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Development of Clinically Viable Non-Muscle Myosin II Small Molecule Inhibitors with Broad Therapeutic Potential
No full textResearch suggests numerous indications, from axon regeneration and cancer, would benefit from a small molecule inhibitor of non-muscle myosin II, a molecular motor that regulates the actin cytoskeleton.• Current chemical probe options are very limited and lack sufficient safety for in vivo studies, which we show is primarily due to potent inhibition of cardiac myosin II. • Rational design that focused on improving target selectivity over the pan-myosin II inhibitor, blebbistatin, led to the identification of MT-228, a small molecule inhibitor with a wide therapeutic window. • High-resolution structure of MT-228 bound to myosin II reveals that selectivity results from a different positioning compared to blebbistatin and an important sequence difference between cardiac and non-muscle myosin II in the inhibitor binding pocket. • A single administration of MT-228 shows long-lasting efficacy in animal models of stimulant use disorder, a current unmet and rapidly escalating need with no FDAapproved treatments.</div
Does Increasing Environmental Policy Stringency Enhance Renewable Energy Consumption in OECD Countries?
No full textInternational audienceThis study explores the impact of environmental policy stringency on GDP per capita in 34 OECD countries over the period 1990 to 2019, using the Instrumental Variables with two-Stage Least Squares IV (2SLS) approach. We test the robustness of the empirical results by the two-step generalized method of moments, the fixed effects with Driscoll-Kraay standard errors and the mixed-effect maximum-likelihood estimator. Data were analyzed using different tests, including cross-section dependence, second-generation panel unit root tests, and endogeneity test. Unlike the previous studies that showed a negative impact of environmental regulations on economic growth, our results suggest that a more strict environmental policy can increase the GDP per capita in the OECD zone in the short term. Based on this findings, relevant policy recommendations are proposed
Explainable Analytics for Operational Research
No full textInternational audienceThe steep rise of analytics and AI in Operational Research (OR) is reflected by its increasing number of academic publications (Hindle et al. 2020) as well as the excitement amongst commercial organizations, governments, and communities to create value from their data. In this feature cluster, we invited authors to submit high-quality contributions addressing theoretical and algorithmic developments advancing the theory and methodology of explainable analytics and AI within OR, as well as real-world innovative implementations in business and society in areas as marketing and sales, supply chain management, education, production and service operations, medicine, bioinformatics, (financial) risk, and fraud
Entrepreneurship as collective action: The next frontier
No full textInternational audienceAnalyses of collective action in entrepreneurship are lacking in the extant literature. Despite entrepreneurship research progressively moving away from a focus on the lone heroic entrepreneur, scholars have yet to absorb the full potential of entrepreneurship as collective action. Also missing is a collective stance on key entrepreneurship concepts such as opportunity discovery or construction and entrepreneurial agency. Accordingly, this article reviews and critiques five articles that constitute this Special Issue seeking to establish ‘entrepreneurship as collective action’ as the next frontier of entrepreneurship theory development. The articles in this Special Issue each investigate a specific instance of collective action in entrepreneurship. This article contributes to extant scholarship by highlighting transversal themes and offering further research avenues
Addressing challenges of digital transformation with modified blockchain
No full textInternational audienceThis conceptual paper challenges the notion that the enhanced data security of blockchain results in superior privacy. Blockchain's fundamental characteristics-immutability, decentralization, and transparency-promote an excessive reliance on historical data. This reliance, in turn, leads to inaccurate predictions and misguides consumer privacy preferences. The paper contends that this stern protection conflicts with the General Data Protection Regulation (GDPR) and the California Consumer Privacy Act (CCPA). We argue that the lack of choice in managing data denies freedom, causing psychological reactance. Additionally, the dependence on past data contributes to an intensified privacy paradox as consumers need to assert accurate privacy preferences. These combined effects result in increased consumer digital vulnerability, which arises from an imbalanced power dynamic in data management. We propose a novel approach, which we call "modified blockchain". The approach is based on three pillars: i) selective immutability, ii) federal decentralization, and iii) supervised transparency. These pillars aim to effectively integrate regulations, organizations, and endusers within advocating for a socio-technical decision-making approach. This work also broadens the scope of the psychological reactance theory and the privacy paradox literature by affirming that a lack of autonomy in data management leads to digital vulnerability.This conceptual paper challenges the notion that the enhanced data security of blockchain results in superior privacy. Blockchain's fundamental characteristics - immutability, decentralization, and transparency - promote an excessive reliance on historical data. This reliance, in turn, leads to inaccurate predictions and misguides consumer privacy preferences. The paper contends that this stern protection conflicts with the General Data Protection Regulation (GDPR) and the California Consumer Privacy Act (CCPA). We argue that the lack of choice in managing data denies freedom, causing psychological reactance. Additionally, the dependence on past data contributes to an intensified privacy paradox as consumers need to assert accurate privacy preferences. These combined effects result in increased consumer digital vulnerability, which arises from an imbalanced power dynamic in data management. We propose a novel approach, which we call “modified blockchain”. The approach is based on three pillars: i) selective immutability, ii) federal decentralization, and iii) supervised transparency. These pillars aim to effectively integrate regulations, organizations, and end-users within advocating for a socio-technical decision-making approach. This work also broadens the scope of the psychological reactance theory and the privacy paradox literature by affirming that a lack of autonomy in data management leads to digital vulnerability
Electronic commerce for development: a conceptual analysis and future research agenda for Africa
No full textInternational audienceDespite the e-commerce boom worldwide, Africa ranks last on all indicators of e-commerce readiness, indicating that it is not sufficiently benefiting from this practice's economic, social, and human development potential. This paper explores the role of research in promoting knowledge on how e-commerce can contribute to Africa’s development. It uses Jakubik’s knowledge creation theory and the scientometric perspective of knowledge diffusion to identify six main conceptual themes that characterize knowledge creation and diffusion through research on e-commerce in Africa using four different science mapping methods. Results show that knowledge created and disseminated through academic research on e-commerce in Africa is not adapted to what practitioners and policymakers need to better understand how e-commerce can promote development in Africa. We discuss six main points regarding this issue and propose recommendations for addressing them in future research
Law, Politics, and Trade Credit in China
No full textInternational audienceThis paper explores the interplay between politics and law enforcement in China and its effects on firm financing decisions. By examining a sample of corporate lawsuits involving listed firms in China, we find that politically connected firms are less likely to be defendants, have higher win rates, and experience shorter litigation durations than non-connected firms. Additionally, we observe that firms with higher legal risk extend more accounts receivable and receive less accounts payable, but this relationship holds only for non-connected firms. Our findings support the financing advantage theory for politically connected firms and the legal risk compensation view for non-connected firms. Moreover, reforms in China's judicial system do not appear to mitigate the disadvantages faced by non-connected firms in terms of lawsuit outcomes and trade credit provision. Our findings suggest that well-functioned judicial independence might be still lacking in China, and that political connections continue to negatively impact law enforcement and corporate policies
Revisiting “The CIA and the Media”: FOIA, Paperwork, and the Dialectic of (Media) Tactics and Strategies
No full textInternational audienceThis chapter focuses on the media tactics and strategies that shape the relationship between American journalism (as a collection of institutions, actors, practices, et cetera) and US state agencies, with the Central Intelligence Agency (CIA) receiving particular attention. The 1966 Freedom of Information Act (FOIA) and the complex paperwork associated with its functioning are considered a key locus for assessing these tactics and strategies, which are discussed both theoretically and through a specific case study: an attempt to write a follow-up historical piece to Carl Bernstein's famous article, “The CIA and the Media”, published in Rolling Stone magazine in 1977. Based on documents obtained through a FOIA demand, this chapter reflexively discusses a CIA training course called “Information Reporting, Reports and Requirements” and its connection to journalistic norms and practices
Le déploiement de l’expérimentation Parcours de Santé des Aînés comme mise en dispositif : temporalités, développement des liens et pilotage
No full textInternational audienceFaire face aux « problèmes pernicieux » ou aux « grands défis sociétaux » nécessite la collaboration de multiples organisations et acteurs afin d’innover dans des politiques publiques dites de gouvernance. Des modalités d’expérimentation sont régulièrement mobilisées pour comprendre et évaluer l’intérêt d’innovations de telles politiques publiques. La motivation de cette communication est assise sur l’intérêt théorique de renouveler la compréhension et la représentation du déploiement des expérimentations de gouvernance, et ce afin de dépasser une approche linéaire de type gestion de projet. Elle propose d’analyser les expérimentations de gouvernance comme « mise en dispositif », croisant la mobilisation en sciences de gestion du concept foucaldien de dispositif avec les approches par les processus. A partir de l’étude rétrospective de deux cas issus de l’expérimentation « Paerpa – Parcours de santé des aînés », les résultats contrastés des processus à l’œuvre permettent de mettre en évidence la variété des éléments du dispositif, au-delà de ceux fournis par le cadrage national. En outre, il est montré que l’intensité des liens entre acteurs est déterminante, prenant appui notamment sur un pilotage de proximité intensif impensé initialement. Enfin la conceptualisation par la mise en dispositif invite à s’écarter de la dichotomie conception/exécution pour appréhender un processus plus continu, dans lequel un dispositif incomplet mais opérationnel, est progressivement complété et les liens entre ses éléments renforcés
