The central kiloparsecs of the Milky Way are known to host an old, spheroidal stellar population, whose spatial and kinematical properties set it apart from the boxy-peanut structure that constitutes ...most of the central stellar mass. The nature of this spheroidal population, whether it is a small classical bulge, the innermost stellar halo, or a population of disk stars with large initial velocity dispersion, remains unclear. This structure is also a promising candidate to play host to some of the oldest stars in the Galaxy. Here we address the topic of the inner stellar spheroid age, using spectroscopic and photometric metallicities for a sample of 935 RR Lyrae stars that are constituents of this component. By means of stellar population synthesis, we derive an age-metallicity relation for RR Lyrae populations. We infer, for the RR Lyrae stars in the bulge spheroid, an extremely ancient age of 13.41 ± 0.54 Gyr and conclude they were among the first stars to form in what is now the Milky Way galaxy. Our age estimate for the central spheroid shows a remarkable agreement with the age profile that has been inferred for the Milky Way stellar halo, suggesting a connection between the two structures. However, we find mild evidence for a transition in the halo properties at
r
GC
∼ 5 kpc. We also investigate formation scenarios for metal-rich RR Lyrae stars, such as binarity and helium variations, and consider whether they can provide alternative explanations for the properties of our sample. We conclude that within our framework, the only viable alternative is to have younger, slightly helium-rich, RR Lyrae stars. This is a hypothesis that would open intriguing questions for the formation of the inner stellar spheroid.
Accurate identification of prostate cancer in frozen sections at the time of surgery can be challenging, limiting the surgeon’s ability to best determine resection margins during prostatectomy. We ...performed desorption electrospray ionization mass spectrometry imaging (DESI-MSI) on 54 banked human cancerous and normal prostate tissue specimens to investigate the spatial distribution of a wide variety of small metabolites, carbohydrates, and lipids. In contrast to several previous studies, our method included Krebs cycle intermediates (m/z <200), which we found to be highly informative in distinguishing cancer from benign tissue. Malignant prostate cells showed marked metabolic derangements compared with their benign counterparts. Using the “Least absolute shrinkage and selection operator” (Lasso), we analyzed all metabolites from the DESI-MS data and identified parsimonious sets of metabolic profiles for distinguishing between cancer and normal tissue. In an independent set of samples, we could use these models to classify prostate cancer from benign specimens with nearly 90% accuracy per patient. Based on previous work in prostate cancer showing that glucose levels are high while citrate is low, we found that measurement of the glucose/citrate ion signal ratio accurately predicted cancer when this ratio exceeds 1.0 and normal prostate when the ratio is less than 0.5. After brief tissue preparation, the glucose/citrate ratio can be recorded on a tissue sample in 1 min or less, which is in sharp contrast to the 20 min or more required by histopathological examination of frozen tissue specimens.
ABSTRACT
We present a kinematical study of 314 RR Lyrae stars in the solar neighbourhood using the publicly available photometric, spectroscopic, and Gaia DR2 astrometric data to explore their ...distribution in the Milky Way. We report an overdensity of 22 RR Lyrae stars in the solar neighbourhood at a pericentre distance of between 5 and 9 kpc from the Galactic Centre. Their orbital parameters and their chemistry indicate that these 22 variables share the kinematics and the Fe/H values of the Galactic disc, with an average metallicity and tangential velocity of Fe/H = −0.60 dex and vθ = 241 km s−1, respectively. From the distribution of the Galactocentric spherical velocity components, we find that these 22 disc-like RR Lyrae variables are not consistent with the Gaia Sausage (Gaia-Enceladus), unlike almost half of the local RR Lyrae stars. Chemical information from the literature shows that the majority of the selected pericentre-peak RR Lyrae variables are α-poor, a property shared by typically much younger stars in the thin disc. Using the available photometry, we rule out a possible misclassification with the known classical and anomalous Cepheids. The similar kinematic, chemical, and pulsation properties of these disc RR Lyrae stars suggest they share a common origin. In contrast, we find that the RR Lyrae stars associated with the Gaia-Enceladus based on their kinematics and chemical composition show a considerable metallicity spread in the old population (∼1 dex).
The Galactic bulge exploration Prudil, Z; Kunder, A; Dékány, I ...
Astronomy and astrophysics (Berlin),
04/2024, Letnik:
684
Journal Article
Recenzirano
Odprti dostop
We present a new set of period–absolute magnitude–metallicity (PMZ) relations for single-mode RR Lyrae stars calibrated for the optical GBP, V, G, GRP, near-infrared I, J, H, and Ks passbands. We ...compiled a large dataset (over 100 objects) of fundamental and first-overtone RR Lyrae pulsators consisting of mean intensity magnitudes, reddenings, pulsation properties, iron abundances, and parallaxes measured by the Gaia astrometric satellite in its third data release. Our newly calibrated PMZ relations encapsulate the most up-to-date ingredients in terms of both data and methodology. They are intended to be used in conjunction with large photometric surveys targeting the Galactic bulge, including the Optical Gravitational Lensing Experiment (OGLE), the Vista Variables in the Vía Láctea Survey (VVV), and the Gaia catalog. In addition, our Bayesian probabilistic approach provides accurate uncertainty estimates of the predicted absolute magnitudes of individual RR Lyrae stars. Our derived PMZ relations provide consistent results when compared to benchmark distances to globular clusters NGC 6121 (also known as M 4), NGC 5139 (also known as omega Cen), and Large and Small Magellanic Clouds, which are stellar systems rich in RR Lyrae stars. Lastly, our Ks-band PMZ relations match well with the previously published PMZ relations based on Gaia data and accurately predict the distance toward the prototype of this class of variables, the eponymic RR Lyr itself.
Patients with diffuse large B cell lymphoma (DLBCL) exhibit marked diversity in tumor behavior and outcomes, yet the identification of poor-risk groups remains challenging. In addition, the biology ...underlying these differences is incompletely understood. We hypothesized that characterization of mutational heterogeneity and genomic evolution using circulating tumor DNA (ctDNA) profiling could reveal molecular determinants of adverse outcomes. To address this hypothesis, we applied cancer personalized profiling by deep sequencing (CAPP-Seq) analysis to tumor biopsies and cell-free DNA samples from 92 lymphoma patients and 24 healthy subjects. At diagnosis, the amount of ctDNA was found to strongly correlate with clinical indices and was independently predictive of patient outcomes. We demonstrate that ctDNA genotyping can classify transcriptionally defined tumor subtypes, including DLBCL cell of origin, directly from plasma. By simultaneously tracking multiple somatic mutations in ctDNA, our approach outperformed immunoglobulin sequencing and radiographic imaging for the detection of minimal residual disease and facilitated noninvasive identification of emergent resistance mutations to targeted therapies. In addition, we identified distinct patterns of clonal evolution distinguishing indolent follicular lymphomas from those that transformed into DLBCL, allowing for potential noninvasive prediction of histological transformation. Collectively, our results demonstrate that ctDNA analysis reveals biological factors that underlie lymphoma clinical outcomes and could facilitate individualized therapy.
Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare and recently described entity associated with hereditary leiomyomatosis and RCC syndrome. FH-deficient RCC may show ...variable clinical and pathologic findings, but commonly presents with locally advanced and metastatic disease and carries a poor prognosis. We identified 32 patients with FH-deficient RCC, confirmed by FH immunohistochemistry (IHC) and/or FH mutation analysis, and performed a retrospective review of the clinical and pathologic features. Median age at presentation was 43 years (range, 18 to 69 y), and the M:F ratio was 2.2:1. Median tumor size was 6.5 cm (range, 2.5 to 28 cm), and 71% presented at stage ≥pT3a. After a median follow-up of 16 months (range, 1 to 118 mo) in 26 patients, 19% showed no evidence of disease, 31% were alive with disease, and 50% were dead of disease. The vast majority of cases showed multiple histologic growth patterns, with papillary (52%) being the most common predominant pattern, followed by solid (21%), cribriform/sieve-like (14%), sarcomatoid (3%), tubular (3%), cystic (3%), and low-grade oncocytic (3%). Viral inclusion-like macronucleoli with perinucleolar clearing were present in almost all cases (96%). All cases were evaluated using FH IHC, and 3 cases (9%) showed retained FH expression. Nineteen cases had germline or tumor mutation analysis confirming a FH mutation, with 79% (11/14) of cases showing mutations within coding regions and 21% (3/14) showing mutations within intronic splice-sites. By IHC, 97% (32/33) of cases were negative for CK7, 93% (27/29) were negative for p63, and 52% (15/29) were negative for GATA3. All cases stained were positive for PAX8 and showed retained succinate dehydrogenase B expression. Our overall findings show that FH-deficient RCC is considerably heterogenous in morphology and frequently behaves aggressively. Suspicion for this entity should be raised even in the absence of predominantly papillary architecture and characteristic nucleolar features. We have included cases with uncommonly seen features, including 4 cases with predominantly cribriform/sieve-like architecture as well as one case with pure low-grade oncocytic morphology (9 y of clinical follow-up without evidence of disease). Although FH IHC is a useful tool for identifying cases of FH-deficient RCC, not all cases of FH-deficient RCC show loss of FH staining, and FH mutation analysis should be considered for patients with suspicious clinical or pathologic features, even in cases with retained FH IHC expression.
Recent studies have shown limited utility of routine surveillance imaging for diffuse large B-cell lymphoma (DLBCL) patients achieving remission. Detection of molecular disease by immunoglobulin ...high-throughput sequencing (Ig-HTS) from peripheral blood provides an alternate strategy for surveillance. We prospectively evaluated the utility of Ig-HTS within 311 blood and 105 tumor samples from 75 patients with DLBCL, comparing Ig-HTS from the cellular (circulating leukocytes) and acellular (plasma cell-free DNA) compartments of peripheral blood to clinical outcomes and 18fluoro-deoxyglucose positron emission tomography combined with computed tomography (PET/CT; n = 173). Clonotypic immunoglobulin rearrangements were detected in 83% of patients with adequate tumor samples to enable subsequent monitoring in peripheral blood. Molecular disease measured from plasma, compared with circulating leukocytes, was more abundant and better correlated with radiographic disease burden. Before treatment, molecular disease was detected in the plasma of 82% of patients compared with 71% in circulating cells (P = .68). However, molecular disease was detected significantly more frequently in the plasma at time of relapse (100% vs 30%; P = .001). Detection of molecular disease in the plasma often preceded PET/CT detection of relapse in patients initially achieving remission. During surveillance time points before relapse, plasma Ig-HTS demonstrated improved specificity (100% vs 56%, P < .0001) and similar sensitivity (31% vs 55%, P = .4) compared with PET/CT. Given its high specificity, Ig-HTS from plasma has potential clinical utility for surveillance after complete remission.
•DLBCL can be detected in the blood by immunoglobulin high-throughput sequencing (Ig-HTS) with high specificity.•Although DLBCL can be detected in leukocytes or plasma by Ig-HTS, plasma has greater sensitivity and more accurately reflects disease.
Smooth muscle tumor of uncertain malignant potential (STUMP) is a rare diagnosis rendered when there is uncertainty concerning the biological potential of a smooth muscle tumor. The initial ...differential diagnosis is often broad, as tumors in this subgroup are morphologically heterogenous. Recent data suggest uterine inflammatory myofibroblastic tumors (IMTs) with anaplastic lymphoma kinase (ALK) rearrangement may be misclassified as STUMPs, but the extent to which this occurs has not been examined. We identified 60 female patients with tumors previously diagnosed as STUMP (48 cases) or prospectively considered for the diagnosis of STUMP (12 cases). Each case underwent histologic review, ALK immunohistochemistry (IHC) and confirmatory break-apart fluorescence in situ hybridization (FISH) for ALK if immunoreactive. Six of the 43 (14%) uterine and cervical tumors were ALK IHC positive, whereas tumors at all other sites were ALK IHC negative. Myxoid features, although limited in some cases, were present in all 6 ALK IHC positive tumors, representing 35% (6/17) of tumors displaying myxoid features at uterine and cervical sites. All ALK immunoreactive tumors were confirmed to have ALK rearrangements by FISH with 1 tumor showing numerous (3 to 8) 3ʼ ALK signals, an unusual FISH pattern not previously described in uterine IMTs. Two patients developed recurrent disease and were treated with ALK-targeted therapy with initial response. Our data demonstrate that a significant proportion of uterine and cervical tumors considered to be STUMPs are ALK—positive by IHC and FISH. Future screening of all uterine and cervical mesenchymal tumors under consideration for the diagnosis of STUMP, particularly those with myxoid features, is recommended to identify ALK-rearranged IMTs that could potentially be treated with targeted therapy using tyrosine kinase inhibitors.
Mast cells (MCs) promote a wide range of localized and systemic inflammatory responses. Their involvement in immediate as well as chronic inflammatory reactions at both local and distal sites points ...to an extraordinarily powerful immunoregulatory capacity with spatial and temporal versatility. MCs are preferentially found in close proximity to both vascular and lymphatic vessels. On activation, they undergo a biphasic secretory response involving the rapid release of prestored vasoactive mediators followed by de novo synthesized products. Many actions of MCs are related to their capacity to regulate vascular flow and permeability and to the recruitment of various inflammatory cells from the vasculature into inflammatory sites. These mediators often work in an additive fashion and achieve their inflammatory effects locally by directly acting on the vascular and lymphatic endothelia, but they also can affect distal sites. Along these lines, the lymphatic and endothelial vasculatures of the host act as a conduit for the dissemination of MC signals during inflammation. The central role of the MC-endothelial cell axis to immune homeostasis is emphasized by the fact that some of the most effective current treatments for inflammatory disorders are directed at interfering with this interaction.
We use data from the Radial Velocity Experiment (RAVE) and the Tycho-Gaia astrometric solution (TGAS) catalogue to compute the velocity fields yielded by the radial (V-R), azimuthal (V-phi), and ...vertical (V-z) components of associated Galactocentric velocity. We search in particular for variation in all three velocity components with distance above and below the disc midplane, as well as how each component of V-z (line-of-sight and tangential velocity projections) modifies the obtained vertical structure. To study the dependence of velocity on proper motion and distance, we use two main samples: a RAVE sample including proper motions from the Tycho-2, PPMXL, and UCAC4 catalogues, and a RAVE-TGAS sample with inferred distances and proper motions from the TGAS and UCAC5 catalogues. In both samples, we identify asymmetries in V-R and V-z. Below the plane, we find the largest radial gradient to be partial derivative V-R/partial derivative R = -7.01 +/- 0.61 km s(-1) kpc(-1), in agreement with recent studies. Above the plane, we find a similar gradient with partial derivative V-R/partial derivative R = -9.42 +/- 1.77 km s(-1) kpc(-1). By comparing our results with previous studies, we find that the structure in V-z is strongly dependent on the adopted proper motions. Using the Galaxia Milky Way model, we demonstrate that distance uncertainties can create artificial wave-like patterns. In contrast to previous suggestions of a breathing mode seen in RAVE data, our results support a combination of bending and breathing modes, likely generated by a combination of external or internal and external mechanisms.
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