Search results for "Aide"
showing 10 items of 1461 documents
Identification of estrogen receptor α ligands with virtual screening techniques.
2016
Utilization of computer-aided molecular discovery methods in virtual screening (VS) is a cost-effective approach to identify novel bioactive small molecules. Unfortunately, no universal VS strategy can guarantee high hit rates for all biological targets, but each target requires distinct, fine-tuned solutions. Here, we have studied in retrospective manner the effectiveness and usefulness of common pharmacophore hypothesis, molecular docking and negative image-based screening as potential VS tools for a widely applied drug discovery target, estrogen receptor α (ERα). The comparison of the methods helps to demonstrate the differences in their ability to identify active molecules. For example,…
Discovery and Biological Evaluation of Potent and Selective N-Methylene Saccharin-Derived Inhibitors for Rhomboid Intramembrane Proteases
2017
Rhomboids are intramembrane serine proteases and belong to the group of structurally and biochemically most comprehensively characterized membrane proteins. They are highly conserved and ubiquitously distributed in all kingdoms of life and function in a wide range of biological processes, including epidermal growth factor signaling, mitochondrial dynamics, and apoptosis. Importantly, rhomboids have been associated with multiple diseases, including Parkinson's disease, type 2 diabetes, and malaria. However, despite a thorough understanding of many structural and functional aspects of rhomboids, potent and selective inhibitors of these intramembrane proteases are still not available. In this …
Recent advances on CDK inhibitors: An insight by means of in silico methods
2017
The cyclin dependent kinases (CDKs) are a small family of serine/threonine protein kinases that can act as a potential therapeutic target in several proliferative diseases, including cancer. This short review is a survey on the more recent research progresses in the field achieved by using in silico methods. All the "armamentarium" available to the medicinal chemists (docking protocols and molecular dynamics, fragment-based, de novo design, virtual screening, and QSAR) has been employed to the discovery of new, potent, and selective inhibitors of cyclin dependent kinases. The results cited herein can be useful to understand the nature of the inhibitor-target interactions, and furnish an ins…
QuBiLS-MAS, open source multi-platform software for atom- and bond-based topological (2D) and chiral (2.5D) algebraic molecular descriptors computati…
2017
Background In previous reports, Marrero-Ponce et al. proposed algebraic formalisms for characterizing topological (2D) and chiral (2.5D) molecular features through atom- and bond-based ToMoCoMD-CARDD (acronym for Topological Molecular Computational Design-Computer Aided Rational Drug Design) molecular descriptors. These MDs codify molecular information based on the bilinear, quadratic and linear algebraic forms and the graph-theoretical electronic-density and edge-adjacency matrices in order to consider atom- and bond-based relations, respectively. These MDs have been successfully applied in the screening of chemical compounds of different therapeutic applications ranging from antimalarials…
Blocking oestradiol synthesis pathways with potent and selective coumarin derivatives
2018
A comprehensive set of 3-phenylcoumarin analogues with polar substituents was synthesised for blocking oestradiol synthesis by 17-b-hydroxysteroid dehydrogenase 1 (HSD1) in the latter part of the sulphatase pathway. Five analogues produced 62% HSD1 inhibition at 5 mM and, furthermore, three of them produced 68% inhibition at 1 mM. A docking-based structure-activity relationship analysis was done to determine the molecular basis of the inhibition and the cross-reactivity of the analogues was tested against oestrogen receptor, aromatase, cytochrome P450 1A2, and monoamine oxidases. Most of the analogues are only modestly active with 17-b-hydroxysteroid dehydrogenase 2 – a requirement for lowe…
An Efficient Cooperative Smearing Technique for Degraded Historical Documents Images Segmentation
2020
Segmentation is one of the critical steps in historical document image analysis systems that determines the quality of the search, understanding, recognition and interpretation processes. It allows isolating the objects to be considered and separating the regions of interest (paragraphs, lines, words and characters) from other entities (figures, graphs, tables, etc.). This stage follows the thresholding, which aims to improve the quality of the document and to extract its background from its foreground, also for detecting and correcting the skew that leads to redress the document. Here, a hybrid method is proposed in order to locate words and characters in both handwritten and printed docu…
The moral work of becoming a professional
2021
Abstract In contemporary working life, art-based initiatives are increasingly used in organizational training and development. For artists, this has created new employment opportunities as creative entrepreneurs who provide specialist services for workplaces. In this article, we study the dynamics of such encounters through the narrated accounts of training professionals. Our data come from a professional mentoring program where the working pairs of artists and consultants shared stories about their customer projects. By using conversation analysis as a method, we analyze the way stories are interactionally accomplished in peer group sessions of the program. In particular, we analyze how pa…
Raising awareness of multilingualism as lived – in the context of teaching English as a foreign language
2020
Tässä artikkelissa esitellään mahdollisuuksia herätellä kielen oppijoiden kieli- ja kulttuuritietoisuutta. Esitellyt mahdollisuudet pohjautuvat 24 empiirisen tutkimuksen kriittiseen arviointiin. Tutkimuksissa käytettiin kuvataiteisiin pohjautuvia visuaalisia menetelmiä. Tällaisten menetelmien avulla on mahdollista pohtia aikaisempia kokemuksia tai kuvitella tulevaisuutta ja näin reflektoida erilaisia monikielisyyden kokemuksia. Näitä voivat olla identiteetin rakentumiseen liittyvät kysymykset, käsitykset eri kielten käytöstä tai tulevaisuuden unelmat. Arviointimme perusteella esitämme, että niitä tehtäviä, joita käytettiin tutkimuksissa, voidaan soveltaa eri tavoin erilaisille vieraan kiele…
Empowerment as an affective-discursive technology in contemporary capitalism: insights from a play
2019
Over recent years, an increasing body of research in social and cultural studies has investigated the contemporary processes of social change from the point of view of affective capitalism. In this article, we take under scrutiny one of its technologies, namely, empowerment, by which we mean a state characterised by feelings of strength, ability and power that enable agency. More specifically, we investigate the way empowerment is presented in a cultural product, a play that tells a story about personnel training in a factory, shown in a city theatre in Finland. By linking recent theorisation of affective capitalism with an investigation of the intertextual and interdiscursive relations of …
Nonlinear femtosecond pulse propagation in an all-solid photonic bandgap fiber
2009
Nonlinear femtosecond pulse propagation in an all-solid photonic bandgap fiber is experimentally and numerically investigated. Guiding light in such fiber occurs via two mechanisms: photonic bandgap in the central silica core or total internal reflection in the germanium doped inclusions. By properly combining spectral filtering, dispersion tailoring and pump coupling into the fiber modes, we experimentally demonstrate efficient supercontinuum generation with controllable spectral bandwidth.