Shaping the Place - A Digital Design Heuristics Tool to Support Creation of Urban Design Proposals by Non-professionals

This paper is exploring a solution to foster civic engagement in urban design projects by applying the concepts of creativity to ICT tools. We propose a framework to support interactions between non-professionals and professionals that will ease the understanding of urban design and creation of design proposals for non-trained people and, on the other hand, offer valuable propositions and inspiration to experts. This make tool should have the presented creativity affordances known as fluency, flexibility and originality during the divergent phase of the creation process. We propose to implement a 3D collage metaphor to facilitate creative expression with 3D models. An underlying technical challenge of our application is to provide an interactive 3D mesh cutting tool to help users to express their creative potential in urban design projects. We present a non-exhaustive survey of mesh segmentation and cutting methodologies and finally, first results of implementation of a cutting algorithm

An Allosteric Inhibitor of Protein Arginine Methyltransferase 3

PRMT3, a protein arginine methyltransferase, has been shown to influence ribosomal biosynthesis by catalyzing the dimethylation of the 40S ribosomal protein S2. Although PRMT3 has been reported to be a cytosolic protein, it has been shown to methylate histone H4 peptide (H4 1-24) in vitro. Here, we report the identification of a PRMT3 inhibitor (1-(benzo[d][1,2,3]thiadiazol-6-yl)-3-(2-cyclohexenylethyl)urea; compound 1) with IC50 value of 2.5 μM by screening a library of 16,000 compounds using H4 (1-24) peptide as a substrate. The crystal structure of PRMT3 in complex with compound 1 as well as kinetic analysis reveals an allosteric mechanism of inhibition. Mutating PRMT3 residues within the allosteric site or using compound 1 analogs that disrupt interactions with allosteric site residues both abrogated binding and inhibitory activity. These data demonstrate an allosteric mechanism for inhibition of protein arginine methyltransferases, an emerging class of therapeutic targets

The ABC transporter MsbA interacts with lipid A and amphipathic drugs at different sites

MsbA is an essential ABC (ATP-binding cassette) transporter involved in lipid A transport across the cytoplasmic membrane of Gram-negative bacteria. The protein has also been linked to efflux of amphipathic drugs. Purified wild-type MsbA was labelled stoichiometrically with the fluorescent probe MIANS [2-(4′-maleimidylanilino)naphthalene-6-sulfonic acid] on C315, which is located within the intracellular domain connecting transmembrane helix 6 and the nucleotide-binding domain. MsbA–MIANS displayed high ATPase activity, and its folding and stability were unchanged. The initial rate of MsbA labelling by MIANS was reduced in the presence of amphipathic drugs, suggesting that binding of these compounds alters the protein conformation. The fluorescence of MsbA–MIANS was saturably quenched by nucleotides, lipid A and various drugs, and estimates of the Kd values for binding fell in the range of 0.35–10 μM. Lipid A and daunorubicin were able to bind to MsbA–MIANS simultaneously, implying that they occupy different binding sites. The effects of nucleotide and lipid A/daunorubicin binding were additive, and binding was not ordered. The Kd of MsbA for binding lipid A was substantially decreased when the daunorubicin binding site was occupied first, and prior binding of nucleotide also modulated lipid A binding affinity. These results indicate that MsbA contains two substrate-binding sites that communicate with both the nucleotide-binding domain and with each other. One is a high affinity binding site for the physiological substrate, lipid A, and the other site interacts with drugs with comparable affinity. Thus MsbA may function as both a lipid flippase and a multidrug transporter

Protein Lysine Methyltransferase G9a Inhibitors: Design, Synthesis, and Structure Activity Relationships of 2,4-Diamino-7-aminoalkoxy-quinazolines.

Protein lysine methyltransferase G9a, which catalyzes methylation of lysine 9 of histone H3 (H3K9) and lysine 373 (K373) of p53, is over expressed in human cancers. Genetic knockdown of G9a inhibits cancer cell growth and the di-methylation of p53 K373 results in the inactivation of p53. Initial SAR exploration of the 2,4-diamino-6,7-dimethoxyquinazoline template represented by 3a (BIX01294), a selective small molecule inhibitor of G9a and GLP, led to the discovery of 10 (UNC0224) as a potent G9a inhibitor with excellent selectivity. A high resolution X-ray crystal structure of the G9a-10 complex, the first co-crystal structure of G9a with a small molecule inhibitor, was obtained. Based on the structural insights revealed by this co-crystal structure, optimization of the 7-dimethylaminopropoxy side chain of 10 resulted in the discovery of 29 (UNC0321) (Morrison Ki = 63 pM), which is the first G9a inhibitor with picomolar potency and the most potent G9a inhibitor to date

'Yes We Camp!' Marseille's artistic and participatory urban camp examined through a socio-materiality lens

International audienceThe presented paper builds on theoretical language borrowed from post-modern philosophy and humanist geography to investigate particular features of the artistic and participatory "Yes We Camp!" The article emphasizes a mutually reinforcing relationship between static properties of the site-its spatial organization, built environment and selection of materials-and its dynamic characteristics-social interactions, organizational form and the emotional resonance evoked in people. The paper shows that place particularity is symbolically conveyed by the spatial organization and built environment and is collectively lived and felt as a unique atmosphere. Thus, our understanding of particular places cannot be complete without accounting for the complex interactions between their spatial, material, social and human dimensions

Externalités de revenu dans le taux d'escompte dans des modèles bi-sectoriels à générations imbriquées : analyse dynamique en autarcie et en économie ouverte

Cette thèse propose de formuler le taux d’escompte comme fonction du revenu individuel et classifie cette spécification comme les externalités de revenu dans le taux d’escompte. La justification de cette relation est trouvée dans la théorie de la hiérarchie des besoins humains par Abraham Maslow (Maslow (1943)) : plus le revenu d’un individu, interprété comme le pouvoir économique à consommer, est élevé, plus l’individu a tendance à penser à des besoins supérieurs, associés à une plus grande patience. Ensuite, la présente étude s’intéresse aux implications des externalités pour deux phénomènes macro-économiques : les fluctuations endogènes, et la convergence/polarisation des revenus par tête entre les pays. Les résultats obtenus indiquent que les externalités de revenu dans le taux d'escompte constituent un mécanisme qui génère des fluctuations endogènes dans une économie fermée. L’extension de ce modèle à une configuration 2x2x2 dynamique permet de conclure qu’en fonction des technologies et des préférences des consommateurs, l'intégration commerciale d'une économie volatile avec une économie stable peut avoir un effet stabilisant ou, au contraire, peut engendrer des fluctuations macro-économiques dans toute la région. Enfin, cette thèse démontre que la libéralisation des échanges commerciaux peut avoir, comme effet de long terme, soit la convergence soit la divergence des revenus par habitant. Pour un certain nombre de paramètres, les externalités génèrent la divergence. Ce résultat est compatible avec les observations empiriques et met en évidence l’importance des interventions politiques pour bénéficier de la libéralisation commerciale.This dissertation proposes a new formulation of time discounting: discount factor as a function of individual income, referred to as income externalities in discounting. The rationale for this relationship is found in the theory of hierarchy of human needs by Abraham Maslow (Maslow (1943)): the greater is income, interpreted as economic power of individuals to consume, the higher layers of needs, associated with greater patience, individuals seek to satisfy. Then, the thesis entails an examination of the linkage between the externalities and two macroeconomic phenomena: endogenous fluctuations and convergence/polarization of per capita incomes across countries. It is established that income externalities in discounting could be a vehicle for endogenous fluctuations in an autarkic economy. In the extension of the autarkic model to a dynamic 2x2x2 framework, it is found that trade integration of a volatile economy with a stable one can make fluctuations to evanesce or, on the contrary, propel them to the whole region depending on technologies and consumer preferences. Last, it is shown that trade liberalization can result in convergence or divergence of long run per capita income. For some range of parameters, externalities produce divergence. The result is consistent with empirical observations and emphasizes the importance of policy interventions for reaping benefits from free trade

Limits to the construction of a community-based open innovation network and implications for specialisation of a small urban area

International audienceThe article studies an ICT collaborative project developed in the framework of the regional innovation policy of the PACA region, France. It seeks to gain a better understanding of the evolution of a community-based open innovation network shaped during the project implementation. Conditions for its emergence, construction and stabilisation are discussed from theoretical and practical viewpoints, including governance design and leadership characteristics as well as factors determining collaboration (IPR, timespan and individual characteristics of participants). Community animation style is highlighted as an important ingredient for emergence of innovative ideas from the cognitive resources of the territory, to favour smart specialisation. A longitudinal and qualitative method of observation is used, covering the period from the emergence of the project until its administrative end, with follow-up of emerged innovative enterprises. A participative research approach is adopted to collect diverse data (minutes of meeting, working documents, etc.) and to conduct interviews during the project

How Can the Governance of the French Clusters (Pôles de Compétitivité) Improve SME’s Competitiveness?

International audienceThis paper focuses on Pôles de compétitivité-the French competitiveness clusters (FCC)-which mobilize national and regional actors and resources for innovation. By reviewing the literature (academic, web and news articles, and official reports) published on the subject, the synthesis emphasizes a collective learning process leading to institutional change reflected by legitimation of SMEs as full-fledged innovation actor. Through reflexive governance of certain poles, centered on their own sustainability, the policy has produced learning at local and national level. It has generated knowledge that has brought transformation of operational tools and societal representations in support of innovation of SMEs. The originality of the article is to show that in the French societal context, new place dependencies within the Pôles are characterized by emergence of a new innovation model of SMEs mainly through collaboration with public research. This model differs from the innovation model of SMEs staying outside of the poles. It is built through intermediary organizations that offer regional filters for national and regional policy adaptation. A major limitation of the policy is the difficulty to enhance cooperation between innovative SMEs and leader firms in the territory mainly because of a lack of social regulation over the protection and share of knowledge assets. The paper contributes to the research on clusters in general