A Survey of Local Group Galaxies Currently Forming Stars: III. A Search for Luminous Blue Variables and Other H-alpha Emission-Lined Stars

We describe a search for H-alpha emission-lined stars in M31, M33, and seven dwarfs in or near the Local Group (IC 10, NGC 6822, WLM, Sextans B, Sextans A, Pegasus and the Phoenix dwarf) using interference filter imaging with the KPNO and CTIO 4-m telescope and Mosaic cameras. The survey is aimed primarily at identifying new Luminous Blue Variables (LBVs) from their spectroscopic similarity to known LBVs, avoiding the bias towards photometric variability, which may require centuries to manifest itself if LBVs go through long quiescent periods. Followup spectroscopy with WIYN confirms that our survey detected a wealth of stars whose spectra are similar to the known LBVs. We "classify" the spectra of known LBVs, and compare these to the spectra of the new LBV candidates. We demonstrate spectacular spectral variability for several of the new LBV candidates, such as AM2, previously classified as a Wolf-Rayet star, which now shows FeI, FeII and Balmer emission lines but neither the NIII 4634,42 nor HeII 4686 emission that it did in 1982. Profound spectral changes are also noted for other suspected and known LBVs. Several of the LBV candidates also show >0.5 mag changes in V over the past 10-20 years. The number of known or suspected LBVs is now 24 in M31, 37 in M33, 1 in NGC 6822, and 3 in IC 10. We estimate that the total number of LBVs in M31 and M33 may be several hundred, in contrast to the 8 known historically through large-scale photometric variability. This has significant implications for the time scale of the LBV phase. We also identify a few new WRs and peculiar emission-lined objects.Comment: Accepted by the Astronomical Journal. Version with higher quality figures may be downloaded from http://www.lowell.edu/users/massey/has.pdf.g

Cosmic Origins (COR) Program Technology Development 2018

No abstract availabl

Clinically Relevant Interactions between Newer Antidepressants and Second-Generation Antipsychotics

INTRODUCTION: Combinations of newer antidepressants and second-generation antipsychotics (SGAs) are frequently used by clinicians. Pharmacokinetic drug interaction (PK DI) and poorly understood pharmacodynamic (PD) drug interaction (PD DI) can occur between them. AREAS COVERED: This paper comprehensively reviews PD DI and PK DI studies. EXPERT OPINION: More PK DI studies are needed to better establish dose correction factors after adding fluoxetine and paroxetine to aripiprazole, iloperidone and risperidone. Further PK DI studies and case reports are also needed to better establish the need for dose correction factors after adding i) fluoxetine to clozapine, lurasidone, quetiapine and olanzapine; ii) paroxetine to olanzapine; iii) fluvoxamine to asenapine, aripiprazole, iloperidone, lurasidone, olanzapine, quetiapine and risperidone; iv) high sertraline doses to aripiprazole, clozapine, iloperidone and risperidone: v) bupropion and duloxetine to aripiprazole, clozapine, iloperidone and risperidone; and vi) asenapine to paroxetine and venlafaxine. Possible beneficial PD DI effects occur after adding SGAs to newer antidepressants for treatment-resistant major depressive and obsessive-compulsive disorders. The lack of studies combining newer antidepressants and SGAs in psychotic depression is worrisome. PD DIs between newer antidepressants and SGAs may be more likely for mirtazapine and bupropion. Adding selective serotonin reuptake inhibitors and SGAs may increase QTc interval and may very rarely contribute to torsades de pointes

Role of complement and antibodies in controlling infection with pathogenic simian immunodeficiency virus (SIV) in macaques vaccinated with replication-deficient viral vectors

<p>Abstract</p> <p>Background</p> <p>We investigated the interplay between complement and antibodies upon priming with single-cycle replicating viral vectors (SCIV) encoding SIV antigens combined with Adeno5-SIV or SCIV pseudotyped with murine leukemia virus envelope boosting strategies. The vaccine was applied via spray-immunization to the tonsils of rhesus macaques and compared with systemic regimens.</p> <p>Results</p> <p>Independent of the application regimen or route, viral loads were significantly reduced after challenge with SIVmac239 (p < 0.03) compared to controls. Considerable amounts of neutralizing antibodies were induced in systemic immunized monkeys. Most of the sera harvested during peak viremia exhibited a trend with an inverse correlation between complement C3-deposition on viral particles and plasma viral load within the different vaccination groups. In contrast, the amount of the observed complement-mediated lysis did not correlate with the reduction of SIV titres.</p> <p>Conclusion</p> <p>The heterologous prime-boost strategy with replication-deficient viral vectors administered exclusively via the tonsils did not induce any neutralizing antibodies before challenge. However, after challenge, comparable SIV-specific humoral immune responses were observed in all vaccinated animals. Immunization with single cycle immunodeficiency viruses mounts humoral immune responses comparable to live-attenuated immunodeficiency virus vaccines.</p

Phase locking the spin precession in a storage ring

This letter reports the successful use of feedback from a spin polarization measurement to the revolution frequency of a 0.97 GeV/$c$ bunched and polarized deuteron beam in the Cooler Synchrotron (COSY) storage ring in order to control both the precession rate ($\approx 121$ kHz) and the phase of the horizontal polarization component. Real time synchronization with a radio frequency (rf) solenoid made possible the rotation of the polarization out of the horizontal plane, yielding a demonstration of the feedback method to manipulate the polarization. In particular, the rotation rate shows a sinusoidal function of the horizontal polarization phase (relative to the rf solenoid), which was controlled to within a one standard deviation range of $\sigma = 0.21$ rad. The minimum possible adjustment was 3.7 mHz out of a revolution frequency of 753 kHz, which changes the precession rate by 26 mrad/s. Such a capability meets a requirement for the use of storage rings to look for an intrinsic electric dipole moment of charged particles

Immunophenotyping of Circulating and Intratumoral Myeloid and T Cells in Glioblastoma Patients

Glioblastoma is the most common and lethal primary brain malignancy that almost inevitably recurs as therapy-refractory cancer. While the success of immune checkpoint blockade (ICB) revealed the immense potential of immune-targeted therapies in several types of cancers outside the central nervous system, it failed to show objective responses in glioblastoma patients as of now. The ability of glioblastoma cells to drive multiple modes of T cell dysfunction while exhibiting low-quality neoepitopes, low-mutational load, and poor antigen priming limits anti-tumor immunity and efficacy of antigen-unspecific immunotherapies such as ICB. An in-depth understanding of the GBM immune landscape is essential to delineate and reprogram such immunosuppressive circuits during disease progression. In this view, the present study aimed to characterize the peripheral and intratumoral immune compartments of 35 glioblastoma patients compared to age- and sex-matched healthy control probands, particularly focusing on exhaustion signatures on myeloid and T cell subsets. Compared to healthy control participants, different immune signatures were already found in the peripheral circulation, partially related to the steroid medication the patients received. Intratumoral CD4+ and CD8+ TEM cells (CD62Llow/CD45ROhigh) revealed a high expression of PD1, which was also increased on intratumoral, pro-tumorigenic macrophages/microglia. Histopathological analysis further identified high PSGL-1 expression levels of the latter, which has recently been linked to increased metastasis in melanoma and colon cancer via P-selectin-mediated platelet activation. Overall, the present study comprises immunophenotyping of a patient cohort to give implications for eligible immunotherapeutic targets in neurooncology in the future

Genome-Wide Association Study and Gene Expression Analysis Identifies CD84 as a Predictor of Response to Etanercept Therapy in Rheumatoid Arthritis

Anti-tumor necrosis factor alpha (anti-TNF) biologic therapy is a widely used treatment for rheumatoid arthritis (RA). It is unknown why some RA patients fail to respond adequately to anti-TNF therapy, which limits the development of clinical biomarkers to predict response or new drugs to target refractory cases. To understand the biological basis of response to anti-TNF therapy, we conducted a genome-wide association study (GWAS) meta-analysis of more than 2 million common variants in 2,706 RA patients from 13 different collections. Patients were treated with one of three anti-TNF medications: etanercept (n = 733), infliximab (n = 894), or adalimumab (n = 1,071). We identified a SNP (rs6427528) at the 1q23 locus that was associated with change in disease activity score (ΔDAS) in the etanercept subset of patients (P = 8×10-8), but not in the infliximab or adalimumab subsets (P>0.05). The SNP is predicted to disrupt transcription factor binding site motifs in the 3′ UTR of an immune-related gene, CD84, and the allele associated with better response to etanercept was associated with higher CD84 gene expression in peripheral blood mononuclear cells (P = 1×10-11 in 228 non-RA patients and P = 0.004 in 132 RA patients). Consistent with the genetic findings, higher CD84 gene expression correlated with lower cross-sectional DAS (P = 0.02, n = 210) and showed a non-significant trend for better ΔDAS in a subset of RA patients with gene expression data (n = 31, etanercept-treated). A small, multi-ethnic replication showed a non-significant trend towards an association among etanercept-treated RA patients of Portuguese ancestry (n = 139, P = 0.4), but no association among patients of Japanese ancestry (n = 151, P = 0.8). Our study demonstrates that an allele associated with response to etanercept therapy is also associated with CD84 gene expression, and further that CD84 expression correlates with disease activity. These findings support a model in which CD84 genotypes and/or expression may serve as a useful biomarker for response to etanercept treatment in RA patients of European ancestry. © 2013 Cui et al

A Spitzer Space Telescope far-infrared spectral atlas of compact sources in the Magellanic Clouds. I. The Large Magellanic Cloud

[abridged] We present 52-93 micron spectra obtained with Spitzer in the MIPS-SED mode, of a representative sample of luminous compact far-IR sources in the LMC. These include carbon stars, OH/IR AGB stars, post-AGB objects and PNe, RCrB-type star HV2671, OH/IR red supergiants WOHG064 and IRAS05280-6910, B[e] stars IRAS04530-6916, R66 and R126, Wolf-Rayet star Brey3a, Luminous Blue Variable R71, supernova remnant N49, a large number of young stellar objects, compact HII regions and molecular cores, and a background galaxy (z~0.175). We use the spectra to constrain the presence and temperature of cold dust and the excitation conditions and shocks within the neutral and ionized gas, in the circumstellar environments and interfaces with the surrounding ISM. Evolved stars, including LBV R71, lack cold dust except in some cases where we argue that this is swept-up ISM. This leads to an estimate of the duration of the prolific dust-producing phase ("superwind") of several thousand years for both RSGs and massive AGB stars, with a similar fractional mass loss experienced despite the different masses. We tentatively detect line emission from neutral oxygen in the extreme RSG WOHG064, with implications for the wind driving. In N49, the shock between the supernova ejecta and ISM is revealed by its strong [OI] 63-micron emission and possibly water vapour; we estimate that 0.2 Msun of ISM dust was swept up. Some of the compact HII regions display pronounced [OIII] 88-micron emission. The efficiency of photo-electric heating in the interfaces of ionized gas and molecular clouds is estimated at 0.1-0.3%. We confirm earlier indications of a low nitrogen content in the LMC. Evidence for solid state emission features is found in both young and evolved object; some of the YSOs are found to contain crystalline water ice.Comment: Accepted for publication in The Astronomical Journal. This paper accompanies the Summer 2009 SAGE-Spec release of 48 MIPS-SED spectra, but uses improved spectrum extraction. (Fig. 2 reduced resolution because of arXiv limit.