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Background: Thrombocytopenia is common in preterm neonates. Platelet transfusions are sometimes given to thrombocytopenic neonates with the hope of reducing the bleeding risk, however, there are little clinical data to support this practice, and platelet transfusions may increase the bleeding risk or lead to adverse complications. Our group previously reported that fetal platelets expressed lower levels of immune-related mRNA compared with adult platelets. In this study, we focused on the effects of adult versus neonatal platelets on monocyte immune functions that may have an impact on neonatal immune function and transfusion complications. Methods: Using RNA sequencing of postnatal day 7 and adult platelets, we determined age-dependent platelet gene expression. Platelets and naive bone marrow–isolated monocytes were cocultured and monocyte phenotypes determined by RNA sequencing and flow cytometry. An in vivo model of platelet transfusion in neonatal thrombocytopenic mice was used in which platelet-deficient TPOR (thrombopoietin receptor) mutant mice were transfused with adult or postnatal day 7 platelets and monocyte phenotypes and trafficking were determined. Results: Adult and neonatal platelets had differential immune molecule expression, including Selp . Monocytes incubated with adult or neonatal mouse platelets had similar inflammatory (Ly6C hi ) but different trafficking phenotypes, as defined by CCR2 and CCR5 mRNA and surface expression. Blocking P-sel (P-selectin) interactions with its PSGL-1 (P-sel glycoprotein ligand-1) receptor on monocytes limited the adult platelet-induced monocyte trafficking phenotype, as well as adult platelet-induced monocyte migration in vitro. Similar results were seen in vivo, when thrombocytopenic neonatal mice were transfused with adult or postnatal day 7 platelets; adult platelets increased monocyte CCR2 and CCR5, as well as monocyte chemokine migration, whereas postnatal day 7 platelets did not. Conclusions: These data provide comparative insights into adult and neonatal platelet transfusion–regulated monocyte functions. The transfusion of adult platelets to neonatal mice was associated with an acute inflammatory and trafficking monocyte phenotype that was platelet P-sel dependent and may have an impact on complications associated with neonatal platelet transfusions.

We present ultraviolet (UV) to near-infrared (NIR) observations and analysis of the nearby Type Ia supernova SN 2021fxy. Our observations include UV photometry from Swift/UVOT, UV spectroscopy from HST/STIS, and high-cadence optical photometry with the Swope 1-m telescope capturing intra-night rises during the early light curve. Early $B-V$ colours show SN 2021fxy is the first "shallow-silicon" (SS) SN Ia to follow a red-to-blue evolution, compared to other SS objects which show blue colours from the earliest observations. Comparisons to other spectroscopically normal SNe Ia with HST UV spectra reveal SN 2021fxy is one of several SNe Ia with flux suppression in the mid-UV. These SNe also show blue-shifted mid-UV spectral features and strong high-velocity Ca II features. One possible origin of this mid-UV suppression is the increased effective opacity in the UV due to increased line blanketing from high velocity material, but differences in the explosion mechanism cannot be ruled out. Among SNe Ia with mid-UV suppression, SNe 2021fxy and 2017erp show substantial similarities in their optical properties despite belonging to different Branch subgroups, and UV flux differences of the same order as those found between SNe 2011fe and 2011by. Differential comparisons to multiple sets of synthetic SN Ia UV spectra reveal this UV flux difference likely originates from a luminosity difference between SNe 2021fxy and 2017erp, and not differing progenitor metallicities as suggested for SNe 2011by and 2011fe. These comparisons illustrate the complicated nature of UV spectral formation, and the need for more UV spectra to determine the physical source of SNe Ia UV diversity., 26 pages, 19 figures, 9 tables; submitted to MNRAS, posted after receiving referee comments

Analysis of spectral line profile variations observed over 6 decades in the Wolf-Rayet system HD 5980 lead to the conclusion that Star A, the variable member of the system, has always dominated the wind collision zone (WCZ), contrary to suggestions that before 1994 the stronger wind belonged to its close companion, Star B. The observed variations are caused by a combination of physical occultations, wind eclipses and emission and absorption originating in the WCZ. The effects caused by the leading WCZ branch, which folds around Star B, are clearly seen as it crosses our line of sight to Star A during the secondary eclipse. These effects can inform on the WCZ velocity and density structures. We speculate that differences in line profiles at the same orbital phase but at different epochs may be linked to changes in the WCZ radiative properties. The 2017-2020 spectra indicate that HD 5980 was in a higher activity state than during 2010-2015.

We use photometric and spectroscopic observations of four detached eclipsing binaries in the globular cluster NGC 3201 to derive masses, radii, and luminosities of the component stars. Spanning across almost three magnitudes in the colour–magnitude diagram, the components offer a unique possibility to test the theory of stellar evolution. Their masses, radii, and luminosities range from 0.66 to 0.84 M⊙, 0.68 to 2.46 R⊙, and 0.38 to 5.56 L⊙, respectively. The distance to the cluster measured from the distance moduli of the component stars amounts to 4.54$^{+0.11}_{-0.14}$ kpc and agrees with the recent estimate based on Gaia parallaxes. By comparing the M − R and M − L diagrams of the component stars and the colour–magnitude diagram of NGC 3201 to Dartmouth model isochrones, we estimate the most probable age of the cluster to be 11.5 ± 0.5 Gyr. This estimate is based on three binaries only, as the fourth one seems to evolve along a different path, probably due to non-standard chemical composition and/or history. We confirm the tendency, observed in earlier CASE papers, for the age indicated by the M − R diagram to be younger than that implied by the colour–magnitude diagram.

BackgroundIn people living with HIV (PLWH) on combination antiretroviral therapy (cART), persistent systemic inflammation is a driving force for the progression of comorbidities, such as cardiovascular and cerebrovascular diseases. In this context, monocyte- and macrophage-related inflammation rather than T cell activation is a major cause of chronic inflammation. However, the underlying mechanism of how monocytes cause persistent systemic inflammation in PLWH is elusive.Methods and ResultsIn vitro, we demonstrated that lipopolysaccharides (LPS) or tumor necrosis factor alpha (TNFα), induced a robust increase of Delta-like ligand 4 (Dll4) mRNA and protein expression in human monocytes and Dll4 secretion (extracellular Dll4, exDll4) from monocytes. Enhanced membrane-bound Dll4 (mDll4) expression in monocytes triggered Notch1 activation to promote pro-inflammatory factors expression. Dll4 silencing and inhibition of Nocth1 activation diminished the LPS or TNFα -induced inflammation. exDll4 releases in response to cytokines occurred in monocytes but not endothelial cells or T cells. In clinical specimens, we found that PLWH, both male and female, on cART, showed a significant increase in mDll4 expression, activation of Dll4-Notch1 signaling, and inflammatory markers in monocytes. Although there was no sex effect on mDII4 in PLWH, plasma exDll4 was significantly elevated in males but not females compared to HIV uninfected individuals. Furthermore, exDll4 plasma levels paralleled with monocytes mDll4 in male PLWH. Circulating exDll4 was also positively associated with pro-inflammatory monocytes phenotype and negatively associated with classic monocytes phenotype in male PLWH.ConclusionPro-inflammatory stimuli increase Dll4 expression and Dll4-Notch1 signaling activation in monocytes and enhance monocyte proinflammatory phenotype, contributing to persistent systemic inflammation in male and female PLWH. Therefore, monocyte mDll4 could be a potential biomarker and therapeutic target of systemic inflammation. Plasma exDll4 may also play an additional role in systemic inflammation but primarily in men.

Classically, platelets have been described as the cellular blood component that mediates hemostasis and thrombosis. This important platelet function has received significant research attention for >150 years. The immune cell functions of platelets are much less appreciated. Platelets interact with and activate cells of all branches of immunity in response to pathogen exposures and infection, as well as in response to sterile tissue injury. In this review, we focus on innate immune mechanisms of platelet activation, platelet interactions with innate immune cells, as well as the intersection of platelets and adaptive immunity. The immune potential of platelets is dependent in part on their megakaryocyte precursor providing them with the molecular composition to be first responders and immune sentinels in initiating and orchestrating coordinated pathogen immune responses. There is emerging evidence that extramedullary megakaryocytes may be immune differentiated compared with bone marrow megakaryocytes, but the physiological relevance of immunophenotypic differences are just beginning to be explored. These concepts are also discussed in this review. The immune functions of the megakaryocyte/platelet lineage have likely evolved to coordinate the need to repair a vascular breach with the simultaneous need to induce an immune response that may limit pathogen invasion once the blood is exposed to an external environment.

We present a JWST/MIRI low-resolution mid-infrared (MIR) spectroscopic observation of the normal Type Ia supernova (SN Ia) SN 2021aefx at +323 days past rest-frame B-band maximum light. The spectrum ranges from 4-14 um, and shows many unique qualities including a flat-topped [Ar III] 8.991 um profile, a strongly tilted [Co III] 11.888 um feature, and multiple stable Ni lines. These features provide critical information about the physics of the explosion. The observations are compared to synthetic spectra from detailed NLTE multi-dimensional models. The results of the best-fitting model are used to identify the components of the spectral blends and provide a quantitative comparison to the explosion physics. Emission line profiles and the presence of electron capture (EC) elements are used to constrain the mass of the exploding white dwarf (WD) and the chemical asymmetries in the ejecta. We show that the observations of SN 2021aefx are consistent with an off-center delayed-detonation explosion of a near-Chandrasekhar mass (Mch) WD at a viewing angle of -30 degrees relative to the point of the deflagration-to-detonation transition. From the strength of the stable Ni lines we determine that there is little to no mixing in the central regions of the ejecta. Based on both the presence of stable Ni and the Ar velocity distributions, we obtain a strict lower limit of 1.2 Msun of the initial WD, implying that most sub-Mch explosions models are not viable models for SN 2021aefx. The analysis here shows the crucial importance of MIR spectra for distinguishing between explosion scenarios for SNe Ia., Comment: 21 pages, 9 figures, 4 tables, accepted to ApJL; updated to accepted version

We present 170 optical spectra of 35 low-redshift stripped-envelope core-collapse supernovae observed by the Carnegie Supernova Project-I between 2004 and 2009. The data extend from as early as -19 days (d) prior to the epoch of B-band maximum to +322 d, with the vast majority obtained during the so-called photospheric phase covering the weeks around peak luminosity. In addition to histogram plots characterizing the red-shift distribution, number of spectra per object, and the phase distribution of the sample, spectroscopic classification is also provided following standard criteria. The CSP-I spectra are electronically available and a detailed analysis of the data set is presented in a companion paper being the fifth and final paper of the series, Comment: Resubmitted to A&A after address referee's comments. Comments welcomed, and let us know if we missed to reference your paper?

Simian immunodeficiency virus (SIV) infection of macaques recapitulates many aspects of HIV pathogenesis and is similarly affected by both genetic and environmental factors. Psychosocial stress is associated with immune system dysregulation and worse clinical outcomes in people with HIV. This study assessed the impact of single housing, as a model of psychosocial stress, on innate immune responses of pigtailed macaques ( Macaca nemestrina ) during acute SIV infection.A retrospective analysis of acute SIV infection of 2- to si6-year-old male pigtailed macaques was performed to compare the innate immune responses of socially ( n = 41) and singly ( n = 35) housed animals. Measures included absolute monocyte count and subsets, and in a subset ( n ≤ 18) platelet counts and activation data.SIV infection resulted in the expected innate immune parameter changes with a modulating effect from housing condition. Monocyte number increased after infection for both groups, driven by classical monocytes (CD14 + CD16 - ), with a greater increase in socially housed animals (227%, p.001, by day 14 compared with preinoculation time points). Platelet numbers recovered more quickly in the socially housed animals. Platelet activation (P-selectin) increased by 65% ( p = .004) and major histocompatibility complex class I surface expression by 40% ( p = .009) from preinoculation only in socially housed animals, whereas no change in these measures occurred in singly housed animals.Chronic psychosocial stress produced by single housing may play an immunomodulatory role in the innate immune response to acute retroviral infection. Dysregulated innate immunity could be one of the pathways by which psychosocial stress contributes to immune suppression and increased disease severity in people with HIV.

S. J. Brennan et al., We present the bolometric light curve, identification and analysis of the progenitor candidate, and preliminary modelling of AT 2016jbu (Gaia16cfr). We find a progenitor consistent with a ∼ 22–25 M⊙ yellow hypergiant surrounded by a dusty circumstellar shell, in agreement with what has been previously reported. We see evidence for significant photometric variability in the progenitor, as well as strong Hα emission consistent with pre-existing circumstellar material. The age of the environment, as well as the resolved stellar population surrounding AT 2016jbu, supports a progenitor age of >10 Myr, consistent with a progenitor mass of ∼22 M⊙. A joint analysis of the velocity evolution of AT 2016jbu and the photospheric radius inferred from the bolometric light curve shows the transient is consistent with two successive outbursts/explosions. The first outburst ejected material with velocity ∼650 km s−1, while the second, more energetic event ejected material at ∼4500 km s−1. Whether the latter is the core collapse of the progenitor remains uncertain. We place a limit on the ejected 56Ni mass of, SJB acknowledges support from Science Foundation Ireland and the Royal Society (RS-EA/3471). MF is supported by a Royal Society–Science Foundation Ireland University Research Fellowship. TMB was funded by CONICYT PFCHA/DOCTORADOBECAS CHILE/2017-72180113 and acknowledges financial support from the Spanish Ministerio de Ciencia e Innovación (MCIN), the Agencia Estatal de Investigación (AEI) 10.13039/501100011033 under the PID2020-115253GA-I00 HOSTFLOWS project, and Centro Superior de Investigaciones Científicas (CSIC) under the PIE project 20215AT016. KM is funded by the EU H2020 ERC grant no. 758638. TWC acknowledges EU Funding under Marie Skłodowska–Curie grant H2020-MSCA-IF-2018-842471, and thanks Thomas Krühler for GROND data reduction. MN is supported by a Royal Astronomical Society Research Fellowship. BJS is supported by NSF grants AST-1908952, AST-1920392, AST-1911074, and NASA award 80NSSC19K1717. MS is supported by generous grants from Villum FONDEN (13261,28021) and by a project grant (8021-00170B) from the Independent Research Fund Denmark. LH acknowledges support for Watcher from Science Foundation Ireland grant 07/RFP/PHYF295. Time-domain research by DJS is supported by NSF grants AST-1821987, 1813466, and 1908972, and by the Heising–Simons Foundation under grant #2020-1864. NER acknowledges support from MIUR, PRIN 2017 (grant 20179ZF5KS). Support for JLP is provided in part by ANID through the Fondecyt regular grant 1191038 and through the Millennium Science Initiative grant ICN12_009, awarded to The Millennium Institute of Astrophysics, MAS. LG acknowledges financial support from the Spanish Ministry of Science, Innovation and Universities (MICIU) under the 2019 Ramón y Cajal program RYC2019-027683 and from the Spanish MICIU project PID2020-115253GA-I00. DAH and DH are supported by AST-1911151, AST19-11225, and NASA Swift grant 80NSSC19K1639. GP acknowledges support by the Ministry of Economy, Development, and Tourism’s Millennium Science Initiative through grant IC120009, awarded to The Millennium Institute of Astrophysics, MAS. LT acknowledges support from MIUR (PRIN 2017 grant 20179ZF5KS). Support for TW-SH was provided by NASA through the NASA Hubble Fellowship grant HST-HF2-51458.001-A awarded by the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., for NASA, under contract NAS5-26555. HK was funded by the Academy of Finland projects 324504 and 328898. This research made use of ASTROPY,8 a community-developed core PYTHON package for Astronomy (Astropy Collaboration 2013; Price-Whelan et al. 2018). This research made use of data provided by Astrometry.net.9 Parts of this research were supported by the Australian Research Council Centre of Excellence for All Sky Astrophysics in Three Dimensions (ASTRO 3D), through project number CE170100013. This research has made use of the NASA/IPAC Extragalactic Database (NED), which is operated by the Jet Propulsion Laboratory, California Institute of Technology, under contract with the National Aeronautics and Space Administration. We acknowledge the Telescope Access Program (TAP) funded by the NAOC, CAS, and the Special Fund for Astronomy from the Ministry of Finance. This work was partially supported by Polish NCN grants: Harmonia No. 2018/30/M/ST9/00311 and Daina No. 2017/27/L/ST9/03221. This work made use of v2.2.1 of the Binary Population and Spectral Synthesis (BPASS) models as described in Eldridge et al. (2017) and Stanway & Eldridge (2018). This research is based on observations made with the NASA/ESA Hubble Space Telescope obtained from the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555. These observations are associated with program 15645. Observations were also obtained from the Hubble Legacy Archive, which is a collaboration between the Space Telescope Science Institute (STScI/NASA), the Space Telescope European Coordinating Facility (ST-ECF/ESAC/ESA), and the Canadian Astronomy Data Centre (CADC/NRC/CSA). This research has made use of the SVO Filter Profile Service10 supported from the Spanish MINECO through grant AYA2017-84089.

We present early-time photometric and spectroscopic observations of the Type Ia supernova (SN Ia) 2021aefx. The early-time u-band light curve shows an excess flux when compared to normal SNe Ia. We suggest that the early excess blue flux may be due to a rapid change in spectral velocity in the first few days post explosion, produced by the emission of the Ca ii H&K feature passing from the u to the B bands on the timescale of a few days. This effect could be dominant for all SNe Ia that have broad absorption features and early-time velocities over 25,000 km s. It is likely to be one of the main causes of early excess u-band flux in SNe Ia that have early-time high velocities. This effect may also be dominant in the UV filters, as well as in places where the SN spectral energy distribution is quickly rising to longer wavelengths. The rapid change in velocity can only produce a monotonic change (in flux-space) in the u band. For objects that explode at lower velocities, and have a more structured shape in the early excess emission, there must also be an additional parameter producing the early-time diversity. More early-time observations, in particular early spectra, are required to determine how prominent this effect is within SNe Ia., C.A. and B.J.S. are supported by NSF grants AST-1907570, AST-1908952, AST-1920392, and AST-1911074. M.D.S. is funded in part by an Experiment grant (No. 28021) from the Villum FONDEN, and by a project 1 grant (No. 8021-00170B) from the Independent Research Fund Denmark (IRFD). P.H. acknowledges support by National Science Foundation (NSF) grant AST- 1715133. E.B. and J.D. are supported in part by NASA grant 80NSSC20K0538. This work has been generously supported by the National Science Foundation under grants AST-1008343, AST-1613426, AST-1613455, and AST1613472. This paper includes data gathered with the 6.5 meter Magellan Telescopes located at the Las Campanas Observatory, Chile. We would like to thank the technical staff for constant support for observations on the Swope telescope. The early-time spectrum that was critical for this analysis came from SALT through Rutgers University time via program 2021-1-MLT-007 (PI: Jha). L.G. acknowledges financial support from the Spanish Ministerio de Ciencia e Innovación (MCIN), the Agencia Estatal de Investigación (AEI) 10.13039/501100011033, and the European Social Fund (ESF) "Investing in your future" under the 2019 Ramón y Cajal program RYC2019-027683-I and the PID2020-115253GA-I00 HOSTFLOWS project, from Centro Superior de Investigaciones Científicas (CSIC) under the PIE project 20215AT016, and the program Unidad de Excelencia María de Maeztu CEX2020-001058-M.

We present photometric and spectroscopic data on three extragalactic luminous red novae (LRNe): AT 2018bwo, AT 2021afy, and AT 2021blu. AT 2018bwo was discovered in NGC 45 (at about 6.8 Mpc) a few weeks after the outburst onset. During the monitoring period, the transient reached a peak luminosity of 1040 erg s−1. AT 2021afy, hosted by UGC 10043 (∼49.2 Mpc), showed a double-peaked light curve, with the two peaks reaching a similar luminosity of 2.1(±0.6)×1041 erg s−1. Finally, for AT 2021blu in UGC 5829 (∼8.6 Mpc), the pre-outburst phase was well-monitored by several photometric surveys, and the object showed a slow luminosity rise before the outburst. The light curve of AT 2021blu was sampled with an unprecedented cadence until the object disappeared behind the Sun, and it was then recovered at late phases. The light curve of LRN AT 2021blu shows a double peak, with a prominent early maximum reaching a luminosity of 6.5 × 1040 erg s−1, which is half of that of AT 2021afy. The spectra of AT 2021afy and AT 2021blu display the expected evolution for LRNe: a blue continuum dominated by prominent Balmer lines in emission during the first peak, and a redder continuum consistent with that of a K-type star with narrow absorption metal lines during the second, broad maximum. The spectra of AT 2018bwo are markedly different, with a very red continuum dominated by broad molecular features in absorption. As these spectra closely resemble those of LRNe after the second peak, AT 2018bwo was probably discovered at the very late evolutionary stages. This would explain its fast evolution and the spectral properties compatible with that of an M-type star. From the analysis of deep frames of the LRN sites years before the outburst, and considerations of the light curves, the quiescent progenitor systems of the three LRNe were likely massive, with primaries ranging from about 13 M⊙ for AT 2018bwo, to 14−1+4 M⊙ for AT 2021blu, and over 40 M⊙ for AT 2021afy.

Heavy drinking among college students is a public health concern in part due to the accessibility of alcohol and promotions such as "happy hours," which discount the price of alcohol. In addition, consuming alcohol at unregulated off-campus parties may result in greater alcohol consumption, higher blood alcohol concentrations, and increased negative consequences. The purpose of the current study was to assess demand for a refillable red "Solo" cup using a new hypothetical purchase task, the Cup-Price Purchase Task (CPPT). The CPPT asked college student participants to read a description of an off-campus party drinking context and indicate the likelihood of purchasing a refillable cup at prices ranging from $0.00-$60.00. We found that at cup prices of $5.00 or below, the likelihood of purchase was 75% or higher; however, probability of purchase decreased to about 47% at a cup price of $10.00. In addition, several CPPT behavioral economic parameters were positively correlated with the Alcohol Purchase Task (APT) and other alcohol-related measures, providing support for the CPPT's construct validity. Finally, hierarchical regression analyses revealed that maximum expenditure on the CPPT was a unique predictor of both alcohol consumption and alcohol-related consequences, even after controlling for the APT metrics. These findings may inform future studies investigating the behavioral economics of high-risk drinking situations and potential strategies to reduce binge drinking. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

We thank the anonymous referee for their comments. W.B.H. acknowledges support from the Research Experience for Undergraduates program at the Institute for Astronomy, University of Hawaii-Manoa, funded through NSF grant #2050710. L.G. acknowledges financial support from the Spanish Ministry of Science, Innovation and Universities (MCIN) under the 2019 Ramon y Cajal program RYC2019-027683 and from the Spanish MCIN project HOSTFLOWS PID2020-115253GA-I00. M.G.M., R.G.D., and S.M.T. were funded by the European Union's Horizon 2020 research and innovation program under the Marie Skodowska-Curie grant agreement No. 839090. Based on observations collected at the European Southern Observatory under ESO program 106.2104. The work of the CSP-II has been generously supported by the National Science Foundation under grant Nos. AST-1008343, AST-1613426, AST-1613455, and AST-1613472. The CSP-II was also supported in part by the Danish Agency for Science and Technology and Innovation through a Sapere Aude Level 2 grant. E.B. was partially supported by NASA grant No. 80NSSC20K0538 J.D.L. acknowledges support from a UK Research and Innovation Fellowship (MR/T020784/1). C.R.B. acknowledges support from NSF grant Nos. AST-1008384, AST-1613426, AST-1613455, and AST-1613472. M.S and S.H. are supported by grants from the VILLUM FONDEN (grant No. 28021) and the Independent Research Fund Denmark (IRFD; 8021-00170B)., We present optical and near-infrared photometric and spectroscopic observations of the fast-declining Type Ia supernova (SN) 2015bo. SN 2015bo is underluminous (MB=−17.50 ± 0.15 mag) and has a fast-evolving light curve (Δm15(B)=1.91 ± 0.01 mag and sBV=0.48 ± 0.01). It has a unique morphology in the observed V −r color curve, where it is bluer than all other supernovae (SNe) in the comparison sample. A 56Ni mass of 0.17±0.03Me was derived from the peak bolometric luminosity, which is consistent with its location on the luminosity–width relation. Spectroscopically, SN 2015bo is a cool SN in the Branch classification scheme. The velocity evolution measured from spectral features is consistent with 1991bg-like SNe. SN 2015bo has a SN twin (similar spectra) and sibling (same host galaxy), SN 1997cn. Distance moduli of μ=34.33±0.01 (stat)± 0.11 (sys) mag and μ=34.34±0.04 (stat)±0.12 (sys) mag are derived for SN 2015bo and SN 1997cn, respectively. These distances are consistent at the 0.06σ level with each other, and they are also consistent with distances derived using surface-brightness fluctuations and redshift-corrected cosmology. This suggests that fast-declining SNe could be accurate distance indicators, which should not be excluded from future cosmological analyses., Research Experience for Undergraduates program at the Institute for Astronomy, University of Hawaii-Manoa, National Science Foundation (NSF) AST-1008384 AST-1613426 AST-1613455 AST-1613472, Spanish Ministry of Science, Innovation and Universities (MCIN) RYC2019-027683, Spanish MCIN project HOSTFLOWS PID2020-115253GA-I00, European Union's Horizon 2020 research and innovation program under the Marie Skodowska-Curie 839090 106.2104, National Science Foundation (NSF) AST-1613426 AST-1613455 AST-1613472 AST-1008343, Danish Agency for Science and Technology and Innovation through a Sapere Aude Level 2 grant, National Aeronautics & Space Administration (NASA) 80NSSC20K0538, UK Research and Innovation Fellowship MR/T020784/1, Villum Fonden 28021, Independent Research Fund Denmark 8021-00170B

Linking supernovae to their progenitors is a powerful method for furthering our understanding of the physical origin of their observed differences, while at the same time testing stellar evolution theory. In this second study of a series of three papers where we characterise SNe II to understand their diversity, we derive progenitor properties (initial and ejecta masses, and radius), explosion energy, $^{56}$Ni mass, and its degree of mixing within the ejecta for a large sample of SNe II. This dataset was obtained by the Carnegie Supernova Project-I and is characterised by a high cadence of their optical and NIR light curves and optical spectra that were homogeneously observed and processed. A large grid of hydrodynamical models and a fitting procedure based on MCMC methods were used to fit the bolometric light curve and the evolution of the photospheric velocity of 53 SNe II. We infer ejecta masses between 7.9 and 14.8 $M_{\odot}$, explosion energies between 0.15 and 1.40 foe, and $^{56}$Ni masses between 0.006 and 0.069 $M_{\odot}$. We define a subset of 24~SNe (the `gold sample') with well-sampled bolometric light curves and expansion velocities for which we consider the results more robust. Most SNe~II in the gold sample ($\sim$88%) are found with ejecta masses in the range of $\sim$8-10 $M_{\odot}$, coming from low zero-age main-sequence masses (9-12 $M_{\odot}$). The modelling of the initial-mass distribution of the gold sample gives an upper mass limit of 21.3$^{+3.8}_{-0.4}$ $M_{\odot}$ and a much steeper distribution than that for a Salpeter massive-star IMF. This IMF incompatibility is due to the large number of low-mass progenitors found -- when assuming standard stellar evolution. This may imply that high-mass progenitors lose more mass during their lives than predicted. However, a deeper analysis of all stellar evolution assumptions is required to test this hypothesis., Comment: Accepted for publication in Astronomy & Astrophysics

OBJECTIVE Connective tissue disease (CTD)-associated pulmonary arterial hypertension (PAH) is the second most common etiology of PAH and carries a poor prognosis. Recently, it has been shown that female human tumor necrosis factor (TNF)-transgenic (Tg) mice die of cardiopulmonary disease by 6 months of age. This study was undertaken to characterize this pathophysiology and assess its potential as a novel model of CTD-PAH. METHODS Histologic analysis was performed on TNF-Tg and wild-type (WT) mice to characterize pulmonary vascular and right ventricular (RV) pathology (n = 40 [4-5 mice per group per time point]). Mice underwent right-sided heart catheterization (n = 29) and micro-computed tomographic angiography (n = 8) to assess vascular disease. Bone marrow chimeric mice (n = 12), and anti-TNF-treated mice versus placebo-treated mice (n = 12), were assessed. RNA sequencing was performed on mouse lung tissue (n = 6). RESULTS TNF-Tg mice displayed a pulmonary vasculopathy marked by collagen deposition (P < 0.001) and vascular occlusion (P < 0.001) with associated RV hypertrophy (P < 0.001) and severely increased RV systolic pressure (mean ± SD 75.1 ± 19.3 mm Hg versus 26.7 ± 1.7 mm Hg in WT animals; P < 0.0001). TNF-Tg mice had increased α-smooth muscle actin (α-SMA) staining, which corresponded to proliferation and loss of von Willebrand factor (vWF)-positive endothelial cells (P < 0.01). There was an increase in α-SMA-positive, vWF-positive cells (P < 0.01), implicating endothelial-mesenchymal transition. Bone marrow chimera experiments revealed that mesenchymal but not bone marrow-derived cells are necessary to drive this process. Treatment with anti-TNF therapy halted the progression of disease. This pathology closely mimics human CTD-PAH, in which patient lungs demonstrate increased TNF signaling and significant similarities in genomic pathway dysregulation. CONCLUSION The TNF-Tg mouse represents a novel model of CTD-PAH, recapitulates key disease features, and can serve as a valuable tool for discovery and assessment of therapeutics.

Background Platelet transfusion is associated with logistical problems with the national storage guidelines of platelets. This results in decreased function in vivo as a result of the platelet storage lesion, and complications such as allergic or hemolytic reactions and thrombosis. We evaluated a new, freshly prepared platelet modified lysate (PML) product designed to be more procoagulant than fresh and stored platelets. Methods Fresh platelets were concentrated, sonicated, and centrifuged to produce PML. Samples of both washed and unwashed PML were evaluated for particle size, concentration, and activity, and then tested for clot kinetics and thrombin generation. PML samples were also stored at various temperatures for durations up to 6 months and evaluated for clot kinetics and thrombin generation throughout. Results PML showed significantly higher concentration of platelet microparticles, increased procoagulant properties, and increased thrombin generation as compared to fresh and stored platelets. In addition, PML maintained its clot kinetics over a 6-month storage period with variable storage conditions. Conclusions The newly proposed PML product is more procoagulant, stable, and has additional potential applications than currently available platelet products. Further studies will be performed to assess its functions in vivo and to assess thrombotic potential.

We present 75 near-infrared (NIR; 0.8-2.5 μm) spectra of 34 stripped-envelope core-collapse supernovae (SESNe) obtained by the Carnegie Supernova Project-II (CSP-II), encompassing optical spectroscopic Types IIb, Ib, Ic, and Ic-BL. The spectra range in phase from pre-maximum to 80 days past maximum. This unique data set constitutes the largest NIR spectroscopic sample of SESNe to date. NIR spectroscopy provides observables with additional information that is not available in the optical. Specifically, the NIR contains the strong lines of He i and allows a more detailed look at whether Type Ic supernovae are completely stripped of their outer He layer. The NIR spectra of SESNe have broad similarities, but closer examination through statistical means reveals a strong dichotomy between NIR "He-rich"and "He-poor"SNe. These NIR subgroups correspond almost perfectly to the optical IIb/Ib and Ic/Ic-BL types, respectively. The largest difference between the two groups is observed in the 2 μm region, near the He i λ2.0581 μm line. The division between the two groups is not an arbitrary one along a continuous sequence. Early spectra of He-rich SESNe show much stronger He i λ2.0581 μm absorption compared to the He-poor group, but with a wide range of profile shapes. The same line also provides evidence for trace amounts of He in half of our SNe in the He-poor group., AST-1008343, AST-1613426, AST-1613455, and AST-1613472. C.A. is supported by NASA grant No. 80NSSC19K1717 and NSF grant Nos. AST-1920392 and AST-1911074. J.T. is funded by the consolidated STFC grant No. R276106. L.G. acknowledges financial support from the Spanish Ministry of Science, Innovation and Universities (MICIU) under the 2019 Ramón y Cajal program RYC2019-027683 and from the Spanish MICIU project PID2020-115253GA-I00. C.G. is supported by a Young Investor Grant (25501) from the VILLUM FONDEN. Time domain research by D.J.S. is also supported by NSF grant Nos. AST-1821987, 1813466, 1908972, & 2108032, and by the Heising-Simons Foundation under grant #2020-1864. M.D.S. is supported by grants from the VILLUM FONDEN (grant No. 28021) and the Independent Research Fund Denmark (IRFD; 8021-00170B).

Brennan, S. J. et al (ASTROPY Collaboration), We present the results from a high-cadence, multiwavelength observation campaign of AT 2016jbu (aka Gaia16cfr), an interacting transient. This data set complements the current literature by adding higher cadence as well as extended coverage of the light-curve evolution and late-time spectroscopic evolution. Photometric coverage reveals that AT 2016jbu underwent significant photometric variability followed by two luminous events, the latter of which reached an absolute magnitude of MV ∼-18.5 mag. This is similar to the transient SN 2009ip whose nature is still debated. Spectra are dominated by narrow emission lines and show a blue continuum during the peak of the second event. AT 2016jbu shows signatures of a complex, non-homogeneous circumstellar material (CSM). We see slowly evolving asymmetric hydrogen line profiles, with velocities of 500 km s-1 seen in narrow emission features from a slow-moving CSM, and up to 10 000 km s-1 seen in broad absorption from some high-velocity material. Late-time spectra (∼+1 yr) show a lack of forbidden emission lines expected from a core-collapse supernova and are dominated by strong emission from H, He i, and Ca ii. Strong asymmetric emission features, a bumpy light curve, and continually evolving spectra suggest an inhibit nebular phase. We compare the evolution of H α among SN 2009ip-like transients and find possible evidence for orientation angle effects. The light-curve evolution of AT 2016jbu suggests similar, but not identical, circumstellar environments to other SN 2009ip-like transients., SJB acknowledges support from Science Foundation Ireland and the Royal Society (RS-EA/3471). MF is supported by a Royal Society - Science Foundation Ireland University Research Fellowship. TMB was funded by the CONICYT PFCHA / DOCTORADOBECAS CHILE/2017-72180113 and acknowledges their financial support from the Spanish Ministerio de Ciencia e Innovación (MCIN), the Agencia Estatal de Investigación (AEI) 10.13039/501100011033 under the PID2020-115253GA-I00 HOSTFLOWS project, and from Centro Superior de Investigaciones Científicas (CSIC) under the PIE project 20215AT016. KM is funded by the EU H2020 ERC grant no. 758638. TWC acknowledges the EU Funding under Marie Skłodowska-Curie grant H2020-MSCA-IF-2018-842471, and thanks to Thomas Krühler for GROND data reduction. MN is supported by a Royal Astronomical Society Research Fellowship. BJS is supported by NSF grants AST-1908952, AST-1920392, AST-1911074, and NASA award 80NSSC19K1717. MS is supported by generous grants from Villum FONDEN (13261, 28021) and by a project grant (8021-00170B) from the Independent Research Fund Denmark. LH acknowledges support for Watcher from Science Foundation Ireland grant 07/RFP/PHYF295. Time domain research by DJS is supported by NSF grants AST-1821987, 1813466, and 1908972, and by the Heising-Simons Foundation under grant #2020-1864. NER acknowledges support from MIUR, PRIN 2017 (grant 20179ZF5KS). LG acknowledges financial support from the Spanish Ministry of Science, Innovation and Universities (MICIU) under the 2019 Ramón y Cajal program RYC2019-027683 and from the Spanish MICIU project PID2020-115253GA-I00. Support for TW-SH was provided by NASA through the NASA Hubble Fellowship grant HST-HF2-51458.001-A awarded by the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., for NASA, under contract NAS5-26555. Support for JLP is provided in part by ANID through the Fondecyt regular grant 1191038 and through the Millennium Science Initiative grant ICN12_009, awarded to The Millennium Institute of Astrophysics, MAS. DAH and DH are supported by AST-1911151, AST19-11225, and NASA Swift grant 80NSSC19K1639. GP acknowledge support by the Ministry of Economy, Development, and Tourism’s Millennium Science Initiative through grant IC120009, awarded to The Millennium Institute of Astrophysics, MAS. LT acknowledges support from MIUR (PRIN 2017 grant 20179ZF5KS). HK was funded by the Academy of Finland projects 324504 and 328898.

We catalog the 443 bright supernovae discovered by the All-Sky Automated Survey for Supernovae (ASAS-SN) in $2018-2020$ along with the 519 supernovae recovered by ASAS-SN and 516 additional $m_{peak}\leq18$ mag supernovae missed by ASAS-SN. Our statistical analysis focuses primarily on the 984 supernovae discovered or recovered in ASAS-SN $g$-band observations. The complete sample of 2427 ASAS-SN supernovae includes earlier $V$-band samples and unrecovered supernovae. For each supernova, we identify the host galaxy, its UV to mid-IR photometry, and the offset of the supernova from the center of the host. Updated light curves, redshifts, classifications, and host galaxy identifications supersede earlier results. With the increase of the limiting magnitude to $g\leq18$ mag, the ASAS-SN sample is roughly complete up to $m_{peak}=16.7$ mag and is $90\%$ complete for $m_{peak}\leq17.0$ mag. This is an increase from the $V$-band sample where it was roughly complete up to $m_{peak}=16.2$ mag and $70\%$ complete for $m_{peak}\leq17.0$ mag., Comment: 14 pages, 7 figures, 4 tables. Updated to reflect changes made in the published version. Tables containing the catalog data presented in this submission are included in machine-readable format as ancillary files

We present multi-wavelength time-series spectroscopy of SN 2013aa and SN 2017cbv, two Type Ia supernovae (SNe Ia) on the outskirts of the same host galaxy, NGC 5643. This work utilizes new nebular-phase near-infrared (NIR) spectra obtained by the Carnegie Supernova Project-II, in addition to previously published optical and NIR spectra. By measuring nebular-phase [Fe II] lines in both the optical and NIR, we examine the explosion kinematics and test the efficacy of several emission line fitting techniques commonly used in the literature. The NIR [Fe II] 1.644 $\mu$m line provides the most robust velocity measurements against variations due to the choice of the fit method and line blending. The resulting effects on velocity measurements due to choosing different fit methods, initial fit parameters, continuum and line profile functions, and fit region boundaries were also investigated. The NIR [Fe II] velocities yield the same radial shift direction as velocities measured using the optical [Fe II] 7155 A line, but the sizes of the shifts are consistently and substantially lower, pointing to a potential issue in optical studies. The NIR [Fe II] 1.644 $\mu$m emission profile shows a lack of significant asymmetry in both SNe Ia, and the observed low velocities elevate the importance for correcting for any radial velocity contribution from the host galaxy's rotation. The low [Fe II] velocities measured in the NIR at nebular phases disfavors most progenitor scenarios in close double-degenerate systems for both SN 2013aa and SN 2017cbv. The time evolution of the NIR [Fe II] 1.644 $\mu$m line also indicates moderately high progenitor white dwarf central density and potentially high magnetic fields. These sibling SNe Ia were well observed at both early and late times, providing an excellent opportunity to study the intrinsic diversity of SNe Ia., Comment: submitted to ApJ on Oct 4, 2022 accepted for publication on Dec 19, 2022

A state of the art lecture titled “Megakaryocytes in the Lung” was presented at the London International Society on Thrombosis and Haemostasis congress in 2022. This lecture highlighted that although most medical teaching presents platelets as bone marrow megakaryocyte-derived cellular mediators of thrombosis, platelets are also a critical part of the immune system with direct roles in responses to sterile tissue injury and pathogens. Bone marrow megakaryocytes differentiate from hematopoietic stem cells and package platelets with immune molecules. Activated platelets, therefore, initiate or accelerate the progression of vascular inflammatory pathologies, as well as being regulators of immune responses to infectious agents. Platelets are now known to have mechanistic roles in immune responses to disease processes, such as heart transplant rejection, myocardial infarction, aortic aneurysm, peripheral vascular disease, and infections. From these studies comes the concept that megakaryocytes are immune cell progenitors and recent emerging information highlights that megakaryocytes may themselves be immune cells. Despite megakaryocytes being described in the lung for >100 years, lung megakaryocytes have only recently been shown to be platelet producing and lung megakaryocytes are immune-differentiated in both phenotype and function. What is still not known is the origin of lung megakaryocytes and roles of lung megakaryocytes in health and disease. This review will discuss the long history of lung megakaryocytes in the literature and potential models for megakaryocyte origins and immune functions. Finally, we summarize relevant new data related to this topic that was presented during the 2022 International Society on Thrombosis and Haemostasis Congress.

Platelets have central roles in both immune responses and development. Stimulated platelets express leukocyte adhesion molecules and release numerous immune modulatory factors that recruit and activate leukocytes, both at the sites of activation and distantly. Monocytes are innate immune cells with dynamic immune modulatory functions that change during the aging process, a phenomenon termed “inflammaging”. We have previously shown that platelets are a major source of plasma beta-2 microglobulin (β2M) and that β2M induced a monocyte pro-inflammatory phenotype. Plasma β2M increases with age and is a pro-aging factor. We hypothesized that platelet derived β2M regulates monocyte phenotypes in the context of aging. Using wild-type (WT) and platelet specific β2M knockout mice (Plt-β2M-/-) mice, we found that plasma β2M increased with age and correlated with increased circulating Ly6CHi monocytes. However, aged Plt-β2M-/- mice had significantly fewer Ly6CHi monocytes compared to WT mice. Quantitative real-time PCR of circulating monocytes showed that WT mouse monocytes were more “pro-inflammatory” with age, while Plt-β2M-/- derived monocytes adopted a “pro-reparative” phenotype. Older Plt-β2M-/- mice had a significant decline in heart function compared to age matched WT mice, as well as increased cardiac fibrosis and pro-fibrotic markers. These data suggest that platelet-derived β2M regulates age associated monocyte polarization, and a loss of platelet derived β2M shifted monocytes and macrophages to a pro-reparative phenotype and increased pro-fibrotic cardiac responses. Platelet regulation of monocyte phenotypes via β2M may maintain a balance between inflammatory and reparative signals that affects age related physiologic outcomes.

We present detailed investigation of a specific i-band light-curve feature in Type Ia supernovae (SNe Ia) using the rapid cadence and high signal-to-noise ratio light curves obtained by the Carnegie Supernova Project. The feature is present in most SNe Ia and emerges a few days after the i-band maximum. It is an abrupt change in curvature in the light curve over a few days and appears as a flattening in mild cases and a strong downward concave shape, or a ‘kink’, in the most extreme cases. We computed the second derivatives of Gaussian Process interpolations to study 54 rapid-cadence light curves. From the second derivatives we measure: (1) the timing of the feature in days relative to i-band maximum; tdm2(i) and (2) the strength and direction of the concavity in mag d−2; dm2(i). 76 per cent of the SNe Ia show a negative dm2(i), representing a downward concavity – either a mild flattening or a strong ‘kink’. The tdm2(i) parameter is shown to correlate with the colour-stretch parameter sBV, a SN Ia primary parameter. The dm2(i) parameter shows no correlation with sBV and therefore provides independent information. It is also largely independent of the spectroscopic and environmental properties. Dividing the sample based on the strength of the light-curve feature as measured by dm2(i), SNe Ia with strong features have a Hubble diagram dispersion of 0.107 mag, 0.075 mag smaller than the group with weak features. Although larger samples should be obtained to test this result, it potentially offers a new method for improving SN Ia distance determinations without shifting to more costly near-infrared or spectroscopic observations., The work of the CSP has been supported by the National Science Foundation under grants AST0306969, AST0607438, AST1008343, AST1613426, AST1613455, and AST1613472. PJP thanks the kindness and support of the FSU SN team. LG acknowledges financial support from the Spanish Ministry of Science and Innovation (MCIN) under the 2019 Ramón y Cajal program RYC2019-027683 and from the Spanish MCIN project HOSTFLOWS PID2020-115253GA-I00. This research has made use of the NASA/IPAC Extragalactic Database (NED), which is operated by the Jet Propulsion Laboratory, California Institute of Technology, under contract with the National Aeronautics and Space Administration.

Circulating platelets interact with leukocytes to modulate host immune and thrombotic responses. In sepsis, platelet-leukocyte interactions are increased and have been associated with adverse clinical events, including increased platelet–T-cell interactions. Sepsis is associated with reduced CD8+ T-cell numbers and functional responses, but whether platelets regulate CD8+ T-cell responses during sepsis remains unknown. In our current study, we systemically evaluated platelet antigen internalization and presentation through major histocompatibility complex class I (MHC-I) and their effects on antigen-specific CD8+ T cells in sepsis in vivo and ex vivo. We discovered that both human and murine platelets internalize and proteolyze exogenous antigens, generating peptides that are loaded onto MHC-I. The expression of platelet MHC-I, but not platelet MHC-II, is significantly increased in human and murine platelets during sepsis and in human megakaryocytes stimulated with agonists generated systemically during sepsis (eg, interferon-γ and lipopolysaccharide). Upregulation of platelet MHC-I during sepsis increases antigen cross-presentation and interactions with CD8+ T cells in an antigen-specific manner. Using a platelet lineage–specific MHC-I–deficient mouse strain (B2Mf/f-Pf4Cre), we demonstrate that platelet MHC-I regulates antigen-specific CD8+ T-cell proliferation in vitro, as well as the number and functional responses of CD8+ T cells in vivo, during sepsis. Loss of platelet MHC-I reduces sepsis-associated mortality in mice in an antigen-specific setting. These data identify a new mechanism by which platelets, through MHC-I, process and cross-present antigens, engage antigen-specific CD8+ T cells, and regulate CD8+ T-cell numbers, functional responses, and outcomes during sepsis.

As blood transitions from steady laminar flow (S-flow) in healthy arteries to disturbed flow (D-flow) in aneurysmal arteries, platelets are subjected to external forces. Biomechanical platelet activation is incompletely understood and is a potential mechanism behind antiplatelet medication resistance. Although it has been demonstrated that antiplatelet drugs suppress the growth of abdominal aortic aneurysms (AAA) in patients, we found that a certain degree of platelet reactivity persisted in spite of aspirin therapy, urging us to consider additional antiplatelet therapeutic targets. Transcriptomic profiling of platelets from patients with AAA revealed upregulation of a signal transduction pathway common to olfactory receptors, and this was explored as a mediator of AAA progression. Healthy platelets subjected to D-flow ex vivo, platelets from patients with AAA, and platelets in murine models of AAA demonstrated increased membrane olfactory receptor 2L13 (OR2L13) expression. A drug screen identified a molecule activating platelet OR2L13, which limited both biochemical and biomechanical platelet activation as well as AAA growth. This observation was further supported by selective deletion of the OR2L13 ortholog in a murine model of AAA that accelerated aortic aneurysm growth and rupture. These studies revealed that olfactory receptors regulate platelet activation in AAA and aneurysmal progression through platelet-derived mediators of aortic remodeling.

Platelets are key mediators of thrombosis. Many agonists of platelet activation are known, but fewer endogenous inhibitors of platelets, such as prostacyclin and nitric oxide (NO), have been identified. Acetylcholinesterase inhibitors, such as donepezil, can cause bleeding in patients, but the underlying mechanisms are not well understood. We hypothesized that acetylcholine is an endogenous inhibitor of platelets. We measured the effect of acetylcholine or analogs of acetylcholine on human platelet activation ex vivo. Acetylcholine and analogs of acetylcholine inhibited platelet activation, as measured by P-selectin translocation and glycoprotein IIb IIIa conformational changes. Conversely, we found that antagonists of the acetylcholine receptor, such as pancuronium, enhance platelet activation. Furthermore, drugs inhibiting acetylcholinesterase, such as donepezil, also inhibit platelet activation, suggesting that platelets release acetylcholine. We found that NO mediates acetylcholine inhibition of platelets. Our data suggest that acetylcholine is an endogenous inhibitor of platelet activation. The cholinergic system may be a novel target for antithrombotic therapies.