An IR Search for Extinguished Supernovae in Starburst Galaxies

IR and Radio band observations of heavily extinguished regions in starburst galaxies suggest a very high SN rate associated with such regions. Optically measured supernova (SN) rates may therefore underestimate the total SN rate by factors of up to 10, due to the high extinction to SNe in starburst regions. The IR/radio SN rates come from a variety of indirect means, however, which suffer from model dependence and other problems. We describe a direct measurement of the SN rate from a regular patrol of starburst galaxies done with K' band imaging to minimize the effects of extinction. A collection of K' measurements of core-collapse SNe near maximum light is presented. Results of a preliminary SN search using the MIRC camera at the Wyoming IR Observatory (WIRO), and an improved search using the ORCA optics are described. A monthly patrol of starburst galaxies within 25 Mpc should yield 1.6 - 9.6 SNe/year. Our MIRC search with low-resolution (2.2" pixels) failed to find extinguished SNe, limiting the SN rate outside the nucleus (at > 15" radius) to less than 3.8 Supernova Rate Units (SRU or SNe/century/10^10 L(solar); 90% confidence). The MIRC camera had insufficient resolution to search nuclear starburst regions, where SN activity is concentrated, explaining why we found no heavily obscured SNe. We conclude that high-resolution, small field SN searches in starburst nuclei are more productive than low resolution, large-field searches, even for our large galaxies. With our ORCA high-resolution optics, we could limit the total SN rate to < 1.3 SRU at 90% confidence in 3 years of observations, lower than the most pessimistic estimate.Comment: AJ Submitted 1998 Dec. 13. View figures and download all as one file at http://panisse.lbl.gov/public/bruce/irs

Probenecid inhibits SARS-CoV-2 replication in vivo and in vitro

Effective vaccines are slowing the COVID-19 pandemic, but SARS-CoV-2 will likely remain an issue in the future making it important to have therapeutics to treat patients. There are few options for treating patients with COVID-19. We show probenecid potently blocks SARS-CoV-2 replication in mammalian cells and virus replication in a hamster model. Furthermore, we demonstrate that plasma concentrations up to 50-fold higher than the protein binding adjusted IC(90) value are achievable for 24 h following a single oral dose. These data support the potential clinical utility of probenecid to control SARS-CoV-2 infection in humans

The Low-Redshift Lyman Alpha Forest toward PKS 0405-123

We present STIS 7km/s resolution data of the Ly-a forest toward PKS0405-123 (z=0.574). We make two samples. The strong sample (60 systems) has column density logNHI>13.3 over 0.002<z<0.423, and the weak sample (44) has logNHI>13.1 at 0.020<z<0.234; 7 absorbers show metals, all with OVI, but often offset in velocity from HI. The strong sample Doppler parameters show =47+-22km/s; for the weak, =44+-21km/s. Line blending and s/n effects likely inflate b. The redshift density dN/dz is consistent with previous, lower resolution results for logNHI>14.0. For 13.1<logNHI<14.0, we find a dN/dz overdensity of ~0.2-0.3 dex at 0.127<z<0.234, which we believe arises from cosmic variance. We find Ly-a clustering over Delta v13.3, consistent with a numerical model. There is a void in the strong sample at 0.0320<z<0.0814. We detect radial velocity correlations for Delta v<250km/s between Ly-a absorbers and 39 galaxies in a 10' field. The correlation grows with minimum NHI, peaking for logNHI ~> 13.5-14.0. The strength is similar to that of the galaxy-galaxy correlation for our sample, implying that such Ly-a systems have mass log M/Msun= 11.3+1.0-0.6. Including lower column density systems in the sample shows correlations only out to Delta v <125km/s, as would be expected for smaller density perturbations. Galaxy counts and local HI column density appear correlated, peaking at ~5000km/s. We also give column densities for Galactic species. (Abridged)Comment: 59 pages, 6 tables, 14 figures, 1 standalone, ApJ, in press; minor revisions/clarifications for acceptance, including galaxy lis

Carbonate-Templated Self-Assembly of an Alkylthiolate-Bridged Cadmium Macrocycle

In the presence of Cd(ClO4)2 and a base, a new mixed N,S-donor alkylthiolate ligand supported both carbonate formation from atmospheric CO2 and the self-assembly of a novel bicapped puckered (CdS)6 molecular wheel. The remarkable stability of the complex was demonstrated by slow intermolecular ligand exchange on the 2J(HH) and J(111/113Cd1H) time scales at elevated temperature. Both CO2 and the base were required to convert amorphous “CdLClO4” precipitated in the absence of air to the carbonate complex. The complex shares structural features with the ζ-carbonic anhydrase class associating cadmium(II) with the biogeochemical cycling of carbon and is the first structurally characterized carbonate complex of any metal involving an alkylthiolate ligand

Worldwide Argus II implantation: recommendations to optimize patient outcomes

Abstract Background A position paper based on the collective experiences of Argus II Retinal Prosthesis System investigators to review strategies to optimize outcomes in patients with retinitis pigmentosa undergoing retinal prosthesis implantation. Methods Retinal surgeons, device programmers, and rehabilitation specialists from Europe, Canada, Middle East, and the United States were convened to the first international Argus II Investigator Meeting held in Ann Arbor, MI in March 2015. The recommendations from the collective experiences were collected. Factors associated with successful outcomes were determined. Results Factors leading to successful outcomes begin with appropriate patient selection, expectation counseling, and preoperative retinal assessment. Challenges to surgical implantation include presence of staphyloma and inadequate Tenon’s capsule or conjunctiva. Modified surgical technique may reduce risks of complications such as hypotony and conjunctival erosion. Rehabilitation efforts and correlation with validated outcome measures following implantation are critical. Conclusions Bringing together Argus II investigators allowed the identification of strategies to optimize patient outcomes. Establishing an on-line collaborative network will foster coordinated research efforts to advance outcome assessment and rehabilitation strategies.http://deepblue.lib.umich.edu/bitstream/2027.42/134581/1/12886_2016_Article_225.pd

Flickering AGN can explain the strong circumgalactic O VI observed by COS-Halos

Proximity zone fossils (PZFs) are ionization signatures around recently active galactic nuclei (AGNs) where metal species in the circumgalactic medium remain overionized after the AGNs have shut off due to their long recombination time scales. We explore cosmological zoom hydrodynamic simulations, using the EAGLE (Evolution and Assembly of GaLaxies and their Environments) model paired with a non-equilibrium ionization and cooling module including time-variable AGN radiation to model PZFs around star-forming disc galaxies in the z ∼ 0.2 Universe. Previous simulations typically underestimated the O VI content of galactic haloes, but we show that plausible PZF models increase O VI column densities by 2 − 3 × to achieve the levels observed around COS-Halos star-forming galaxies out to 150 kpc. Models with AGN bolometric luminosities 1043.6erg s−1, duty cycle fractions 10 per cent, and AGN lifetimes 106 yr are the most promising, because their supermassive black holes grow at the cosmologically expected rate and they mostly appear as inactive AGN, consistent with COS-Halos. The central requirement is that the typical star-forming galaxy hosted an active AGN within a time-scale comparable to the recombination time of a high metal ion, which for circumgalactic O VI is ≈107 yr. H I, by contrast, returns to equilibrium much more rapidly due to its low neutral fraction and does not show a significant PZF effect. O VI absorption features originating from PZFs appear narrow, indicating photoionization, and are often well aligned with lower metal ion species. PZFs are highly likely to affect the physical interpretation of circumgalactic high ionization metal lines if, as expected, normal galaxies host flickering AGN

Enhanced Immunogenicity, Mortality Protection, and Reduced Viral Brain Invasion by Alum Adjuvant with an H5N1 Split-Virion Vaccine in the Ferret

Pre-pandemic development of an inactivated, split-virion avian influenza vaccine is challenged by the lack of pre-existing immunity and the reduced immunogenicity of some H5 hemagglutinins compared to that of seasonal influenza vaccines. Identification of an acceptable effective adjuvant is needed to improve immunogenicity of a split-virion avian influenza vaccine.No serum antibodies were detected after vaccination with unadjuvanted vaccine, whereas alum-adjuvanted vaccination induced a robust antibody response. Survival after unadjuvanted dose regimens of 30 µg, 7.5 µg and 1.9 µg (21-day intervals) was 64%, 43%, and 43%, respectively, yet survivors experienced weight loss, fever and thrombocytopenia. Survival after unadjuvanted dose regimen of 22.5 µg (28-day intervals) was 0%, suggesting important differences in intervals in this model. In contrast to unadjuvanted survivors, either dose of alum-adjuvanted vaccine resulted in 93% survival with minimal morbidity and without fever or weight loss. The rarity of brain inflammation in alum-adjuvanted survivors, compared to high levels in unadjuvanted vaccine survivors, suggested that improved protection associated with the alum adjuvant was due to markedly reduced early viral invasion of the ferret brain.Alum adjuvant significantly improves efficacy of an H5N1 split-virion vaccine in the ferret model as measured by immunogenicity, mortality, morbidity, and brain invasion

Immunoproteomics Analysis of the Murine Antibody Response to Vaccination with an Improved Francisella tularensis Live Vaccine Strain (LVS)

Background: Francisella tularensis subspecies tularensis is the causative agent of a spectrum of diseases collectively known as tularemia. An attenuated live vaccine strain (LVS) has been shown to be efficacious in humans, but safety concerns have prevented its licensure by the FDA. Recently, F. tularensis LVS has been produced under Current Good Manufacturing Practice (CGMP guidelines). Little is known about the immunogenicity of this new vaccine preparation in comparison with extensive studies conducted with laboratory passaged strains of LVS. Thus, the aim of the current work was to evaluate the repertoire of antibodies produced in mouse strains vaccinated with the new LVS vaccine preparation. Methodology/Principal Findings: In the current study, we used an immunoproteomics approach to examine the repertoire of antibodies induced following successful immunization of BALB/c versus unsuccessful vaccination of C57BL/6 mice with the new preparation of F. tularensis LVS. Successful vaccination of BALB/c mice elicited antibodies to nine identified proteins that were not recognized by antisera from vaccinated but unprotected C57BL/6 mice. In addition, the CGMP formulation of LVS stimulated a greater repertoire of antibodies following vaccination compared to vaccination with laboratory passaged ATCC LVS strain. A total of 15 immunoreactive proteins were identified in both studies, however, 16 immunoreactive proteins were uniquely reactive with sera from the new formulation of LVS. Conclusions/Significance: This is the first report characterising the antibody based immune response of the new formulation of LVS in the widely used murine model of tularemia. Using two mouse strains, we show that successfully vaccinated mice can be distinguished from unsuccessfully vaccinated mice based upon the repertoire of antibodies generated. This opens the door towards downselection of antigens for incorporation into tularemia subunit vaccines. In addition, this work also highlights differences in the humoral immune response to vaccination with the commonly used laboratory LVS strain and the new vaccine formulation of LVS.Peer reviewed: YesNRC publication: Ye

Enhancement of a modified Mediterranean-style, low glycemic load diet with specific phytochemicals improves cardiometabolic risk factors in subjects with metabolic syndrome and hypercholesterolemia in a randomized trial

<p>Abstract</p> <p>Background</p> <p>As the worldwide dietary pattern becomes more westernized, the metabolic syndrome is reaching epidemic proportions. Lifestyle modifications including diet and exercise are recommended as first-line intervention for treating metabolic syndrome. Previously, we reported that a modified Mediterranean-style, low glycemic load diet with soy protein and phytosterols had a more favorable impact than the American Heart Association Step 1 diet on cardiovascular disease (CVD) risk factors. Subsequently, we screened for phytochemicals with a history of safe use that were capable of increasing insulin sensitivity through modulation of protein kinases, and identified hops <it>rho </it>iso-alpha acid and acacia proanthocyanidins. The objective of this study was to investigate whether enhancement of a modified Mediterranean-style, low glycemic load diet (MED) with specific phytochemicals (soy protein, phytosterols, <it>rho </it>iso-alpha acids and proanthocyanidins; PED) could improve cardiometabolic risk factors in subjects with metabolic syndrome and hypercholesterolemia.</p> <p>Methods</p> <p>Forty-nine subjects with metabolic syndrome and hypercholesterolemia, aged 25–80, entered a randomized, 2-arm, 12-week intervention trial; 23 randomized to the MED arm; 26 to the PED arm. Forty-four subjects completed at least 8 weeks [MED (<it>n </it>= 19); PED (<it>n </it>= 25)]. All subjects were instructed to follow the same aerobic exercise program. Three-day diet diaries and 7-day exercise diaries were assessed at each visit. Fasting blood samples were collected at baseline, 8 and 12 weeks for analysis.</p> <p>Results</p> <p>Both arms experienced equal weight loss (MED: -5.7 kg; PED: -5.9 kg). However, at 12 weeks, the PED arm experienced greater reductions (<it>P </it>< 0.05) in cholesterol, non-HDL cholesterol, triglycerides (TG), cholesterol/HDL and TG/HDL compared with the MED arm. Only the PED arm experienced increased HDL (<it>P </it>< 0.05) and decreased TG/HDL (<it>P </it>< 0.01), and continued reduction in apo B/apo A-I from 8 to 12 weeks. Furthermore, 43% of PED subjects vs. only 22% of MED subjects had net resolution of metabolic syndrome. The Framingham 10-year CVD risk score decreased by 5.6% in the PED arm (<it>P </it>< 0.01) and 2.9% in the MED arm (<it>P </it>< 0.05).</p> <p>Conclusion</p> <p>These results demonstrate that specific phytochemical supplementation increased the effectiveness of the modified Mediterranean-style low glycemic load dietary program on variables associated with metabolic syndrome and CVD.</p