Mechanism-based model characterizing bidirectional interaction between PEGylated liposomal CKD-602 (S-CKD602) and monocytes in cancer patients

S-CKD602 is a PEGylated liposomal formulation of CKD-602, a potent topoisomerase I inhibitor. The objective of this study was to characterize the bidirectional pharmacokinetic-pharmacodynamic (PK-PD) interaction between S-CKD602 and monocytes. Plasma concentrations of encapsulated CKD-602 and monocytes counts from 45 patients with solid tumors were collected following intravenous administration of S-CKD602 in the phase I study. The PK-PD models were developed and fit simultaneously to the PK-PD data, using NONMEM®. The monocytopenia after administration of S-CKD602 was described by direct toxicity to monocytes in a mechanism-based model, and by direct toxicity to progenitor cells in bone marrow in a myelosuppression-based model. The nonlinear PK disposition of S-CKD602 was described by linear degradation and irreversible binding to monocytes in the mechanism-based model, and Michaelis-Menten kinetics in the myelosuppression-based model. The mechanism-based PK-PD model characterized the nonlinear PK disposition, and the bidirectional PK-PD interaction between S-CKD602 and monocytes. © 2012 Cárdenas et al, publisher and licensee Dove Medical Press Ltd

Multipoint measurements of the solar wind: A proposed advance for studying magnetized turbulence

A multi-institutional, multi-national science team will soon submit a NASA proposal to build a constellation of spacecraft to fly into the near-Earth solar wind in a swarm spanning a multitude of scales in order to obtain critically needed measurements that will reveal the underlying dynamics of magnetized turbulence. This white paper, submitted to the Plasma 2020 Decadal Survey Committee, provides a brief overview of turbulent systems that constitute an area of compelling plasma physics research, including why this mission is needed, and how this mission will achieve the goal of revealing how energy is transferred across scales and boundaries in plasmas throughout the universe

HelioSwarm: A Multipoint, Multiscale Mission to Characterize Turbulence

Acknowledgements: We are deeply indebted to the incredible members of the HelioSwarm science, engineering, and proposal teams whose tireless efforts enabled this mission.AbstractHelioSwarm (HS) is a NASA Medium-Class Explorer mission of the Heliophysics Division designed to explore the dynamic three-dimensional mechanisms controlling the physics of plasma turbulence, a ubiquitous process occurring in the heliosphere and in plasmas throughout the universe. This will be accomplished by making simultaneous measurements at nine spacecraft with separations spanning magnetohydrodynamic and sub-ion spatial scales in a variety of near-Earth plasmas. In this paper, we describe the scientific background for the HS investigation, the mission goals and objectives, the observatory reference trajectory and instrumentation implementation before the start of Phase B. Through multipoint, multiscale measurements, HS promises to reveal how energy is transferred across scales and boundaries in plasmas throughout the universe.</jats:p