We present a catalog of 99,203 wide binary systems, initially identified as common proper motion (CPM) pairs from a subset of ∼5.2 million stars with proper motions , selected from Gaia data release ...2 (DR2) and the SUPERBLINK high proper motion catalog. CPM pairs are found by searching for pairs of stars with angular separations <1° and proper motion differences . A Bayesian analysis is then applied in two steps. In a first pass, we use proper motion differences and angular separations to distinguish between real binaries and chance alignments. In a second pass, we use parallax data from Gaia DR2 to refine our Bayesian probability estimates. We present a table of 119,390 pairs which went through the full analysis, 99,203 of which have probabilities >95% of being real wide binaries. Of those 99,203 high-probability pairs, we estimate that only about 364 pairs are most likely to be false positives. In addition, we identify 57,506 pairs that have probabilities greater than 10% from the first pass but have high parallax errors and therefore were not vetted in the second pass. We examine the projected physical separation distribution of our highest probability pairs and note that the distribution is a simple exponential tail and shows no evidence of being bimodal. Among pairs with lower probability, wide binaries are detected at larger separations (>104-105 au), consistent with the very wide population suggested in previous studies; however, our analysis suggests that these do not represent a distinct population, but instead represent either the exponential tail of the "normal" wide binary distribution or are simply chance alignments of unrelated field stars. We examine the Hertzsprung-Russell diagram of this set of high-probability wide binaries and find evidence for 980 overluminous components among 2227 K + K wide binaries; assuming these represent unresolved subsystems, we determine that the higher-order multiplicity fraction for K + K wide systems is at least 39.6%.
Monoclonal antibodies (mAb) are a major component of cancer therapy. In this review, we summarize the different therapeutic mAbs that have been successfully developed against various tumor-expressed ...antigens and examine our current understanding of their different mechanisms of antitumor action. These mechanisms of action (MOA) largely center on the stimulation of different innate immune effector processes, which appear to be principally responsible for the efficacy of most unconjugated mAb therapies against cancer. This is evident in studies of mAbs targeting antigens for hematologic cancers, with emerging data also demonstrating the critical nature of innate immune-mediated mechanisms in the efficacy of anti-HER2 mAbs against solid HER2
cancers. Although HER2-targeted mAbs were originally described as inhibitors of HER2-mediated signaling, multiple studies have since demonstrated these mAbs function largely through their engagement with Fc receptors to activate innate immune effector functions as well as complement activity. Next-generation mAbs are capitalizing on these MOAs through improvements to enhance Fc-activity, although regulation of these mechanisms may vary in different tumor microenvironments. In addition, novel antibody-drug conjugates have emerged as an important means to activate different MOAs. Although many unknowns remain, an improved understanding of these immunologic MOAs will be essential for the future of mAb therapy and cancer immunotherapy.
Triple-negative breast cancers (TNBC) are aggressive with no effective targeted therapies. A combined database analysis identified 32 inflammation-related genes differentially expressed in TNBCs and ...10 proved critical for anchorage-independent growth. In TNBC cells, an LPA-LPAR2-EZH2 NF-κB signaling cascade was essential for expression of interleukin (IL)-6, IL-8, and CXCL1. Concurrent inhibition of IL-6 and IL-8 expression dramatically inhibited colony formation and cell survival in vitro and stanched tumor engraftment and growth in vivo. A Cox multivariable analysis of patient specimens revealed that IL-6 and IL-8 expression predicted patient survival times. Together these findings offer a rationale for dual inhibition of IL-6/IL-8 signaling as a therapeutic strategy to improve outcomes for patients with TNBCs.
Abstract
Over the past decade, the number of known wide-binary systems has expanded exponentially, thanks to the release of data from the Gaia Mission. Some of these wide-binary systems are actually ...higher-order multiples, where one of the components is an unresolved binary itself. One way to search for these systems is by identifying the overluminous components in the systems. In this study, we examine 4947 K+K wide-binary pairs from the SUPERWIDE catalog, and quantify the relative colors and luminosities of the components to find evidence for additional unresolved companions. The method is best illustrated in a graph that we call the “Lobster” diagram. To confirm that the identified overluminous components are close binary systems, we cross-match our wide binaries with the TESS, K2, and Kepler archives, and search for signs of eclipses and fast stellar rotation modulation in the light curves. We find that 78.9% ± 20.7% of the wide binaries that contain an eclipsing system are identified as overluminous in the “Lobster” diagram, and that 73.5% ± 12.4% of the wide binaries that contain a component showing fast rotation (
P
< 5 days) also show an overluminous component. From these results, we calculate a revised lower limit on the higher-order multiplicity fraction for K+K wide binaries of 40.0% ± 1.6%. We also examine the higher-order multiplicity fraction as a function of projected physical separation and metallicity. The fraction is unusually constant as a function of projected physical separation, while we see no statistically significant evidence that the fraction varies with metallicity.
Abstract
We present high-angular-resolution imaging observations of 517 host stars of TESS exoplanet candidates using the ‘Alopeke and Zorro speckle cameras at Gemini North and South. The sample ...consists mainly of bright F, G, K stars at distances of less than 500 pc. Our speckle observations span angular resolutions of ∼20 mas out to 1.″2, yielding spatial resolutions of <10–500 au for most stars, and our contrast limits can detect companion stars 5–9 mag fainter than the primary at optical wavelengths. We detect 102 close stellar companions and determine the separation, magnitude difference, mass ratio, and estimated orbital period for each system. Our observations of exoplanet host star binaries reveal that they have wider separations than field binaries, with a mean orbital semimajor axis near 100 au. Other imaging studies have suggested this dearth of very closely separated binaries in systems which host exoplanets, but incompleteness at small separations makes it difficult to disentangle unobserved companions from a true lack of companions. With our improved angular resolution and sensitivity, we confirm that this lack of close exoplanet host binaries is indeed real. We also search for a correlation between planetary orbital radii versus binary star separation; but, given the very short orbital periods of the TESS planets, we do not find any clear trend. We do note that in exoplanet systems containing binary host stars, there is an observational bias against detecting Earth-size planet transits due to transit depth dilution caused by the companion star.
T cell recognition of specific antigens mediates protection from pathogens and controls neoplasias, but can also cause autoimmunity. Our knowledge of T cell antigens and their implications for human ...health is limited by the technical limitations of T cell profiling technologies. Here, we present T-Scan, a high-throughput platform for identification of antigens productively recognized by T cells. T-Scan uses lentiviral delivery of antigen libraries into cells for endogenous processing and presentation on major histocompatibility complex (MHC) molecules. Target cells functionally recognized by T cells are isolated using a reporter for granzyme B activity, and the antigens mediating recognition are identified by next-generation sequencing. We show T-Scan correctly identifies cognate antigens of T cell receptors (TCRs) from viral and human genome-wide libraries. We apply T-Scan to discover new viral antigens, perform high-resolution mapping of TCR specificity, and characterize the reactivity of a tumor-derived TCR. T-Scan is a powerful approach for studying T cell responses.
Display omitted
•T-Scan is a high-throughput method to identify the functional targets of CD8 T cells•We apply T-Scan to multiplex discovery of CMV antigens from bulk memory T cells•Genome-wide T-Scan finds the cognate antigen and off-targets of a self-reactive TCR
T-Scan is a cell-based, pooled screening approach for high-throughput identification of antigens productively recognized by T cells.
The development and success of RNA-based vaccines targeting SARS-CoV-2 has awakened new interest in utilizing RNA vaccines against cancer, particularly in the emerging use of self-replicating RNA ...(srRNA) viral vaccine platforms. These vaccines are based on different single-stranded RNA viruses, which encode RNA for target antigens in addition to replication genes that are capable of massively amplifying RNA messages after infection. The encoded replicase genes also stimulate innate immunity, making srRNA vectors ideal candidates for anti-tumor vaccination. In this review, we summarize different types of srRNA platforms that have emerged and review evidence for their efficacy in provoking anti-tumor immunity to different antigens. These srRNA platforms encompass the use of naked RNA, DNA-launched replicons, viral replicon particles (VRP), and most recently, synthetic srRNA replicon particles. Across these platforms, studies have demonstrated srRNA vaccine platforms to be potent inducers of anti-tumor immunity, which can be enhanced by homologous vaccine boosting and combining with chemotherapies, radiation, and immune checkpoint inhibition. As such, while this remains an active area of research, the past and present trajectory of srRNA vaccine development suggests immense potential for this platform in producing effective cancer vaccines.
Abstract Here we present speckle observations of 16 low-separation ( s < 30 au) high-probability candidate binaries from the catalog by Medan et al., where secondaries typically lack astrometric ...solutions in Gaia. From these speckle observations, we find a second component is always detected within the field of view. To determine if the detection is consistent with a physical companion or a chance alignment with a background source, we utilize a statistic from Tokovinin & Kiyaeva that compares the apparent motion of the systems to the expected orbital motion ( μ ′ ). Using simulated binary orbits, we construct likelihood distributions of μ ′ assuming various total errors on the measurements. With the hypothesis that the system is a true binary, we show that large measurement errors can result in μ ′ values higher than expected for bound systems. Using simulated chance alignments, we also create similar likelihoods to test this alternative hypothesis. By combining likelihoods of both true binaries and chance alignments, we find that 15 of the 16 candidates are physical systems regardless of the level of measurement error. Our findings also accommodate all 16 as physical systems if the average, relative measurement error on the binary separations and position angles is ∼4.3%, which is consistent with our knowledge of the Gaia and Gemini speckle pipelines. Importantly, beyond assessing the likelihood of a true binary versus chance alignment, this quantitative assessment of the true average measurement error will allow more robust error estimates of mass determinations from short separation binaries with Gaia and/or Gemini speckle data.
The Src homology phosphotyrosyl phosphatase 2 (SHP2) is a positive effector of receptor tyrosine kinases (RTK) signaling. Furthermore, SHP2 is known to promote cell migration and invasiveness, key ...steps in cancer metastasis. To date, however, the mechanism by which SHP2 regulates cell movement is not fully understood. In the current report, a new role for SHP2 in regulating cell migration has been suggested. We show that SHP2 mediates lamellipodia persistence and cell polarity to promote directional cell migration in the MDA-MB231 and the MDA-MB468 basal-like and triple-negative breast cancer cell lines. We further show that SHP2 modulates the activity of focal adhesion kinase (FAK) by dephosphorylating pTyr397, the autophosphorylation site that primes FAK function. Because hyperactivation of FAK is known to counter the maturation of nascent focal complexes to focal adhesions, we propose that one of the mechanisms by which SHP2 promotes lamellipodia persistence is by downregulating FAK activity through dephosphorylation of pTyr397. The finding that inhibition of FAK activity partially restores EGF-induced lamellipodia persistence and cell migration in SHP2-silenced cells supports our proposition that SHP2 promotes growth factor-induced cell movement by acting, at least in part, on FAK. However, the effect of SHP2 inhibition in nonstimulated cells seems FAK independent as there was no significant difference between the control and the SHP2-silenced cells in pY397-FAK levels. Also, FAK inhibition did not rescue Golgi orientation defects in SHP2-silenced cells, suggesting that SHP2 acts through other mechanisms to promote cell polarity.
PDF
