STIS spectroscopy of newborn massive stars in SMC N81

Using Hubble Space Telescope observations with STIS, we study the main exciting stars of N81, a high excitation compact Hii region in the Small Magellanic Cloud (SMC). These far UV observations are the first spectroscopic measurements of stars in such a region and reveal features characteristic of an O6-O8 stellar type. The astonishing weakness of their wind profiles and their sub-luminosity (up to ~ 2 mag fainter in Mv than the corresponding dwarfs) make these stars a unique stellar population in the Magellanic Clouds. Our analysis suggests that they are probably in the Hertzsprung-Russell diagram locus of a particularly young class of massive stars, the so-called Vz luminosity class, as they are arriving on the zero age main sequence.Comment: 9 pages, 3 figure

Conditional disruption of interactions between Gαi2 and regulator of G protein signaling (RGS) proteins protects the heart from ischemic injury

Abstract Background Regulator of G protein signaling (RGS) proteins suppress G protein coupled receptor signaling by catalyzing the hydrolysis of Gα-bound guanine nucleotide triphosphate. Transgenic mice in which RGS-mediated regulation of Gαi2 is lost (RGS insensitive Gαi2 G184S) exhibit beneficial (protection against ischemic injury) and detrimental (enhanced fibrosis) cardiac phenotypes. This mouse model has revealed the physiological significance of RGS/Gαi2 interactions. Previous studies of the Gαi2 G184S mutation used mice that express this mutant protein throughout their lives. Thus, it is unclear whether these phenotypes result from chronic or acute Gαi2 G184S expression. We addressed this issue by developing mice that conditionally express Gαi2 G184S. Methods Mice that conditionally express RGS insensitive Gαi2 G184S were generated using a floxed minigene strategy. Conditional expression of Gαi2 G184S was characterized by reverse transcription polymerase chain reaction and by enhancement of agonist-induced inhibition of cAMP production in isolated cardiac fibroblasts. The impact of conditional RGS insensitive Gαi2 G184S expression on ischemic injury was assessed by measuring contractile recovery and infarct sizes in isolated hearts subjected to 30 min ischemia and 2 hours reperfusion. Results We demonstrate tamoxifen-dependent expression of Gαi2 G184S, enhanced inhibition of cAMP production, and cardioprotection from ischemic injury in hearts conditionally expressing Gαi2 G184S. Thus the cardioprotective phenotype previously reported in mice expressing Gαi2 G184S does not require embryonic or chronic Gαi2 G184S expression. Rather, cardioprotection occurs following acute (days rather than months) expression of Gαi2 G184S. Conclusions These data suggest that RGS proteins might provide new therapeutic targets to protect the heart from ischemic injury. We anticipate that this model will be valuable for understanding the time course (chronic versus acute) and mechanisms of other phenotypic changes that occur following disruption of interactions between Gαi2 and RGS proteins.http://deepblue.lib.umich.edu/bitstream/2027.42/109553/1/40360_2014_Article_315.pd

Membrane organization in G‐protein mechanisms

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154346/1/fsb2008012006.pd

Synthetic High-Resolution Line Spectra of Star-Forming Galaxies Below 1200A

We have generated a set of far-ultraviolet stellar libraries using spectra of OB and Wolf-Rayet stars in the Galaxy and the Large and Small Magellanic Cloud. The spectra were collected with the Far Ultraviolet Spectroscopic Explorer and cover a wavelength range from 1003.1 to 1182.7A at a resolution of 0.127A. The libraries extend from the earliest O- to late-O and early-B stars for the Magellanic Cloud and Galactic libraries, respectively. Attention is paid to the complex blending of stellar and interstellar lines, which can be significant, especially in models using Galactic stars. The most severe contamination is due to molecular hydrogen. Using a simple model for the H$_2$ line strength, we were able to remove the molecular hydrogen lines in a subset of Magellanic Cloud stars. Variations of the photospheric and wind features of CIII 1176, OVI 1032, 1038, PV 1118, 1128, and SIV 1063, 1073, 1074 are discussed as a function of temperature and luminosity class. The spectral libraries were implemented into the LavalSB and Starburst99 packages and used to compute a standard set of synthetic spectra of star-forming galaxies. Representative spectra are presented for various initial mass functions and star formation histories. The valid parameter space is confined to the youngest ages of less than 10 Myr for an instantaneous burst, prior to the age when incompleteness of spectral types in the libraries sets in. For a continuous burst at solar metallicity, the parameter space is not limited. The suite of models is useful for interpreting the restframe far-ultraviolet in local and high-redshift galaxies.Comment: 33 pages including 13 figures, accepted for publication in Ap

Local delivery of novel MRTF/SRF inhibitors prevents scar tissue formation in a preclinical model of fibrosis

The myocardin-related transcription factor/serum response factor (MRTF/SRF) pathway represents a promising therapeutic target to prevent fibrosis. We have tested the effects of new pharmacological inhibitors of MRTF/SRF signalling in a preclinical model of fibrosis. CCG-222740, a novel MRTF/SRF inhibitor, markedly decreased SRF reporter gene activity and showed a greater inhibitory effect on MRTF/SRF target genes than the previously described MRTF-A inhibitor CCG-203971. CCG-222740 was also five times more potent, with an IC50 of 5 μM, in a fibroblast-mediated collagen contraction assay, was less cytotoxic, and a more potent inhibitor of alpha-smooth muscle actin protein expression than CCG-203971. Local delivery of CCG-222740 and CCG-203971 in a validated and clinically relevant rabbit model of scar tissue formation after glaucoma filtration surgery increased the long-term success of the surgery by 67% (P < 0.0005) and 33% (P < 0.01), respectively, and significantly decreased fibrosis and scarring histologically. Unlike mitomycin-C, neither CCG-222740 nor CCG-203971 caused any detectable epithelial toxicity or systemic side effects with very low drug levels measured in the aqueous, vitreous, and serum. We conclude that inhibitors of MRTF/SRF-regulated gene transcription such as CCG-222740, potentially represent a new therapeutic strategy to prevent scar tissue formation in the eye and other tissues

Neutrino Oscillations and the Supernova 1987A Signal

We study the impact of neutrino oscillations on the interpretation of the supernova (SN) 1987A neutrino signal by means of a maximum-likelihood analysis. We focus on oscillations between $\overline\nu_e$ with $\overline\nu_\mu$ or $\overline\nu_\tau$ with those mixing parameters that would solve the solar neutrino problem. For the small-angle MSW solution ($\Delta m^2\approx10^{-5}\,\rm eV^2$, $\sin^22\Theta_0\approx0.007$), there are no significant oscillation effects on the Kelvin-Helmholtz cooling signal; we confirm previous best-fit values for the neutron-star binding energy and average spectral $\overline\nu_e$ temperature. There is only marginal overlap between the upper end of the 95.4\% CL inferred range of $\langle E_{\overline\nu_e}\rangle$ and the lower end of the range of theoretical predictions. Any admixture of the stiffer $\overline\nu_\mu$ spectrum by oscillations aggravates the conflict between experimentally inferred and theoretically predicted spectral properties. For mixing parameters in the neighborhood of the large-angle MSW solution ($\Delta m^2\approx10^{-5}\,\rm eV^2$, $\sin^22\Theta_0\approx0.7$) the oscillations in the SN are adiabatic, but one needs to include the regeneration effect in the Earth which causes the Kamiokande and IMB detectors to observe different $\overline\nu_e$ spectra. For the solar vacuum solution ($\Delta m^2\approx10^{-10}\,\rm eV^2$, $\sin^22\Theta_0\approx1$) the oscillations in the SN are nonadiabatic; vacuum oscillations take place between the SN and the detector. If either of the large-angle solutions were borne out by the upcoming round of solar neutrino experiments, one would have to conclude that the SN~1987A $\overline\nu_\mu$ and/or $\overline\nu_e$ spectra had been much softer than predicted by currentComment: Final version with very minor wording changes, to be published in Phys. Rev.

He Said, She Said: Style Transfer for Shifting the Perspective of Dialogues

In this work, we define a new style transfer task: perspective shift, which reframes a dialogue from informal first person to a formal third person rephrasing of the text. This task requires challenging coreference resolution, emotion attribution, and interpretation of informal text. We explore several baseline approaches and discuss further directions on this task when applied to short dialogues. As a sample application, we demonstrate that applying perspective shifting to a dialogue summarization dataset (SAMSum) substantially improves the zero-shot performance of extractive news summarization models on this data. Additionally, supervised extractive models perform better when trained on perspective shifted data than on the original dialogues. We release our code publicly.Comment: Findings of EMNLP 2022, 18 page

G protein-coupled estrogen receptor (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

The G protein-coupled estrogen receptor (GPER, nomenclature as agreed by the NC-IUPHAR Subcommittee on the G protein-coupled estrogen receptor [24]) was identified following observations of estrogen-evoked cyclic AMP signalling in breast cancer cells [2], which mirrored the differential expression of an orphan 7-transmembrane receptor GPR30 [5]. There are observations of both cell-surface and intracellular expression of the GPER receptor [27, 32]. Selective agonist/ antagonists for GPER have been characterized [24]. Antagonists of the nuclear estrogen receptor, such as fulvestrant [10], tamoxifen [27, 32] and raloxifene [23], as well as the flavonoid 'phytoestrogens' genistein and quercetin [16], are agonists of GPER. A complete review of GPER pharmacology has been recently published [24]. The roles of GPER in physiological systems throughout the body (cardiovascular, metabolic, endocrine, immune, reproductive) and in cancer have also been reviewed [24, 25, 18, 15, 8]