Identifying new isatin derivatives with GSK-3 inhibition capacity through molecular docking and bioassays

The semi-synthesis of 11 isatin derivatives was achieved through bimolecular nucleophilic substitution and click chemistry. Seven new compounds were obtained. All chemical structures were determined by infrared spectroscopy (IR), nuclear magnetic resonance spectrometry (NMR) and high-resolution mass spectrometry (HRMS) data. These derivatives were evaluated for their anti-GSK-3 activity and all isatin derivatives (N-alkyl and 1,2,3-triazolic) exhibited strong inhibitory activity, with 2b and 4h exhibiting remarkable potency. In addition, docking studies were performed with 2b and 2e models to unravel the molecular mechanism underlying the polar interactions on the GSK-3 ATP-binding site.This study was funded by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brasil (CAPES), Finance Code 001, by the National Council of Scientific and Technological Development (CNPq) and Foundation of Support to Research and Innovation of Espírito Santo (FAPES PPE-Agro No. 76418880/16). We also would like to acknowledge INCTBioNat (CNPq 465637/2014-0) for additional support and NCQP-UFES, as well as the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2019 unit and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020, Programa Operacional Regional do Norte. L. R. R. also acknowledges her sabbatical leave fellowship (SFRH/BSAB/142991/2018) funded by FCT. D. F. is recipient of a doctoral fellowship (call NORTE-69-2015-15) funded by the European Social Fund under the scope of Norte2020, Programa Operacional Regional do Norte.info:eu-repo/semantics/publishedVersio

Declining partisan representation at the sub-national level: assessing and explaining the strengthening of local lists in Italian municipalities (1995–2014)

In Western democracies political representation at the national level is still dominated by (old and new) political parties. This article shows that, instead, the representative role of parties may have declined at the local level. In Italy, for instance, the average share of municipal seats held by non-partisan councillors has almost tripled in the last 20 years. By using an original data set, this article classifies different types of Italian local lists, assesses their relationship with traditional parties and explains territorial variation in their success. The results suggest that local lists have become substantially stronger in small municipalities, in regions characterised by weak or declining political subcultures and where regionalist parties are absent or irrelevant. Finally, contrary to the expectation that declining partisanship is linked to modernisation processes and direct civic engagement, local lists have achieved their best results in the less developed areas of the country

Assessment, control, and prevention of microbiological and chemical hazards in seasonal swimming pools of the Versilia district (Tuscany, central Italy).

Abstract Although in Europe the quality of swimming pools (SPs) is dictated by regulations, microbiological and chemical hazards are described in the literature. Environmental bacteria or toxic disinfection by-product (DBP) compounds may indeed be recovered in waters even after disinfection. We evaluated the water quality from 26 outdoor seasonal SPs of the Versilia district, according to requirements of Regional Decree 54R/2015. In spring 2017, supply and reinstatement waters were collected after shock hyperchlorination (10 mg/L) while in summertime, a second sampling of waters before entering the pools, as well as in the pools, was performed after SPs were open to the public. In all samples, microbiological and chemical parameters were determined as defined by Directive 98/83/EC and the Italian Health Ministry. Microbiological data were within suggested limits. The first chemical analyses showed that in 35% of the feeding-pool seawater samples, the halogenated organic compounds were higher than the maximum permissible concentrations (30 μg/L). Pool waters were then dechlorinated and re-treated with hydrogen peroxide (10 mg/L) to ensure the abatement of DBPs (from 164 ± 107 to 0.9 ± 0.8 μg/L; p = 0.002). Results highlighted the need of self-controlled procedures for the SPs waters to prevent waterborne diseases and suggested hydrogen peroxide as the most appropriate disinfection method

Bonding of the Inner Tracker Silicon Microstrip Modules

Microbonding of the CMS Tracker Inner Barrel (TIB) and Tracker Inner Disks (TID) modules was shared among six different Italian Institutes. The organization devised and the infrastructure deployed to handle this task is illustrated. Microbonding specifications and procedures for the different types of TIB and TID modules are given. The tooling specially designed and developed for these types of modules is described. Experience of production is presented. Attained production rates are given. An analysis of the microbonding quality achieved is presented, based on bond strengths measured in sample bond pull tests as well as on rates of bonding failures. Italian Bonding Centers routinely performed well above minimum specifications and a very low global introduced failure rate, at the strip level, of only $\sim$0.015 \% is observed

The Belle II SVD detector

The Silicon Vertex Detector (SVD) is one of the main detectors in the Belle II experiment at KEK, Japan. In combination with a pixel detector, the SVD determines precise decay vertex and low-momentum track reconstruction. The SVD ladders are being developed at several institutes. For the development of the tracking algorithm as well as the performance estimation of the ladders, beam tests for the ladders were performed. We report an overview of the SVD development, its performance measured in the beam test, and the prospect of its assembly and commissioning until installation

Performance studies of the Belle II Silicon Vertex Detector with data taken at the DESY test beam in April 2016

Belle II is a multipurpose detector currently under construction which will be operated at the next generation B-factory SuberKEKB in Japan. Its main devices for the vertex reconstruction are the Silicon Vertex Detector (SVD) and the Pixel Detector (PXD). In April 2016 a sector of the Belle II SVD and PXD have been tested in a beam of high energetic electrons at the test beam facility at DESY Hamburg (Germany). We report here the results for the hit efficiency estimation and the measurement of the resolution for the Belle II silicon vertex etector. We find that the hit efficiencies are on average above 99.5% and that the measured resolution is within the expectations

Performance studies of the Belle II Silicon Vertex Detector with data taken at the DESY test beam in April 2016

Belle II is a multipurpose detector currently under construction which will be operated at the next generation B-factory SuberKEKB in Japan. Its main devices for the vertex reconstruction are the Silicon Vertex Detector (SVD) and the Pixel Detector (PXD). In April 2016 a sector of the Belle II SVD and PXD have been tested in a beam of high energetic electrons at the test beam facility at DESY Hamburg (Germany). We report here the results for the hit efficiency estimation and the measurement of the resolution for the Belle II silicon vertex etector. We find that the hit efficiencies are on average above 99.5% and that the measured resolution is within the expectations

Belle-II VXD radiation monitoring and beam abort with sCVD diamond sensors

The Belle-II VerteX Detector (VXD) has been designed to improve the performances with respect to Belle and to cope with an unprecedented luminosity of View the MathML source8 71035cm 122s 121 achievable by the SuperKEKB. Special care is needed to monitor both the radiation dose accumulated throughout the life of the experiment and the instantaneous radiation rate, in order to be able to promptly react to sudden spikes for the purpose of protecting the detectors. A radiation monitoring and beam abort system based on single-crystal diamond sensors is now under an active development for the VXD. The sensors will be placed in several key positions in the vicinity of the interaction region. The severe space limitations require a challenging remote readout of the sensors

Belle II silicon vertex detector (SVD)

The Belle II experiment at the SuperKEKB collider in Japan will operate at an unprecedented luminosity of 8 71035 cm 122s 121, about 40 times larger than its predecessor, Belle. Its vertex detector is composed of a two-layer DEPFET pixel detector (PXD) and a four layer double-sided silicon microstrip detector (SVD). To achieve a precise decay-vertex position determination and excellent low-momentum tracking under a harsh background condition and high trigger rate of 10 kHz, the SVD employs several innovative techniques. In order to minimize the parasitic capacitance in the signal path, 1748 APV25 ASIC chips, which read out signal from 224 k strip channels, are directly mounted on the modules with the novel Origami concept. The analog signal from APV25 are digitized by a flash ADC system, and sent to the central DAQ as well as to online tracking system based on SVD hits to provide region of interests to the PXD for reducing the latter\u2019s data size to achieve the required bandwidth and data storage space. Furthermore, the state-of-the-art dual phase CO2 cooling solution has been chosen for a combined thermal management of the PXD and SVD system. In this proceedings, we present key design principles, module construction and integration status of the Belle II SVD

Design, construction, and test of the Gas Pixel Detectors for the IXPE mission

Due to be launched in late 2021, the Imaging X-Ray Polarimetry Explorer (IXPE) is a NASA Small Explorer mission designed to perform polarization measurements in the 2-8 keV band, complemented with imaging, spectroscopy and timing capabilities. At the heart of the focal plane is a set of three polarization-sensitive Gas Pixel Detectors (GPD), each based on a custom ASIC acting as a charge-collecting anode. In this paper we shall review the design, manufacturing, and test of the IXPE focal-plane detectors, with particular emphasis on the connection between the science drivers, the performance metrics and the operational aspects. We shall present a thorough characterization of the GPDs in terms of effective noise, trigger efficiency, dead time, uniformity of response, and spectral and polarimetric performance. In addition, we shall discuss in detail a number of instrumental effects that are relevant for high-level science analysis -- particularly as far as the response to unpolarized radiation and the stability in time are concerned.Comment: To be published in Astroparticle Physic