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Immunomodulatory agents (IMiDs) are a cornerstone of treatment for patients with multiple myeloma. IMiDs are used in therapeutic combinations at all stages of disease and are approved ...as a single-agent maintenance treatment after autologous stem cell transplantation. However, patients become resistant to ongoing therapy over time and inevitably relapse. It is only in the last decade that the mechanism of IMiD action has been elucidated; through binding to the cereblon component of the CRL4CRBN E3 ubiquitin ligase, a set of neosubstrates is designated for degradation by the proteasome. In myeloma cells, this includes the zinc-finger B-cell transcription factors Ikaros and Aiolos, which, in turn, lead to decreased levels of IRF4 and c-MYC and cell death. As our knowledge of IMiD mechanism of action has advanced, the ability to study resistance mechanisms has also developed. This review explores the existing work on IMiD resistance and proposes areas of future research that may advance our understanding and management of this common clinical condition.
Bird and Pawlyn review what we know about resistance to a critical class of drugs for the treatment of multiple myeloma: immunomodulatory imide drugs (IMiDs). This class includes thalidomide, lenalidomide, and pomalidomide, all identified initially by empiric means, as well as the cereblon E3 ligase modulators, such as iberdomide and mezigdomide, identified after the mechanism of action of this class of drug was discovered. The authors highlight mechanisms of resistance that directly interfere with the targeting of cereblon, as well as other mechanisms, and discuss potential options to overcome this resistance.
When Sarah Bird arrived in Austin in 1973 in pursuit of a boyfriend who was “hotter than lava," she found an abundance of inspiration for storytelling (her sweetheart left her for Scientology, but ...she got to taste a morsel of Lynda Bird Johnson’s poorly preserved wedding cake as a temp worker at the LBJ Library). Sarah Bird went on to write ten acclaimed novels and contribute hundreds of articles to publications coast to coast, developing a signature voice that combines laser-sharp insight with irreverent, wickedly funny prose in the tradition of Molly Ivins and Nora Ephron Now collecting forty of Bird’s best nonfiction pieces, from publications that range from Texas Monthly to the New York Times and others, Recent Studies Indicate presents some of Bird’s earliest work, including a prescient 1976 profile of a transgender woman, along with recent calls to political action, such as her 2017 speech at a benefit for Annie’s List. Whether Bird is hanging out with socialites and sanitation workers or paying homage to her army-nurse mom, her collection brings a poignant perspective to the experience of being a woman, a feminist, a mother, and a Texan—and a writer with countless, spectacular true tales to tell us.
With the increasing number of large stellar survey projects, the quality and quantity of excellent tracers for studying the Milky Way are rapidly growing, one of which is the classical Cepheids. ...Classical Cepheids are high-precision standard candles with very low typical uncertainties (<3%) available via the mid-infrared period-luminosity relation. About 3500 classical Cepheids identified from the Optical Gravitational Lensing Experiment, All-Sky Automated Survey for Supernova, Gaia, Wide-field Infrared Survey Explorer, and Zwicky Transient Facility survey data have been analyzed in this work, and their spatial distributions show a clear signature of Galactic warp. Two kinematical methods are adopted to measure the Galactic rotation curve (RC) in the Galactocentric distance range of . Gently declining RCs are derived by both the proper motion (PM) method and three-dimensional velocity vector (3DV) method. The largest sample of classical Cepheids with the most accurate 6D phase-space coordinates available to date are modeled in the 3DV method, and the resulting RC is found to decline at the relatively smaller gradient of (−1.33 0.1) . Comparing to results from the PM method, a higher rotation velocity ((232.5 0.83) ) is derived at the position of the Sun in the 3DV method. The virial mass and local dark matter density are estimated from the 3DV method, which is the more reliable method, and GeV, respectively.
The anisotropy parameter β characterizes the extent to which orbits in stellar systems are predominantly radial or tangential and is likely to constrain, for the stellar halo of the Milky Way, ...scenarios for its formation and evolution. We have measured β as a function of Galactocentric radius from 5 to 100 kpc for 7664 metal-poor (Fe/H < −1.3) halo K giants from the LAMOST catalog with line-of-sight velocities and distances, matched to proper motions from the second Gaia data release. We construct full 6D positions and velocities for the K giants to directly measure the three components of the velocity dispersion ( r, θ, φ) (in spherical coordinates). We find that the orbits in the halo are radial over our full Galactocentric distance range reaching over 100 kpc. The anisotropy remains remarkably unchanged with Galactocentric radius from approximately 5-25 kpc, with an amplitude that depends on the metallicity of the stars, dropping from β 0.9 for −1.8 ≤ Fe/H < −1.3 (for the bulk of the stars) to β 0.6 for the lowest metallicities (Fe/H < −1.8). Considering our sample as a whole, β 0.8 and beyond 25 kpc, the orbits gradually become less radial and anisotropy decreases to β < 0.3 past 100 kpc. Within 8 kpc, β < 0.8. The measurement of anisotropy is affected by substructure and streams, particularly beyond a Galactocentric distance of approximately 25 kpc, where the Sagittarius stream is prominent in the data. These results are complimentary to recent analysis of simulations by Loebman et al. and of SDSS/Gaia DR1 data by Belokurov et al.
ABSTRACT
A wealth of recent studies have shown that the LMC is likely massive, with a halo mass >1011 M⊙. One consequence of having such a nearby and massive neighbour is that the inner Milky Way is ...expected to be accelerated with respect to our Galaxy’s outskirts (beyond ∼30 kpc). In this work, we compile a sample of ∼500 stars with radial velocities in the distant stellar halo, rGC > 50 kpc, to test this hypothesis. These stars span a large fraction of the sky and thus give a global view of the stellar halo. We find that stars in the Southern hemisphere are on average blueshifted, while stars in the North are redshifted, consistent with the expected, mostly downwards acceleration of the inner halo due to the LMC. We compare these results with simulations and find the signal is consistent with the infall of a 1.5 × 1011 M⊙ LMC. We cross-match our stellar sample with Gaia DR2 and find that the mean proper motions are not yet precise enough to discern the LMC’s effect. Our results show that the Milky Way is significantly out of equilibrium and that the LMC has a substantial effect on our Galaxy.
What is it that distinguishes Texas women—the famous Yellow Rose and her descendants? Is it that combination of graciousness and grit that we revere in First Ladies Laura Bush and Lady Bird Johnson? ...The rapier-sharp wit that Ann Richards and Molly Ivins used to skewer the good ole boy establishment? The moral righteousness with which Barbara Jordan defended the US constitution? An unnatural fondness for Dr Pepper and queso? In her inimitable style, Sarah Bird pays tribute to the Texas Woman in all her glory and all her contradictions. She humorously recalls her own early bewildered attempts to understand Lone Star gals, from the big-haired, perfectly made-up ladies at the Hyde Park Beauty Salon to her intellectual, quinoa-eating roommates at Seneca House Co-op for Graduate Women. After decades of observing Texas women, Bird knows the species as few others do. A Love Letter to Texas Women is a must-have guide for newcomers to the state and the ideal gift to tell any Yellow Rose how special she is.
Abstract
We explore the contribution of the Gaia Sausage to the stellar halo of the Milky Way by making use of a Gaussian mixture model (GMM) and applying it to halo star samples of Large Sky Area ...Multi-Object Fiber Spectroscopic Telescope K giants, Sloan Extension for Galactic Understanding and Exploration K giants, and Sloan Digital Sky Survey blue horizontal branch stars. The GMM divides the stellar halo into two parts, of which one represents a more metal-rich and highly radially biased component associated with an ancient, head-on collision referred to as the Gaia Sausage, and the other one is a more metal-poor and isotropic halo. A symmetric bimodal Gaussian is used to describe the distribution of spherical velocity of the Gaia Sausage, and we find that the mean absolute radial velocity of the two lobes decreases with the Galactocentric radius. We find that the Gaia Sausage contributes about 41%–74% of the inner (Galactocentric radius
r
gc
< 30 kpc) stellar halo. The fraction of stars of the Gaia Sausage starts to decline beyond
r
gc
∼ 25–30 kpc, and the outer halo is found to be significantly less influenced by the Gaia Sausage than the inner halo. After the removal of halo substructures found by integrals of motion, the contribution of the Gaia Sausage falls slightly within
r
gc
∼ 25 kpc but is still as high as 30%–63%. Finally, we select several possible Sausage-related substructures consisting of stars on highly eccentric orbits. The GMM/Sausage component agrees well with the selected substructure stars in their chemodynamical properties, which increases our confidence in the reliability of the GMM fits.
ABSTRACT
We select 1052 469 (754 635) thin disc stars from Gaia eDR3 and LAMOST DR7 in the range of Galactocentric radius R (guiding centre radius Rg) from 8 to 11 kpc to investigate the asymmetries ...between the North and South of the disc mid-plane. More specifically, we analyse the vertical velocity dispersion profiles ($\sigma _{v_{z}}(z$)) in different bins of R (Rg) and Fe/H. We find troughs in the profiles of $\sigma _{v_{z}}(z)$ located in both the North (z ∼ 0.7 kpc) and South (z ∼ −0.5 kpc) of the disc at all radial and chemical bins studied. The difference between the Northern and Southern vertical velocity dispersion profiles ($\Delta \sigma _{v_{z}}(|z|)$) shows a shift between curves of different R and Rg. A similar shift exists in these North–South (NS) asymmetry profiles further divided into different Fe/H ranges. The sample binned with Rg more clearly displays the features in the velocity dispersion profiles. The shift in the peaks of the $\Delta \sigma _{v_{z}}$ profiles and the variation in the phase spiral shape binned by metallicity indicate the variation of the vertical potential profiles and the radial metallicity gradient. The wave-like signal in NS asymmetry of $\sigma _{v_{z}}(z)$ largely originates from phase spiral; while the NS asymmetry profiles of Fe/H only display a weak wave-like feature near solar radius. We perform a test particle simulation to qualitatively reproduce the observed results. A quantitative explanation of the NS asymmetry in the metallicity profile needs careful consideration of the spiral shape and the perturbation model, and we leave this for future work.
Abstract
We analyze the anisotropy profile of the Milky Way’s smooth, diffuse stellar halo using the Sloan Digital Sky Survey (SDSS) SEGUE blue horizontal branch stars and the SDSS/SEGUE and LAMOST K ...giants. These intrinsically luminous stars allow us to probe the halo to approximately 100 kpc from the Galactic center. Line-of-sight velocities, distances, metallicities, and proper motions are available for all stars via SDSS/SEGUE, LAMOST, and Gaia, and we use these data to construct a full 7D set consisting of positions, space motions, and metallicity. We remove substructure from our samples using integrals of motion based on the method of Xue et al. We find radially dominated kinematic profiles with nearly constant anisotropy within 20 kpc, beyond which the anisotropy profile gently declines but remains radially dominated to the farthest extents of our sample. Independent of star type or substructure removal, the anisotropy depends on metallicity, such that the orbits of the stars become less radial with decreasing metallicity. For −1.7 < Fe/H < −1, the smooth, diffuse halo anisotropy profile begins to decline at Galactocentric distances ∼20 kpc, from
β
∼
0.9
to 0.7 for K giants and from
β
∼
0.8
to 0.1 for blue horizontal branch stars. For Fe/H < −1.7, the smooth, diffuse halo anisotropy remains constant along all distances with
0.2
<
β
<
0.7
depending on the metallicity range probed, but independent of star type. These samples are ideal for estimating the total Galactic mass as they represent the virialized stellar halo system.
ABSTRACT
We measure the enclosed Milky Way mass profile to Galactocentric distances of ∼70 and ∼50 kpc using the smooth, diffuse stellar halo samples of Bird et al. The samples are Large Sky Area ...Multi-Object Fiber Spectroscopic Telescope (LAMOST) and Sloan Digital Sky Survey/Sloan Extension for Galactic Understanding and Exploration (SDSS/SEGUE) K giants (KG) and SDSS/SEGUE blue horizontal branch (BHB) stars with accurate metallicities. The 3D kinematics are available through LAMOST and SDSS/SEGUE distances and radial velocities and Gaia DR2 proper motions. Two methods are used to estimate the enclosed mass: 3D spherical Jeans equation and Evans et al. tracer mass estimator (TME). We remove substructure via the Xue et al. method based on integrals of motion. We evaluate the uncertainties on our estimates due to random sampling noise, systematic distance errors, the adopted density profile, and non-virialization and non-spherical effects of the halo. The tracer density profile remains a limiting systematic in our mass estimates, although within these limits we find reasonable agreement across the different samples and the methods applied. Out to ∼70 and ∼50 kpc, the Jeans method yields total enclosed masses of 4.3 ± 0.95 (random) ±0.6 (systematic) × 1011 M⊙ and 4.1 ± 1.2 (random) ±0.6 (systematic) × 1011 M⊙ for the KG and BHB stars, respectively. For the KG and BHB samples, we find a dark matter virial mass of $M_{200}=0.55^{+0.15}_{-0.11}$ (random) ±0.083 (systematic) × 1012 M⊙ and $M_{200}=1.00^{+0.67}_{-0.33}$ (random) ±0.15 (systematic) × 1012 M⊙, respectively.
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