| 1. |
- Balint, Monika, et al.
(författare)
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Binding Networks Identify Targetable Protein Pockets for Mechanism-Based Drug Design
- 2022
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 23:13
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Tidskriftsartikel (refereegranskat)abstract
- The human genome codes only a few thousand druggable proteins, mainly receptors and enzymes. While this pool of available drug targets is limited, there is an untapped potential for discovering new drug-binding mechanisms and modes. For example, enzymes with long binding cavities offer numerous prerequisite binding sites that may be visited by an inhibitor during migration from a bulk solution to the destination site. Drug design can use these prerequisite sites as new structural targets. However, identifying these ephemeral sites is challenging. Here, we introduce a new method called NetBinder for the systematic identification and classification of prerequisite binding sites at atomic resolution. NetBinder is based on atomistic simulations of the full inhibitor binding process and provides a networking framework on which to select the most important binding modes and uncover the entire binding mechanism, including previously undiscovered events. NetBinder was validated by a study of the binding mechanism of blebbistatin (a potent inhibitor) to myosin 2 (a promising target for cancer chemotherapy). Myosin 2 is a good test enzyme because, like other potential targets, it has a long internal binding cavity that provides blebbistatin with numerous potential prerequisite binding sites. The mechanism proposed by NetBinder of myosin 2 structural changes during blebbistatin binding shows excellent agreement with experimentally determined binding sites and structural changes. While NetBinder was tested on myosin 2, it may easily be adopted to other proteins with long internal cavities, such as G-protein-coupled receptors or ion channels, the most popular current drug targets. NetBinder provides a new paradigm for drug design by a network-based elucidation of binding mechanisms at an atomic resolution.
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| 2. |
- Brasko, Csilla, et al.
(författare)
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Intelligent image-based in situ single-cell isolation
- 2018
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Quantifying heterogeneities within cell populations is important for many fields including cancer research and neurobiology; however, techniques to isolate individual cells are limited. Here, we describe a high-throughput, non-disruptive, and cost-effective isolation method that is capable of capturing individually targeted cells using widely available techniques. Using high-resolution microscopy, laser microcapture microscopy, image analysis, and machine learning, our technology enables scalable molecular genetic analysis of single cells, targetable by morphology or location within the sample.
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| 3. |
- Česnuitytė, Vida, et al.
(författare)
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The State and Future Prospects of the Sharing Economy in Europe
- 2022
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Ingår i: The Sharing Economy in Europe: Developments, practices, and contradictions. - : Palgrave. ; , s. 365-382
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Bokkapitel (refereegranskat)abstract
- The chapter is the final one in the volume of collected papers aiming to discuss the sharing economy in Europe. The idea of the book emerged within the research network created by the COST Action CA16121 ‘From Sharing to Caring: Examining Socio-Technical Aspects of the Collaborative Economy.’ The authors of the chapter sum up theoretical and empirical materials as well as country-specific cases provided in the book. The article critically assesses the current status of the sharing economy in European countries by highlighting major controversial issues related to deregulation, market disruption, or social inequality. The authors conclude that, considering the comprehensive and up-to-date materials collected and analysed in the book, it may become an outstanding source of knowledge and a practical tool in the process of expansion of the sharing economy in Europe and beyond.
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| 4. |
- Dombovari, Balazs, et al.
(författare)
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In vivo validation of the electronic depth control probes
- 2014
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Ingår i: Biomedizinische Technik (Berlin. Zeitschrift). - : Walter de Gruyter GmbH. - 1862-278X .- 0013-5585. ; 59:4, s. 283-289
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Tidskriftsartikel (refereegranskat)abstract
- In this article, we evaluated the electrophysiological performance of a novel, high-complexity silicon probe array. This brain-implantable probe implements a dynamically reconfigurable voltage-recording device, coordinating large numbers of electronically switchable recording sites, referred to as electronic depth control (EDC). Our results show the potential of the EDC devices to record good-quality local field potentials, and single- and multiple-unit activities in cortical regions during pharmacologically induced cortical slow wave activity in an animal model.
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| 5. |
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| 6. |
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| 7. |
- Kovacs, Péter, 1987, et al.
(författare)
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On the convergence of driver centric zone pricing for traffic networks
- 2018
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Ingår i: RM18: Swedish Control Confrence 2018 (Reglermöte 2018). - : EasyChair.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Congestion fees with dynamical zone pricing provide an easy-to-implement solution to urban traffic control agencies for improved efficiency of the traffic network. In order to design a pricing strategy it is necessary to understand how it affects the route choices of drivers in the system. This work explores this question by providing an idealized dynamical model for re-routing as traffic flows change to cheaper routes. Results show a convergence to a Wardrop-equilibrium, which is also proven formally and demonstrated via simulation.
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| 8. |
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| 9. |
- Miguel, Cristina, 1979, et al.
(författare)
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The Sharing Economy in Europe: From Idea to Reality
- 2022
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Ingår i: The Sharing Economy in Europe: Developments, practices, and contradictions. - : Palgrave. ; , s. 3-18
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Bokkapitel (refereegranskat)abstract
- This chapter explains the rationale behind the book. It provides basic definitions of the concept of the sharing economy as well as the primary meanings related to the subject of the analysis undertaken in the subsequent chapters. This Introduction also includes a description of the main benefits of the analysis of the sharing economy from a European perspective. It highlights that the idea of the book emerged from the collaboration of most co-authors in the COST Action CA16121 ‘From Sharing to Caring: Examining Socio-Technical Aspects of the Collaborative Economy.’ Finally, the outline of the book is presented, providing a description of the content of each chapter within this academic collection.
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| 10. |
- Sisask, M, et al.
(författare)
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Teacher satisfaction with school and psychological well-being affects their readiness to help children with mental health problems
- 2014
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Ingår i: HEALTH EDUCATION JOURNAL. - : SAGE Publications. - 0017-8969 .- 1748-8176. ; 73:4, s. 382-393
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In support of a whole-school approach to mental health promotion, this study was conducted to find out whether and how significantly teachers’ satisfaction with school and their subjective psychological well-being are related to the belief that they can help pupils with mental health problems. Design: Cross-sectional data were collected as a part of the European Union’s, Seventh Framework Programme for Research (FP7) Saving and Empowering Young Lives in Europe (SEYLE) study. One of the elements of the SEYLE study was to evaluate teachers’ attitudes and knowledge related to pupils’ mental health issues and their own psychological well-being, as well as their satisfaction with the school environment. Setting: The sample of schools from the SEYLE study sites representing 11 European countries was randomly chosen according to prior defined inclusion and exclusion criteria. The final cross-sectional database used for analysis in the current study comprised 2485 teachers from 158 randomly selected schools. Method: Respondents’ belief that teachers can help pupils with mental health problems served as the outcome variable in our predictions with probability of the positive answer being modelled in the logistic regression analysis. Teachers’ subjective psychological well-being and school satisfaction were included as independent variables in the logistic regression model and several other relevant variables were added to statistically control for them. Multiple models were tested in order to obtain the final model. Results: Logistic regression models showed that better satisfaction with general school climate, higher psychological well-being, and the ability to understand pupils’ mental health problems increased the odds of teachers’ readiness to help pupils with mental health problems. Conclusion: By providing a good school environment, by valuing the subjective psychological well-being of the teachers, and by providing adequate training to fulfil their ‘gatekeeper’ role, the preconditions to improve the mental health of the pupils they teach will be achieved. These suggestions are in line with a whole-school approach to mental health promotion.
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