hunting strategy with a higher impact energy and a potential subsistence advantage over other populations and specie

The GBAP1 pseudogene acts as a ceRNA for the glucocerebrosidase gene GBA by sponging miR-22-3p.

Mutations in the GBA gene, encoding lysosomal glucocerebrosidase, represent the major predisposing factor for Parkinson's disease (PD), and modulation of the glucocerebrosidase activity is an emerging PD therapy. However, little is known about mechanisms regulating GBA expression. We explored the existence of a regulatory network involving GBA, its expressed pseudogene GBAP1, and microRNAs. The high level of sequence identity between GBA and GBAP1 makes the pseudogene a promising competing-endogenous RNA (ceRNA), functioning as a microRNA sponge. After selecting microRNAs potentially targeting both transcripts, we demonstrated that miR-22-3p binds to and down-regulates GBA and GBAP1, and decreases their endogenous mRNA levels up to 70%. Moreover, over-expression of GBAP1 3'-untranslated region was able to sequester miR-22-3p, thus increasing GBA mRNA and glucocerebrosidase levels. The characterization of GBAP1 splicing identified multiple out-of-frame isoforms down-regulated by the nonsense-mediated mRNA decay, suggesting that GBAP1 levels and, accordingly, its ceRNA effect, are significantly modulated by this degradation process. Using skin-derived induced pluripotent stem cells of PD patients with GBA mutations and controls, we observed a significant GBA up-regulation during dopaminergic differentiation, paralleled by down-regulation of miR-22-3p. Our results describe the first microRNA controlling GBA and suggest that the GBAP1 non-coding RNA functions as a GBA ceRNA

Legal and other institutional aspects of groundwater governance

This chapter defines the linked concepts of groundwater governance and groundwater management, explaining how they differ from each other. Then, it describes the prevailing legal instruments for, and the institutional aspects of, groundwater management and governance

A Theoretical and Experimental Investigation on the Measurement of the Electromagnetic Field Level Radiated by 5G Base Stations

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