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In this Work in Progress (WIP) paper, we detail the initial steps taken to study NSF grants that seek to benefit the LGBTQ+ community through understanding their experiences or by working toward their full participation in society. To this end, we have identified active and expired NSF grants that either advance knowledge of LGBTQ+ experiences or offer some benefit to the community (e.g., tailored professional development, addressing and changing the marginalizing culture of STEM, etc.). We then developed a coding scheme to categorize these grants with respect to the level of positive impact they have on the LGBTQ+ community using modified Intellectual Merit and Broader Impacts criteria that parallels the NSF’s own criteria for evaluating proposals. The work established in this paper to identify and code LGBTQ-focused NSF grants will next allow us to extract trends in these grants over a period of over 4 decades. 

Simultaneous spatial localization and structural characterization of molecules in complex biological samples currently represents an analytical challenge for mass spectrometry imaging (MSI) techniques. In this study, we describe a novel experimental platform, which substantially expands the capabilities and enhances the depth of chemical information obtained in high spatial resolution MSI experiments performed using nanospray desorption electrospray ionization (nano-DESI). Specifically, we designed and constructed a portable nano-DESI MSI platform and coupled it with a drift tube ion mobility spectrometer-mass spectrometer (IM-MS). Separation of biomolecules observed in MSI experiments based on their drift times provides unique molecular descriptors necessary for their identification by comparison with databases. Furthermore, it enables isomer-specific imaging, which is particularly important for unraveling the complexity of biological systems. Imaging of day 4 pregnant mouse uterine sections using the newly developed nano-DESI-IM-MSI system demonstrates rapid isobaric and isomeric separation and reduced chemical noise in MSI experiments. A direct comparison of the performance of the new nano-DESI-MSI platform operated in the MS mode with the more established nano-DESI-Orbitrap platform indicates a comparable performance of these two systems. A spatial resolution of better than ~16 μm and similar molecular coverage was obtained using both platforms. The structural information provided by the ion mobility separation expands the molecular specificity of high-resolution MSI necessary for the detailed understanding of biological systems. 

Glucuronidation is a common phase II metabolic process for drugs and xenobiotics which increases their solubility for excretion. Acyl glucuronides (glucuronides of carboxylic acids) present concerns of toxicity as they have been implicated in gastrointestinal toxicity and hepatic failure. Despite the substantial success in the bulk analysis of these species, little is known about their localization in tissues. Herein, we used nanospray desorption electrospray ionization mass spectrometry imaging (nano-DESI-MSI) to examine the localization of diclofenac, a widely used nonsteroidal anti-inflammatory drug, and its metabolites in mouse kidney and liver tissues. Nano-DESI allows for label-free imaging with high spatial resolution and sensitivity without special sample pretreatment. Using nano-DESI-MSI, ion images for diclofenac and its major metabolites were produced. MSI data acquired over a broad m/z range showed fairly low signals of the drug and its metabolites. At least an order of magnitude improvement in the signals was obtained using selected ion monitoring (SIM), with m/z windows centered around the low-abundance ions of interest. Using nano-DESI MSI in SIM mode, we observed that diclofenac acyl glucuronide is localized to the inner medulla and hydroxydiclofenac to the cortex of the kidney. The distributions observed for both metabolites closely match the previously reported localization of enzymes that process diclofenac into its respective metabolites. The localization of diclofenac acyl glucuronide to medulla likely indicates that the toxic metabolite is being excreted from the tissue. In contrast, a uniform distribution of diclofenac, hydroxydiclofenac and the diclofenac acyl glucuronide metabolite was observed in the liver tissue. Semiquantitative analysis found the metabolite to diclofenac ratios calculated from nano-DESI in agreement to those calculated from liquid chromatography tandem mass spectrometry (LC-MS/MS) experiments. Collectively, our results demonstrate nano-DESI-MSI can be successfully used to image diclofenac and its primary metabolites in dosed liver and kidney tissues from mice and derive semi-quantitative data from localized tissue regions. 

Abstract The results of gamma-ray observations of the binary system HESS J0632 + 057 collected during 450 hr over 15 yr, between 2004 and 2019, are presented. Data taken with the atmospheric Cherenkov telescopes H.E.S.S., MAGIC, and VERITAS at energies above 350 GeV were used together with observations at X-ray energies obtained with Swift-XRT, Chandra, XMM-Newton, NuSTAR, and Suzaku. Some of these observations were accompanied by measurements of the H α emission line. A significant detection of the modulation of the very high-energy gamma-ray fluxes with a period of 316.7 ± 4.4 days is reported, consistent with the period of 317.3 ± 0.7 days obtained with a refined analysis of X-ray data. The analysis of data from four orbital cycles with dense observational coverage reveals short-timescale variability, with flux-decay timescales of less than 20 days at very high energies. Flux variations observed over a timescale of several years indicate orbit-to-orbit variability. The analysis confirms the previously reported correlation of X-ray and gamma-ray emission from the system at very high significance, but cannot find any correlation of optical H α parameters with fluxes at X-ray or gamma-ray energies in simultaneous observations. The key finding is that the emission of HESS J0632 + 057 in the X-ray and gamma-ray energy bands is highly variable on different timescales. The ratio of gamma-ray to X-ray flux shows the equality or even dominance of the gamma-ray energy range. This wealth of new data is interpreted taking into account the insufficient knowledge of the ephemeris of the system, and discussed in the context of results reported on other gamma-ray binary systems.