The Energetic Particle Detector (EPD) Investigation is one of five particles and fields investigations on the Magnetospheric Multiscale (MMS) mission. This mission consists of four satellites operating in close proximity in elliptical, low-inclination orbits, and is focused upon the fundamental physics of magnetic reconnection. The Energetic Particle Detector (EPD) investigation aboard the four MMS spacecraft consists of two instrument designs, the EIS (Energetic Ion Spectrometer) and the FEEPS (Fly's Eye Electron Proton Spectrometer). This present paper describes FEEPS from an instrument physics and engineering point of view, and provides some test and calibration data to facilitate effective analysis and use of the flight data for scientific purposes.A FEEPS consists of six Heads, each composed of two Eyes. Each eye is a particle telescope with a single silicon detector; there are nine electron eyes and three ion eyes per FEEPS. The energy coverage is from 25 keV to 650 keV for electrons and 45 keV to 650 keV for ions. Each eye has sixteen energy channels, the spacing of which can be modified by command. The fields of view and pointing of each eye are designed to provide a broad, instantaneous field of view for the twelve eyes per FEEPS.There are two FEEPS per MMS spacecraft mounted such that the pair along with the single EIS provide more than 3π-sr instantaneous solid-angle coverage and complete coverage in the equatorial region. A twenty-second spacecraft rotation period is divided into sixty-four sectors to provide detailed temporal and spatial sampling.

No abstract

The effect of surface PEGylation on nanoparticle transport through an extracellular matrix (ECM) is an important determinant for tumor targeting success. Fluorescent stealth liposomes (base lipid DOPC) were prepared incorporating different proportions of PEG-grafted lipids (2.5, 5 and 10% of the total lipid content) for a series of PEG molecular weights (1000, 2000 and 5000 Da). The ECM was modelled using a collagen matrix. The kinetics of PEGylated liposome adhesion to and transport in collagen matrices were tracked using fluorescence correlation spectroscopy (FCS) and confocal microscopy, respectively.Generalized least square regressions were used to determine the temporal correlations between PEG molecular weight, surface density and conformation, and the liposome transport in a collagen hydrogel over 15 hours. PEG conformation determined the interaction of liposomes with the collagen hydrogel and their transport behaviour. Interestingly, liposomes with mushroom PEG conformation accumulated on the interface of the collagen hydrogel, creating a dense liposomal front with short diffusion distances into the hydrogels. On the other hand, liposomes with dense brush PEG conformation interacted to a lesser extent with the collagen hydrogel and diffused to longer distances. In conclusion, a better understanding of PEG surface coating as a modifier of transport in a model ECM matrix has resulted. This knowledge will improve design of future liposomal drug carrier systems.

Nanoparticles are increasingly used in medical applications such as drug delivery, imaging, and biodiagnostics, particularly for cancer. The design of nanoparticles for tumor delivery has been largely empirical, owing to a lack of quantitative data on angiogenic tissue sequestration. Using fluorescence correlation spectroscopy, the deposition rate constants of nanoparticles into angiogenic blood vessel tissue are determined. It is shown that deposition is dependent on surface charge. Moreover, the size dependency strongly suggests that nanoparticles are taken up by a passive mechanism that depends largely on geometry. These findings imply that it is possible to tune nanoparticle pharmacokinetics simply by adjusting nanoparticle size.

Currently, the molecular mechanism for membrane fusion remains unconfirmed. The most compelling suggested mechanism is the stalk hypothesis, which states that membrane fusion proceeds via stalk formation/hemifusion, among other steps. Because the stalk would have a very high radius of curvature, small lipophilic molecules could enhance fusion by lowering the energy barrier to stalk formation. We previously showed that the general anesthetic halothane is capable of inducing membrane fusion in 1,2-dileoyl-sn-3-glycero-3-phospocholine (DOPC) vesicles. In the present study, we examined other small molecules, general anesthetics (chloroform, isoflurane, enflurane, and sevoflurane), to determine whether they exhibit fusion properties with model lipid membranes similar to those of halothane. We employed both two-photon excitation fluorescence cross-correlation spectroscopy (TPE-FCCS) and steady-state fluorescence dequenching (FD) assays. Using volatile general anesthetics as novel fusion agents, we also aimed to gain a better understanding of the membrane fusion mechanism at a molecular level. We found that lipid mixing or lipid rearrangement, which is required for the formation of the fusion-state intermediates and the fusion pore, rather than the association of lipid vesicles, is rate-limiting. In addition, halothane and chloroform were found to induce lipid mixing (rearrangement) to a greater extent than isoflurane, enflurane, and sevoflurane. Finally, it is proposed that the efficiency of these general anesthetics as fusion agents is related to their partition coefficients, water solubilities, polarities, and molecular volumes, all of which affect the ability of each anesthetic to perturb the contacting bilayer membranes of fusing vesicles.