SDRS—an algorithm for analyzing large-scale dose–response data

Summary: Dose–response information is critical to understanding drug effects, yet analytical methods for dose–response assays cannot cope with the dimensionality of large-scale screening data such as the microarray profiling data. To overcome this limitation, we developed and implemented the Sigmoidal Dose Response Search (SDRS) algorithm, a grid search-based method designed to handle large-scale dose–response data. This method not only calculates the pharmacological parameters for every assay, but also provides built-in statistic that enables downstream systematic analyses, such as characterizing dose response at the transcriptome level

The First Flight of the Marshall Grazing Incidence X-ray Spectrometer (MaGIXS)

The Marshall Grazing Incidence X-ray Spectrometer (MaGIXS) sounding rocket experiment launched on July 30, 2021 from the White Sands Missile Range in New Mexico. MaGIXS is a unique solar observing telescope developed to capture X-ray spectral images, in the 6 - 24 Angstrom wavelength range, of coronal active regions. Its novel design takes advantage of recent technological advances related to fabricating and optimizing X-ray optical systems as well as breakthroughs in inversion methodologies necessary to create spectrally pure maps from overlapping spectral images. MaGIXS is the first instrument of its kind to provide spatially resolved soft X-ray spectra across a wide field of view. The plasma diagnostics available in this spectral regime make this instrument a powerful tool for probing solar coronal heating. This paper presents details from the first MaGIXS flight, the captured observations, the data processing and inversion techniques, and the first science results.Comment: 20 pages, 18 figure

Transcriptional Profiling of the Dose Response: A More Powerful Approach for Characterizing Drug Activities

The dose response curve is the gold standard for measuring the effect of a drug treatment, but is rarely used in genomic scale transcriptional profiling due to perceived obstacles of cost and analysis. One barrier to examining transcriptional dose responses is that existing methods for microarray data analysis can identify patterns, but provide no quantitative pharmacological information. We developed analytical methods that identify transcripts responsive to dose, calculate classical pharmacological parameters such as the EC50, and enable an in-depth analysis of coordinated dose-dependent treatment effects. The approach was applied to a transcriptional profiling study that evaluated four kinase inhibitors (imatinib, nilotinib, dasatinib and PD0325901) across a six-logarithm dose range, using 12 arrays per compound. The transcript responses proved a powerful means to characterize and compare the compounds: the distribution of EC50 values for the transcriptome was linked to specific targets, dose-dependent effects on cellular processes were identified using automated pathway analysis, and a connection was seen between EC50s in standard cellular assays and transcriptional EC50s. Our approach greatly enriches the information that can be obtained from standard transcriptional profiling technology. Moreover, these methods are automated, robust to non-optimized assays, and could be applied to other sources of quantitative data

The Marshall Grazing Incidence X-ray Spectrometer (MaGIXS)

The Marshall Grazing Incidence X-ray Spectrometer (MaGIXS) is a sounding rocket instrument that flew on July 30, 2021 from the White Sands Missile Range, NM. The instrument was designed to address specific science questions that require differential emission measures of the solar soft X-ray spectrum from 6 – 25[Formula: see text]Å(0.5 – 2.1[Formula: see text]keV). MaGIXS comprises a Wolter-I telescope, a slit-jaw imaging system, an identical pair of grazing incidence paraboloid mirrors, a planar grating and a CCD camera. While implementing this design, some limitations were encountered in the production of the X-ray mirrors, which ended up as a catalyst for the development of a deterministic polishing approach and an improved meteorological technique that utilizes a computer-generated hologram (CGH). The opto-mechanical design approach addressed the need to have adjustable and highly repeatable interfaces to allow for the complex alignment between the optical sub-assemblies. The alignment techniques employed when mounting the mirrors and throughout instrument integration and end-to-end testing are discussed. Also presented are spatial resolution measurements of the end-to-end point-spread-function that were obtained during testing in the X-ray Cryogenic Facility (XRCF) at NASA Marshall Space Flight Center. Lastly, unresolved issues and off-nominal performance are discussed

The First Flight of the Marshall Grazing Incidence X-Ray Spectrometer (MaGIXS)

The Marshall Grazing Incidence X-ray Spectrometer (MaGIXS) sounding rocket experiment launched on 2021 July 30 from the White Sands Missile Range in New Mexico. MaGIXS is a unique solar observing telescope developed to capture X-ray spectral images of coronal active regions in the 6–24 Å wavelength range. Its novel design takes advantage of recent technological advances related to fabricating and optimizing X-ray optical systems, as well as breakthroughs in inversion methodologies necessary to create spectrally pure maps from overlapping spectral images. MaGIXS is the first instrument of its kind to provide spatially resolved soft X-ray spectra across a wide field of view. The plasma diagnostics available in this spectral regime make this instrument a powerful tool for probing solar coronal heating. This paper presents details from the first MaGIXS flight, the captured observations, the data processing and inversion techniques, and the first science results