14 resultados para ligand-based virtual screening


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Dissertation submitted in partial fulfillment of the requirements for the Degree of Master of Science in Geospatial Technologies.

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J Biol Inorg Chem. 2008 Jun;13(5):737-53. doi: 10.1007/s00775-008-0359-6

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Dissertação para obtenção do Grau de Doutor em Química, especialidade Química Orgânica

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The paper will present the central discourse of the knowledge-based society. Already in the 1960s the debate of the industrial society already raised the question whether there can be considered a paradigm shift towards a knowledge-based society. Some prominent authors already foreseen ‘knowledge’ as the main indicator in order to displace ‘labour’ and ‘capital’ as the main driving forces of the capitalistic development. Today on the political level and also in many scientific disciplines the assumption that we are already living in a knowledge-based society seems obvious. Although we still do not have a theory of the knowledge-based society and there still exist a methodological gap about the empirical indicators, the vision of a knowledge-based society determines at least the perception of the Western societies. In a first step the author will pinpoint the assumptions about the knowledge-based society on three levels: on the societal, on the organisational and on the individual level. These assumptions are relied on the following topics: a) The role of the information and communication technologies; b) The dynamic development of globalisation as an ‘evolutionary’ process; c) The increasing importance of knowledge management within organisations; d) The changing role of the state within the economic processes. Not only the differentiation between the levels but also the revision of the assumptions of a knowledge-based society will show that the ‘topics raised in the debates’ cannot be considered as the results of a profound societal paradigm shift. However what seems very impressive is the normative and virtual shift towards a concept of modernity, which strongly focuses on the role of technology as a driving force as well as on the global economic markets, which has to be accepted. Therefore – according to the official debate - the successful adaptation of these processes seems the only way to meet the knowledge-based society. Analysing the societal changes on the three levels, the label ‘knowledge-based society’ can be seen critically. Therefore the main question of Theodor W. Adorno during the 16th Congress of Sociology in 1968 did not loose its actuality. Facing the societal changes he asked whether we are still living in the industrial society or already in a post-industrial state. Thinking about the knowledge-based society according to these two options, this exercise would enrich the whole debate in terms of social inequality, political, economic exclusion processes and at least the power relationship between social groups.

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This paper appears in International Journal of Projectics. Vol 4(1), pp. 39-49

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Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina

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Web 2.0 software in general and wikis in particular have been receiving growing attention as they constitute new and powerful tools, capable of supporting information sharing, creation of knowledge and a wide range of collaborative processes and learning activities. This paper introduces briefly some of the new opportunities made possible by Web 2.0 or the social Internet, focusing on those offered by the use of wikis as learning spaces. A wiki allows documents to be created, edited and shared on a group basis; it has a very easy and efficient markup language, using a simple Web browser. One of the most important characteristics of wiki technology is the ease with which pages are created and edited. The facility for wiki content to be edited by its users means that its pages and structure form a dynamic entity, in permanent evolution, where users can insert new ideas, supplement previously existing information and correct errors and typos in a document at any time, up to the agreed final version. This paper explores wikis as a collaborative learning and knowledge-building space and its potential for supporting Virtual Communities of Practice (VCoPs). In the academic years (2007/8 and 2008/9), students of the Business Intelligence module at the Master's programme of studies on Knowledge Management and Business Intelligence at Instituto Superior de Estatistica e Gestao de Informacao of the Universidade Nova de Lisboa, Portugal, have been actively involved in the creation of BIWiki - a wiki for Business Intelligence in the Portuguese language. Based on usage patterns and feedback from students participating in this experience, some conclusions are drawn regarding the potential of this technology to support the emergence of VCoPs; some provisional suggestions will be made regarding the use of wikis to support information sharing, knowledge creation and transfer and collaborative learning in Higher Education.

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Dissertação para obtenção do Grau de Doutor em Bioquímica – Ramo Bioquímica Estrutural

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Dissertação para obtenção do Grau de Mestrado em Engenharia de Informática

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Dissertação para obtenção do Grau de Mestre em Engenharia Electrotécnica e de Computadores

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Dissertação para obtenção do Grau de Doutor em Química Sustentável

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This work aimed at the development of a (bio)polymeric monolithic support for biopharmaceuticals purification and/or capture. For that, it was assured that functional groups on its surface were ready to be involved in a plethora of chemical reactions for incorporation of the desired and most suitable ligand. Using cryogelation as preparation method a screening on multiple combinations of materials was performed in order to create a potentially efficient support with the minimal footprint, i.e. a monolithic support with reasonable mechanical properties, highly permeable, biocompatible, ready to use, with gravitational performance and minimal unspecific interactions towards the target molecules, but also biodegradable and produced from renewable materials. For the pre-selection all monoliths were characterized physico-chemically and morphologically; one agarose-based and two chitosan-based monoliths were then subjected to further characterizations before and after their modification with magnetic nanoparticles. These three specimens were finally tested towards adenovirus and the recovery reached 84% for the chitosan-GMA plain monolith prepared at -80°C. Monoliths based on chitosan and PVA were prepared in the presence and absence of magnetic particles, and tested for the isolation of GFP directly from crude cellular extracts. The affinity ligand A4C7 previously selected for GFP purification was synthesized on the monolith. The results indicated that the solid-phase synthesis of the ligand directly onto the monolith might require optimization and that the large pores of the monoliths are unsuitable for the purification of small proteins, such as GFP.

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DNA may fold into a diversity of structures and topologies such as duplexes and triplexes. Some specific guanine-rich DNA sequences may even fold into a higher order structures denominated guanine G-quadruplexes (G4). These G-quadruplex forming sequences have shown biological interest since were found in telomeres and in promoter region of oncogenes. Thus, these G4 forming sequences have been explored as therapeutic targets for cancer therapy, since G4 formation was demonstrated to inhibit RNA-polymerase and telomerase activity. However, the G4 structures are transient and are only formed under specific conditions. Hence the main objective of this work is to develop new G4-specific ligands which may potentially find applications in the therapeutic area. Several potential G4-binding ligands were synthesized and characterized. The synthesis of these compounds consisted on a procedure based on van Leusen chemistry and a cross-coupling reaction through C-H activation, affording phenanthroline compounds (Phen-1, 50%; Phen-2, 20%), phenyl (Iso-1, 61%; Iso-2, 21%; Ter-1, 85%; Ter-2, 35%), and quinolyl (Quin-1, 85%; Quin-2, 45%) compounds. Screening assays for selecting the potential G4 compounds were performed by FRET-melting, G4-FID, CD-melting and DSF. Qualitative biophysical studies were performed by fluorescence and CD spectroscopy. Two high-specific G-quadruplex ligands, Phen-1 and Phen-2, were found to effectively bind telomeric and c-myc G4 structures. Phen-1 was found to stabilize parallel telomeric 22AG and c-myc sequence by 4.1 and 4.3 ˚C, respectively. Phen-2 also displayed high affinity towards 22AG (

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This project aimed to engineer new T2 MRI contrast agents for cell labeling based on formulations containing monodisperse iron oxide magnetic nanoparticles (MNP) coated with natural and synthetic polymers. Monodisperse MNP capped with hydrophobic ligands were synthesized by a thermal decomposition method, and further stabilized in aqueous media with citric acid or meso-2,3-dimercaptosuccinic acid (DMSA) through a ligand exchange reaction. Hydrophilic MNP-DMSA, with optimal hydrodynamic size distribution, colloidal stability and magnetic properties, were used for further functionalization with different coating materials. A covalent coupling strategy was devised to bind the biopolymer gum Arabic (GA) onto MNPDMSA and produce an efficient contrast agent, which enhanced cellular uptake in human colorectal carcinoma cells (HCT116 cell line) compared to uncoated MNP-DMSA. A similar protocol was employed to coat MNP-DMSA with a novel biopolymer produced by a biotechnological process, the exopolysaccharide (EPS) Fucopol. Similar to MNP-DMSA-GA, MNP-DMSA-EPS improved cellular uptake in HCT116 cells compared to MNP-DMSA. However, MNP-DMSA-EPS were particularly efficient towards the neural stem/progenitor cell line ReNcell VM, for which a better iron dose-dependent MRI contrast enhancement was obtained at low iron concentrations and short incubation times. A combination of synthetic and biological coating materials was also explored in this project, to design a dynamic tumortargeting nanoprobe activated by the acidic pH of tumors. The pH-dependent affinity pair neutravidin/iminobiotin, was combined in a multilayer architecture with the synthetic polymers poy-L-lysine and poly(ethylene glycol) and yielded an efficient MRI nanoprobe with ability to distinguish cells cultured in acidic pH conditions form cells cultured in physiological pH conditions.