We present an online catalog of distance determinations for 6036 K giants, most of which are members of the Milky Way's stellar halo. Their medium-resolution spectra from the Sloan Digital Sky ...Survey/Sloan Extension for Galactic Understanding and Exploration are used to derive metallicities and rough gravity estimates, along with radial velocities. Distance moduli are derived from a comparison of each star's apparent magnitude with the absolute magnitude of empirically calibrated color-luminosity fiducials, at the observed (g - r) sub(0) color and spectroscopic fFe/H, We employ a probabilistic approach that makes it straightforward to properly propagate the errors in metallicities, magnitudes, and colors into distance uncertainties. We also fold in prior information about the giant-branch luminosity function and the different metallicity distributions of the SEGUE K-giant targeting sub-categories. We show that the metallicity prior plays a small role in the distance estimates, but that neglecting the luminosity prior could lead to a systematic distance modulus bias of up to 0.25 mag, compared to the case of using the luminosity prior. We find a median distance precision of 16%, with distance estimates most precise for the least metal-poor stars near the tip of the red giant branch. The precision and accuracy of our distance estimates are validated with observations of globular and open clusters. The stars in our catalog are up to 125 kpc from the Galactic center, with 283 stars beyond 50 kpc, forming the largest available spectroscopic sample of distant tracers in the Galactic halo.
Toxicity is a major cause of failure in drug discovery and development, and whilst robust toxicological testing occurs, efficiency could be improved if compounds with cytotoxic characteristics were ...identified during primary compound screening. The use of high-content imaging in primary screening is becoming more widespread, and by utilising phenotypic approaches it should be possible to incorporate cytotoxicity counter-screens into primary screens. Here we present a novel phenotypic assay that can be used as a counter-screen to identify compounds with adverse cellular effects. This assay has been developed using U2OS cells, the PerkinElmer Operetta high-content/high-throughput imaging system and Columbus image analysis software. In Columbus, algorithms were devised to identify changes in nuclear morphology, cell shape and proliferation using DAPI, TOTO-3 and phosphohistone H3 staining, respectively. The algorithms were developed and tested on cells treated with doxorubicin, taxol and nocodazole. The assay was then used to screen a novel, chemical library, rich in natural product-like molecules of over 300 compounds, 13.6% of which were identified as having adverse cellular effects. This assay provides a relatively cheap and rapid approach for identifying compounds with adverse cellular effects during screening assays, potentially reducing compound rejection due to toxicity in subsequent in vitro and in vivo assays.
We employ measurements of the Delta *a/Fe ratio derived from low-resolution (R ~ 2000) spectra of 17,277 G-type dwarfs from the SEGUE survey to separate them into likely thin- and thick-disk ...subsamples. Both subsamples exhibit strong gradients of orbital rotational velocity with metallicity, of opposite signs, --20 to --30 km s--1 dex--1 for the thin-disk and +40 to +50 km s--1 dex--1 for the thick-disk population. The rotational velocity is uncorrelated with Galactocentric distance for the thin-disk subsample and exhibits a small trend for the thick-disk subsample. The rotational velocity decreases with distance from the plane for both disk components, with similar slopes (--9.0 ? 1.0 km s--1 kpc--1). Thick-disk stars exhibit a strong trend of orbital eccentricity with metallicity (about --0.2 dex--1), while the eccentricity does not change with metallicity for the thin-disk subsample. The eccentricity is almost independent of Galactocentric radius for the thin-disk population, while a marginal gradient of the eccentricity with radius exists for the thick-disk population. Both subsamples possess similar positive gradients of eccentricity with distance from the Galactic plane. The shapes of the eccentricity distributions for the thin- and thick-disk populations are independent of distance from the plane, and include no significant numbers of stars with eccentricity above 0.6. Among several contemporary models of disk evolution that we consider, radial migration appears to have played an important role in the evolution of the thin-disk population, but possibly less so for the thick disk, relative to the gas-rich merger or disk heating scenarios. We emphasize that more physically realistic models and simulations need to be constructed in order to carry out the detailed quantitative comparisons that our new data enable.
Kinases are important therapeutic targets, and their inhibitors are classified according to their mechanism of action, which range from blocking ATP binding to covalent inhibition. Here, a mechanism ...of inhibition is highlighted by capturing p21-activated kinase 5 (PAK5) in an intermediate state of activation using an Affimer reagent that binds in the P+1 pocket. PAK5 was identified from a non-hypothesis-driven high-content imaging RNAi screen in urothelial cancer cells. Silencing of PAK5 resulted in reduced cell number, G1/S arrest, and enlargement of cells, suggesting it to be important in urothelial cancer cell line survival and proliferation. Affimer reagents were isolated to identify mechanisms of inhibition. The Affimer PAK5-Af17 recapitulated the phenotype seen with siRNA. Co-crystallization revealed that PAK5-Af17 bound in the P+1 pocket of PAK5, locking the kinase into a partial activation state. This mechanism of inhibition indicates that another class of kinase inhibitors is possible.
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•PAK5 siRNA knockdown leads to G1/S arrest, cell enlargement, and reduced cell number•PAK5 inhibition with biologic, Affimer 17, mimics siRNA knockdown phenotype•Affimer 17 locks PAK5 in an intermediate activation state resulting in inhibition•Affimer 17 binding PAK5 Arg653 confers selectivity for PAK5
Martin et al. report that inhibition of p21 activated kinase 5 (PAK5) leads to G1/S transition arrest, cell enlargement, and reduced cell number. They identify a biologic inhibitor, Affimer 17, which locks PAK5 in a conformation representing an intermediate state of activation resulting in kinase inhibition.
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.
The objective of the study was to assess the agreement of the Lunar Prodigy with the newer Lunar iDXA dual-energy X-ray absorptiometer for determining total body and regional (arms, legs, trunk) bone ...mineral density (BMD), bone mineral content (BMC), fat mass (FM), lean tissue mass (LTM), total body mass, and percent fat. Ninety-two healthy adult males (n = 36) and females (n = 56) were scanned consecutively on the iDXA and the Prodigy dual-energy X-ray absorptiometers. For iDXA, relative to Prodigy, paired t tests indicated significantly lower estimates for total body and regional BMD and BMC (p < 0.001). Measures of total body and trunk FM, LTM, and percent fat did not differ between the instruments. In regional analyses, estimates of FM and percent fat were greater, and that of LTM was lower, in the arms (p < 0.001). In contrast, iDXA estimates of LTM were higher in the legs (p < 0.001). All body composition measures were significantly correlated (p < 0.001). Bland-Altman analyses indicated that significant bias existed between iDXA and Prodigy for total body and regional BMD estimates (p < 0.001) such that iDXA underestimated BMD to a greater extent in persons with higher values. In addition, iDXA overestimation bias existed for FM in total body, arms, and legs, and the overestimation was primarily observed in participants with greater body fat (p < 0.001). When combining or comparing data from iDXA with those from Prodigy, investigators should be aware that certain total body and regional estimates are significantly different. The greatest percent differences were observed for arm BMD, FM, and percent fat.
The observed radial and vertical metallicity distribution of old stars in the Milky Way disk provides a powerful constraint on the chemical enrichment and dynamical history of the disk system. We ...present the radial metallicity gradient, DeltaFe/H/DeltaR, as a function of height above the plane, |Z|, using 7010 main-sequence turnoff stars observed by the Sloan Extension for Galactic Understanding and Exploration survey. The sample consists of mostly old thin and thick disk stars, with a minimal contribution from the stellar halo, in the region 6 kpc < R < 16 kpc, 0.15 kpc < |Z| < 1.5 kpc. The data reveal that the radial metallicity gradient becomes flat at heights |Z| > 1 kpc. The median metallicity at large |Z| is consistent with the metallicities seen in outer disk open clusters, which exhibit a flat radial gradient at Fe/H ~-0.5. We note that the outer disk clusters are also located at large |Z|; because the flat gradient extends to small R for our sample, there is some ambiguity in whether the observed trends for clusters are due to a change in R or |Z|. We therefore stress the importance of considering both the radial and vertical directions when measuring spatial abundance trends in the disk. The flattening of the gradient at high |Z| also has implications on thick disk formation scenarios, which predict different metallicity patterns in the thick disk. A flat gradient, such as we observe, is predicted by a turbulent disk at high redshift, but may also be consistent with radial migration, as long as mixing is strong. We test our analysis methods using a mock catalog based on the model of Schonrich & Binney, and we estimate our distance errors to be ~25%. We also show that we can properly correct for selection biases by assigning weights to our targets.
To summarize the anesthetic events of snakes seen at a large university hospital, identify challenges with record keeping, and assess patient and anesthesia-related morbidity and death.
139 ...anesthetic events were performed; only 106 cases had detailed anesthetic reports available for further analyses.
Medical records of snakes that underwent general anesthesia between October 2000 and January 2022 were retrospectively reviewed. Only cases with complete anesthesia records were used to assess anesthetic parameters. Collected data included general patient details, diagnoses, procedures, premedication, induction, maintenance, monitoring, and recovery.
A thorough review of the records identified issues or scenarios that resulted in poor record management as well as highlighted the most frequently used anesthetics in snakes. For premedication this was alfaxalone, butorphanol, and hydromorphone, whereas isoflurane, alfaxalone, or propofol were the most common with induction. Lastly, with maintenance, isoflurane was the most popular choice. Of the 139 cases performed, 127 animals recovered, 8 were euthanatized due to poor prognosis, and 4 failed to recover. All snakes that failed to recover had preexisting disease identified pre-, peri-, or postoperatively at necropsy.
General anesthesia can be reliably and safely undertaken in snakes without severe preexisting disease. Efforts should be directed at identifying preexisting disease and maintaining and completing anesthesia records, and we recommend an auditing system to identify and correct issues as they arise.
We examine the alpha -element abundance ratio, alpha /Fe, of 5620 stars, observed by the Sloan Extension for Galactic Understanding and Exploration survey in the region 6 kpc < R < 16 kpc, 0.15 kpc ...< |Z| < 1.5 kpc, as a function of Galactocentric radius R and distance from the Galactic plane |Z|. Our results show that the high- alpha thick-disk population has a short scale length (L sub(thick) ~ 1.8 kpc) compared to the low- alpha population, which is typically associated with the thin disk. We find that the fraction of high- alpha stars in the inner disk increases at large |Z| and that high- alpha stars lag in rotation compared to low- alpha stars. In contrast, the fraction of high- alpha stars in the outer disk is low at all |Z|, and high- and low- alpha stars have similar rotational velocities up to 1.5 kpc from the plane. We interpret these results to indicate that different processes were responsible for the high- alpha populations in the inner and outer disk. The high- alpha population in the inner disk has a short scale length and large scale height, consistent with a scenario in which the thick disk forms during an early gas-rich accretion phase. Stars far from the plane in the outer disk may have reached their current locations through heating by minor mergers. The lack of high- alpha stars at large R and |Z| also places strict constraints on the strength of radial migration via transient spiral structure.
Progressive debilitating neurological defects characterize feline G(M1) gangliosidosis, a lysosomal storage disease caused by deficiency of lysosomal β-galactosidase. No effective therapy exists for ...affected children, who often die before age 5 years. An adeno-associated viral vector carrying the therapeutic gene was injected bilaterally into two brain targets (thalamus and deep cerebellar nuclei) of a feline model of G(M1) gangliosidosis. Gene therapy normalized β-galactosidase activity and storage throughout the brain and spinal cord. The mean survival of 12 treated G(M1) animals was >38 months, compared to 8 months for untreated animals. Seven of the eight treated animals remaining alive demonstrated normalization of disease, with abrogation of many symptoms including gait deficits and postural imbalance. Sustained correction of the G(M1) gangliosidosis disease phenotype after limited intracranial targeting by gene therapy in a large animal model suggests that this approach may be useful for treating the human version of this lysosomal storage disorder.
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