44 research outputs found

    A framework for accessible m-government implementation

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    The great popularity and rapid diffusion of mobile technologies at worldwide level has also been recognised by the public sector, leading to the creation of m-government. A major challenge for m-government is accessibility – the provision of an equal service to all citizens irrespective of their psychical, mental or technical capabilities. This paper sketches the profiles of six citizen groups: Visually Impaired, Hearing Impaired, Motor Impaired, Speech Impaired, Cognitive Impaired and Elderly. M-government examples that target the aforementioned groups are discussed and a framework for accessible m-government implementation with reference to the W3C Mobile Web Best Practices is proposed

    pH-stat versus pH-shift lipolysis model:Exploring in vitro-in vivo relationships for lipid-based formulations of nilotinib

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    The pH-stat in vitro lipolysis method is well established for evaluating lipid-based formulations (LBFs), however the absence of a simulated gastrointestinal transition may lead to an overestimation of drug precipitation particularly in the case of weakly basic drugs. This study aimed to compare the conventional pH-stat method with a pH-shift lipolysis approach by evaluating a diverse set of LBFs using nilotinib, a weakly basic model drug. Additionally, the study sought to assess in vitro–in vivo relationships (IVIVRs) and enhance understanding of the predictive capabilities of these models. Four nilotinib-containing LBFs were tested in vitro, and pharmacokinetic profiles were evaluated in Sprague Dawley rats. The formulations included a supersaturated Peceol® solution (sLBF), a Peceol® lipid suspension (type I according to the Lipid Formulation Classification System (LFCS)), a type III LFCS medium-chain suspension, and a type IV LFCS suspension. The highest bioavailability was achieved with the Peceol® sLBF and the type III LFCS formulation. Strong IVIVRs were established for both in vitro lipolysis models. In conclusion, utilizing both in vitro models offered distinct advantages depending on the stage of development and the specific questions being addressed. This approach contributes to more efficient formulation development and a reduced reliance on animal studies in early-stage drug development.</p

    Comprehensive Fragment Screening of the SARS-CoV-2 Proteome Explores Novel Chemical Space for Drug Development

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    12 pags., 4 figs., 3 tabs.SARS-CoV-2 (SCoV2) and its variants of concern pose serious challenges to the public health. The variants increased challenges to vaccines, thus necessitating for development of new intervention strategies including anti-virals. Within the international Covid19-NMR consortium, we have identified binders targeting the RNA genome of SCoV2. We established protocols for the production and NMR characterization of more than 80 % of all SCoV2 proteins. Here, we performed an NMR screening using a fragment library for binding to 25 SCoV2 proteins and identified hits also against previously unexplored SCoV2 proteins. Computational mapping was used to predict binding sites and identify functional moieties (chemotypes) of the ligands occupying these pockets. Striking consensus was observed between NMR-detected binding sites of the main protease and the computational procedure. Our investigation provides novel structural and chemical space for structure-based drug design against the SCoV2 proteome.Work at BMRZ is supported by the state of Hesse. Work in Covid19-NMR was supported by the Goethe Corona Funds, by the IWBEFRE-program 20007375 of state of Hesse, the DFG through CRC902: “Molecular Principles of RNA-based regulation.” and through infrastructure funds (project numbers: 277478796, 277479031, 392682309, 452632086, 70653611) and by European Union’s Horizon 2020 research and innovation program iNEXT-discovery under grant agreement No 871037. BY-COVID receives funding from the European Union’s Horizon Europe Research and Innovation Programme under grant agreement number 101046203. “INSPIRED” (MIS 5002550) project, implemented under the Action “Reinforcement of the Research and Innovation Infrastructure,” funded by the Operational Program “Competitiveness, Entrepreneurship and Innovation” (NSRF 2014–2020) and co-financed by Greece and the EU (European Regional Development Fund) and the FP7 REGPOT CT-2011-285950—“SEE-DRUG” project (purchase of UPAT’s 700 MHz NMR equipment). The support of the CERM/CIRMMP center of Instruct-ERIC is gratefully acknowledged. This work has been funded in part by a grant of the Italian Ministry of University and Research (FISR2020IP_02112, ID-COVID) and by Fondazione CR Firenze. A.S. is supported by the Deutsche Forschungsgemeinschaft [SFB902/B16, SCHL2062/2-1] and the Johanna Quandt Young Academy at Goethe [2019/AS01]. M.H. and C.F. thank SFB902 and the Stiftung Polytechnische Gesellschaft for the Scholarship. L.L. work was supported by the French National Research Agency (ANR, NMR-SCoV2-ORF8), the Fondation de la Recherche Médicale (FRM, NMR-SCoV2-ORF8), FINOVI and the IR-RMN-THC Fr3050 CNRS. Work at UConn Health was supported by grants from the US National Institutes of Health (R01 GM135592 to B.H., P41 GM111135 and R01 GM123249 to J.C.H.) and the US National Science Foundation (DBI 2030601 to J.C.H.). Latvian Council of Science Grant No. VPP-COVID-2020/1-0014. National Science Foundation EAGER MCB-2031269. This work was supported by the grant Krebsliga KFS-4903-08-2019 and SNF-311030_192646 to J.O. P.G. (ITMP) The EOSC Future project is co-funded by the European Union Horizon Programme call INFRAEOSC-03-2020—Grant Agreement Number 101017536. Open Access funding enabled and organized by Projekt DEALPeer reviewe

    Large-Scale Recombinant Production of the SARS-CoV-2 Proteome for High-Throughput and Structural Biology Applications

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    The highly infectious disease COVID-19 caused by the Betacoronavirus SARS-CoV-2 poses a severe threat to humanity and demands the redirection of scientific efforts and criteria to organized research projects. The international COVID19-NMR consortium seeks to provide such new approaches by gathering scientific expertise worldwide. In particular, making available viral proteins and RNAs will pave the way to understanding the SARS-CoV-2 molecular components in detail. The research in COVID19-NMR and the resources provided through the consortium are fully disclosed to accelerate access and exploitation. NMR investigations of the viral molecular components are designated to provide the essential basis for further work, including macromolecular interaction studies and high-throughput drug screening. Here, we present the extensive catalog of a holistic SARS-CoV-2 protein preparation approach based on the consortium’s collective efforts. We provide protocols for the large-scale production of more than 80% of all SARS-CoV-2 proteins or essential parts of them. Several of the proteins were produced in more than one laboratory, demonstrating the high interoperability between NMR groups worldwide. For the majority of proteins, we can produce isotope-labeled samples of HSQC-grade. Together with several NMR chemical shift assignments made publicly available on covid19-nmr.com, we here provide highly valuable resources for the production of SARS-CoV-2 proteins in isotope-labeled form

    Problemy współczesności. Recenzja książki Re-Engineering Humanity autorstwa Bretta Frischmanna i Evana Selingera

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    The image of mother in social media - an attempt at typologization

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    Sposób postrzegania matki oraz macierzyństwa na przestrzeni ostatnich wieków uległ wielu modyfikacjom. Największy przełom w tym zakresie dał się zauważyć po zmianie ustroju politycznego w Polsce. Poprawa sytuacji gospodarczej, coraz większa dostępność towarów na rynku, a także rozwój technologii informacyjnych istotnie przełożyło się na jakość macierzyństwa. Współcześnie wizerunek matki jest zróżnicowany, co widać przede wszystkim w mediach społecznościowych. Na portalach można spotkać wiele zróżnicowanych wizerunków (typów) matki, między innymi: typ Matki Polki, typ matki nowoczesnej pracującej, typ matki celebrytki, typ matki parającej się sharentingiem i typ samotnej matki. Celem niniejszej pracy jest zdefiniowanie najczęściej powtarzających się typów (wizerunków) matek w mediach społecznościowych, które wyszczególniono na podstawie literatury przedmiotu i próba ich typologizacji. Analizując wyniki badań trzeba wskazać, że wizerunek matki w polskich mediach społecznościowych jest niejednolity, a krótka analiza wykonana w niniejszej pracy wskazuje na to, iż omówione typy matek występujące na wielu blogach stanowią swoistą formę hybrydową, przenikając się wzajemnie.The way mothers and motherhood are perceived has undergone many modifications over the past centuries. The biggest transition in this respect took place after the changes in the political system in Poland. The improvement of the economic situation, the increasing availability of goods on the market, as well as the development of information technologies significantly translated into the quality of motherhood. The diversity of the recent mother's image (type) can be seen primarily in social media. On portals, you can find many different images (types) of a mother, inter alia: the type of Polish mother, the type of modern working mother, the type of celebrity mother, the type of sharenting mother and the type of single mother. The aim of this study is to define the most frequently repeated types (images) of mothers in social media, which have been identified on the basis of the literature on the subject, and to try to typologize them. When analyzing the research results, it should be pointed out that the image of the mother in Polish social media is not uniform and the short analysis carried out in this paper indicates that the discussed types of mothers appearing on many blogs are a kind of hybrid form interpenetrating one another
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