Looper: Towards a Methodology of Co-Design Approaches

When setting up their own participatory process, researchers and citizens alike are confronted with a wide array of online and offline tools targeted towards facilitating co-creation. With such a multitude of solutions available and approaches differing across countries and fields, how can one make an informed choice? This paper lays out the first results of a methods review that will create a co-creation and co-design toolbox for Living Labs. The review scopes across various disciplines and fields of application. Two promising physical toolkits and three comprehensive handbooks for facilitators are presented, detailing the circumstances under which they are potentially the most useful. The research takes place within LOOPER (Learning Loops in the Public Realm), a JPI Europe funded research project with Living Labs running in Brussels, Manchester and Verona. The aim of this project is to build a participatory co-creation methodology and platform to demonstrate ‘learning loops’, bringing together citizens, stakeholders and policy-makers to iteratively learn how to address urban challenges (road safety, traffic calming, air and noise pollution). The review of existing tools serves as a preparatory activity for the Living Labs by developing the preliminary methodology which will form the backbone for the co-design of solutions in the living labs

Barokk irodalom Sziléziában és a Duna mentén (források, tanulmányok) = Baroque literature in Silesia and alongside the Duna (text, studies)

A pályázat a barokk misztikus irodalom alakulását és kölcsönkapcsolatait vizsgálja Kelet-Közép-Európa térségben a XVII. században. A kutatás nemzetközi jellegénél fogva külföldi kapcsolatainkat erősítettük: nemzetközi konferenciát és nyári szemináriumot rendeztünk Szegeden, előadóként résztvettünk hazai és külföldi konferenciákon. Munkánk nagy része intenzív forrásgyűjtésen, hazai és külföldi könyv- és levéltári kutatáson alapult. Ehhez a feladathoz egyéni kutatási megbízással külső szakembereket is bevontunk. PhD-hallgatóinkat sikeresen motíváltuk a közös munkára, a szakma figyelmét is felkeltő előadásokat tartottak külföldi és hazai fórumokon. A kutatást figyelemmel kísérte és levélben tanácsaival segítette például olyan vezető német barokk szakértő, mint Hans-Georg Kemper (Tübingen) és Klaus Garber (Osnabrück.) Konferencia-előadásaink részint megjelentek, részint sajtó alatt vannak, kiemelt témakörökhöz (Johann Permeier, Johann Theodor von Tschesch, Ch. von Greiffenberg és a nürnbergi irodalmi kör) teljességre törekvő anyagot gyűjtöttünk, ez sajtókész, lektorálásra érett állapotban van. | Our research project examines the development and connections of the 17th century baroque mystic literature in the East/Middle European region. Since the research involved international collaborations, we organized an international conference and a summer seminar in Szeged, and also attended several domestic and international conferences. Most of our work was based on an intensive collecting of resources and doing research in domestic and foreign archives and libraries. To achieve this goal, external experts with research contracts were also asked to participate. We motivated our PhD students successfully to do joint research; their presentations both in Hungary and abroad proved to be very useful and interesting for the audience skilled in the art. The research was monitored and helped by means of useful written advices by such leading German baroque experts as Hans-Georg Kemper (Tübingen) and Klaus Garber (Osnabrück). Our conference materials are already published or under publication. For selected topics (Johann Permeier, Johann Theodor von Tschesch, Ch. von Greiffenberg and the literary circle of Nürnberg) we collected all resources available, the resulting publication is also ready for submission

Using Co-Creation Methods to Solve Mobility Problems in Brussels

In recent years, urban problems such as congestion and traffic safety have jumped to the top of the political agenda in many European cities. At the same time, governments are increasingly shying away from formalconsultation methods to using more participatory methods to find solutions to urban problems. In the Brussels LOOPER Living Lab, bottom-up co-creation methods are tested in a full planning cycle, from problem identification to co-design and evaluation of alternative solutions to implementation and monitoring of these solutions. The research takes place within LOOPER (Learning Loops in the Public Realm), a JPIEurope funded research project with Living Labs running in Brussels, Manchester and Verona. The LOOPER project seeks to improve co-creation processes in urban governance and planning by building a participatory co-creation methodology and platform to demonstrate ‘learning loops’ i.e. new ways of decision-making, which bring together citizens, stakeholders, researchers and policy-makers to address urban challenges. In Brussels, offline and online co-creation methods have been used to define a problem (traffic safety), collect data on this problem, co-design solutions that solve this problem, evaluate the stakeholder support for these solutions, and implement a solution. This paper discusses how a combination of co-creation tools was used to contribute to a better understanding of traffic safety issues, led to co-designed alternatives and finally implementation overarching the full planning cycle in Brussels. Furthermore, the paper discusses how online and offline tools have been combined in the Living Lab

Enhancing Stakeholder Participation in Urban Mobility Planning: the NISTO Evaluation Framework

Public participation and stakeholder involvement have become core prerequisites of a comprehensive and fair transport planning process. In this paper, we show how the multi-actor multi-criteria analysis (MAMCA) methodology can enhance urban and regional mobility planning and decision-making by considering conflicting stakeholder objectives and helping to identify synergies and disagreement between different stakeholder groups. We suggest the application of MAMCA as part of the NISTO evaluation framework that offers tools to appraise small-scale mobility projects through a toolkit of multi-criteria analysis, MAMCA and target monitoring. MAMCA provides a tool to appraise the preferences of the stakeholders involved or affected by a project. It is based on assessing the evaluation criteria of the different stakeholder groups rather than appraising the project based on a set of common criteria agreed on with all stakeholders at the beginning of the process. Therefore the evaluation shows which implementation alternatives or scenarios each group would prefer and allows for a straightforward comparison of preferences across all stakeholder groups. The application of the MAMCA is demonstrated through the initial results of the evaluation of five demonstration projects in North-West Europe. We show that MAMCA is suitable for a range of mobility projects since it can handle the diversity of stakeholder groups and their objectives. In addition it offers the practitioner a well-structured way of carrying out the whole evaluation process. The application of MAMCA also has the added value of broadening the evaluation process to a wide range of stakeholders instead of limiting it to experts. As opposed to previous approaches, the MAMCA methodology aims to provide a balanced evaluation process where the stakeholders have equal weight, i.e. no priority is given to decision makers, users groups or experts. Our analysis of the process of the identification of stakeholders and their objectives also suggests that there is no generic recipe for the range of stakeholders to be involved in different projects, their objectives and the data that needs to be collected for the evaluation. The MAMCA methodology will be offered to practitioners as a simple-to-use web-based software tool that can collect stakeholder objectives and weights, as well as the input of experts and monitoring data for the evaluation of the alternatives and display the outcome on graphs. Therefore we hope that the tool will improve participation in urban decision-making and evaluation thorough the better integration of diverse stakeholder preferences

Solving urban problems through co-creation: The LOOPER project

The aim of this paper is to present the LOOPER participatory co-creation methodology and platform developed in the Learning Loops in the Public Realm (LOOPER) project to demonstrate ‘learning loops’ i.e. new ways of decision-making which bring together citizens, stakeholders and policy-makers to iteratively learn how to address urban challenges. The methodology and platform are demonstrated in three Living Labs with different spatial, cultural and thematic contexts. The main issues are traffic and mobility in Brussels; traffic and green space in Manchester; and air and noise pollution in Verona. The paper discusses the LOOPER approach to support finding solutions to urban problems in a participatory co-creation process. The experiences from the LOOPER Living Labs show that combining offline and online participation tools is often necessary in co-creation and that online tools should have a low entry threshold. Furthermore, formal evaluation methods can be effective tools in ensuring stakeholder participation

DUckCov: a Dynamic Undocking‐based Virtual Screening Protocol for Covalent Binders

Thanks to recent guidelines, the design of safe and effective covalent drugs has gained significant interest. Other than targeting non‐conserved nucleophilic residues, optimizing the noncovalent binding framework is important to improve potency and selectivity of covalent binders toward the desired target. Significant efforts have been made in extending the computational toolkits to include a covalent mechanism of protein targeting, like in the development of covalent docking methods for binding mode prediction. To highlight the value of the noncovalent complex in the covalent binding process, here we describe a new protocol using tethered and constrained docking in combination with Dynamic Undocking (DUck) as a tool to privilege strong protein binders for the identification of novel covalent inhibitors. At the end of the protocol, dedicated covalent docking methods were used to rank and select the virtual hits based on the predicted binding mode. By validating the method on JAK3 and KRas, we demonstrate how this fast iterative protocol can be applied to explore a wide chemical space and identify potent targeted covalent inhibitors

When fragments link : a bibliometric perspective on the development of fragment-based drug discovery

Fragment-based drug discovery (FBDD) is a highly interdisciplinary field, rich in ideas integrated from pharmaceutical sciences, chemistry, biology, and physics, among others. To enrich our understanding of the development of the field, we used bibliometric techniques to analyze 3642 publications in FBDD, complementing accounts by key practitioners. Mapping its core papers, we found the transfer of knowledge from academia to industry. Co-authorship analysis showed that university–industry collaboration has grown over time. Moreover, we show how ideas from other scientific disciplines have been integrated into the FBDD paradigm. Keyword analysis showed that the field is organized into four interconnected practices: library design, fragment screening, computational methods, and optimization. This study highlights the importance of interactions among various individuals and institutions from diverse disciplines in newly emerging scientific fields. We study the organizational aspects of the development of fragment-based drug discovery (FBDD), using tools from bibliometrics

Pharmacological and SAR analysis of the LINS01 compounds at the human histamine H1, H2 and H3 receptors

Histamine is a transmitter that activates the four receptors H1R to H4R. The H3R is found in the nervous system as an auto and heteroreceptor, and controls the release of neurotransmitters, making it a potential drug target for neuropsychiatric conditions. We have previously reported that the 1?(2,3?dihydro?1?benzofuran?2?yl)methylpiperazines (LINS01 compounds) have selectivity for the H3R over the H4R. Here we describe their pharmacological properties at the human H1R, H2R in parallel with the H3R, thus providing a full analysis of these compounds as histamine receptor ligands through reporter gene assays. Eight of the nine LINS01 compounds inhibited H3R?induced histamine responses but no inhibition of H2R?induced responses were seen. Three compounds were weakly able to inhibit H1R?induced responses. No agonist responses were seen to any of the compounds at any receptor. SAR analysis shows that the N?methyl group improves H3R affinity whilst the N?phenyl group is detrimental. The methoxy derivative, LINS01009, had the highest affinity

S55746 is a novel orally active BCL-2 selective and potent inhibitor that impairs hematological tumor growth

Escape from apoptosis is one of the major hallmarks of cancer cells. The B-cell Lymphoma 2 (BCL-2) gene family encodes pro-apoptotic and anti-apoptotic proteins that are key regulators of the apoptotic process. Overexpression of the pro-survival member BCL-2 is a well-established mechanism contributing to oncogenesis and chemoresistance in several cancers, including lymphoma and leukemia. Thus, BCL-2 has become an attractive target for therapeutic strategy in cancer, as demonstrated by the recent approval of ABT-199 (Venclexta™) in relapsed or refractory Chronic Lymphocytic Leukemia with 17p deletion. Here, we describe a novel orally bioavailable BCL-2 selective and potent inhibitor called S55746 (also known as BCL201). S55746 occupies the hydrophobic groove of BCL-2. Its selectivity profile demonstrates no significant binding to MCL-1, BFL-1 (BCL2A1/A1) and poor affinity for BCL-XL. Accordingly, S55746 has no cytotoxic activity on BCL-XL-dependent cells, such as platelets. In a panel of hematological cell lines, S55746 induces hallmarks of apoptosis including externalization of phosphatidylserine, caspase-3 activation and PARP cleavage. Ex vivo, S55746 induces apoptosis in the low nanomolar range in primary Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma patient samples. Finally, S55746 administered by oral route daily in mice demonstrated robust anti-tumor efficacy in two hematological xenograft models with no weight lost and no change in behavior. Taken together, these data demonstrate that S55746 is a novel, well-tolerated BH3-mimetic targeting selectively and potently the BCL-2 protein