Presence Of Multiple Populations Research Articles

The chemical compositions of multiple stellar populations in the globular cluster NGC 2808

ABSTRACT Pseudo two-colour diagrams or Chromosome maps (ChM) indicate that NGC 2808 host five different stellar populations. The existing ChMs have been derived by the Hubble Space Telescope photometry, and comprise of stars in a small field of view around the cluster centre. To overcome these limitations, we built a ChM with U, B, I photometry from ground-based facilities that disentangle the multiple stellar populations of NGC 2808 over a wider field of view. We used spectra collected by GIRAFFE@VLT in a sample of 70 red giant branch and seven asymptotic giant branch (AGB) stars to infer the abundances of C, N, O, Al, Fe, and Ni, which combined with literature data for other elements (Li, Na, Mg, Si, Ca, Sc, Ti, Cr, and Mn), and together with both the classical and the new ground-based ChMs, provide the most complete chemical characterization of the stellar populations in NGC 2808 available to date. As typical of the multiple population phenomenon in globular clusters, the light elements vary from one stellar population to another; whereas the iron peak elements show negligible variation between the different populations (at a level of ≲0.10 dex). Our AGB stars are also characterized by the chemical variations associated with the presence of multiple populations, confirming that this phase of stellar evolution is affected by the phenomenon as well. Intriguingly, we detected one extreme O-poor AGB star (consistent with a high He abundance), challenging stellar evolution models that suggest that highly He-enriched stars should avoid the AGB phase and evolve as AGB-manqué star.

Abstract CT156: Changes in circulating tumor associated cells predicts progression free and overall survival in metastatic TNBC patients after induction of the anti-CCR5 drug leronlimab

Abstract Background: Metastatic triple negative breast cancer (mTNBC) is a highly invasive breast cancer subtype that has limited treatment options and poor clinical outcomes for patients. Recently, the C-C chemokine receptor 5 (CCR5) was identified in preclinical models as a potential drug target that inhibits pro-migratory tumor progression in breast cancer by blocking tumor motility and subsequent tumor cell spread. Leronlimab (PRO140), a humanized IgG4κ monoclonal antibody, is a competitive inhibitor of CCR5, with 3 active clinical trials ongoing in TNBC patients. Here we report on a preliminary pooled analysis of n=28 mTNBC patients to evaluate effects of Leronlimab on circulating tumor-associated cells (TACs) found in peripheral blood as an early predictor of drug response, with end point outcomes of progression free survival (PFS) and Overall Survival (OS). Methods: Blood samples were drawn from mTNBC patients from 3 blinded prospective clinical drug studies, Phase 1b/2 (NCT03838367), Compassionate Use (NCT04313075), and Basket Study (NCT04504942) to evaluate the predictive value of TACs, measured by the LifeTracDx assay. All subjects received ≥1 dose of Leronlimab (range 1-33 doses), ranging from 350mg - 700mg, with 4 subjects having dose escalation. Anonymized blinded peripheral blood samples were available from (n=28) patients, obtained as part of the exploratory portion of the trials, prior to drug induction (BL) and after one treatment cycle (T1), ~26 days. TACs, i.e. Circulating tumor cells (CTCs) and Cancer Associated Macrophage-like cells (CAMLS), were isolated using a low-flow CellSieve microfiltration system and changes in TACs were quantified by the LifeTracDx assay. A univariate analysis was used to analyze changes in TACs to predict for PFS and OS over 12 months. Results: A total of 28 mTNBC patients were pooled from Phase 1b/2 (n=10), Compassionate Use (n =16), and Basket Study (n=2) all of which had available BL blood samples, or T1 samples. CTCs were found in 29% (n=8/28) of patients at BL, and CAMLs were found in 96% (n=27/28). Evaluating CTC change was limited, as only 5 patients had any CTC increase, although the absence or drop of CTCs at T1 was significant for better PFS (HR=13.7 CI 95% 2.0-93.8, p=0.0296) and better OS (HR=397.7 CI 95% 19.3-100+, p=0.0019). By comparison, CAMLs or CTCs were evaluable in 100% of patients, with an increases of either population at T1 also significantly predicting for worse PFS (HR=5.8 CI 95% 1.4-23.6, p=0.0354) and worse OS (HR=36.0 CI 95% 6.2-207.6, p=0.0004). Conclusions: We observed that treatment with Leronlimab resulted in rapid decreases in the presence of multiple populations of TACs in 75% of patients, which also significantly correlated with better PFS and OS after 1 year analysis. Citation Format: Daniel L. Adams, Ashvathi Raghavakaimal, Cha-Mei Tang, Kirby P. Gardner, Nitya G. Ray, Nader Pourhassan. Changes in circulating tumor associated cells predicts progression free and overall survival in metastatic TNBC patients after induction of the anti-CCR5 drug leronlimab [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT156.

Consideration of the limitations of thermal maturity with respect to vitrinite reflectance, Tmax, and other proxies

Many of those assessing geochemical data have taken a “cookbook” approach to interpretation. Such an approach generally does not take into consideration the limitations of the different data sets. Among these data sets are those associated with thermal maturity, which guides the interpretation of the extent of generation and hydrocarbon phase. The temperature of peak pyrolysis generation (Tmax) is commonly used to map thermal maturity directly or through a conversion to vitrinite reflectance equivalent values. Such efforts do not take into consideration analytical uncertainties or natural variability within a stratigraphic unit at any given locality. Furthermore, when presented as vitrinite reflectance equivalents, the associated error in the conversion is not considered, yet the values are presented as “absolutes.” When examining vitrinite reflectance, there are also several issues that should be considered. Individual mean values are commonly considered out of context. All thermal maturity indicators, including vitrinite reflectance, need to be placed into a geologic framework, and trends rather than discrete values should be considered. The nature of the studied samples is also significant. Whole-rock and isolated kerogen analyses yield different results, commonly because of the lack of a statistically meaningful number of individual measurements because of either low organic carbon or low concentrations of vitrinite when examining whole-rock samples. Such differences are not trivial, with final interpretation of hydrocarbon phase boundaries potentially being shifted. Bitumen reflectance shares some of the same issues as vitrinite reflectance measurement, including misidentification, the presence of multiple populations and insufficient measurements, and the possibility that environmental factors may influence the observed reflectance. Conversion issues of bitumen to vitrinite reflectance are similar to those identified for the Tmax conversion.

Mass-loss law for red giant stars in simple population globular clusters

ABSTRACT The amount of mass lost by stars during the red-giant branch (RGB) phase is one of the main parameters to understand and correctly model the late stages of stellar evolution. Nevertheless, a fully comprehensive knowledge of the RGB mass-loss is still missing. Galactic Globular Clusters (GCs) are ideal targets to derive empirical formulations of mass-loss, but the presence of multiple populations with different chemical compositions has been a major challenge to constrain stellar masses and RGB mass-losses. Recent work has disentangled the distinct stellar populations along the RGB and the horizontal branch (HB) of 46 GCs, thus providing the possibility to estimate the RGB mass-loss of each stellar population. The mass-losses inferred for the stellar populations with pristine chemical composition (called first-generation or 1G stars) tightly correlate with cluster metallicity. This finding allows us to derive an empirical RGB mass-loss law for 1G stars. In this paper, we investigate seven GCs with no evidence of multiple populations and derive the RGB mass-loss by means of high-precision Hubble-Space Telescope photometry and accurate synthetic photometry. We find a cluster-to-cluster variation in the mass-loss ranging from ∼0.1 to ∼0.3 M⊙. The RGB mass-loss of simple-population GCs correlates with the metallicity of the host cluster. The discovery that simple-population GCs and 1G stars of multiple population GCs follow similar mass-loss versus metallicity relations suggests that the resulting mass-loss law is a standard outcome of stellar evolution.

RGB mass loss: inferences from CMD-fitting and asteroseismology

AbstractThe amount of mass lost by stars during the red-giant branch (RGB) phase is one of the main parameters needed to fully understand later stages of stellar evolution. In spite of its importance, a fully-comprehensive physical understanding of this phenomenon is still missing, and we, mostly, rely on empirical formulations. The Galactic Globular Clusters are ideal targets to derive such formulations, but, until recently, the presence of multiple populations has been a major challenge.We will discuss the insights on RGB mass loss that can be obtained from the study of the horizontal branch stars in such stellar associations. The estimates obtained via the study of the photometric data will be compared with recent and newly obtained estimates derived for few high metallicity open clusters and a large sample of field stars with asteroseismic techniques.

Lessons from the reintroduction of listed plant species in California

Reintroduction is an increasingly common practice to conserve and recover threatened and endangered plant species, so understanding how practitioners view their work and identifying persistent resource mismatches are key to the long-term viability of these listed species. We interviewed practitioners involved in reintroduction projects for 14 species in the state of California to understand (1) how they defined recovery; (2) their assessment of the likelihood of recovery; (3) what advice they would share with other practitioners to improve reintroduction efforts; and (4) what resources could make future projects more successful. Practitioners’ definitions of recovery aligned with ecological theory and emphasized the importance of self-sustaining populations and large populations, as well as the presence of multiple populations. However, most practitioners felt that recovery was unlikely or did not think the species they worked with should or would be de-listed without the guarantee of perpetual future interventions. Practitioners thought that studying basic biology and natural history, using experiments to determine the best techniques, and repeatedly planting populations were important to project success. However, practitioners also felt they were missing critical resources, including long-term funding for implementation and maintenance, successful and positive relationships between members of the practitioner-agency-scientist-landowner nexus, and assurances/safe harbor agreements for experimental populations. Overall, rare plant reintroductions are complicated by persistent mismatches in timing and goals, but some individuals have been able to successfully navigate these challenges. Longer duration funding mechanisms for monitoring and maintenance and better data handling, storage, and dissemination would benefit future projects.

Chemical abundance analysis of red giant branch stars in the globular cluster E3

Context. Globular clusters are known to host multiple stellar populations, which are a signature of their formation process. The globular cluster E3 is one of the few low-mass globulars that is thought not to host multiple populations. Aims. We investigate red giant branch stars in E3 with the aim of providing a first detailed chemical inventory for this cluster, we determine its radial velocity, and we provide additional insights into the possible presence of multiple populations in this cluster. Methods. We obtained high-resolution FLAMES-UVES/VLT spectra of four red giant branch stars likely members of E3. We performed a local thermodynamic equilibrium abundance analysis based on one-dimensional plane parallel ATLAS9 model atmospheres. Abundances were derived from line equivalent widths or spectrum synthesis. Results. We measured abundances of Na and of iron peak (Fe, V, Cr, Ni, Mn), α(Mg, Si, Ca, Ti), and neutron capture elements (Y, Ba, Eu). The mean cluster heliocentric radial velocity, metallicity, and sodium abundance ratio are νhelio = 12.6 ± 0.4 km s−1(σ = 0.6 ± 0.2 km s−1), [Fe/H] = −0.89 ± 0.08 dex, and [Na/Fe] = 0.18 ± 0.07 dex, respectively. The low Na abundance with no appreciable spread is suggestive of a cluster dominated by first-generation stars in agreement with results based on lower resolution spectroscopy. The low number of stars observed does not allow us to rule out a minor population of second-generation stars. The observed chemical abundances are compatible with the trends observed in Milky Way stars.

Not-so-simple stellar populations in nearby, resolved massive star clusters

Around the turn of the last century, star clusters of all kinds were considered ‘simple’ stellar populations. Over the past decade, this situation has changed dramatically. At the same time, star clusters are among the brightest stellar population components and, as such, they are visible out to much greater distances than individual stars, even the brightest, so that understanding the intricacies of star cluster composition and their evolution is imperative for understanding stellar populations and the evolution of galaxies as a whole. In this review of where the field has moved to in recent years, we place particular emphasis on the properties and importance of binary systems, the effects of rapid stellar rotation, and the presence of multiple populations in Magellanic Cloud star clusters across the full age range. Our most recent results imply a reverse paradigm shift, back to the old simple stellar population picture for at least some intermediate-age (∼1–3 Gyr old) star clusters, opening up exciting avenues for future research efforts.

First evidence of multiple populations along the AGB from Strömgren photometry

Spectroscopic studies have demonstrated that nearly all Galactic globular clusters (GCs) harbour multiple stellar populations with different chemical compositions. Moreover, colour-magnitude diagrams based exclusively on Str\"omgrem photometry have allowed us to identify and characterise multiple populations along the RGB of a large number of clusters. In this paper we show for the first time that Str\"omgren photometry is also very effcient at identifying multiple populations along the AGB, and demonstrate that the AGB of M3, M92, NGC362, NGC1851, and NGC6752 are not consistent with a single stellar population. We also provide a catalogue of RGB and AGB stars photometrically identified in these clusters for further spectroscopic follow-up studies.We combined photometry and elemental abundances from the literature for RGB and AGB stars in NGC6752 where the presence of multiple populations along the AGB has been widely debated. We find that, while the MS, SGB, and RGB host three stellar populations with different helium and light element abundances, only two populations of AGB stars are present in the cluster. These results are consistent with standard evolutionary theory.

Searching for globular cluster-like abundance patterns in young massive clusters – II. Results from the Antennae galaxies

The presence of multiple populations (MPs) with distinctive light element abundances is a widespread phenomenon in clusters older than 6 Gyr. Clusters with masses, luminosities, and sizes comparable to those of ancient globulars are still forming today. Nonetheless, the presence of light element variations has been poorly investigated in such young systems, even if the knowledge of the age at which this phenomenon develops is crucial for theoretical models on MPs. We use J-band integrated spectra of three young (7-40 Myr) clusters in NGC 4038 to look for Al variations indicative of MPs. Assuming that the large majority (>70%) of stars are characterised by high Al content - as observed in Galactic clusters with comparable mass; we find that none of the studied clusters show significant Al variations. Small Al spreads have been measured in all the six young clusters observed in the near-infrared. While it is unlikely that young clusters only show low Al whereas old ones display different levels of Al variations; this suggests the possibility that MPs are not present at such young ages at least among the high-mass stellar component. Alternatively, the fraction of stars with field-like chemistry could be extremely large, mimicking low Al abundances in the integrated spectrum. Finally, since the near-infrared stellar continuum of young clusters is almost entirely due to luminous red supergiants, we can also speculate that MPs only manifest themselves in low mass stars due to some evolutionary mechanism.

Subclonal diversity arises early even in small colorectal tumours and contributes to differential growth fates

Objective and designThe goal of the study was to determine whether the mutational profile of early colorectal polyps correlated with growth behaviour. The growth of small polyps (6–9 mm) that...

A class of spherical, truncated, anisotropic models for application to globular clusters

Recently, a class of non-truncated radially-anisotropic models (the so-called $f^{(\nu)}$-models), originally constructed in the context of violent relaxation and modeling of elliptical galaxies, has been found to possess interesting qualities in relation to observed and simulated globular clusters. In view of new applications to globular clusters, we improve this class of models along two directions. To make them more suitable for the description of small stellar systems hosted by galaxies, we introduce a 'tidal' truncation (by means of a procedure that guarantees full continuity of the distribution function). The new $f_T^{(\nu)}$-models are shown to provide a better fit to the observed photometric and spectroscopic profiles for a sample of 13 globular clusters studied earlier by means of non-truncated models; interestingly, the best-fit models also perform better with respect to the radial-orbit instability. Then we design a flexible but simple two-component family of truncated models, to study the separate issues of mass segregation and of multiple populations. We do not aim at a fully realistic description of globular clusters, to compete with the description currently obtained by means of dedicated simulations. The goal here is to try to identify the simplest models, that is, those with the smallest number of free parameters, but still able to provide a reasonable description for clusters that are evidently beyond the reach of one-component models: with this tool we aim at identifying the key factors that characterize mass segregation or the presence of multiple populations. To reduce the relevant parameter space, we formulate a few physical arguments (based on recent observations and simulations). A first application to two well-studied globular clusters is briefly described and discussed.

RR Lyrae stars as probes of the Milky Way structure and formation

AbstractRR Lyrae stars being distance indicators and tracers of old population serve as excellent probes of the structure, formation, and evolution of our Galaxy. Thousands of them are being discovered in ongoing wide-field surveys. The OGLE project conducts the Galaxy Variability Survey with the aim to detect and analyze variable stars, in particular of RRab type, toward the Galactic bulge and disk, covering a total area of 3000 deg2. Observations in these directions also allow detecting background halo variables and unique studies of their properties and distribution at distances from the Galactic Center to even 40 kpc. In this contribution, we present the first results on the spatial distribution of the observed RRab stars, their metallicity distribution, the presence of multiple populations, and relations with the old bulge. We also show the most recent results from the analysis of RR Lyrae stars of the Sgr dwarf spheroidal galaxy, including its center, the globular cluster M54.

Lithium abundances in globular cluster giants: NGC 1904, NGC 2808, and NGC 362★

The presence of multiple populations in globular clusters has been well established thanks to high-resolution spectroscopy. It is widely accepted that distinct populations are a consequence of different stellar generations: intra-cluster pollution episodes are required to produce the peculiar chemistry observed in almost all clusters. Unfortunately, the progenitors responsible have left an ambiguous signature and their nature remains unresolved. To constrain the candidate polluters, we have measured lithium and aluminium abundances in more than 180 giants across three systems: NGC~1904, NGC~2808, and NGC~362. The present investigation along with our previous analysis of M12 and M5 affords us the largest database of simultaneous determinations of Li and Al abundances. Our results indicate that Li production has occurred in each of the three clusters. In NGC~362 we detected an M12-like behaviour, with first and second-generation stars sharing very similar Li abundances favouring a progenitor that is able to produce Li, such as AGB stars. Multiple progenitor types are possible in NGC~1904 and NGC~2808, as they possess both an intermediate population comparable in lithium to the first generation stars and also an extreme population, that is enriched in Al but depleted in Li. A simple dilution model fails in reproducing this complex pattern. Finally, the internal Li variation seems to suggest that the production efficiency of this element is a function of the cluster's mass and metallicity - low-mass or relatively metal-rich clusters are more adept at producing Li.

Micellar-cluster association of ureidopyrimidone functionalized monochelic polybutadiene

A series of monochelic polybutadienes with a ureidopyrimidone terminal group (MPBd-UPy) has been synthesized using anionic polymerization and chain-end transformation. Monochelic polybutadiene with two UPy terminal groups, MPBd-(UPy)2, has also been synthesized to study the effect of chain-end concentration on hydrogen bonding association. The transformation of the precursor ω-hydroxyl terminated polybutadiene into the ureidopyrimidone functionality via the reaction with 1-(6-isocyanatohexyl)-3-(6-methyl-4-oxo-1,4-dihydropyrimidin-2-yl) urea (UPy-NCO) turns free-flowing liquid samples into a semi-solid, viscous material, due to the well-known quadruple hydrogen bonding ability of UPy. The dimerization association of MPBd-UPy has been studied thoroughly using size exclusion chromatography, intrinsic viscosity and dynamic light scattering. Solutions of MPBd-UPy exhibit a high Huggins parameter, 0.40 < KH > 0.63, depending on the molecular weight and the number of UPy groups at the chain-end. Studies reveal that along with hydrogen bonded dimers, (MPBd-UPy)2, they also aggregate intermolecularly to form star-like micelles that are in equilibrium with the dimers. The presence of multiple populations with Rh as high as 700 nm, which decreases with increasing temperature in toluene has been identified. The UPy aggregated micellar clusters have distinct endothermic transitions in the solid-state and atomic force microscopy studies show the presence of micellar-clusters forming a well-defined assembly of fibrous like parallel lines on a mica surface.

Monitoring reveals two genetically distinct brown trout populations remaining in stable sympatry over 20 years in tiny mountain lakes

Detecting population subdivision when apparent barriers to gene flow are lacking is important in evolutionary and conservation biology. Recent research indicates that intraspecific population complexity can be crucial for maintaining a species 0 evolutionary potential, productivity, and ecological role. We monitored the genetic relationships at 14 allozyme loci among *4,000 brown trout (Salmo trutta) collected during 19 years from two small intercon- nected mountain lakes (0.10 and 0.17 km 2 , respectively) in central Sweden. There were no allele frequency differences between the lakes. However, heterozygote deficiencies within lakes became obvious after a few years of monitoring. Detailed analyses were then carried out without a priori grouping of samples, revealing unexpected differentiation patterns: (i) the same two genetically distinct (FST C 0.10) populations occur sympatrically at about equal frequencies within both lakes, (ii) the genetic subdivision is not coupled with apparent phenotypical dichotomies, (iii) this cryptic structure remains stable over the two decades monitored, and (iv) the point estimates of effective population size are c. 120 and 190, respectively, indicating that genetic drift is important in this system. A subsample of 382 fish was also analyzed for seven microsatellites. The genetic pattern does not follow that of the allozymes, and in this subsample the presence of multiple populations would have gone unde- tected if only scoring microsatellites. Sympatric populations may be more common than anticipated, but difficult to detect when individuals cannot be grouped appropriately, or when markers or sample sizes are insufficient to provide adequate statistical power with approaches not requiring prior grouping.

The horizontal branch morphology of M 31 globular clusters

We use deep, high quality colour magnitude diagrams obtained with the Hubble Space Telescope to compute a simplified version of the Mironov index [SMI; B/(B+R)] to parametrize the horizontal branch (HB) morphology for 23 globular clusters in the M31 galaxy (Sample-A), all located in the outer halo at projected distances between 10 kpc and 100 kpc. This allows us to compare them with their Galactic counterparts, for which we estimated the SMI exactly in the same way, in the SMI vs. [Fe/H] plane. We find that the majority of the considered M31 clusters lie in a significantly different locus, in this plane, with respect to Galactic clusters lying at any distance from the center of the Milky Way. In particular they have redder HB morphologies at a given metallicity, or, in other words, clusters with the same SMI value are ~0.4 dex more metal rich in the Milky Way than in M31. We discuss the possible origin of this difference and we conclude that the most likely explanation is that many globular clusters in the outer halo of M31 formed ~1-2 Gyr later than their counterparts in the outer halo of the Milky Way, while differences in the cluster-to-cluster distribution of He abundance of individual stars may also play a role. The analysis of another sample of 25 bright M31 clusters (eighteen of them with M_V<= -9.0, Sample-B), whose SMI estimates are much more uncertain as they are computed on shallow colour magnitude diagrams, suggests that extended blue HB tails can be relatively frequent among the most massive M31 globular clusters, possibly hinting at the presence of multiple populations.

Interaction of the novel adenosine uptake inhibitor 3-[1-(6,7-diethoxy-2-morpholinoquinazolin-4-yl)piperidin-4-yl]-1,6-dimethyl-2,4(1H,3H)-quinazolinedione hydrochloride (KF24345) with the es and ei subtypes of equilibrative nucleoside transporters.

Nucleosides such as adenosine, as well as many nucleoside-based drugs, permeate cell membranes via a family of equilibrative nucleoside transporters (ENTs). We assessed the effects of (3-[1-(6,7-diethoxy-2-morpholino-quinazolin-4-yl)piperidin-4-yl]-1,6-dimethyl-2,4(1H,3H)-quinazolinedione hydrochloride (KF24345), a novel anti-inflammatory agent that potentiates the actions of adenosine, on the es (inhibitor-sensitive) and ei (inhibitor-resistant) subtypes of ENTs in human, mouse, and rat cells. KF24345 was similar to the prototypical high-affinity inhibitor nitrobenzylthioinosine (NBMPR) for blocking the human es transporter (K(I) of approximately 0.4 nM), but was 50-fold more effective than NBMPR at blocking the human ei transporter (K(I) of approximately 100 nM). KF24345 displayed significantly less species heterogeneity in its affinity for the es transporter than did dipyridamole, a widely used inhibitor of nucleoside transport; KF24345 may thus prove useful as an inhibitor for studies of nucleoside metabolism in a range of animal models. Furthermore, KF24345 seemed to act as a noncompetitive inhibitor of both [(3)H]NBMPR binding and [(3)H]nucleoside uptake by human es transporters, and these kinetics were consistent with an observed slow dissociation of KF24345 from the inhibitor binding site. KF24345 also exhibited unusual biphasic profiles for inhibition of [(3)H]NBMPR binding to membranes prepared from a recombinant human es transporter model (PK15-hENT1), suggesting the presence of multiple populations of NBMPR binding proteins in these membranes. The atypical tight binding interaction of KF24345 with the es transporter may prove useful for the molecular delineation of inhibitor binding domains and will facilitate its use as an in vivo inhibitor of nucleoside transport in studies focused on the biological effects of adenosine.