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At least 73 records · Page 4

Signature analysis of high-throughput transcriptomics screening data for mechanistic inference and chemical grouping

Abstract High-throughput transcriptomics (HTTr) uses gene expression profiling to characterize the biological activity of chemicals in in vitro cell-based test systems. As an extension of a previous study testing 44 chemicals, HTTr was used to screen an additional 1,751 unique chemicals from the EPA’s ToxCast collection in MCF7 cells using 8 concentrations and an exposure duration of 6 h. We hypothesized that concentration-response modeling of signature scores could be used to identify putative molecular targets and cluster chemicals with similar bioactivity. Clustering and enrichment analyses were conducted based on signature catalog annotations and ToxPrint chemotypes to facilitate molecular target prediction and grouping of chemicals with similar bioactivity profiles. Enrichment analysis based on signature catalog annotation identified known mechanisms of action (MeOAs) associated with well-studied chemicals and generated putative MeOAs for other active chemicals. Chemicals with predicted MeOAs included those targeting estrogen receptor (ER), glucocorticoid receptor (GR), retinoic acid receptor (RAR), the NRF2/KEAP/ARE pathway, AP-1 activation, and others. Using reference chemicals for ER modulation, the study demonstrated that HTTr in MCF7 cells was able to stratify chemicals in terms of agonist potency, distinguish ER agonists from antagonists, and cluster chemicals with similar activities as predicted by the ToxCast ER Pathway model. Uniform manifold approximation and projection (UMAP) embedding of signature-level results identified novel ER modulators with no ToxCast ER Pathway model predictions. Finally, UMAP combined with ToxPrint chemotype enrichment was used to explore the biological activity of structurally related chemicals. The study demonstrates that HTTr can be used to inform chemical risk assessment by determining in vitro points of departure, predicting chemicals’ MeOA and grouping chemicals with similar bioactivity profiles.

Toxicology↗

Gantryless Associated-Particle Neutron Radiography

The present work reports on the development of techniques for in-field fast-neutron radiography measurements using the associated-particle imaging (API) method. The API method employs alpha-neutron coincidences from the d+t→α+n reaction to enable fast neutron transmission imaging with excellent contrast using a wide cone beam. However, for field radiography applications, the API method is burdened by the need for the relative positions of the source and detector to be known. Fortunately, these relative positions can be inferred from transmission data. The inferred positions also enable accurate stitching of multiple images into a composite image even when using a low-resolution detector panel and acquiring images having few overlapping pixels. The developed techniques address analysis of measurements where (1) the source and detector panel are separately hand positioned rather than held in registration by a gantry, (2) multiple detector panel positions within the “coincident cone” of tagged neutrons are required to piece together an image of an item of interest, and (3) normalization measurements that have identical source-detector positioning but without the inspected object are not possible. The present work will describe the system calibrations (including timing calibrations and neutron direction calibrations) necessary for subsequent analyses, the method of locating the detector in the coincident cone of neutrons with millimeter precision using the timing and directions of coincident neutrons, the method of calculating a normalization image for a given detector panel position, and the method used to project multiple images into a common image.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Scale dependence of the 200-mb divergence inferred from EOLE data.

The EOLE experiment with 480 constant-volume balloons distributed over the Southern Hemisphere approximately at the 200-mb level, has provided a unique, highly accurate set of tracer trajectories in the general westerly circulation. The trajectories of neighboring balloons are analyzed to estimate the horizontal divergence from the Lagrangian derivative of the area of one cluster. The variance of the divergence estimates results from two almost comparable effects: the true divergence of the horizontal flow and eddy diffusion due to small-scale, two-dimensional turbulence. Taking this into account, the rms divergence is found to be of the order of 0.00001 per sec and decreases logarithmically with cluster size. This scale dependence is shown to be consistent with the quasi-geostrophic turbulence model of the general circulation in midlatitudes.

Morel, P.↗

Dynamics of two-year cosmic ray variations inferred from the data of spacecraft and stratospheric measurements and from the neutron monitor data in 1959-1981

The two year cosmic ray variations are studied using the spacecraft measurements of 1967 to 1976, the sonde measurements at high latitudes in the stratosphere (Murmansk, Mirny), and the neutron monitor data of 1959 to 1981. The two year variations are most pronounced from 1967 to 1975. An anticorrelation is observed between the two year variations in cosmic rays and in geomagnetic activity.

Charakhchyan, T. N.↗

Application of satellite data to tropic/subtropic moisture coupling

The objective is to develop analysis tools for use of satellite data to interpret synoptic-scale systems in data-void regions. Interim goals are to: (1) quantify the synoptic information content of satellite data; and (2) utilize these data in the diagnosis of moisture bursts in the eastern tropical Pacific Ocean. Researchers developed and implemented a statistical procedure for using TIROS N microwave data to infer infrared channel data for overcast conditions; they used the same procedure for deducing full TIROS N channel radiance profiles from NOAA 5 VTPR channel data over regions where the TIROS N data are missing. An empirical orthogonal function analysis of twice-daily channel radiance fields over the tropical eastern Pacific was completed. The vertically oriented eigenfunctions were interpreted in terms of typical meteorological events. The horizontal distribution of the eigenfunction amplitudes relates these meteorological signals to moisture bursts. A pair of moisture burst climatologies is complete: one of four years using infrared imagery (including the highly anomalous 1982 to 83 cold season); the other implementing 850 to 200 mb wind analyses in conjunction with GOES imagery. A number of different evaluations of the synoptic evolution of moisture fields (enhanced infrared imagery, moisture channel data, FGGE humidity analysis, and in situ station and sounding observations) are compared. All have limitations; all can be utilized together; all together are still less than adequate in the tropical Pacific.

Mcguirk, J. P.↗

Polar stratospheric clouds inferred from satellite data

Anomalously high radiances from the ozone channel of the Limb Infrared Monitor of the Stratosphere (LIMS) sounding instrument have been observed in the Northern Hemisphere winter lower stratosphere. Such events, thought to be due to polar stratospheric clouds (PSCs), are examined further by computing relative humidities using Stratospheric Sounding Unit temperatures and water vapor measurements from the LIMS Map Archive Tape analyses. Regions identified as PSCs are found to correspond closely to regions of high humidity. While instances of saturation were found, the average humidity at the centers of 39 PSCs was calculated to be 58 percent. Possible reasons for this apparent discrepancy are discussed. Applying a similar approach to the Southern Hemisphere, in 1979, virtually no PSCs are found in the vortex after September 10 at 20 km. This result has important implications for a number of proposed explanations for the Antarctic ozone hole.

Austin, J.↗

Implications of the giant planets for the formation and evolution of planetary systems

The giant planet region in the solar system appears to be bounded inside by the limit of water condensation, suggesting that the most abundant astrophysical condensate plays an important role in giant planet formation. Indeed, Jupiter and Saturn exhibit evidence for rock and/or ice cores or central concentrations that probably accumulated first, acting as nuclei for subsequent gas accumulation. This is a 'planetary' accumulation process, distinct from the stellar formation process, even though most of Jupiter has a similar composition to the primordial sun. Uranus and Neptune appear to exhibit evidence of an important role for giant impacts in their structure and evolution. No simple picture emerges for the temperature structure of the solar nebula from observations alone. However, it seems likely that Jupiter is the key to the planetary system, and a similar planet could be expected for other systems. The data and inferences from these data are summarized for the entire known solar system beyond the asteroid belt.

Stevenson, David J.↗

Constraints on the thermal evolution of Venus inferred from Magellan data

The impact craters with diameters from 1.5 to 280 km compiled from Magellan observations indicate that the crater population on Venus has a completely spatially random distribution and the size/density distribution of craters with diameters greater than or equal to 35 km is consistent with a 'production' population with an age of 500 plus or minus 250 m.y. The similarity in size distribution from area to area indicates that the crater distribution is independent of crater size. Also, the forms of the modified craters are virtually identical to those of the pristine craters. These observations imply that Venus reset its cratering record by global resurfacing 500 m.y. ago, and resurfacing declined relatively fast. The fact that less than 40 percent of all craters have been modified and that the few volcanically embayed craters are located on localized tectonic regions indicate that only minor and localized volcanism and tectonism have occurred since the latest vigorous resurfacing event approximately 500 m.y. ago and the interior of Venus has been solid and possibly colder than Earth's. This is because the high-temperature lithosphere of Venus would facilitate upward ascending of mantle plumes and result in extensive volcanism if the venusian upper mantle were as hot as or hotter than Earth's. Therefore, the present surface morphology of Venus may provide useful constraints on the pattern of that vigorous convection, and possibly on the thermal state of the venusian mantle. We examine this possibility through numerical calculations of three-dimensional thermal convection models in a spherical shell with temperature- and pressure-dependent Newtonian viscosity, temperature-dependent thermal diffusivity, pressure-dependent thermal expansion coefficient, and time-dependent internal heat production rate solar magnitude.

Arkani-Hamed, Jafar↗

Constraints on the thermal evolution of Venus inferred from Magellan data

One interpretation of the Magellan data suggests that the cratering record on Venus was erased by a global resurfacing event, or events, the latest ending about 500 m.y. ago. In this global-resurfacing model the resurfacing was followed by minor volcanism and tectonism that has been concentrated primarily in the equatorial highland regions characterized by extensive fracture belts and rifts. A thermal evolution model of Venus that can explain these observations is one in which a deformable lithosphere, capable of being incorporated in mantle circulations, provides an almost stress-free condition at the surface. Mantle convection with an almost stress-free boundary at the surface cools the interior more efficiently. Rapid cooling decreases the Rayleigh number of mantle convection below a transition value required for oscillatory convection, and the vigor of convection diminishes as the mantle changes to a quasi-steady circulation after about 500 m.y. ago.

Arkani-Hamed, J.↗

Use of Satellite Data Assimilation to Infer Land Surface Thermal Inertia

There are two important but observationally uncertain parameters in the grid averaged surface energy budgets of mesoscale models - surface moisture availability and thermal heat capacity. A technique has been successfully developed for assimilating Geostationary Operational Environmental Satellite (GOES) skin temperature tendencies during the mid-morning time frame to improve specification of surface moisture. In a new application of the technique, the use of satellite skin temperature tendencies in early evening is explored to improve specification of the surface thermal heat capacity. Together, these two satellite assimilation constraints have been shown to significantly improve the characterization of the surface energy budget of a mesoscale model on fine spatial scales. The GOES assimilation without the adjusted heat capacity was run operationally during the International H2O Project on a 12-km grid. This paper presents the results obtained when using both the moisture availability and heat capacity retrievals in concert. Preliminary results indicate that retrieved moisture availability alone improved the verification statistics of 2-meter temperature and dew point forecasts. Results from the 1.5 month long study period using the bulk heat capacity will be presented at the meeting.

Lapenta, William↗

Horizontal Temperature Variability in the Stratosphere: Global Variations Inferred from CRISTA Data

In two separate orbital campaigns (November, 1994 and August, 1997), the Cryogenic Infrared Spectrometers and Telescopes for the Atmosphere (CRISTA) instrument acquired global stratospheric data of high accuracy and high spatial resolution. The standard limb-scanned CRISTA measurements resolved atmospheric spatial structures with vertical dimensions greater than or equal to 1.5 - 2 km and horizontal dimensions is greater than or equal to 100 - 200 km. A fluctuation analysis of horizontal temperature distributions derived from these data is presented. This method is somewhat complementary to conventional power-spectral analysis techniques.

FLUCTUATION ANALYSIS↗

Expected Geochemical and Mineralogical Properties of Meteorites from Mercury: Inferences from Messenger Data

Meteorites from the Moon, Mars, and many types of asteroid bodies have been identified among our global inventory of meteorites, however samples of Mercury and Venus have not been identified. The absence of mercurian and venusian meteorites could be attributed to an inability to recognize them in our collections due to a paucity of geochemical information for Venus and Mercury. In the case of mercurian meteorites, this possibility is further supported by dynamical calculations that suggest mercurian meteorites should be present on Earth at a factor of 2-3 less than meteorites from Mars [1]. In the present study, we focus on the putative mineralogy of mercurian meteorites using data obtained from the MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft, which has provided us with our first quantitative constraints on the geochemistry of planet Mercury. We have used the MESSENGER data to compile a list of mineralogical and geochemical characteristics that a meteorite from Mercury is likely to exhibit.

McCubbin, F. M.↗

A Low Density Ocean Inside Titan Inferred From Cassini Data

The Cassini mission has provided measurements of the gravity of several moons of Saturn, as well as an estimate of the tidal response, expressed as the degree 2 Love number k 2 , of its largest moon, Titan. The first estimates of Titan’s Love number were larger than pre-Cassini expectations. Interior modeling suggested it may be explained with a dense ocean, but interpretation remained unclear. We have analyzed Cassini tracking data to determine Titan’s gravity field and its Love number. Our gravity results are consistent with earlier studies, but we find a lower Love number for Titan of k 2 =0.375±0.06. This lower value follows from an elaborate investigation of the tidal effects. We show that a dense ocean is not implied by the obtained Love number; instead, a water or ammonia ocean is more likely. A lower density ocean can increase the likeliness of contact between the silicate core and ocean, which can leach minerals into the ocean and could promote its habitability.

Sander Goossens↗