NASA Standing Review Board Handbook

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A multi-targeted approach to suppress tumor-promoting inflammation

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes

Seasonal Change on Saturn from Cassini/CIRS Observations, 2004-2009

Five years of thermal infrared spectra from the Cassini Composite Infrared Spectrometer (CIRS) are analyzed to determine the response of Saturn's atmosphere to seasonal changes in insolation. Hemispheric mapping sequences at 15.0 cm-1 spectral resolution are used to retrieve the variation in the zonal mean temperatures in the stratosphere (0.5-5.0 mbar) and upper troposphere (75-800 mbar) between October 2004 (shortly after the summer solstice in the southern hemisphere) and July 2009 (shortly before the autumnal equinox). Saturn's northern mid-latitudes show signs of dramatic warming in the stratosphere (by 6-10 K) as they emerge from ring-shadow into springtime conditions, whereas southern mid-latitudes show evidence for cooling (4-6 K). The 40-K asymmetry in stratospheric temperatures between northern and southern hemispheres (at 1 mbar) slowly decreased during the timespan of the observations. Tropospheric temperatures also show temporal variations but with a smaller range, consistent with the increasing radiative time constant of the atmospheric response with increasing pressure. The tropospheric response to the insolation changes shows the largest magnitude at the locations of the broad retrograde jets. Saturn's warm south-polar stratospheric hood has cooled over the course of the mission, but remains present. Stratospheric temperatures are compared to a radiative climate model which accounts for the spatial distribution of the stratospheric coolants. The model successfully predicts the magnitude and morphology of the observed changes at most latitudes. However, the model fails at locations where strong dynamical perturbations dominate the temporal changes in the thermal field, such as the hot polar vortices and the equatorial semi-annual oscillation (Orton, G., and 27 colleagues [2008]. Nature 453, 196-198). Furthermore, observed temperatures in Saturn's ring-shadowed regions are larger than predicted by all radiative-climate models to date due to the incomplete characterization of the dynamical response to the shadow. Finally, far-infrared CIRS spectra are used to demonstrate variability of the para-hydrogen distribution over the 5-year span of the dataset, which may be related to observed changes in Saturn's tropospheric haze in the spring hemisphere

Understanding Temporal and Spatial Variability of the Lunar Helium Atmosphere Using Simultaneous Observations from LRO, LADEE, and ARTEMIS

Simultaneous measurements of helium in the exosphere of the Moon are made from the Lunar Reconnaissance Orbiter (LRO) Lyman Alpha Mapping Project (LAMP) and the Lunar Atmosphere and Dust Environment Explorer (LADEE) Neutral Mass Spectrometer (NMS) through the entire 5-month span of the LADEE mission. In addition, the ARTEMIS mission monitored the solar wind alpha particle flux to the Moon. Modeling the lunar helium exosphere, we relate the LAMP polar observations to the LADEE equatorial observations. Further, using the ARTEMIS alpha flux in the Monte Carlo model reproduces the temporal variations in helium density. Comparing the LAMP data to the LADEE data shows excellent agreement. Comparing those with the ARTEMIS data reveals that the solar wind alpha flux is the primary driver to variability in the helium exosphere throughout the LADEE mission. Using a decay time for exospheric helium of 5 days, we determine that the solar wind contributes 64 +/- 5% of the helium to the lunar exosphere. The remaining 36 +/- 5% is presumed to come from outgassing of radiogenic helium from the interior of the Moon. Furthermore, the model reproduces the measurements if 63 +/- 6% of the incident alpha particles are converted to thermalized helium atoms through the interaction between the alphas and the lunar surface. However, these values are dependent on both inferred source rates from LAMP and LADEE observations and on the assumed time constant of the exospheric decay rate

Synthesis and Characterization of Structurally Diverse Alkaline-Earth Salen Compounds for Subterranean Fluid Flow Tracking

A family of magnesium and calcium salen-derivatives was synthesized and characterized for use as subterranean fluid flow monitors. For the Mg complexes, di-<i>n</i>-butyl magnesium ([Mg­(Bu^<i>n</i>)₂]) was reacted with <i>N</i>,<i>N</i>′-ethylene bis­(salicylideneimine) (H₂-salen), <i>N</i>,<i>N</i>′-bis­(salicylidene)-1,2-phenylenediamine (H₂-saloPh), <i>N</i>,<i>N</i>′-bis­(3,5-di-<i>t</i>-butylsalicylidene)-ethylenediamine (H₂-salo-Bu^<i>t</i>), or <i>N</i>,<i>N</i>′-bis­(3,5-di-<i>t</i>-butylsalicylidene)-1,2-phenylenediamine (H₂-saloPh-Bu^<i>t</i>), and the products were identified by single-crystal X-ray diffraction as [(κ³-(O,N,N′),μ-(O′)­saloPh)­(μ-(O),(κ²-(N,N′),μ-(O′)­saloPh)₂­(μ-(O),κ³-(N,N′,O′)­saloPh′)­Mg₄]·2tol (<b>1</b>·2tol; saloPh′ = an alkyl-modified saloPh derivative generated in situ), [(κ⁴-(O,N,N′,O′)­saloPh)­Mg­(py)₂]·py (<b>2</b>·py), [(κ⁴-(O,N,N′,O′)­salo-Bu^<i>t</i>)­Mg­(py)₂] (<b>3</b>), [(κ⁴-(O,N,N′,O′)­saloPh-Bu^<i>t</i>)­Mg­(py)₂]·tol (<b>4</b>·tol), and [(κ³-(O,N,N′),μ-(O′)­saloPh-Bu^<i>t</i>)­Mg]₂ (<b>5</b>), where tol = toluene; py = pyridine. For the Ca species, a calcium amide was independently reacted with H₂-salo-Bu^<i>t</i> and H₂-saloPh-Bu^<i>t</i> to generate the crystallographcially characterized compounds: [(κ⁴-(O,N,N′,O′)­salo-Bu^<i>t</i>)­Ca­(py)₃] (<b>6</b>), [(κ⁴-(O,N,N′,O′)­saloPh-Bu^<i>t</i>)­Ca­(py)₃]·py (<b>7</b>·py). The bulk powders of these compounds were further characterized by a number of analytical tools, where <b>2</b>–<b>7</b> were found to be distinguishable by Fourier transform infrared and resonance Raman spectroscopies. Structural properties obtained from quantum calculations of gas-phase analogues are in good agreement with the single-crystal results. The potential utility of these compounds as taggants for monitoring subterranean fluid flows was demonstrated through a series of experiments to evaluate their stability to high temperature and pressure, interaction with mineral surfaces, and elution behavior from a loaded proppant pack