Identification of carotid artery atherosclerosis is conventionally based on measurements of luminal stenosis and surface irregularities using in vivo imaging techniques including sonography, CT and ...MR angiography, and digital subtraction angiography. However, histopathologic studies demonstrate considerable differences between plaques with identical degrees of stenosis and indicate that certain plaque features are associated with increased risk for ischemic events. The ability to look beyond the lumen using highly developed vessel wall imaging methods to identify plaque vulnerable to disruption has prompted an active debate as to whether a paradigm shift is needed to move away from relying on measurements of luminal stenosis for gauging the risk of ischemic injury. Further evaluation in randomized clinical trials will help to better define the exact role of plaque imaging in clinical decision-making. However, current carotid vessel wall imaging techniques can be informative. The goal of this article is to present the perspective of the ASNR Vessel Wall Imaging Study Group as it relates to the current status of arterial wall imaging in carotid artery disease.
The burden of human disease related to medically important fungal pathogens is substantial. An improved understanding of antifungal pharmacology and antifungal pharmacokinetics-pharmacodynamics has ...resulted in therapeutic drug monitoring (TDM) becoming a valuable adjunct to the routine administration of some antifungal agents. TDM may increase the probability of a successful outcome, prevent drug-related toxicity and potentially prevent the emergence of antifungal drug resistance. Much of the evidence that supports TDM is circumstantial. This document reviews the available literature and provides a series of recommendations for TDM of antifungal agents.
ABSTRACT X-ray bursts are thermonuclear flashes on the surface of accreting neutron stars, and reliable burst models are needed to interpret observations in terms of properties of the neutron star ...and the binary system. We investigate the dependence of X-ray burst models on uncertainties in (p, γ), ( , γ), and ( , p) nuclear reaction rates using fully self-consistent burst models that account for the feedbacks between changes in nuclear energy generation and changes in astrophysical conditions. A two-step approach first identified sensitive nuclear reaction rates in a single-zone model with ignition conditions chosen to match calculations with a state-of-the-art 1D multi-zone model based on the Kepler stellar evolution code. All relevant reaction rates on neutron-deficient isotopes up to mass 106 were individually varied by a factor of 100 up and down. Calculations of the 84 changes in reaction rate with the highest impact were then repeated in the 1D multi-zone model. We find a number of uncertain reaction rates that affect predictions of light curves and burst ashes significantly. The results provide insights into the nuclear processes that shape observables from X-ray bursts, and guidance for future nuclear physics work to reduce nuclear uncertainties in X-ray burst models.
Over the past decade, a suite of new mass-spectrometry-based proteomics methods has been developed that now enables the conformational properties of proteins and protein-ligand complexes to be ...studied in complex biological mixtures, from cell lysates to intact cells. Highlighted here are seven of the techniques in this new toolbox. These techniques include chemical cross-linking (XL-MS), hydroxyl radical footprinting (HRF), Drug Affinity Responsive Target Stability (DARTS), Limited Proteolysis (LiP), Pulse Proteolysis (PP), Stability of Proteins from Rates of Oxidation (SPROX), and Thermal Proteome Profiling (TPP). The above techniques all rely on conventional bottom-up proteomics strategies for peptide sequencing and protein identification. However, they have required the development of unconventional proteomic data analysis strategies. Discussed here are the current technical challenges associated with these different data analysis strategies as well as the relative analytical capabilities of the different techniques. The new biophysical capabilities that the above techniques bring to bear on proteomic research are also highlighted in the context of several different application areas in which these techniques have been used, including the study of protein ligand binding interactions (e.g., protein target discovery studies and protein interaction network analyses) and the characterization of biological states.
SEGUE-2: Old Milky Way Stars Near and Far Rockosi, Constance M.; Sun Lee, Young; Morrison, Heather L. ...
The Astrophysical journal. Supplement series,
04/2022, Letnik:
259, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Abstract
The Sloan Extension for Galactic Understanding and Exploration 2 (SEGUE-2) obtained 128,288 low-resolution spectra (
R
∼ 1800) of 118,958 unique stars in the first year of the Sloan Digital ...Sky Survey III (2008–2009). SEGUE-2 targeted prioritized distant halo tracers (blue horizontal-branch stars, K giants, and M giants) and metal-poor or kinematically hot populations. The main goal of SEGUE-2 was to target stars in the distant halo and measure their kinematics and chemical abundances to learn about the formation and evolution of the Milky Way. We present the SEGUE-2 field placement and target selection strategies. We discuss the success rate of the targeting based on the SEGUE-2 spectra and other spectroscopic and astrometric surveys. We describe the final SEGUE-2/SDSS-III improvements to the stellar parameter determinations based on the SEGUE Stellar Parameter Pipeline. We report a (
g
−
i
) color−effective temperature relation calibrated to the IRFM. We evaluate the accuracy and uncertainties associated with these stellar parameters by comparing with fundamental parameters, a sample of high-resolution spectra of SEGUE stars analyzed homogeneously, stars in well-studied clusters, and stars observed in common by the APOGEE survey. The final SEGUE spectra, calibration data, and derived parameters described here were released in SDSS-III Data Release 9 and continue to be included in all subsequent SDSS Data Releases. Because of its faint limiting magnitude and emphasis on the distant halo, the public SEGUE-2 data remain an important resource for the spectroscopy of stars in the Milky Way.
We have used in vitro scratch assays to examine the relative contribution of dermal fibroblasts and keratinocytes in the wound repair process and to test the influence of mesenchymal stem cell (MSC) ...secreted factors on both skin cell types. Scratch assays were established using single cell and co-cultures of L929 fibroblasts and HaCaT keratinocytes, with wound closure monitored via time-lapse microscopy. Both in serum supplemented and serum free conditions, wound closure was faster in L929 fibroblast than HaCaT keratinocyte scratch assays, and in co-culture the L929 fibroblasts lead the way in closing the scratches. MSC-CM generated under serum free conditions significantly enhanced the wound closure rate of both skin cell types separately and in co-culture, whereas conditioned medium from L929 or HaCaT cultures had no significant effect. This enhancement of wound closure in the presence of MSC-CM was due to accelerated cell migration rather than increased cell proliferation. A number of wound healing mediators were identified in MSC-CM, including TGF-β1, the chemokines IL-6, IL-8, MCP-1 and RANTES, and collagen type I, fibronectin, SPARC and IGFBP-7. This study suggests that the trophic activity of MSC may play a role in skin wound closure by affecting both dermal fibroblast and keratinocyte migration, along with a contribution to the formation of extracellular matrix.
Here, we utilize the stability of proteins from rates of oxidation (SPROX) technique, to profile the thermodynamic stabilities of proteins in brain tissue cell lysates from Huα-Syn(A53T) transgenic ...mice at three time points including at 1 month (
= 9), at 6 months (
= 7), and at the time (between 9 and 16 months) a mouse became symptomatic (
= 8). The thermodynamic stability profiles generated here on 332 proteins were compared to thermodynamic stability profiles generated on the same proteins from similarly aged wild-type mice using a two-way unbalanced analysis of variance (ANOVA) analysis. This analysis identified a group of 22 proteins with age-related protein stability changes and a group of 11 proteins that were differentially stabilized in the Huα-Syn(A53T) transgenic mouse model. A total of 9 of the 11 proteins identified here with disease-related stability changes have been previously detected in human cerebral spinal fluid and thus have potential utility as biomarkers of Parkinson's disease (PD). The differential stability observed for one protein, glutamate decarboxylase 2 (Gad2), with an age-related change in stability, was consistent with the differential presence of a known, age-related truncation product of this protein, which is shown here to have a higher folding stability than full-length Gad2. Mass spectrometry data were deposited at ProteomeXchange (PXD016985).
Glioma intratumoral heterogeneity enables adaptation to challenging microenvironments and contributes to therapeutic resistance. We integrated 914 single-cell DNA methylomes, 55,284 single-cell ...transcriptomes and bulk multi-omic profiles across 11 adult IDH mutant or IDH wild-type gliomas to delineate sources of intratumoral heterogeneity. We showed that local DNA methylation disorder is associated with cell-cell DNA methylation differences, is elevated in more aggressive tumors, links with transcriptional disruption and is altered during the environmental stress response. Glioma cells under in vitro hypoxic and irradiation stress increased local DNA methylation disorder and shifted cell states. We identified a positive association between genetic and epigenetic instability that was supported in bulk longitudinally collected DNA methylation data. Increased DNA methylation disorder associated with accelerated disease progression and recurrently selected DNA methylation changes were enriched for environmental stress response pathways. Our work identified an epigenetically facilitated adaptive stress response process and highlights the importance of epigenetic heterogeneity in shaping therapeutic outcomes.
Three periastron passages of the PSR B1259−63/LS 2883 binary system, consisting of a 48 ms rotation-powered pulsar and a Be star, have been observed by the Large Area Telescope (LAT) on board the ...Fermi Gamma-ray Space Telescope, in 2010, 2014, and 2017. During the most recent periastron passage, sustained low-level gamma-ray emission was observed over a ∼3-week-long interval immediately after periastron, which was followed by an interval of no emission. Sporadic flares were detected starting 40 days post-periastron and lasted approximately 50 days, during which the emission displayed significant spectral curvature, variability on timescales as short as 1.5 minutes, and peak flux levels well in excess of the pulsar spin-down power. By contrast, during the 2010 and 2014 periastron passages, significant gamma-ray emission was not observed with the LAT until 30 and 32 days post-periastron, respectively. The previous flares did not exhibit spectral curvature, showed no short term variability, and did not exceed the pulsar spin-down power. The high flux and short timescales observed in 2017 suggest significant beaming of the emission is required and constrain the size of the emission region. The flares occur long enough after periastron that the neutron star should already have passed through the extended disk-like outflow, thus constraining options for target material and seed photon sources for inverse Compton models.
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