Pre-main sequence stars in the stellar association N11 in the Large Magellanic Cloud

Magellanic Clouds are of extreme importance to the study of the star formation process in low metallicity environments. In this paper we report on the discovery of pre-main sequence candidates and young embedded stellar objects in N11 located in the Large Magellanic Cloud to cast light on the star formation scenario. We would like to remind that this comparison is complicated by the presence of a large age dispersion detected in the fields. Deep archive HST/ACS photometry is used to derive color-magnitude diagrams of the associations in N~11 and of the foreground field population. These data are complemented by archive IR Spitzer data which allow the detection of young embedded stellar objects. The spatial distribution of the pre-main sequence candidates and young embedded stellar objects is compared with literature data observed at different wavelengths, such as H$_{\alpha}$ and CO maps, and with the distribution of OB and Herbig Ae/Be stars. The degree of clustering is derived using the Minimal Spanning Tree method and the two point correlation function to get insights about the formation process. A large population of pre-main sequence candidates is found in N11. Their masses are in the range of 1.3-2 MSun for ages from 2 to 10 Myr. Young embedded stellar objects having ages of 0.1-1 Myr are found to be intermixed with the candidate pre-main sequence stars. The spatial distribution of the stars shows that this region is the product of clustered star formation. No significant difference is found in the clustering degree of young blue main sequence stars and faint pre-main sequence candidates, suggesting that they might be part of the same formation process. The data suggest that the star formation in the region is a long-lasting process where stars from 0.1 to 10 Myr are widely distributed.Comment: 18 pages, 21 figures, accepted for publication in A&

Spitzer IRAC observations of newly-discovered planetary nebulae from the Macquarie-AAO-Strasbourg H-alpha Planetary Nebula Project

We compare H-alpha, radio continuum, and Spitzer Space Telescope (SST) images of 58 planetary nebulae (PNe) recently discovered by the Macquarie-AAO-Strasbo- urg H-alpha PN Project (MASH) of the SuperCOSMOS H-alpha Survey. Using InfraRed Array Camera (IRAC) data we define the IR colors of PNe and demonstrate good isolation between these colors and those of many other types of astronomical object. The only substantive contamination of PNe in the color-color plane we illustrate is due to YSOs. However, this ambiguity is readily resolved by the unique optical characteristics of PNe and their environs. We also examine the relationships between optical and MIR morphologies from 3.6 to 8.0um and explore the ratio of mid-infrared (MIR) to radio nebular fluxes, which is a valuable discriminant between thermal and nonthermal emission. MASH emphasizes late evolutionary stages of PNe compared with previous catalogs, enabling study of the changes in MIR and radio flux that attend the aging process. Spatially integrated MIR energy distributions were constructed for all MASH PNe observed by the GLIMPSE Legacy Project, using the H-alpha morphologies to establish the dimensions for the calculations of the Midcourse Space Experiment (MSX), IRAC, and radio continuum (from the Molonglo Observatory Synthesis Telescope and the Very Large Array) flux densities. The ratio of IRAC 8.0-um to MSX 8.3-um flux densities provides a measure of the absolute diffuse calibration of IRAC at 8.0 um. We independently confirm the aperture correction factor to be applied to IRAC at 8.0um to align it with the diffuse calibration of MSX. The result agrees with the recommendations of the Spitzer Science Center and with results from a parallel study of HII regions. These PNe probe the diffuse calibration of IRAC on a spatial scale of 9-77 arcsec.Comment: 48 pages, LaTeX (aastex), incl. 18 PostScript (eps) figures and 3 tables. Accepted by Astrophysical Journa

G313.3+00.3: A New Planetary Nebula discovered by the Australia Telescope Compact Array and the Spitzer Space Telescope

We present a new planetary nebula, first identified in images from the Australia Telescope Compact Array, although not recognized at that time. Recent observations with the Spitzer Space Telescope during the GLIMPSE Legacy program have rediscovered the object. The high-resolution radio and infrared images enable the identification of the central star or its wind, the recognition of the radio emission as thermal, and the probable presence of polycylic aromatic hydrocarbons in and around the source. These lead to the conclusion that G313.3+00.3 is a planetary nebula. This object is of particular interest because it was discovered solely through radio and mid-infrared imaging, without any optical (or near-infrared) confirmation, and acts as a proof of concept for the discovery of many more highly extinguished planetary nebulae. G313.3+00.3 is well-resolved by both the instruments with which it was identified, and suffers extreme reddening due to its location in the Scutum-Crux spiral arm.Comment: 18 pages, LaTeX (aastex), incl. 8 PostScript (eps) figures and 1 table. Accepted by ApJ (Part 1

Sequential Star Formation in RCW 34: A Spectroscopic Census of the Stellar Content of High-mass Star-forming Regions

We present VLT/SINFONI integral field spectroscopy of RCW 34 along with Spitzer/IRAC photometry of the surroundings. RCW 34 consists of three different regions. A large bubble has been detected on the IRAC images in which a cluster of intermediate- and low-mass class II objects is found. At the northern edge of this bubble, an HII region is located, ionized by 3 OB stars. Intermediate mass stars (2 - 3 Msun) are detected of G- and K- spectral type. These stars are still in the pre-main sequence (PMS) phase. North of the HII region, a photon-dominated region is present, marking the edge of a dense molecular cloud traced by H2 emission. Several class 0/I objects are associated with this cloud, indicating that star formation is still taking place. The distance to RCW 34 is revised to 2.5 +- 0.2 kpc and an age estimate of 2 - 1 Myrs is derived from the properties of the PMS stars inside the HII region. The most likely scenario for the formation of the three regions is that star formation propagates from South to North. First the bubble is formed, produced by intermediate- and low-mass stars only, after that, the HII region is formed from a dense core at the edge of the molecular cloud, resulting in the expansion as a champagne flow. More recently, star formation occurred in the rest of the molecular cloud. Two different formation scenarios are possible: (a) The bubble with the cluster of low- and intermediate mass stars triggered the formation of the O star at the edge of the molecular cloud which in turn induces the current star-formation in the molecular cloud. (b) An external triggering is responsible for the star-formation propagating from South to North. [abridged]Comment: 19 pages, 11 figures, accepted by Ap

Stimulating TAM-mediated anti-tumor immunity with mannose-decorated nanoparticles in ovarian cancer

BACKGROUND: Current cancer immunotherapies have made tremendous impacts but generally lack high response rates, especially in ovarian cancer. New therapies are needed to provide increased benefits. One understudied approach is to target the large population of immunosuppressive tumor-associated macrophages (TAMs). Using inducible transgenic mice, we recently reported that upregulating nuclear factor-kappaB (NF-κB) signaling in TAMs promotes the M1, anti-tumor phenotype and limits ovarian cancer progression. We also developed a mannose-decorated polymeric nanoparticle system (MnNPs) to preferentially deliver siRNA payloads to M2, pro-tumor macrophages in vitro. In this study, we tested a translational strategy to repolarize ovarian TAMs via MnNPs loaded with siRNA targeting the inhibitor of NF-κB alpha (IκBα) using mouse models of ovarian cancer. METHODS: We evaluated treatment with MnNPs loaded with IκBα siRNA (IκBα-MnNPs) or scrambled siRNA in syngeneic ovarian cancer models. ID8 tumors in C57Bl/6 mice were used to evaluate consecutive-day treatment of late-stage disease while TBR5 tumors in FVB mice were used to evaluate repetitive treatments in a faster-developing disease model. MnNPs were evaluated for biodistribution and therapeutic efficacy in both models. RESULTS: Stimulation of NF-κB activity and repolarization to an M1 phenotype via IκBα-MnNP treatment was confirmed using cultured luciferase-reporter macrophages. Delivery of MnNPs with fluorescent payloads (Cy5-MnNPs) to macrophages in the solid tumors and ascites was confirmed in both tumor models. A three consecutive-day treatment of IκBα-MnNPs in the ID8 model validated a shift towards M1 macrophage polarization in vivo. A clear therapeutic effect was observed with biweekly treatments over 2-3 weeks in the TBR5 model where significantly reduced tumor burden was accompanied by changes in immune cell composition, indicative of reduced immunosuppressive tumor microenvironment. No evidence of toxicity associated with MnNP treatment was observed in either model. CONCLUSIONS: In mouse models of ovarian cancer, MnNPs were preferentially associated with macrophages in ascites fluid and solid tumors. Evidence of macrophage repolarization, increased inflammatory cues, and reduced tumor burden in IκBα-MnNP-treated mice indicate beneficial outcomes in models of established disease. We have provided evidence of a targeted, TAM-directed approach to increase anti-tumor immunity in ovarian cancer with strong translational potential for future clinical studies

Priorities for HIV and chronic pain research results from a survey of individuals with lived experience

The Global Task Force on Chronic Pain in HIV published seven research priorities in the field of HIV-associated chronic pain in 2019: (1) causes; (2) management; (3) treatment individualization and integration with addiction treatment; (4) mental and social health factors; (5) prevalence; (6) treatment cost effectiveness; and (7) prevention. The current study used a web-based survey to determine whether the research topics were aligned with the priorities of adults with lived experiences of HIV and chronic pain. We also collected information about respondents' own pain and treatment experiences. We received 311 survey responses from mostly US-based respondents. Most respondents reported longstanding, moderate to severe, multisite pain, commonly accompanied by symptoms of anxiety and/or depression. The median number of pain treatments tried was 10 (IQR = 8, 13), with medications and exercise being the most common modalities, and opioids being viewed as the most helpful. Over 80% of respondents considered all research topics either "extremely important" or "very important". Research topic #2, which focused on optimizing management of pain in people with HIV, was accorded the greatest importance by respondents. These findings suggest good alignment between the priorities of researchers and US-based people with lived experience of HIV-associated chronic pain.</p

The VLT-FLAMES Tarantula Survey I: Introduction and observational overview

The VLT-FLAMES Tarantula Survey (VFTS) is an ESO Large Programme that has obtained multi-epoch optical spectroscopy of over 800 massive stars in the 30 Doradus region of the Large Magellanic Cloud (LMC). Here we introduce our scientific motivations and give an overview of the survey targets, including optical and near-infrared photometry and comprehensive details of the data reduction. One of the principal objectives was to detect massive binary systems via variations in their radial velocities, thus shaping the multi-epoch observing strategy. Spectral classifications are given for the massive emission-line stars observed by the survey, including the discovery of a new Wolf-Rayet star (VFTS 682, classified as WN5h), 2' to the northeast of R136. To illustrate the diversity of objects encompassed by the survey, we investigate the spectral properties of sixteen targets identified by Gruendl & Chu from Spitzer photometry as candidate young stellar objects or stars with notable mid-infrared excesses. Detailed spectral classification and quantitative analysis of the O- and B-type stars in the VFTS sample, paying particular attention to the effects of rotational mixing and binarity, will be presented in a series of future articles to address fundamental questions in both stellar and cluster evolution.Comment: Accepted by A&A, 52 pages (main body: 19 pages, supplementary tables: 33 pages), v3: two classifications updated to match a parallel pape

The intramembrane protease Sppl2a is required for B cell and DC development and survival via cleavage of the invariant chain

The protease Sppl2a cleaves the N-terminal fragment of invariant chain (CD74) and is required for efficient B cell development and function.B cell development requires tight regulation to allow for the generation of a diverse repertoire while preventing the development of autoreactive cells. We report, using N-ethyl-N-nitrosourea (ENU)–induced mutagenesis, the identification of a mutant mouse (chompB) with a block in early B cell development. The blockade occurs after the transitional 1 (T1) stage and leads to a decrease in mature B cell subsets and deficits in T cell–dependent antibody responses. Additionally, chompB mice have decreases in myeloid dendritic cells (DCs). The mutation was mapped to the intramembrane protease signal peptide peptidase-like 2a (Sppl2a), a gene not previously implicated in immune cell development. Proteomic analysis identified the invariant chain (CD74) as a key substrate of Sppl2a and suggests that regulated intramembrane proteolysis of CD74 by Sppl2a contributes to B cell and DC survival. Moreover, these data suggest that modulation of Sppl2a may be a useful therapeutic strategy for treatment of B cell dependent autoimmune disorders

Assessment of Medical Students’ Shared Decision-Making in Standardized Patient Encounters

BackgroundShared decision-making, in which physicians and patients openly explore beliefs, exchange information, and reach explicit closure, may represent optimal physician-patient communication. There are currently no universally accepted methods to assess medical students' competence in shared decision-making.ObjectiveTo characterize medical students' shared decision-making with standardized patients (SPs) and determine if students' use of shared decision-making correlates with SP ratings of their communication.DesignRetrospective study of medical students' performance with four SPs.ParticipantsSixty fourth-year medical students.MeasurementsObjective blinded coding of shared decision-making quantified as decision moments (exploration/articulation of perspective, information sharing, explicit closure for a particular decision); SP scoring of communication skills using a validated checklist.ResultsOf 779 decision moments generated in 240 encounters, 312 (40%) met criteria for shared decision-making. All students engaged in shared decision-making in at least two of the four cases, although in two cases 5% and 12% of students engaged in no shared decision-making. The most commonly discussed decision moment topics were medications (n = 98, 31%), follow-up visits (71, 23%), and diagnostic testing (44, 14%). Correlations between the number of decision moments in a case and students' communication scores were low (rho = 0.07 to 0.37).ConclusionsAlthough all students engaged in some shared decision-making, particularly regarding medical interventions, there was no correlation between shared decision-making and overall communication competence rated by the SPs. These findings suggest that SP ratings of students' communication skill cannot be used to infer students' use of shared decision-making. Tools to determine students' skill in shared decision-making are needed

Contributions of Mamu-A*01 Status and TRIM5 Allele Expression, But Not CCL3L Copy Number Variation, to the Control of SIVmac251 Replication in Indian-Origin Rhesus Monkeys

CCL3 is a ligand for the HIV-1 co-receptor CCR5. There have recently been conflicting reports in the literature concerning whether CCL3-like gene (CCL3L) copy number variation (CNV) is associated with resistance to HIV-1 acquisition and with both viral load and disease progression following infection with HIV-1. An association has also been reported between CCL3L CNV and clinical sequelae of the simian immunodeficiency virus (SIV) infection in vivo in rhesus monkeys. The present study was initiated to explore the possibility of an association of CCL3L CNV with the control of virus replication and AIDS progression in a carefully defined cohort of SIVmac251-infected, Indian-origin rhesus monkeys. Although we demonstrated extensive variation in copy number of CCL3L in this cohort of monkeys, CCL3L CNV was not significantly associated with either peak or set-point plasma SIV RNA levels in these monkeys when MHC class I allele Mamu-A*01 was included in the models or progression to AIDS in these monkeys. With 66 monkeys in the study, there was adequate power for these tests if the correlation of CCL3L and either peak or set-point plasma SIV RNA levels was 0.34 or 0.36, respectively. These findings call into question the premise that CCL3L CNV is important in HIV/SIV pathogenesis