Learning from failure

We study decentralized learning in organizations. Decentralization is captured through a symmetry constraint on agents’ strategies. Among such attainable strategies, we solve for optimal and equilibrium strategies. We model the organization as a repeated game with imperfectly observable actions. A fixed but unknown subset of action profiles are successes and all other action profiles are failures. The game is played until either there is a success or the time horizon is reached. For any time horizon, including infinity, we demonstrate existence of optimal attainable strategies and show that they are Nash equilibria. For some time horizons, we can solve explicitly for the optimal attainable strategies and show uniqueness. The solution connects the learning behavior of agents to the fundamentals that characterize the organization: Agents in the organization respond more slowly to failure as the future becomes more important, the size of the organization increases and the probability of success decreases.Game theory

MEK inhibition is a promising therapeutic strategy for MLL-rearranged infant acute lymphoblastic leukemia patients carrying RAS mutations

Acute lymphoblastic leukemia (ALL) in infants is an aggressive malignancy with a poor clinical outcome, and is characterized by translocations of the Mixed Lineage Leukemia (MLL) gene. Previously, we identified RAS mutations in 14-24% of infant ALL patients, and showed that the presence of a RAS mutation decreased the survival chances even further. We hypothesized that targeting the RAS signaling pathway could be a therapeutic strategy for RAS-mutant infant ALL patients. Here we show that the MEK inhibitors Trametinib, Selumetinib and MEK162 severely impair primary RAS-mutant MLL-rearranged infant ALL cells in vitro. While all RAS-mutant samples were sensitive to MEK inhibitors, we found both sensitive and resistant samples among RAS-wildtype cases. We confirmed enhanced RAS pathway signaling in RASmutant samples, but found no apparent downstream over-activation in the wildtype samples. However, we did confirm that MEK inhibitors reduced p-ERK levels, and induced apoptosis in the RAS-mutant MLL-rearranged ALL cells. Finally, we show that MEK inhibition synergistically enhances prednisolone sensitivity,

Organizing for Sustainability:A Guide to Developing New Business Models

This upper-level Open Access textbook aims to educate students and professionals on how to develop business models that have a positive impact on people, society, and the social and ecological environment. It explores a different view of how to organize value creation, from a focus on an almost exclusively monetary value creation to one that creates positive impact through multiple values. The book offers students and entrepreneurs a structured approach based through the Business Model Template (BMT). It consists of three stages and ten building blocks to facilitate the development of a business model. Users, be they students or practitioners, need to choose from one of the three offered business model archetypes, namely the platform, community, or circular business models. Each archetype offers a dedicated logic for vale creation. The book can be used to develop a business model from scratch (turning an idea into a working prototype) or to transform an existing business model into one of the three archetypes. Throughout the book extra sources, links to relevant online video clips, assignments and literature are offered to facilitate the development process. This book will be of interest to students studying the development of business models, sustainable management, innovation, and value creation. It will also be of interest executives, and professionals such as consultants or social entrepreneurs seeking further education

Seeing blue: negotiating the politics of Avatar media activism

This thesis examines how the Hollywood blockbuster Avatar (2009) has been taken-up in media activism directed towards Indigenous struggles against imperialism. It assumes the importance of locating this phenomenon within the discursive and material regimes that mediate, enable, and constrain it. I therefore offer a contextualised analysis of the film and media relating to its appropriation, which focuses on the representational practices and structural mechanisms that inform the production, circulation, and reception of the texts. This approach emphasises the tensions and contradictions that underpin activists’ relationship to the media they mobilise. Such contradictions are particularly apparent in relation to the politics of race that shape Avatar, the Indigenous activism that references it, and the media regimes that make this possible. The very forces that marginalise Indigenous voices empower auteur James Cameron to speak on their behalf and to be heard. Activists must also negotiate the tension between co-opting media spectacle and being commercialised as spectacle. However, refusing a simple critique of the representations activists deploy as media spectacles, I argue for a model that foregrounds the alliances that they seek to engender. Drawing on the work of feminist scholars Oliver (2001) and Deslandes (2010), I signal a theoretical approach that focuses on how the mediated spectator relates to such representations and insists on the spectator’s responsibility to respond. Acknowledging that the tensions that animate Avatar media activism can be both constrictive and creative, this project seeks a model that maximises the potential for the latter. It thus resists the paralysis of activism that can come with critiquing how we fight for the world we imagine