Lessons learned from (and since) the Voyager 2 flybys of Uranus and Neptune
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES
Authors: Hammel, Heidi B.
Abstract
More than 30 years have passed since the Voyager 2 flybys of Uranus and Neptune. This paper outlines a range of lessons learned from Voyager, broadly grouped into 'process, planning and people.' In terms of process, we must be open to new concepts, whether new instrument technologies, new propulsion systems or operational modes. Examples from recent decades that could open new vistas in the exploration of the deep outer Solar System include the Cassini Resource Exchange and the 'sleep' mode from the New Horizons mission. Planning is crucial: mission gaps that last over three decades leave much scope for evolution both in mission development and in the targets themselves. The science is covered in other papers in this issue, but this paper addresses the structure of the US Planetary Decadal Surveys, with a specific urging to move from a 'destination-based' organization to a structure based on fundamental science. Coordination of distinct and divergent international planning timelines brings both challenges and opportunity. Complexity in the funding and political processes is amplified when multiple structures must be navigated; but the science is enriched by the diversity of international perspectives, as were represented at the Ice Giant discussion meeting that motivated this review. Finally, the paper turns to people: with generational-length gaps between missions, continuity in knowledge and skills requires careful attention to people. Lessons for the next generation of voyagers include: how to lead and inspire; how to develop the perspective to see their missions through decades-long development phases; and cultivation of strategic thinking, altruism and above all, patience. This article is part of a discussion meeting issue 'Future exploration of ice giant systems'.
Identification of CD24 as a potential diagnostic and therapeutic target for malignant pleural mesothelioma
CELL DEATH DISCOVERY
Authors: Karnan, Sivasundaram; Ota, Akinobu; Murakami, Hideki; Rahman, Lutfur; Hasan, Muhammad Nazmul; Wahiduzzaman; Hanamura, Ichiro; Lam Quang Vu; Inoko, Akihito; Hyodo, Toshinori; Konishi, Hiroyuki; Tsuzuki, Shinobu; Hosokawa, Yoshitaka
Abstract
Malignant pleural mesothelioma (MPM) is an aggressive malignancy of the pleura that is currently incurable due to the lack of an effective early diagnostic method and specific medication. The CDKN2A (p16) and NF2 genes are both frequently mutated in MPM. To understand how these mutations contribute to MPM tumor growth, we generated NF2/p16 double-knockout (DKO) cell clones using human MeT-5A and HOMC-B1 mesothelial cell lines. Cell growth and migration activities were significantly increased in DKO compared with parental cells. cDNA microarray analysis revealed differences in global gene expression profiles between DKO and parental cells. Quantitative PCR and western blot analyses showed upregulation of CD24 concomitant with increased phosphorylation of AKT, p70S6K, and c-Jun in DKO clones. This upregulation was abrogated by exogenous expression of NF2 and p16. CD24 knockdown in DKO cells significantly decreased TGF-beta 1 expression and increased expression of E-cadherin, an epithelial-mesenchymal transition marker. CD24 was highly expressed in human mesothelioma tissues (28/45 cases, 62%) and associated with the loss of NF2 and p16. Public data analysis revealed a significantly shorter survival time in MPM patients with high CD24 gene expression levels. These results strongly indicate the potential use of CD24 as a prognostic marker as well as a novel diagnostic and therapeutic target for MPM.