Star Formation History of a Young Super-Star Cluster in NGC 4038/39: Direct Detection of Low Mass Pre-Main Sequence Stars

We present an analysis of the near-infrared spectrum of a young massive star cluster in the overlap region of the interacting galaxies NGC 4038/39 using population synthesis models. Our goal is to model the cluster population as well as provide rough constraints on its initial mass function (IMF). The cluster shows signs of youth such as thermal radio emission and strong hydrogen emission lines in the near-infrared. Late-type absorption lines are also present which are indicative of late-type stars in the cluster. The strength and ratio of these absorption lines cannot be reproduced through either late-type pre-main sequence (PMS) stars or red supergiants alone. Thus we interpret the spectrum as a superposition of two star clusters of different ages, which is feasible since the 1" spectrum encompasses a physical region of ~90 pc and radii of super-star clusters are generally measured to be a few parsecs. One cluster is young (<= 3 Myr) and is responsible for part of the late-type absorption features, which are due to PMS stars in the cluster, and the hydrogen emission lines. The second cluster is older (6 Myr - 18 Myr) and is needed to reproduce the overall depth of the late-type absorption features in the spectrum. Both are required to accurately reproduce the near-infrared spectrum of the object. Thus we have directly detected PMS objects in an unresolved super-star cluster for the first time using a combination of population synthesis models and pre-main sequence tracks. This analysis serves as a testbed of our technique to constrain the low-mass IMF in young super-star clusters as well as an exploration of the star formation history of young UC HII regions.Comment: 26 pages, 5 figures, accepted for publication in the Astrophysical Journa

Constraining the IMF in Extreme Environments: Detecting Young Low Mass Stars in Unresolved Starbursts

We demonstrate the feasibility of detecting directly low mass stars in unresolved super-star clusters with ages < 10 Myr using near-infrared spectroscopy at modest resolution (R ~ 1000). Such measurements could constrain the ratio of high to low mass stars in these extreme star-forming events, providing a direct test on the universal nature of the initial mass function (IMF) compared to the disk of the Milky Way (Chabrier, 2003). We compute the integrated light of super-star clusters with masses of 10^6 Msun drawn from the Salpeter (1955) and Chabrier (2003) IMFs for clusters aged 1, 3, and 10 Myr. We combine, for the first time, results from Starburst99 (Leitherer et al. 1999) for the main sequence and post-main sequence population (including nebular emission) with pre-main sequence (PMS) evolutionary models (Siess et al. 2000) for the low mass stars as a function of age. We show that ~ 4-12 % of the integrated light observed at 2.2 microns comes from low mass PMS stars with late-type stellar absorption features at ages < 3 Myr. This light is discernable using high signal-to-noise spectra (> 100) at R=1000 placing constraints on the ratio of high to low mass stars contributing to the integrated light of the cluster.Comment: Accepted for publication in the Astrophysical Journal Letter

Würde und Selbstbestimmung in der stationären Langzeitpflege: Herausforderungen an die Pflegearbeit aus soziologischer und ethischer Perspektive

Selbstbestimmung und Würde sind zunehmend zentrale normative Orientierungen in der stationären Altenpflege. Insbesondere für Bewohnerinnen und Bewohner gilt es, die Erfahrung von Mitgestaltung des eigenen Lebens und eines würdevollen Miteinanders im Pflegealltag herzustellen. Das Projekt SeLeP bietet einen Einblick in die praktischen Herstellungsprozesse und deren Herausforderungen. Dabei spielt Pflege als Interaktionsarbeit eine zentrale Rolle, aber auch deren organisationale Rahmenbedingungen. Ein aus dem Projekt heraus entwickeltes Schulungskonzept knüpft hier an und soll die Umsetzung von Selbstbestimmung und Würde im Pflegealltag stärken.Self-determination and dignity are increasingly essential normative orientations in the care for the elderly. Especially for residents in nursing homes, it is important to create the experience of co-determination of one's own life and dignified togetherness in everyday care. The SeLeP project offers an insight into the practical creation processes and their challenges. In this context, care as interaction work as well as its organizational framework has a central role. A training concept developed by the project starts here and intends to strengthen the implementation of self-determination and dignity in everyday care

HST/NICMOS Observations of NGC 1333: The Ratio of Stars to Sub-Stellar Objects

We present an analysis of NICMOS photometry and low-resolution grism spectroscopy of low-mass stars and sub-stellar objects in the young star-forming region NGC 1333. Our goal is to constrain the ratio of low-mass stars to sub- stellar objects down to 20 Mjup in the cluster as well as constrain the cluster IMF down to 30 Mjup in combination with a previous survey of NGC 1333 by Wilking et al. Our survey covers 4 fields of 51.2" x 51.2", centered on brown dwarf candidates previously identified in Wilking et al. We extend previous work based on the use of a water vapor index for spectral typing to wavelengths accessible with NICMOS on the HST. Spectral types were derived for the 14 brightest objects in our fields, ranging from <M0 - M8, which at the age of the cluster (0.3 Myr) corresponds to a range in mass of >0.25 - 0.02 Msun. In addition to the spectra, we present an analysis of the color-magnitude diagram using pre-main sequence evolutionary models of D'Antona & Mazzitelli. Using an extinction-limited sample, we derive the ratio of low-mass stars to brown dwarfs. Comparisons of the observed ratio to that expected from the field IMF of Chabrier indicate that the two results are consistent. We combine our data with that of Wilking et al. to compute the ratio of intermediate-mass stars (0.1 - 1.0 Msun) to low-mass objects (0.03 - 0.1 Msun) in the cluster. We also report the discovery of a faint companion to the previously confirmed brown dwarf ASR 28, as well as a possible outflow surrounding ASR 16. If the faint companion is confirmed as a cluster member, it would have a mass of ~ 5 Mjup (mass ratio 0.15) at a projected distance of 350 AU, similar to 2MASS 1207-3923 B.Comment: 33 pages, 6 figures, accepted for publication by A

Large-scale statistical mapping of T-cell receptor β sequences to human leukocyte antigens

IntroductionT-cell receptors (TCRs) interacting with peptides presented by human leukocyte antigens (HLAs) are the foundation of the adaptive immune system, but population-level analysis of TCR–HLA interactions is lacking.MethodsWe statistically associated approximately 106 public TCRβs to specific HLAs using TCRβ repertoires sampled from 4,144 HLA-genotyped subjects. The TCRβs we associated were specific to unique HLA allotypes, not allelic groups, and to the paired α–β heterodimer of class II HLAs, though exceptions were observed.ResultsThis specificity permitted highly accurate imputation of 248 class I and II HLAs from the TCRβ repertoire. Notably, 45 HLA-DP and -DQ heterodimers lacked associated TCRs because they likely arise from non-functional trans-complementation. The public class I and II HLA-associated TCRβs we identified were primarily expressed on CD8+ and CD4+ memory T cells, respectively, which were responding to various common antigens.DiscussionOur results recapitulate fundamental biology, provide insights into the functionality of HLAs, and demonstrate the power and potential of population-level TCRβ repertoire sequencing

Magnitude and dynamics of the T-cell response to SARS-CoV-2 infection at both individual and population levels

IntroductionT cells are involved in the early identification and clearance of viral infections and also support the development of antibodies by B cells. This central role for T cells makes them a desirable target for assessing the immune response to SARS-CoV-2 infection.MethodsHere, we combined two high-throughput immune profiling methods to create a quantitative picture of the T-cell response to SARS-CoV-2. First, at the individual level, we deeply characterized 3 acutely infected and 58 recovered COVID-19 subjects by experimentally mapping their CD8 T-cell response through antigen stimulation to 545 Human Leukocyte Antigen (HLA) class I presented viral peptides. Then, at the population level, we performed T-cell repertoire sequencing on 1,815 samples (from 1,521 COVID-19 subjects) as well as 3,500 controls to identify shared “public” T-cell receptors (TCRs) associated with SARS-CoV-2 infection from both CD8 and CD4 T cells.ResultsCollectively, our data reveal that CD8 T-cell responses are often driven by a few immunodominant, HLA-restricted epitopes. As expected, the T-cell response to SARS-CoV-2 peaks about one to two weeks after infection and is detectable for at least several months after recovery. As an application of these data, we trained a classifier to diagnose SARS-CoV-2 infection based solely on TCR sequencing from blood samples, and observed, at 99.8% specificity, high early sensitivity soon after diagnosis (Day 3–7 = 85.1% [95% CI = 79.9–89.7]; Day 8–14 = 94.8% [90.7–98.4]) as well as lasting sensitivity after recovery (Day 29+/convalescent = 95.4% [92.1–98.3]).DiscussionThe approaches described in this work provide detailed insights into the adaptive immune response to SARS-CoV-2 infection, and they have potential applications in clinical diagnostics, vaccine development, and monitoring

Constraints on the Low-Mass IMF in Young Super-Star Clusters in Starburst Galaxies

As evidence for variations in the initial mass function (IMF) in nearby star forming regions remains elusive we are forced to expand our search to more extreme regions of star formation. Starburst galaxies, which contain massive young clusters have in the past been reported to have IMFs different than that characterizing the field star IMF. In this thesis we use high signal-to-noise near-infrared spectra to place constraints on the shape of the IMF in extreme regions of extragalactic star formation and also try to understand the star formation history in these regions.Through high signal-to-noise near-infrared spectra it is possible to directly detect low-mass PMS stars in unresolved young super-star clusters, using absorption features that trace cool stars. Combining Starburst99 and available PMS tracks it is then possible to constrain the IMF in young super-star clusters using a combination of absorption lines each tracing different ranges of stellar masses and comparing observed spectra to models. Our technique can provide a direct test of the universality of the IMF compared to the Milky Way.We have obtained high signal-to-noise H- and K-band spectra of two young super-star clusters in the starburst galaxies NGC 4039/39 and NGC 253 in order to constrain the low-mass IMF and star formation history in the clusters. The cluster in NGC 4038/39 shows signs of youth such as thermal radio emission and strong hydrogen emission lines as well as late-type absorption lines indicative of cool stars. The strength and ratio of these absorption lines cannot be reproduced through either late-type pre-main sequence stars or red supergiants alone. We interpret the spectrum as a superposition of two star clusters of different ages over the physical region of 90 pc our spectrum represents. One cluster is young (< 3 Myr) and is responsible for part of the late-type absorption features, which are due to PMS stars in the cluster, and the hydrogen emission lines. The second cluster is older (6 Myr - 18 Myr) and is needed to reproduce the overall depth of the late-type absorption features in the spectrum. While the superposition of clusters does not allow us to place stringent constraints on the IMF there is no evidence of a low-mass cutoff in the cluster and the IMF is consistent with a Chabrier and Kroupa IMF typical of the field.The cluster in NGC 253 shows the same signs of youth as the cluster in NGC 4038/39 and sits in front of a background population of older stars. The background population has an age of $approx$ 12 Myr and thus contains red supergiants. After carefully subtracting this background we model the spectrum of the young cluster. We find that its IMF is consistent with a Chabrier and Kroupa IMF with a best-fit power-law slope of 1.0 in linear units. Slopes of 0.0 - 1.5 are also formally consistent with the cluster spectrum. We conclude that there is no strong evidence for an unusual IMF or a lack of low-mass stars (< 1 Msun) in either of these galaxies

LB17. Immunosequencing of the T-Cell Receptor Repertoire Reveals Signatures Specific for Diagnosis and Characterization of Early Lyme Disease

Abstract Background Changing climate and demographic trends have led to recent increases in the incidence of tick-borne illnesses. Early diagnosis of Lyme disease (LD) is critical for initiation of antibiotics to mitigate symptoms and prevent late manifestations. In patients not presenting with a typical erythema migrans rash, 2-tiered serologic testing is recommended to support a diagnosis of LD. However, 2-tiered testing is limited by ambiguity in interpretation and low sensitivity in early disease, highlighting an unmet clinical need for alternative diagnostic approaches. We identified a clinical signal for early LD based on evaluation of the T-cell response to B. burgdorferi infection. Methods We immunosequenced T-cell receptor (TCR) repertoires in blood samples from 3 independent cohorts of patients with laboratory-confirmed or clinically diagnosed early LD and endemic/non-endemic controls to identify 251 public, LD-associated TCRs. These TCRs were used to train a classifier that identified early LD with 99% specificity. Classifier sensitivity was evaluated in 211 LD cases and 2631 endemic controls and compared to that of standard 2-tiered testing (STTT). Biologic specificity was assessed by correlating TCR assay scores with clinical measures and by mapping the antigen specificity of Lyme-associated TCRs to B. burgdorferi antigens. Figure 1. LD-associated TCRs distinguish cases (orange) from controls (blue) in training cohorts. (A) Logistic-growth curve used to define a scoring function. (B) Positive-call threshold (99th percentile in endemic controls). Results In early LD, TCR testing demonstrated a 1.9-fold increase in sensitivity compared to STTT (56% vs 30%), with a 3.1-fold increase ≤4 days from the onset of symptoms (44% vs 14%). TCR positivity predicted subsequent seroconversion in 37% of initially STTT-negative patients, suggesting the T-cell response is detectable before the humoral response. While positivity for both tests declined following treatment, greater declines in posttreatment sensitivity were observed for STTT compared to TCR testing. Higher TCR scores were associated with measures of disease severity, including abnormal liver function tests, disseminated rash, and number of symptoms. A subset of LD-associated TCRs mapped to B. burgdorferi antigens, demonstrating the high specificity of a TCR immunosequencing approach. Figure 2. Validation of the TCR classifier in the JHU cohort and other holdout endemic controls. Distribution of model scores (A) and assay sensitivity (B). Model scores (C) and ROC (D) curves by serostatus. Figure 3. Clinical correlates of TCR scoring. (A) Liver function test; (B) lymphocyte count, (C) rash presentation, (D) number of symptoms. Conclusion T-cell-based testing has potential clinical utility as a sensitive and specific diagnostic for early LD, particularly in the initial days of illness. Disclosures Sudeb C. Dalai, MD, PhD, Adaptive Biotechnologies (Employee, Shareholder) Julia Greissl, PhD, Microsoft (Employee, Shareholder) Mitch Pesesky, PhD, Adaptive Biotechnologies (Employee, Shareholder) Allison W. Rebman, MPH, Global Lyme Alliance (Research Grant or Support)Steven and Alexandra Cohen Foundation (Research Grant or Support) Mark J. Soloski, PhD, NIH grant P30 AR070254 (Grant/Research Support)Steven and Alexandra Cohen Foundation (Research Grant or Support) Elizabeth J. Horn, PhD, Adaptive Biotechnologies (Research Grant or Support)Bay Area Lyme Foundation (Research Grant or Support)Lyme Disease Biobank (Employee)Steven and Alexandra Cohen Foundation (Research Grant or Support) Jennifer N. Dines, MD, Adaptive Biotechnologies (Employee, Shareholder) Rachel M. Gittelman, PhD, Adaptive Biotechnologies (Employee, Shareholder) Thomas M. Snyder, PhD, Adaptive Biotechnologies (Employee, Shareholder) Ryan O. Emerson, PhD, Adaptive Biotechnologies (Other Financial or Material Support, Employment with Adaptive Biotechnologies during the time of this study) Edward Meeds, PhD, Microsoft (Employee, Shareholder) Thomas Manley, MD, Adaptive Biotechnologies (Other Financial or Material Support, Declares employment with Adaptive Biotechnologies during the time of this study) Ian M. Kaplan, PhD, Adaptive Biotechnologies (Employee, Shareholder) Lance Baldo, MD, Adaptive Biotechnologies (Employee, Shareholder, Leadership Interest) Jonathan M. Carlson, PhD, Microsoft (Employee, Shareholder) Harlan S. Robins, PhD, Adaptive Biotechnologies (Board Member, Employee, Shareholder) John Aucott, MD, Adaptive Biotechnologies (Advisor or Review Panel member)Bay Area Lyme Foundation (Other Financial or Material Support, Scientific Advisory Board member)Department of Health and Human Services (Other Financial or Material Support, Past Chair, 2018, HHS Tick-borne Disease Working Group, Office of HIV/AIDS and Infectious Disease Policy, Office of the Assistant Secretary of Health)Expert testimony (Other Financial or Material Support, Expert testimony)Global Lyme Alliance (Research Grant or Support)Pfizer (Consultant)Steven and Alexandra Cohen Foundation (Research Grant or Support)Tarsus Pharmaceuticals (Consultant) </jats:sec