The Johns Hopkins Applied Physics Laboratory
The Johns Hopkins Applied Physics Laboratory
Vrana J.A.,West Virginia University |
Boggs N.,The Johns Hopkins Applied Physics Laboratory |
Currie H.N.,West Virginia University |
Boyd J.,West Virginia University
Toxicon | Year: 2013
The pharmaceutical world has greatly benefited from the well-characterized structure-function relationships of toxins with endogenous biomolecules, such as ion-channels, receptors, and signaling molecules. Thus, therapeutics derived from toxins have been aggressively pursued. However, the multifunctional role of various toxins may lead to undesirable off-target effects, hindering their use as therapeutic agents. In this paper, we suggest that previously unsuccessful toxins (due to off-target effects) may be revisited with mixtures by utilizing the pharmacodynamic response to the potential primary therapeutic as a starting point for finding new targets to ameliorate the unintended responses. In this proof of principle study, the pharmacodynamic response of HepG2 cells to a potential primary therapeutic (deguelin, a plant-derived chemopreventive agent) was monitored, and a possible secondary target (p38MAPK) was identified. As a single agent, deguelin decreased cellular viability at higher doses (>10μM), but inhibited oxygen consumption over a wide dosing range (1.0-100μM). Our results demonstrate that inhibition of oxygen consumption is related to an increase in p38MAPK phosphorylation, and may only be an undesired side effect of deguelin (i.e., one that does not contribute to the decrease in HepG2 viability). We further show that deguelin's negative effect on oxygen consumption can be diminished while maintaining efficacy when used as a therapeutic mixture with the judiciously selected secondary inhibitor (SB202190, p38MAPK inhibitor). These preliminary findings suggest that an endogenous response-directed mixtures approach, which uses a pharmacodynamic response to a primary therapeutic to determine a secondary target, allows previously unsuccessful toxins to be revisited as therapeutic mixtures. © 2013 Elsevier Ltd.
Wilson J.T.,Durham University |
Wilson J.T.,The Johns Hopkins Applied Physics Laboratory |
Eke V.R.,Durham University |
Massey R.J.,Durham University |
And 4 more authors.
Icarus | Year: 2018
We present a map of the near subsurface hydrogen distribution on Mars, based on epithermal neutron data from the Mars Odyssey Neutron Spectrometer. The map's spatial resolution is approximately improved two-fold via a new form of the pixon image reconstruction technique. We discover hydrogen-rich mineralogy far from the poles, including ∼10 wt.% water equivalent hydrogen (WEH) on the flanks of the Tharsis Montes and >40 wt.% WEH at the Medusae Fossae Formation (MFF). The high WEH abundance at the MFF implies the presence of bulk water ice. This supports the hypothesis of recent periods of high orbital obliquity during which water ice was stable on the surface. We find the young undivided channel system material in southern Elysium Planitia to be distinct from its surroundings and exceptionally dry; there is no evidence of hydration at the location in Elysium Planitia suggested to contain a buried water ice sea. Finally, we find that the sites of recurring slope lineae (RSL) do not correlate with subsurface hydration. This implies that RSL are not fed by large, near-subsurface aquifers, but are instead the result of either small (< 120 km diameter) aquifers, deliquescence of perchlorate and chlorate salts or dry, granular flows. © 2017 Elsevier Inc.
Calderon-Colon X.,The Johns Hopkins Applied Physics Laboratory |
Benkoski J.J.,The Johns Hopkins Applied Physics Laboratory |
Patrone J.B.,The Johns Hopkins Applied Physics Laboratory
Journal of Visualized Experiments | Year: 2015
Nanoparticle-based delivery vehicles have shown great promise for intracellular targeting applications, providing a mechanism to specifically alter cellular signaling and gene expression. In a previous investigation, the synthesis of ultra-small solid lipid nanoparticles (SLNs) for topical drug delivery and biomarker detection applications was demonstrated. SLNs are a well-studied example of a nanoparticle delivery system that has emerged as a promising drug delivery vehicle. In this study, SLNs were loaded with a fluorescent dye and used as a model to investigate particle-cell interactions. The phase inversion temperature (PIT) method was used for the synthesis of ultra-small populations of biocompatible nanoparticles. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylphenyltetrazolium bromide (MTT) assay was utilized in order to establish appropriate dosing levels prior to the nanoparticle-cell interaction studies. Furthermore, primary human dermal fibroblasts and mouse dendritic cells were exposed to dye-loaded SLN over time and the interactions with respect to toxicity and particle uptake were characterized using fluorescence microscopy and flow cytometry. This study demonstrated that ultra-small SLNs, as a nanoparticle delivery system, are suitable for intracellular targeting of different cell types. © 2015 Journal of Visualized Experiments.
PubMed | The Johns Hopkins Applied Physics Laboratory
Type: | Journal: Journal of visualized experiments : JoVE | Year: 2015
Nanoparticle-based delivery vehicles have shown great promise for intracellular targeting applications, providing a mechanism to specifically alter cellular signaling and gene expression. In a previous investigation, the synthesis of ultra-small solid lipid nanoparticles (SLNs) for topical drug delivery and biomarker detection applications was demonstrated. SLNs are a well-studied example of a nanoparticle delivery system that has emerged as a promising drug delivery vehicle. In this study, SLNs were loaded with a fluorescent dye and used as a model to investigate particle-cell interactions. The phase inversion temperature (PIT) method was used for the synthesis of ultra-small populations of biocompatible nanoparticles. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylphenyltetrazolium bromide (MTT) assay was utilized in order to establish appropriate dosing levels prior to the nanoparticle-cell interaction studies. Furthermore, primary human dermal fibroblasts and mouse dendritic cells were exposed to dye-loaded SLN over time and the interactions with respect to toxicity and particle uptake were characterized using fluorescence microscopy and flow cytometry. This study demonstrated that ultra-small SLNs, as a nanoparticle delivery system, are suitable for intracellular targeting of different cell types.
Thomson B.J.,The Johns Hopkins Applied Physics Laboratory |
Bridges N.T.,The Johns Hopkins Applied Physics Laboratory |
Milliken R.,University of Notre Dame |
Baldridge A.,Planetary Science Institute |
And 6 more authors.
Icarus | Year: 2011
Gale Crater contains a 5.2. km-high central mound of layered material that is largely sedimentary in origin and has been considered as a potential landing site for both the MER (Mars Exploration Rover) and MSL (Mars Science Laboratory) missions. We have analyzed recent data from Mars Reconnaissance Orbiter to help unravel the complex geologic history evidenced by these layered deposits and other landforms in the crater. Results from imaging data from the High Resolution Imaging Science Experiment (HiRISE) and Context Camera (CTX) confirm geomorphic evidence for fluvial activity and may indicate an early lacustrine phase. Analysis of spectral data from the CRISM (Compact Reconnaissance Imaging Spectrometer for Mars) instrument shows clay-bearing units interstratified with sulfate-bearing strata in the lower member of the layered mound, again indicative of aqueous activity. The formation age of the layered mound, derived from crater counts and superposition relationships, is ∼3.6-3.8. Ga and straddles the Noachian-Hesperian time-stratigraphic boundary. Thus Gale provides a unique opportunity to investigate global environmental change on Mars during a period of transition from an environment that favored phyllosilicate deposition to a later one that was dominated by sulfate formation. © 2011 Elsevier Inc.
McSween H.Y.,University of Tennessee at Knoxville |
Labotka T.C.,University of Tennessee at Knoxville |
Viviano-Beck C.E.,The Johns Hopkins Applied Physics Laboratory
Meteoritics and Planetary Science | Year: 2015
Compositions of basaltic and ultramafic rocks analyzed by Mars rovers and occurring as Martian meteorites allow predictions of metamorphic mineral assemblages that would form under various thermophysical conditions. Key minerals identified by remote sensing roughly constrain temperatures and pressures in the Martian crust. We use a traditional metamorphic approach (phase diagrams) to assess low-grade/hydrothermal equilibrium assemblages. Basaltic rocks should produce chlorite + actinolite + albite + silica, accompanied by laumontite, pumpellyite, prehnite, or serpentine/talc. Only prehnite-bearing assemblages have been spectrally identified on Mars, although laumontite and pumpellyite have spectra similar to other uncharacterized zeolites and phyllosilicates. Ultramafic rocks are predicted to produce serpentine, talc, and magnesite, all of which have been detected spectrally on Mars. Mineral assemblages in both basaltic and ultramafic rocks constrain fluid compositions to be H2O-rich and CO2-poor. We confirm the hypothesis that low-grade/hydrothermal metamorphism affected the Noachian crust on Mars, which has been excavated in large craters. We estimate the geothermal gradient (>20 °C km-1) required to produce the observed assemblages. This gradient is higher than that estimated from radiogenic heat-producing elements in the crust, suggesting extra heating by regional hydrothermal activity. © The Meteoritical Society, 2014.
News Article | January 19, 2016
Since the 1950s, when scientists first began forming a picture of these rings of energetic particles, our understanding of their shape has largely remained unchanged—a small, inner belt, a largely-empty space known as the slot region, and then the outer belt, which is dominated by electrons and which is the larger and more dynamic of the two. But a new study of data from NASA's Van Allen Probes reveals that the story may not be so simple. "The shape of the belts is actually quite different depending on what type of electron you're looking at," said Geoff Reeves from Los Alamos National Laboratory and the New Mexico Consortium in Los Alamos, New Mexico, lead author on the study published on Dec. 28, 2015, in the Journal of Geophysical Research. "Electrons at different energy levels are distributed differently in these regions." Rather than the classic picture of the radiation belts—small inner belt, empty slot region and larger outer belt—this new analysis reveals that the shape can vary from a single, continuous belt with no slot region, to a larger inner belt with a smaller outer belt, to no inner belt at all. Many of the differences are accounted for by considering electrons at different energy levels separately. "It's like listening to different parts of a song," said Reeves. "The bass line sounds different from the vocals, and the vocals are different from the drums, and so on." The researchers found that the inner belt—the smaller belt in the classic picture of the belts—is much larger than the outer belt when observing electrons with low energies, while the outer belt is larger when observing electrons at higher energies. At the very highest energies, the inner belt structure is missing completely. So, depending on what one focuses on, the radiation belts can appear to have very different structures simultaneously. These structures are further altered by geomagnetic storms. When fast-moving magnetic material from the sun—in the form of high-speed solar wind streams or coronal mass ejections—collide with Earth's magnetic field, they send it oscillating, creating a geomagnetic storm. Geomagnetic storms can increase or decrease the number of energetic electrons in the radiation belts temporarily, though the belts return to their normal configuration after a time. These storm-driven electron increases and decreases are currently unpredictable, without a clear pattern showing what type or strength of storm will yield what outcomes. There's a saying in the space physics community: if you've seen one geomagnetic storm, you've seen one geomagnetic storm. As it turns out, those observations have largely been based on electrons at only a few energy levels. "When we look across a broad range of energies, we start to see some consistencies in storm dynamics," said Reeves. "The electron response at different energy levels differs in the details, but there is some common behavior. For example, we found that electrons fade from the slot regions quickly after a geomagnetic storm, but the location of the slot region depends on the energy of the electrons." Often, the outer electron belt expands inwards toward the inner belt during geomagnetic storms, completely filling in the slot region with lower-energy electrons and forming one huge radiation belt. At lower energies, the slot forms further from Earth, producing an inner belt that is bigger than the outer belt. At higher energies, the slot forms closer to Earth, reversing the comparative sizes. The twin Van Allen Probes satellites expand the range of energetic electron data we can capture. In addition to studying the extremely high-energy electrons—carrying millions of electron volts—that had been studied before, the Van Allen Probes can capture information on lower-energy electrons that contain only a few thousand electron volts. Additionally, the spacecraft measure radiation belt electrons at a greater number of distinct energies than was previously possible. "Previous instruments would only measure five or ten energy levels at a time," said Reeves. "But the Van Allen Probes measure hundreds." Measuring the flux of electrons at these lower energies has proved difficult in the past because of the presence of protons in the radiation belt regions closest to Earth. These protons shoot through particle detectors, creating a noisy background from which the true electron measurements needed to be picked out. But the higher-resolution Van Allen Probes data found that these lower-energy electrons circulate much closer to Earth than previously thought. "Despite the proton noise, the Van Allen Probes can unambiguously identify the energies of the electrons it's measuring," said Reeves. Precise observations like this, from hundreds of energy levels, rather than just a few, will allow scientists to create a more precise and rigorous model of what, exactly, is going on in the radiation belts, both during geomagnetic storms and during periods of relative calm. "You can always tweak a few parameters of your theory to get it to match observations at two or three energy levels," said Reeves. "But having observations at hundreds of energies constrain the theories you can match to observations." The Johns Hopkins Applied Physics Laboratory in Laurel, Maryland, built and operates the Van Allen Probes for NASA's Science Mission Directorate. The mission is the second mission in NASA's Living With a Star program, managed by NASA's Goddard Space Flight Center in Greenbelt, Maryland. Explore further: Los Alamos provides HOPE for radiation belt storm probes
Pham K.H.,University of Texas at Arlington |
Pham K.H.,West Virginia University |
Lopez R.E.,University of Texas at Arlington |
Bruntz R.,The Johns Hopkins Applied Physics Laboratory
Journal of Geophysical Research A: Space Physics | Year: 2016
In this paper we examine the response of the magnetosphere-ionopshere (M-I) system to a transient northward excursion in the interplanetary magnetic field (IMF) using the Lyon-Fedder-Mobarry (LFM) global MHD simulation. The simulated IMF transitions hold from a steady southward IMF to a steady northward IMF before suddenly transitioning back to southward IMF after 20 min. Once the IMF returns southward, the M-I system is in a state of reduced energy dissipation for approximately an hour as it reconfigures back into a standard southward IMF configuration. We find that the northward IMF excursion affects both the viscous and reconnection interactions with the solar wind. The flow of plasma in the magnetosphere is significantly disrupted by the reconnection cycle under northward IMF. This reduce the transfer of mechanical energy from the solar wind due to the viscous interaction, and the magnetosphere-ionosphere system is in a mixed topological configuration containing elements produced by both of southward IMF reconnection and the Dungey cycle, as well as northward IMF reconnection and the presence of reverse cell convection at high latitudes. The effects of the transient northward IMF must be completely cleared out before the system can return to an optimal state of energy transfer characteristic of steady southward IMF. As a result, a simple 20 min excursion of northward IMF can put the magnetosphere-ionosphere system into a reduced state of coupling to the solar wind for some time following the return to steady southward IMF; for LFM we saw a reduced state lasting an hour. ©2016. American Geophysical Union. All Rights Reserved.
Drivas T.D.,The Johns Hopkins Applied Physics Laboratory |
Drivas T.D.,Johns Hopkins University |
Wunsch S.,The Johns Hopkins Applied Physics Laboratory
Ocean Modelling | Year: 2016
Weakly nonlinear theory is used to explore the effect of vertical shear on surface gravity waves in three dimensions. An idealized piecewise-linear shear profile motivated by wind-driven profiles and ambient currents in the ocean is used. It is shown that shear may mediate weakly nonlinear resonant triad interactions between gravity and vorticity waves. The triad results in energy exchange between gravity waves of comparable wavelengths propagating in different directions. For realistic ocean shears, shear-mediated energy exchange may occur on timescales of minutes for shorter wavelengths, but slows as the wavelength increases. Hence this triad mechanism may contribute to the larger angular spreading (relative to wind direction) for shorter wind-waves observed in the oceans. © 2015 Elsevier Ltd.
Bucior S.,The Johns Hopkins Applied Physics Laboratory |
Sepan R.,The Johns Hopkins Applied Physics Laboratory |
Bechtold K.,The Johns Hopkins Applied Physics Laboratory |
Jones M.R.,The Johns Hopkins Applied Physics Laboratory |
Dharmavaram P.,The Johns Hopkins Applied Physics Laboratory
IEEE Aerospace Conference Proceedings | Year: 2016
The New Horizons (NH) mission, part of NASA's New Frontiers Program, completed the first reconnaissance flyby of the Pluto system on July 14, 2015. NH successfully passed through the Pluto/Charon system taking hundreds of observations of never before seen worlds. To make this flyby successful, the Mission Operations Team carried numerous responsibilities. One part of the Mission Ops Team is the Flight Control Team, which handles real-time communications with the spacecraft. This paper will discuss the main Flight Controller tasks that were needed for success and how each was unique to the New Horizons mission. These include how the large Round Trip Light Time (RTLT), just under 9 hours at the time of the Pluto encounter, affected real-time operations. Other aspects affecting flight control included the separation of uplink and downlink tracks as the spacecraft began to perform more operations, spacecraft ranging, 2-Way to 3-Way mode transitions with the Deep Space Network (DSN), Critical Optical Navigation processing that team members needed to perform in a specific time window, and Solid State Recording (SSR) downlink maintenance. Also, many different unique DSN configurations needed to be tested and executed, including 2 TWTA dual-polarization downlink tracks, multiple antenna arraying tracks, and Radio science EXperiment (REX) uplinks. In the months leading up to closest approach, the number of shifts for the Flight Controllers (FCs) increased once the spacecraft left hibernation but shift times remained erratic per the DSN scheduling constraints with other missions. The team needed to make sure that people were given enough time to be rested and also that the correct information was being passed on to the next shift without a real-time handover. For the 9-day encounter sequence, we had near 24-hour antenna coverage. Outside of these 9 days, each shift consisted of a two-person crew. During the encounter period we used 3 people per shift on a staggered rotation for smoother shift handovers and well rested controllers. The FC team also added two full-time interns that were trained before the encounter to help the team with schedule relief. The FCs used many tools to keep track of pertinent information, including an electronic console log, a command tracker spreadsheet for command verification after the 9 hour wait, and a status board for quick-glance information about the most recent contact with the spacecraft. The flyby was a success and the healthy spacecraft is now continuing through the Kuiper Belt. Amazing pictures are coming down now and will for many months to come, giving the scientists many years' worth of data for analysis. © 2016 IEEE.