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p53 is a crucial regulator of cell response to DNA damage. MDM4 and MDM2 are the two main negative regulators of p53 activity. Upon DNA damage, their constraint is released and p53 becomes activated and exerts its safeguard function by arresting cell growth or by killing excessively damaged cells. Under these conditions, increasing data suggest that MDM4 and MDM2 play novel roles. In this respect, we recently published that MDM4 exerts a positive activity towards p53 mitochondrial apoptosis. We observed that a fraction of MDM4 stably localizes at the mitochondria where upon lethal stress conditions, promotes the mitochondrial localization of p53 phosphorylated at Ser46 (p53Ser46(P)) and facilitates its binding to BCL2, cytochrome C release and apoptosis. Most importantly, we observed a correlation of MDM4 expression with cisplatin-resistance in a group of human ovarian cancers suggesting that MDM4 proapoptotic activity may have in vivo relevance. Here, we discuss about these and some new findings and compare them with previous data trying to settle some apparent contradictions. In addition, this review discusses the potential relevance of our data to the field of human cancer.
Exploring Gridmap-based Interfaces for the Remote Control of UAVs under Bandwidth Limitations
(2017)
This book constitutes the thoroughly refereed post-conference proceedings of the 15th International Conference on Smart Card Research and Advanced Applications, CARDIS 2016, held in Cannes, France, in November 2016. The 15 revised full papers presented in this book were carefully reviewed and selected from 29 submissions. The focus of the conference was on all aspects of the design, development, deployment, validation, and application of smart cards or smart personal devices.
Unternehmen stehen oft vor der Frage, nach welchen Kriterien Investitionsentscheidungen in anderen Ländern und an ausländischen Standorten – ggf. im Wettbewerb zu anderen Geografien – zu treffen sind. Aufgrund der schwierigen Revidierbarkeit von Standortentscheidungen ist zu erwarten, dass die Unternehmen eine Vielzahl von Kriterien in ihre Überlegungen einbeziehen und die in Betracht kommenden Standorte diesbezüglich komparativ prüfen.
The MAP-Elites algorithm produces a set of high-performing solutions that vary according to features defined by the user. This technique has the potential to be a powerful tool for design space exploration, but is limited by the need for numerous evaluations. The Surrogate-Assisted Illumination algorithm (SAIL), introduced here, integrates approximative models and intelligent sampling of the objective function to minimize the number of evaluations required by MAP-Elites.
The ability of SAIL to efficiently produce both accurate models and diverse high performing solutions is illustrated on a 2D airfoil design problem. The search space is divided into bins, each holding a design with a different combination of features. In each bin SAIL produces a better performing solution than MAP-Elites, and requires several orders of magnitude fewer evaluations. The CMA-ES algorithm was used to produce an optimal design in each bin: with the same number of evaluations required by CMA-ES to find a near-optimal solution in a single bin, SAIL finds solutions of similar quality in every bin.