Evryscope-south survey of upper-and pre-main sequence solar neighborhood stars

Using photometric data collected by Evryscope-South, we search for nearby young variable systems on the upper main sequence (UMS) and pre-main sequence (PMS). The Evryscopes are all-sky high-cadence telescope arrays operating in the Northern and Southern hemispheres. We base our search on a Gaia-selected catalog of young neighborhood upper-and pre-main sequence stars which were chosen through both astrometric and photometric criteria. We analyze 44,971 Evryscope-South light curves in search of variability. We recover 615 variables, with 378 previously known, and 237 new discoveries including 84 young eclipsing binaries (EB) candidates. We discover a new highly eccentric binary system and recover a further four previously known systems, with periods ranging from 299 to 674 hr. We find 158 long-period (>50 hr) candidate EB systems, 9 from the PMS and 149 from the UMS, which will allow constraints on the mass/radius/age relation. These long-period EBs include a 179.3 hr PMS system and a 867.8 hr system from the UMS. For PMS variable candidates we estimate system ages, which range from 1 to 23 Myr for non-EBs and from 2 to 17 Myr for EBs. Other non-EB discoveries that show intrinsic variability will allow relationships between stellar rotation rates, ages, activity, and mass to be characterized

EvryFlare. II. Rotation Periods of the Cool Flare Stars in TESS across Half the Southern Sky

We measure rotation periods and sinusoidal amplitudes in Evryscope light curves for 122 two-minute K5-M4 TESS targets selected for strong flaring. The Evryscope array of telescopes has observed all bright nearby stars in the south, producing 2-minute cadence light curves since 2016. Long-term, high-cadence observations of rotating flare stars probe the complex relationship between stellar rotation, starspots, and superflares. We detect periods from 0.3487 to 104 days and observe amplitudes from 0.008 to 0.216 g′ mag. We find that the Evryscope amplitudes are larger than those in TESS with the effect correlated to stellar mass (p-value = 0.01). We compute the Rossby number (R o ) and find that our sample selected for flaring has twice as many intermediate rotators (0.04 0.44) rotators; this may be astrophysical or a result of period detection sensitivity. We discover 30 fast, 59 intermediate, and 33 slow rotators. We measure a median starspot coverage of 13% of the stellar hemisphere and constrain the minimum magnetic field strength consistent with our flare energies and spot coverage to be 500 G, with later-type stars exhibiting lower values than earlier-type stars. We observe a possible change in superflare rates at intermediate periods. However, we do not conclusively confirm the increased activity of intermediate rotators seen in previous studies. We split all rotators at R o ∼ 0.2 into bins of P Rot 10 days to confirm that short-period rotators exhibit higher superflare rates, larger flare energies, and higher starspot coverage than do long-period rotators, at p-values of 3.2 × 10-5, 1.0 × 10-5, and 0.01, respectively

Rotation Periods of TESS Objects of Interest from the Magellan-TESS Survey with Multiband Photometry from Evryscope and TESS

Stellar radial-velocity (RV) jitter due to surface activity may bias the RV semiamplitude and mass of rocky planets. The amplitude of the jitter may be estimated from the uncertainty in the rotation period, allowing the mass to be more accurately obtained. We find candidate rotation periods for 17 out of 35 TESS Objects of Interest (TOI) hosting <3 R ⊕ planets as part of the Magellan-TESS survey, which is the first-ever statistically robust study of exoplanet masses and radii across the photoevaporation gap. Seven periods are ≥3σ detections, two are ≥1.5σ, and eight show plausible variability, but the periods remain unconfirmed. The other 18 TOIs are nondetections. Candidate rotators include the host stars of the confirmed planets L 168-9 b, the HD 21749 system, LTT 1445 A b, TOI 1062 b, and the L 98-59 system. Thirteen candidates have no counterpart in the 1000 TOI rotation catalog of Canto Martins et al. We find periods for G3-M3 dwarfs using combined light curves from TESS and the Evryscope all-sky array of small telescopes, sometimes with longer periods than would be possible with TESS alone. Secure periods range from 1.4 to 26 days with Evryscope-measured photometric amplitudes as small as 2.1 mmag in g′. We also apply Monte Carlo sampling and a Gaussian process stellar activity model from exoplanet to the TESS light curves of six TOIs to confirm the Evryscope periods

EvryFlare. III. Temperature Evolution and Habitability Impacts of Dozens of Superflares Observed Simultaneously by Evryscope and TESS

Superflares may provide the dominant source of biologically relevant UV radiation to rocky habitable-zone M-dwarf planets (M-Earths), altering planetary atmospheres and conditions for surface life. The combined line and continuum flare emission has usually been approximated by a 9000 K blackbody. If superflares are hotter, then the UV emission may be 10 times higher than predicted from the optical. However, it is unknown for how long M-dwarf superflares reach temperatures above 9000 K. Only a handful of M-dwarf superflares have been recorded with multiwavelength high-cadence observations. We double the total number of events in the literature using simultaneous Evryscope and Transiting Exoplanet Survey Satellite observations to provide the first systematic exploration of the temperature evolution of M-dwarf superflares. We also increase the number of superflaring M dwarfs with published time-resolved blackbody evolution by ∼10×. We measure temperatures at 2 minutes cadence for 42 superflares from 27 K5-M5 dwarfs. We find superflare peak temperatures (defined as the mean of temperatures corresponding to flare FWHM) increase with flare energy and impulse. We find the amount of time flares emit at temperatures above 14,000 K depends on energy. We discover that 43% of the flares emit above 14,000 K, 23% emit above 20,000 K and 5% emit above 30,000 K. The largest and hottest flare briefly reached 42,000 K. Some do not reach 14,000 K. During superflares, we estimate M-Earths orbiting <200 Myr stars typically receive a top-of-atmosphere UV-C flux of ∼120 W m-2 and up to 103 W m-2, 100-1000 times the time-averaged X-ray and UV flux from Proxima Cen

Identification of Kinases Regulating Prostate Cancer Cell Growth Using an RNAi Phenotypic Screen

As prostate cancer progresses to castration-resistant disease, there is an increase in signal transduction activity. Most castration-resistant prostate tumors continue to express the androgen receptor (AR) as well as androgen-responsive genes, despite the near absence of circulating androgen in these patients. The AR is regulated not only by its cognate steroid hormone, but also by interactions with a constellation of co-regulatory and signaling molecules. Thus, the elevated signaling activity that occurs during progression to castration resistance can affect prostate cancer cell growth either through the AR or independent of the AR. In order to identify signaling pathways that regulate prostate cancer cell growth, we screened a panel of shRNAs targeting 673 human kinases against LNCaP prostate cancer cells grown in the presence and absence of hormone. The screen identified multiple shRNA clones against known and novel gene targets that regulate prostate cancer cell growth. Based on the magnitude of effect on growth, we selected six kinases for further study: MAP3K11, DGKD, ICK, CIT, GALK2, and PSKH1. Knockdown of these kinases decreased cell growth in both androgen-dependent and castration-resistant prostate cancer cells. However, these kinases had different effects on basal or androgen-induced transcriptional activity of AR target genes. MAP3K11 knockdown most consistently altered transcription of AR target genes, suggesting that MAP3K11 affected its growth inhibitory effect by modulating the AR transcriptional program. Consistent with MAP3K11 acting on the AR, knockdown of MAP3K11 inhibited AR Ser 650 phosphorylation, further supporting stress kinase regulation of AR phosphorylation. This study demonstrates the applicability of lentiviral-based shRNA for conducting phenotypic screens and identifies MAP3K11, DGKD, ICK, CIT, GALK2, and PSKH1 as regulators of prostate cancer cell growth. The thorough evaluation of these kinase targets will pave the way for developing more effective treatments for castration-resistant prostate cancer

Low-cost Access to the Deep, High-cadence Sky: the Argus Optical Array

New mass-produced, wide-field, small-aperture telescopes have the potential to revolutionize ground-based astronomy by greatly reducing the cost of collecting area. In this paper, we introduce a new class of large telescope based on these advances: an all-sky, arcsecond-resolution, 1000 telescope array which builds a simultaneously high-cadence and deep survey by observing the entire sky all night. As a concrete example, we describe the Argus Array, a 5 m-class telescope with an all-sky field of view and the ability to reach extremely high cadences using low-noise CMOS detectors. Each 55 GPix Argus exposure covers 20% of the entire sky to m g = 19.6 each minute and m g = 21.9 each hour; a high-speed mode will allow sub-second survey cadences for short times. Deep coadds will reach m g = 23.6 every five nights over 47% of the sky; a larger-aperture array telescope, with an étendue close to the Rubin Observatory, could reach m g = 24.3 in five nights. These arrays can build two-color, million-epoch movies of the sky, enabling sensitive and rapid searches for high-speed transients, fast-radio-burst counterparts, gravitational-wave counterparts, exoplanet microlensing events, occultations by distant solar system bodies, and myriad other phenomena. An array of O(1000) telescopes, however, would be one of the most complex astronomical instruments yet built. Standard arrays with hundreds of tracking mounts entail thousands of moving parts and exposed optics, and maintenance costs would rapidly outpace the mass-produced-hardware cost savings compared to a monolithic large telescope. We discuss how to greatly reduce operations costs by placing all optics in thermally controlled, sealed domes with only a few moving parts. Coupled with careful software scope control and use of existing pipelines, we show that the Argus Array could become the deepest and fastest Northern sky survey, with total costs in the $20M range

Michigan's Continuing Abolition of the Death Penalty and the Conceptual Components of Symbolic Legislation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68316/2/10.1177_096466399300200304.pd

SFRP1 reduction results in an increased sensitivity to TGF-β signaling

Background Transforming growth factor (TGF)-β plays a dual role during mammary gland development and tumorigenesis and has been shown to stimulate epithelial-mesenchymal transition (EMT) as well as cellular migration. The Wnt/β-catenin pathway is also implicated in EMT and inappropriate activation of the Wnt/β-catenin signaling pathway leads to the development of several human cancers, including breast cancer. Secreted frizzled-related protein 1 (SFRP1) antagonizes this pathway and loss of SFRP1 expression is frequently observed in breast tumors and breast cancer cell lines. We previously showed that when SFRP1 is knocked down in immortalized non-malignant mammary epithelial cells, the cells (TERT-siSFRP1) acquire characteristics associated with breast tumor initiating cells. The phenotypic and genotypic changes that occur in response to SFRP1 loss are consistent with EMT, including a substantial increase in the expression of ZEB2. Considering that ZEB2 has been shown to interact with mediators of TGF-β signaling, we sought to determine whether TGF-β signaling is altered in TERT-siSFRP1 cells. Methods Luciferase reporter assays and real-time PCR analysis were employed to measure TGF-β transcriptional targets. Western blot analysis was used to evaluate TGF-β-mediated ERK1/2 phosphorylation. Migration chamber assays were utilized to quantify cellular migration. TERT-siSFRP1 cells were transfected with Stealth RNAi™ siRNA in order to knock-down the expression of ZEB2. Results TERT-siSFRP1 cells exhibit a significant increase in both TGF-β-mediated luciferase activity as well as TGF-β transcriptional targets, including Integrin β3 and PAI-1. Phosphorylation of ERK1/2 is increased in TERT-siSFRP1 cells in response to enhanced TGF-β signaling. Furthermore, when the TGF-β pathway is blocked with a TGF-βR antagonist (LY364947), cellular migration is significantly hindered. Finally, we found that when ZEB2 is knocked-down, there is a significant reduction in the expression of exogeneous and endogenous TGF-β transcriptional targets and cellular migration is impeded. Conclusions We demonstrate that down-regulation of SFRP1 renders mammary epithelial cells more sensitive to TGF-β signaling which can be partially ameliorated by blocking the expression of ZEB2

Pro-asthmatic cytokines regulate unliganded and ligand-dependent glucocorticoid receptor signaling in airway smooth muscle

To elucidate the regulation of glucocorticoid receptor (GR) signaling under pro-asthmatic conditions, cultured human airway smooth muscle (HASM) cells were treated with proinflammatory cytokines or GR ligands alone and in combination, and then examined for induced changes in ligand-dependent and -independent GR activation and downstream signaling events. Ligand stimulation with either cortisone or dexamethsone (DEX) acutely elicited GR translocation to the nucleus and, comparably, ligand-independent stimulation either with the Th2 cytokine, IL-13, or the pleiotropic cytokine combination, IL-1β/TNFα, also acutely evoked GR translocation. The latter response was potentiated by combined exposure of cells to GR ligand and cytokine. Similarly, treatment with either DEX or IL-13 alone induced GR phosphorylation at its serine-211 residue (GRSer211), denoting its activated state, and combined treatment with DEX+IL-13 elicited heightened and sustained GRSer211phosphorylation. Interestingly, the above ligand-independent GR responses to IL-13 alone were not associated with downstream GR binding to its consensus DNA sequence or GR transactivation, whereas both DEX-induced GR:DNA binding and transcriptional activity were significantly heightened in the presence of IL-13, coupled to increased recruitment of the transcriptional co-factor, MED14. The stimulated GR signaling responses to DEX were prevented in IL-13-exposed cells wherein GRSer211 phosphorylation was suppressed either by transfection with specific serine phosphorylation-deficient mutant GRs or treatment with inhibitors of the MAPKs, ERK1/2 and JNK. Collectively, these novel data highlight a heretofore-unidentified homeostatic mechanism in HASM cells that involves pro-asthmatic cytokine-driven, MAPK-mediated, non-ligand-dependent GR activation that confers heightened glucocorticoid ligand-stimulated GR signaling. These findings raise the consideration that perturbations in this homeostatic cytokine-driven GR signaling mechanism may be responsible, at least in part, for the insensirtivity to glucocorticoid therapy that is commonly seen in individuals with severe asthma