Photometric identification and MMT spectroscopy of new extremely metal-poor galaxies: towards a better understanding of young stellar populations at low metallicity

Extremely metal-poor star-forming galaxies (XMPs) represent one of our only laboratories for study of the low-metallicity stars we expect to encounter at early epochs. But as our understanding of the $z>6$ universe has improved, it has become clear that the majority of known XMPs within 100 Mpc host significantly less prominent massive star populations than their reionization-era counterparts, severely limiting their utility as testbeds for interpreting spectral features found at the highest redshifts. Here we present a new photometric selection technique designed to identify nearby XMPs dominated by young stellar populations comparable to those expected in the reionization era. We apply our technique to uncover candidate XMPs in SDSS imaging at magnitudes $16<i'<23$, extending significantly below the completeness limits of the SDSS spectroscopic survey. Spectroscopic observations with the MMT confirm that 32 of the 53 uniformly metal-poor and high specific star formation rate targets we observed have gas-phase oxygen abundances $12+\log\mathrm{O/H}<7.7$ ($Z/Z_\odot<0.1$), including two in the range of the lowest-metallicity galaxies known, $Z/Z_\odot<0.05$. Our observations shed new light onto the longstanding mystery of He II emission in star-forming galaxies: we find that the equivalent width of the He II $\lambda 4686$ high-ionization emission line does not scale with that of H$\beta$ in our sample, suggesting that binary evolution or other processes on $>10$ Myr timescales contribute substantially to the $\mathrm{He^+}$-ionizing photon budget in this metallicity regime. Applying such selection techniques coupled with deep spectroscopy to next-generation photometric surveys like LSST may eventually provide a basis for an empirical understanding of metal-poor massive stars.Comment: 16 pages, 10 figures, accepted for publication in MNRA

Quantitative assessment of tear production: A review of methods and utility in dry eye drug discovery

The successful development of a therapeutic agent targeting treatment of dry eye syndrome necessitates the demonstration of drug efficacy for both sign and symptom endpoints. As numerous therapeutic strategies incorporate a secretagogue function into their overall mechanism of action, the quantitative assessment of tear production serves as a logical endpoint to anchor “sign” efficacy. Although several methods including the Schirmer, the phenol red thread and tear clearance tests exist, their utility in clinical evaluations of novel therapeutics is unclear. The purpose of this review is to summarize findings and conclusions describing the performance of each of these tests so as to gain insight into which, if any, is most applicable for use in discovering new dry eye therapeutics

Ultraviolet spectra of extreme nearby star-forming regions --- approaching a local reference sample for JWST

Nearby dwarf galaxies provide a unique laboratory in which to test stellar population models below $Z_\odot/2$. Such tests are particularly important for interpreting the surprising high-ionization UV line emission detected at $z>6$ in recent years. We present HST/COS ultraviolet spectra of ten nearby metal-poor star-forming galaxies selected to show He II emission in SDSS optical spectra. The targets span nearly a dex in gas-phase oxygen abundance ($7.8<12+\log\mathrm{O/H}<8.5$) and present uniformly large specific star formation rates (sSFR $\sim 10^2$ $\mathrm{Gyr}^{-1}$). The UV spectra confirm that metal-poor stellar populations can power extreme nebular emission in high-ionization UV lines, reaching C III] equivalent widths comparable to those seen in systems at $z\sim 6-7$. Our data reveal a marked transition in UV spectral properties with decreasing metallicity, with systems below $12+\log\mathrm{O/H}\lesssim 8.0$ ($Z/Z_\odot \lesssim 1/5$) presenting minimal stellar wind features and prominent nebular emission in He II and C IV. This is consistent with nearly an order of magnitude increase in ionizing photon production beyond the $\mathrm{He^+}$-ionizing edge relative to H-ionizing flux as metallicity decreases below a fifth solar, well in excess of standard stellar population synthesis predictions. Our results suggest that often neglected sources of energetic radiation such as stripped binary products and very massive O-stars produce a sharper change in the ionizing spectrum with decreasing metallicity than expected. Consequently, nebular emission in C IV and He II powered by these stars may provide useful metallicity constraints in the reionization era.Comment: 27 pages, 13 figures, 11 tables, accepted for publication in MNRA

Quantification of MUCIN 1, cell surface associated and MUCIN16, cell surface associated proteins in tears and conjunctival epithelial cells collected from postmenopausal women

Srinivasan, S., Heynen, M. L., Martell, E., Ritter, R., Jones, L., & Senchyna, M. (2013). Quantification of MUCIN 1, cell surface associated and MUCIN16, cell surface associated proteins in tears and conjunctival epithelial cells collected from postmenopausal women. Molecular Vision, 19, 970–979.Purpose: To quantify the expression of mucin 1, cell surface associated (MUC1) and mucin 16, cell surface associated (MUC16) proteins and messenger ribonucleic acid (mRNA) in a cohort of postmenopausal women (PMW), to explore the relationship between mucin expression, dry eye symptomology, and tear stability.Methods: Thirty-nine healthy PMW (>50 years of age) were enrolled in this study. No specific inclusion criteria were used to define dry eye; instead, a range of subjects were recruited based on responses to the Allergan Ocular Surface Disease Index (OSDI) questionnaire and tear stability measurements as assessed by non-invasive tear breakup time (NITBUT). Tears were collected from the inferior tear meniscus using a disposable glass capillary tube, and total RNA and total protein were isolated from conjunctival epithelial cells collected via impression cytology. Expression of membrane-bound and soluble MUC1 and MUC16 were quantified with western blotting, and expression of MUC1 and MUC16 mRNA was assessed with real-time PCR.Results: OSDI responses ranged from 0 to 60, and NITBUT ranged from 18.5 to 2.9 s. Only two statistically significant correlations were found: soluble MUC16 protein concentration and MUC16 mRNA expression with OSDI vision related (−0.47; p=0.01) and ocular symptom (0.39; p=0.02) subscores, respectively. Post hoc exploratory analysis on absolute expression values was performed on two subsets of subjects defined as asymptomatic (OSDI ≤6, n=12) and moderate to severe symptomatic (OSDI ≥20, n=12). The only significant difference between the two subgroups was a significant reduction in MUC16 mRNA expression found in the symptomatic dry eye group (1.52±1.19 versus 0.57±0.44; p=0.03).Conclusions: A broad exploration of mucin expression compared to either a sign (NITBUT) or symptoms of dry eye failed to reveal compelling evidence supporting a significant relationship, other than a potential association between MUC16 with specific symptoms. Furthermore, comparison of mucin protein and expression levels between the asymptomatic and moderate to severe symptomatic subgroups revealed only one significant difference, a reduction in MUC16 mRNA expression in the symptomatic subgroup.Funding for this study was provided by Alcon Research Ltd and the Natural Sciences and Engineering Research Council of Canada (NSERC)

Diversity of resistance mechanisms in carbapenem-resistant Enterobacteriaceae at a health care system in Northern California, from 2013 to 2016

The mechanism of resistance in carbapenem-resistant Enterobacteriaceae (CRE) has therapeutic implications. We comprehensively characterized emerging mechanisms of resistance in CRE between 2013 and 2016 at a health system in Northern California. A total of 38.7% (24/62) of CRE isolates were carbapenemase gene-positive, comprising 25.0% (6/24) blaOXA-48 like, 20.8% (5/24) blaKPC, 20.8% (5/24) blaNDM, 20.8% (5/24) blaSME, 8.3% (2/24) blaIMP, and 4.2% (1/24) blaVIM. Between carbapenemases and porin loss, the resistance mechanism was identified in 95.2% (59/62) of CRE isolates. Isolates expressing blaKPC were 100% susceptible to ceftazidime–avibactam, meropenem–vaborbactam, and imipenem–relebactam; blaOXA-48 like–positive isolates were 100% susceptible to ceftazidime–avibactam; and metallo β-lactamase–positive isolates were nearly all nonsusceptible to above antibiotics. Carbapenemase gene-negative CRE were 100% (38/38), 92.1% (35/38), 89.5% (34/38), and 31.6% (12/38) susceptible to ceftazidime–avibactam, meropenem–vaborbactam, imipenem–relebactam, and ceftolozane–tazobactam, respectively. None of the CRE strains were identical by whole genome sequencing. At this health system, CRE were mediated by diverse mechanisms with predictable susceptibility to newer β-lactamase inhibitors

A Panchromatic Study of Massive Stars in the Extremely Metal-poor Local Group Dwarf Galaxy Leo A*

We characterize massive stars (M > 8 M⊙) in the nearby (D ∼ 0.8 Mpc) extremely metal-poor (Z ∼ 5% Z⊙) galaxy Leo A using Hubble Space Telescope ultraviolet (UV), optical, and near-infrared (NIR) imaging along with Keck/Low-Resolution Imaging Spectrograph and MMT/Binospec optical spectroscopy for 18 main-sequence OB stars. We find that: (a) 12 of our 18 stars show emission lines, despite not being associated with an H ii region, suggestive of stellar activity (e.g., mass loss, accretion, binary star interaction), which is consistent with previous predictions of enhanced activity at low metallicity; (b) six are Be stars, which are the first to be spectroscopically studied at such low metallicity—these Be stars have unusual panchromatic SEDs; (c) for stars well fit by the TLUSTY nonlocal thermodynamic equilibrium models, the photometric and spectroscopic values of $\mathrm{log}({T}_{\mathrm{eff}})$ and $\mathrm{log}(g)$ agree to within ∼0.01 dex and ∼0.18 dex, respectively, indicating that near-UV/optical/NIR imaging can be used to reliably characterize massive (M ∼ 8–30 M⊙) main-sequence star properties relative to optical spectroscopy; (d) the properties of the most-massive stars in H II regions are consistent with constraints from previous nebular emission line studies; and (e) 13 stars with M > 8M⊙ are >40 pc from a known star cluster or H II region. Our sample comprises ∼50% of all known massive stars at Z ≲ 10% Z⊙with derived stellar parameters, high-quality optical spectra, and panchromatic photometry