Search

The motuporamines are natural products isolated from the New Guinea sea sponge Xestospongia exigua. Dihydromotuporamine C contains a large macrocycle and an appended polyamine component and was shown to be both antimetastatic and cytotoxic to human L3.6pl pancreatic cancer cells. A series of macrocycle-polyamine conjugates were prepared, and the sequence of the polyamine component was varied to optimize the antimigration properties (as measured in L3.6pl cells) of this molecular class. A one-carbon spacer between the 15-membered carbocycle and the appended polyamine showed improved antimigration properties. A survey of different polyamine sequences containing two, three, or four carbon spacers revealed that the natural polyamine sequence (norspermidine, a 3,3-triamine) was superior in terms of inhibiting the migration of L3.6pl cells in vitro. An investigation of the respective ceramide and sphingomyelin populations in L3.6pl cells revealed that these molecules can modulate both ceramide and sphingomyelin pools in cells and inhibit cell migration.

Background A study to investigate transmission of classical scrapie via goat milk was carried out in sheep: firstly, lambs were challenged orally with goat scrapie brain homogenate to confirm transmission of scrapie from goats to sheep. In the second study phase, milk from scrapie-infected goats was fed to lambs. Lambs were selected according to their prion protein gene (PRNP) genotype, which was either VRQ/VRQ or ARQ/ARQ, with or without additional polymorphisms at codon 141 (FF141, LF141 or LL141) of the ovine PRNP. This report describes the clinical, pathological and molecular phenotype of goat scrapie in those sheep that progressed to clinical end-stage. Results Ten sheep (six VRQ/VRQ and four ARQ/ARQ, of which three FF141 and one LL141) challenged with one of two scrapie brain homogenates, and six pairs of sheep (ARQ, of which five LL141 and seven LF141) fed milk from six different goats, developed clinical disease, which was characterised by a pruritic (all VRQ/VRQ and LL141 sheep) or a non-pruritic form (all LF141 and FF141 sheep). Immunohistochemical (IHC) examination revealed that the pattern of intra- and extracellular accumulation of disease-associated prion protein in the brain was also dependent on PRNP polymorphisms at codon 141, which was similar in VRQ and LL141 sheep but different from LF141 and FF141 sheep. The influence of codon 141 was also seen in discriminatory Western blot (WB), with LF141 and FF141 sheep showing a bovine spongiform encephalopathy-like profile (diminished reactivity with P4 antibody) on brain tissue. However, discriminatory WB in lymphoid tissues, and IHC pattern and profile both in lymphoid and brain tissue was consistent with classical scrapie in all sheep. Conclusions This study provided further evidence that the clinical presentation and the pathological and molecular phenotypes of scrapie in sheep are influenced by PRNP polymorphisms, particularly at codon 141. Differences in the truncation of disease-associated prion protein between LL141 sheep and those carrying the F141 allele may be responsible for these observations. Electronic supplementary material The online version of this article (doi:10.1186/s12917-017-1036-1) contains supplementary material, which is available to authorized users.

Doppler-based planet surveys point to an increasing occurrence rate of giant planets with stellar mass. Such surveys rely on evolved stars for a sample of intermediate-mass stars (so-called retired A stars), which are more amenable to Doppler observations than their main-sequence progenitors. However, it has been hypothesised that the masses of subgiant and low-luminosity red-giant stars targeted by these surveys --- typically derived from a combination of spectroscopy and isochrone fitting --- may be systematically overestimated. Here, we test this hypothesis for the particular case of the exoplanet-host star HD 212771 using K2 asteroseismology. The benchmark asteroseismic mass ($1.45^{+0.10}_{-0.09}\:\text{M}_{\odot}$) is significantly higher than the value reported in the discovery paper ($1.15\pm0.08\:\text{M}_{\odot}$), which has been used to inform the stellar mass-planet occurrence relation. This result, therefore, does not lend support to the above hypothesis. Implications for the fates of planetary systems are sensitively dependent on stellar mass. Based on the derived asteroseismic mass, we predict the post-main-sequence evolution of the Jovian planet orbiting HD 212771 under the effects of tidal forces and stellar mass loss., Accepted for publication in MNRAS; 10 pages, 3 figures, 2 tables

The magnitude of expression of cathepsin L, often upregulated in the tumor microenvironment, correlates with the invasive and metastatic nature of certain tumors. Inhibition of cathepsin L represents an emerging strategy for the treatment of metastatic cancer. A potent, small-molecule inhibitor (referred to as KGP94) of cathepsin L, and new KGP94 analogues were synthesized. (3,5-Dibromophenyl)-(3-hydroxyphenyl) ketone thiosemicarbazone (22), with an IC50 value of 202nM, exhibited similar inhibitory activity against cathepsin L compared to KGP94 (IC50=189nM). Due to limited aqueous solubility of KGP94, a water-soluble phosphate salt (KGP420) was prepared in order to facilitate future in vivo studies. Enzymatic hydrolysis with alkaline phosphatase (ALP) demonstrated that the phosphate prodrug, KGP420, was readily converted to the parent compound, KGP94.

We present scintillation noise profiles captured at the Observatorio del Teide, Iza��a, Tenerife, over a one-week period in September 2017. Contemporaneous data from the Birmingham Solar Oscillations Network (BiSON) and the Stellar Activity (STELLA) robotic telescopes provides estimates of daily atmospheric extinction allowing the scintillation noise to be placed within the context of overall atmospheric conditions. We discuss the results both in terms of the impact on BiSON spectrophotometer design, and for astronomical observations more generally. We find that scintillation noise power reduces by half at about~\SI{5}{\hertz}, and is reduced to one tenth between~\SIrange{20}{30}{\hertz} even during periods of mild Calima, where visibility is reduced due to high concentrations of mineral dust in the atmosphere. We show that the common accepted exposure time of~\SI{, 10 pages, 3 figures, 3 tables. Accepted by Publications of the Astronomical Society of the Pacific: 2019 December 26

Orhan, Zeynep Celik/0000-0002-9424-2339; Serenelli, Aldo/0000-0001-6359-2769; Monteiro, Mario J. P. F. G./0000-0003-0513-8116; Huber, Daniel/0000-0001-8832-4488; Adibekyan, Vardan/0000-0002-0601-6199; Reffert, Sabine/0000-0002-0460-8289; Stock, Stephan/0000-0002-1166-9338; Stassun, Keivan/0000-0002-3481-9052; Cunha, Margarida/0000-0001-8237-7343; Kuszlewicz, James/0000-0002-3322-5279; Lund, Mikkel Norup/0000-0001-9214-5642; Mathur, Savita/0000-0002-0129-0316; Nielsen, Martin Bo/0000-0001-9169-2599; Mosser, Benoit/0000-0002-7547-1208; Pereira, Filipe/0000-0002-2157-7146; Lucas, Miles/0000-0001-6341-310X; miglio, andrea/0000-0001-5998-8533; Ball, Warrick/0000-0002-4773-1017; Basu, Sarbani/0000-0002-6163-3472; Veras, Dimitri/0000-0001-8014-6162; Handberg, Rasmus/0000-0001-8725-4502; Christensen-Dalsgaard, Jorgen/0000-0001-5137-0966; Delgado Mena, Elisa/0000-0003-4434-2195, WOS: 000498546800001, The Transiting Exoplanet Survey Satellite (TESS) is performing a near all-sky survey for planets that transit bright stars. in addition, its excellent photometric precision enables asteroseismology of solar-type and red-giant stars, which exhibit convection-driven, solar-like oscillations. Simulations predict that TESS will detect solar-like oscillations in nearly 100 stars already known to host planets. in this paper, we present an asteroseismic analysis of the known red-giant host stars HD;212771 and HD;203949, both systems having a long-period planet detected through radial velocities. These are the first detections of oscillations in previously known exoplanet-host stars by TESS, further showcasing the mission?s potential to conduct asteroseismology of red-giant stars. We estimate the fundamental properties of both stars through a grid-based modeling approach that uses global asteroseismic parameters as input. We discuss the evolutionary state of HD;203949 in depth and note the large discrepancy between its asteroseismic mass (M-* = 1.23 0.15 MM* = 1.00 0.16 M if in the clump) and the mass quoted in the discovery paper (M-* = 2.1 0.1 M), implying a change >30% in the planet?s mass. Assuming HD;203949 to be in the clump, we investigate the planet?s past orbital evolution and discuss how it could have avoided engulfment at the tip of the red-giant branch. Finally, HD;212771 was observed by K2 during its Campaign 3, thus allowing for a preliminary comparison of the asteroseismic performances of TESS and K2. We estimate the ratio of the observed oscillation amplitudes for this star to be, NASA Explorer ProgramNational Aeronautics & Space Administration (NASA); ESA PRODEXEuropean Space Agency [PEA 4000119301]; Stellar Astrophysics Centre (SAC) - Danish National Research Foundation [DNRF106]; European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grantEuropean Union (EU) [792848, 664931]; FCT/MCTESPortuguese Foundation for Science and Technology [UID/FIS/04434/2019]; FCTPortuguese Foundation for Science and Technology [PTDC/FIS-AST/30389/2017, PTDC/FIS-AST/28953/2017, PTDC/FIS-AST/32113/2017, CEECIND/02619/2017, IF/00650/2015/CP1273/CT0001, IF/00028/2014/CP1215/CT0002]; FEDER through COMPETE2020 [POCI-01-0145-FEDER-030389, POCI-01-0145-FEDER-028953, POCI-01-0145-FEDER-032113]; National Science Foundation under the Kavli Institute for Theoretical Physics program "Better Stars, Better Planets" [NSF PHY-1748958]; European Research Council under the European Community's Seventh Framework Programme (FP7/2007-2013)/ERC grant [338251]; ESA PRODEX programme; CNES through the PLATO grants; Spanish GovernmentSpanish Government [ESP2017-82674-R]; Generalitat de CatalunyaGeneralitat de Catalunya [2017-SGR-1131]; STFC via an Ernest Rutherford Fellowship [ST/P003850/1]; NSFNational Science Foundation (NSF) [AST-1514676]; NASANational Aeronautics & Space Administration (NASA) [NNX16AI09G]; Spanish Ministry through the Ramon y Cajal fellowship [RYC-2015-17697]; NYUAD Institute [G1502]; DFGGerman Research Foundation (DFG) [SPP 1992, RE 2694/5-1]; Scientific and Technological Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [TUBITAK:118F352]; National Aeronautics and Space Administration through the TESS Guest Investigator Program [80NSSC18K1585, 80NSSC19K0379]; European Social Fund via the Lithuanian Science Council [09.3.3-LMT-K-712-01-0103], This paper includes data collected by the TESS mission. Funding for the TESS mission is provided by the NASA Explorer Program. Funding for the TESS Asteroseismic Science Operations Center at Aarhus University is provided by ESA PRODEX (PEA 4000119301) and Stellar Astrophysics Centre (SAC), funded by the Danish National Research Foundation (Grant agreement No.: DNRF106). the project leading to this publication has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No..792848 (PULSATION). This work was supported by FCT/MCTES through national funds (UID/FIS/04434/2019). This work was supported by FCT through national funds (PTDC/FIS-AST/30389/2017, PTDC/FIS-AST/28953/2017, and PTDC/FIS-AST/32113/2017) and by FEDER through COMPETE2020 (POCI-01-0145-FEDER-030389, POCI-01-0145-FEDER-028953, and POCI-01-0145-FEDER-032113). This research was supported in part by the National Science Foundation under grant No.NSF PHY-1748958 through the Kavli Institute for Theoretical Physics program "Better Stars, Better Planets". the research leading to the presented results has received funding from the European Research Council under the European Community's Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement No..338251 (StellarAges). E.C.is funded by the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No..664931. M.N.L.acknowledges support from the ESA PRODEX programme. B.M.and R.A.G. acknowledge the support received from CNES through the PLATO grants. A. S.is partially supported by grants ESP2017-82674-R (Spanish Government) and 2017-SGR-1131 (Generalitat de Catalunya). D.V.gratefully acknowledges the support of the STFC via an Ernest Rutherford Fellowship (grant ST/P003850/1). V. A.and S.G.S. acknowledge support from FCT through Investigador FCT contracts No..IF/00650/2015/CP1273/CT0001 and No..IF/00028/2014/CP1215/CT0002, respectively. S. B. acknowledges NSF grant AST-1514676 and NASA grant NNX16AI09G. S.M..acknowledges support from the Spanish Ministry through the Ramon y Cajal fellowship No. RYC-2015-17697. M.B.N..acknowledges support from NYUAD Institute grant G1502. S.R..acknowledges support from the DFG priority program SPP 1992 "Exploring the Diversity of Extrasolar Planets (RE 2694/5-1)". M.Y., Z.C.O., and S. O. acknowledge the Scientific and Technological Research Council of Turkey (TUBITAK:118F352). D.H. acknowledges support by the National Aeronautics and Space Administration (80NSSC18K1585, 80NSSC19K0379) awarded through the TESS Guest Investigator Program. M.S.C. is supported in the form of a work contract funded by FCT (CEECIND/02619/2017). H.K. acknowledges support from the European Social Fund via the Lithuanian Science Council grant No. 09.3.3-LMT-K-712-01-0103.

The importance of studying the Gaia DR2 parallax zero-point by external means was underlined by Lindegren et al. (2018), and initiated by several works making use of Cepheids, eclipsing binaries, and asteroseismology. Despite a very efficient elimination of basic-angle variations, a small fluctuation remains and shows up as a small offset in the Gaia DR2 parallaxes. By combining astrometric, asteroseismic, spectroscopic, and photometric constraints, we undertake a new analysis of the Gaia parallax offset for nearly 3000 red-giant branch (RGB) and 2200 red clump (RC) stars observed by Kepler, as well as about 500 and 700 red giants (both RGB and RC) selected by the K2 Galactic Archaeology Program in campaigns 3 and 6. Engaging into a thorough comparison of the astrometric and asteroseismic parallaxes, we are able to highlight the influence of the asteroseismic method, and measure parallax offsets in the Kepler field that are compatible with independent estimates from literature and open clusters. Moreover, adding the K2 fields to our investigation allows us to retrieve a clear illustration of the positional dependence of the zero-point, in general agreement with the information provided by quasars. Lastly, we initiate a two-step methodology to make progress in the simultaneous calibration of the asteroseismic scaling relations and of the Gaia DR2 parallax offset, which will greatly benefit from the gain in precision with the third Data Release of Gaia., Comment: 15 pages, 17 figures, Accepted for publication in A&A

The stellar inclination angle-the angle between the rotation axis of a star and our line of sight-provides valuable information in many different areas, from the characterisation of the geometry of exoplanetary and eclipsing binary systems, to the formation and evolution of those systems. We propose a method based on asteroseismology and a Bayesian hierarchical scheme for extracting the inclination angle of a single star. This hierarchical method therefore provides a means to both accurately and robustly extract inclination angles from red giant stars. We successfully apply this technique to an artificial dataset with an underlying isotropic inclination angle distribution to verify the method. We also apply this technique to 123 red giant stars observed with $\textit{Kepler}$. We also show the need for a selection function to account for possible population-level biases, that are not present in individual star-by-star cases, in order to extend the hierarchical method towards inferring underlying population inclination angle distributions., 20 pages, 12 figures, accepted for publication in MNRAS

By combining ground-based spectrographic observations of variability in the chromospheric emission from Sun-like stars with the variability seen in their eigenmode frequencies, it is possible to relate the changes observed at the surfaces of these stars to the changes taking place in the interior. By further comparing this variability to changes in the relative flux from the stars, one can obtain an expression for how these activity indicators relate to the energy output from the stars. Such studies become very pertinent when the variability can be related to stellar cycles as they can then be used to improve our understanding of the solar cycle and its effect on the energy output from the Sun. Here we present observations of chromospheric emission in 20 Sun-like stars obtained over the course of the nominal 4-year Kepler mission. Even though 4 years is too short to detect stellar equivalents of the 11-year solar cycle, observations from the Kepler mission can still be used to analyse the variability of the different activity indicators thereby obtaining information of the physical mechanism generating the variability. The analysis reveals no strong correlation between the different activity indicators, except in very few cases. We suggest that this is due to the sparse sampling of our ground-based observations on the one hand and that we are likely not tracing cyclic variability on the other hand. We also discuss how to improve the situation., accepted for publication in MNRAS

Cool main-sequence, sub-giant and red-giant stars all show solar-like oscillations, pulsations that are excited and intrinsically damped by near-surface convection. Many overtones are typically excited to observable amplitudes, giving a rich spectrum of detectable modes. These modes provide a wealth of information on fundamental stellar properties. However, the radial velocity shifts induced by these oscillations can also be problematic when searching for low-mass, long-period planets; this is because their amplitudes are large enough to completely mask such minute planetary signals. Here we show how fine-tuning exposure times to the stellar parameters can help efficiently average out the solar-like-oscillation-induced shifts. To reduce the oscillation signal to the radial velocity precision commensurate with an Earth-analogue, we find that for cool, low-mass stars (near spectral type K) the necessary exposure times may be as short as 4 minutes, while for hotter, higher-mass stars (near spectral type F, or slightly evolved) the required exposure times can be longer than 100 minutes. We provide guideline exposure durations required to suppress the total observed amplitude due to oscillations to a level of $0.1\,\rm m\,s^{-1}$, and a level corresponding to the Earth-analogue reflex amplitude for the star. Owing to the intrinsic stochastic variability of the oscillations, we recommend in practice choosing short exposure durations at the telescope and then averaging over those exposures later, as guided by our predictions. To summarize, as we enter an era of $0.1\,\rm m\,s^{-1}$ instrumental precision, it is critical to tailor our observing strategies to the stellar properties., 22 pages, 6 figures; accepted for publication in Astronomical Journal (AAS Journals)

[ABRIDGED] The purpose of this work is to evaluate how several elements produced by different nucleosynthesis processes behave with stellar age and provide empirical relations to derive stellar ages from chemical abundances. We derive different sets of ages using Gaia parallaxes for a sample of more than 1000 FGK dwarf stars for which he have spectra from the HARPS-GTO program. We analyze the temporal evolution of different abundance ratios to find the best chemical clocks. We find that [$\alpha$/Fe] ratio (average of Mg, Si and Ti), [O/Fe] and [Zn/Fe] are good age proxies with a lower dispersion than the age-metallicity dispersion. Several abundance ratios present a significant correlation with age for chemically separated thin disk stars (i.e. low-$\alpha$) but in the case of the chemically defined thick disk stars (i.e. high-$\alpha$) only the elements Mg, Si, Ca and TiII show a clear correlation with age. We find that the thick disk stars are more enriched in light-s elements than thin disk stars of similar age. The maximum enrichment of s-process elements in the thin disk occurs in the youngest stars which in turn have solar metallicity. The slopes of the [X/Fe]-age relations are quite constant for O, Mg, Si, Ti, Zn, Sr and Eu regardless of the metallicity. However, this is not the case for Al, Ca, Cu and most of the s-process elements, which display very different trends depending on the metallicity. This demonstrates the limitations of using simple linear relations based on certain abundance ratios to obtain ages for stars of different metallicities. Finally, we show that by using 3D relations with a chemical clock and two stellar parameters (either Teff, [Fe/H] or stellar mass) we can explain up to 89% of age variance in a star. A similar result is obtained when using 2D relations with a chemical clock and one stellar parameter, being up to a 87% of the variance explained., Comment: accepted for publication in A&A, version after language revision

A key aspect in the determination of stellar properties is the comparison of observational constraints with predictions from stellar models. Asteroseismic Inference on a Massive Scale (AIMS) is an open source code that uses Bayesian statistics and a Markov Chain Monte Carlo approach to find a representative set of models that reproduce a given set of classical and asteroseismic constraints. These models are obtained by interpolation on a pre-calculated grid, thereby increasing computational efficiency. We test the accuracy of the different operational modes within AIMS for grids of stellar models computed with the Li\`ege stellar evolution code (main sequence and red giants) and compare the results to those from another asteroseismic analysis pipeline, PARAM. Moreover, using artificial inputs generated from models within the grid (assuming the models to be correct), we focus on the impact on the precision of the code when considering different combinations of observational constraints (individual mode frequencies, period spacings, parallaxes, photospheric constraints,...). Our tests show the absolute limitations of precision on parameter inferences using synthetic data with AIMS, and the consistency of the code with expected parameter uncertainty distributions. Interpolation testing highlights the significance of the underlying physics to the analysis performance of AIMS and provides caution as to the upper limits in parameter step size. All tests demonstrate the flexibility and capability of AIMS as an analysis tool and its potential to perform accurate ensemble analysis with current and future asteroseismic data yields., Comment: Accepted for publication in MNRAS. 17 pages, 17 figures

The kinematics of the Milky Way disc as a function of age are well measured at the solar radius, but have not been studied over a wider range of Galactocentric radii. Here, we measure the kinematics of mono-age, mono-$\mathrm{[Fe/H]}$ populations in the low and high $\mathrm{[\alpha/Fe]}$ discs between $4 \lesssim R \lesssim 13$ kpc and $|z| \lesssim 2$ kpc using 65,719 stars in common between APOGEE DR14 and $\it{Gaia}$ DR2 for which we estimate ages using a Bayesian neural network model trained on asteroseismic ages. We determine the vertical and radial velocity dispersions, finding that the low and high $\mathrm{[\alpha/Fe]}$ discs display markedly different age--velocity-dispersion relations (AVRs) and shapes $\sigma_z/\sigma_R$. The high $\mathrm{[\alpha/Fe]}$ disc has roughly flat AVRs and constant $\sigma_z/\sigma_R = 0.64\pm 0.04$, whereas the low $\mathrm{[\alpha/Fe]}$ disc has large variations in this ratio which positively correlate with the mean orbital radius of the population at fixed age. The high $\mathrm{[\alpha/Fe]}$ disc component's flat AVRs and constant $\sigma_z/\sigma_R$ clearly indicates an entirely different heating history. Outer disc populations also have flatter radial AVRs than those in the inner disc, likely due to the waning effect of spiral arms. Our detailed measurements of AVRs and $\sigma_z/\sigma_R$ across the disc indicate that low $\mathrm{[\alpha/Fe]}$, inner disc ($R \lesssim 10\,\mathrm{kpc}$) stellar populations are likely dynamically heated by both giant molecular clouds and spiral arms, while the observed trends for outer disc populations require a significant contribution from another heating mechanism such as satellite perturbations. We also find that outer disc populations have slightly positive mean vertical and radial velocities, likely because they are part of the warped disc., Comment: Accepted for publication in MNRAS - The revised version has various updates to the text following suggestions from the referee, but general results remain the same. Code is available https://github.com/jmackereth/monoage-velocity-dispersion, and the APOGEE DR14 age catalogue can be found alongside a paper summary http://www.astro.ljmu.ac.uk/~astjmack/dynamical-heating.html

The discovery of thousands of planetary systems by Kepler has demonstrated that planets are ubiquitous. However, a major challenge has been the confirmation of Kepler planet candidates, many of which still await confirmation. One of the most enigmatic examples is KOI 4.01, Kepler's first discovered planet candidate detection (as KOI 1.01, 2.01, and 3.01 were known prior to launch). Here we present the confirmation and characterization of KOI 4.01 (now Kepler-1658), using a combination of asteroseismology and radial velocities. Kepler-1658 is a massive, evolved subgiant (M star = 1.45 ± 0.06 M ⊙, R star = 2.89 ± 0.12 R ⊙) hosting a massive Mp = 5.88 ± 0.47 Ms, Rp =1.07±0.05 RJ) hot Jupiter that orbits every 3.85 days. Kepler-1658 joins a small population of evolved hosts with short-period (≤100 days) planets and is now the closest known planet in terms of orbital period to an evolved star. Because of its uniqueness and short orbital period, Kepler-1658 is a new benchmark system for testing tidal dissipation and hot Jupiter formation theories. Using all four years of the Kepler data, we constrain the orbital decay rate to be P ≤ −0.42 s yr−1, corresponding to a strong observational limit of Q' star ≥ 4.826 × 103 for the tidal quality factor in evolved stars. With an effective temperature of Teff ~ 6200 K, Kepler-1658 sits close to the spin–orbit misalignment boundary at ~6250 K, making it a prime target for follow-up observations to better constrain its obliquity and to provide insight into theories for hot Jupiter formation and migration.

Analyses of data from spectroscopic and astrometric surveys have led to conflicting results concerning the vertical characteristics of the Milky Way. Ages are often used to provide clarity, but typical uncertainties of $>$ 40\,\% restrict the validity of the inferences made. Using the \textit{Kepler} APOKASC sample for context, we explore the global population trends of two K2 campaign fields (3 and 6), which extend further vertically out of the Galactic plane than APOKASC. We analyse the properties of red giant stars utilising three asteroseismic data analysis methods to cross-check and validate detections. The Bayesian inference tool PARAM is used to determine the stellar masses, radii and ages. Evidence of a pronounced red giant branch bump and an [$\alpha$/Fe] dependence on the position of the red clump is observed from the radii distribution of the K2 fields. Two peaks in the age distribution centred at $\sim$5 and and $\sim$12 Gyr are found using a sample with $\sigma_{\rm{age}}$ $$ 0.1) [$\alpha$/Fe] stars. As a function of vertical distance from the Galactic mid-plane ($|Z|$), the age distribution shows a transition from a young to old stellar population with increasing $|Z|$ for the K2 fields. Further coverage of campaign targets with high resolution spectroscopy is required to increase the yield of precise ages achievable with asteroseismology., Comment: 17 pages, 16 figures. Accepted to MNRAS 01/08/2019. Updated manuscript

Asteroseismology provides fundamental stellar parameters independent of distance, but subject to systematics under calibration. Gaia DR2 has provided parallaxes for a billion stars, which are offset by a parallax zero-point. Red Clump (RC) stars have a narrow spread in luminosity, thus functioning as standard candles to calibrate these systematics. This work measures how the magnitude and spread of the RC in the Kepler field are affected by changes to temperature and scaling relations for seismology, and changes to the parallax zero-point for Gaia. We use a sample of 5576 RC stars classified through asteroseismology. We apply hierarchical Bayesian latent variable models, finding the population level properties of the RC with seismology, and use those as priors on Gaia parallaxes to find the parallax zero-point offset. We then find the position of the RC using published values for the zero-point. We find a seismic temperature insensitive spread of the RC of ~0.03 mag in the 2MASS K band and a larger and slightly temperature-dependent spread of ~0.13 mag in the Gaia G band. This intrinsic dispersion in the K band provides a distance precision of ~1% for RC stars. Using Gaia data alone, we find a mean zero-point of -41 $\pm$ 10 $\mu$as. This offset yields RC absolute magnitudes of -1.634 $\pm$ 0.018 in K and 0.546 $\pm$ 0.016 in G. Obtaining these same values through seismology would require a global temperature shift of ~-70 K, which is compatible with known systematics in spectroscopy., Comment: Accepted for publication in MNRAS

We present the target list of solar-type stars to be observed in short-cadence (2-min) for asteroseismology by the NASA Transiting Exoplanet Survey Satellite (TESS) during its 2-year nominal survey mission. The solar-like Asteroseismic Target List (ATL) is comprised of bright, cool main-sequence and subgiant stars and forms part of the larger target list of the TESS Asteroseismic Science Consortium (TASC). The ATL uses Gaia DR2 and the Extended Hipparcos Compilation (XHIP) to derive fundamental stellar properties, calculate detection probabilities and produce a rank-ordered target list. We provide a detailed description of how the ATL was produced and calculate expected yields for solar-like oscillators based on the nominal photometric performance by TESS. We also provide publicly available source code which can be used to reproduce the ATL, thereby enabling comparisons of asteroseismic results from TESS with predictions from synthetic stellar populations., Comment: 13 pages, 11 figures; accepted for publication in Astrophysical Journal Supplement Series

We present a new method for determining the location of active bands of latitude on solar-type stars, which uses stellar-cycle-induced frequency shifts of detectable solar-like oscillations. When near-surface activity is distributed in a non-homogeneous manner, oscillation modes of different angular degree and azimuthal order will have their frequencies shifted by different amounts. We use this simple concept, coupled to a model for the spatial distribution of the near-surface activity, to develop two methods that use the frequency shifts to infer minimum and maximum latitudes for the active bands. Our methods respond to the range in latitude over which there is significant magnetic flux present, over and above weak basal ephemeral flux levels. We verify that we are able to draw accurate inferences in the solar case, using Sun-as-a-star helioseismic data and artificial data. We then apply our methods to Kepler data on the solar analogue HD173701, and find that its active bands straddle a much wider range in latitude than do the bands on the Sun., 13 pages, 15 figures, MNRAS accepted

We have studied long-term variations of galactic cosmic ray (GCR) intensity in relation to the sunspot number (SSN) during the most recent solar cycles. This study analyses the time-lag between the GCR intensity and SSN, and hysteresis plots of the GCR count rate against SSN for solar activity cycles 20-23 to validate a methodology against previous results in the literature, before applying the method to provide a timely update on the behaviour of cycle 24. Cross-plots of SSN vs GCR show a clear difference between the odd-numbered and even-numbered cycles. Linear and elliptical models have been fit to the data with the linear fit and elliptical model proving the more suitable model for even-numbered and odd-numbered solar activity cycles respectively, in agreement with previous literature. Through the application of these methods for the 24th solar activity cycle, it has been shown that cycle 24 experienced a lag of 2-4 months and follows the trend of the preceding activity cycles albeit with a slightly longer lag than previous even-numbered cycles. It has been shown through the hysteresis analysis that the linear fit is a better representative model for cycle 24, as the ellipse model doesn't show a significant improvement, which is also in agreement with previous even-numbered cycles., Comment: 19 pages, 10 figures, 6 tables; accepted for publication in Solar Physics

In spite of the huge advances in exoplanet research provided by the NASA Kepler Mission, there remain only a small number of transit detections around evolved stars. Here we present a reformulation of the noise properties of red-giant stars, where the intrinsic stellar granulation, and the stellar oscillations described by asteroseismology play a key role. The new noise model is a significant improvement on the current Kepler results for evolved stars. Our noise model may be used to help understand planet detection thresholds for the ongoing K2 and upcoming TESS missions, and serve as a predictor of stellar noise for these missions. As an application of our noise model, we explore the minimum detectable planet radii for red giant stars, and find that Neptune sized planets should be detectable around low luminosity red giant branch stars., Comment: Accepted for publication in MNRAS, 9 pages, 10 figures

The natural products colchicine and combretastatin A-4 (CA4) have been inspirational for the design and synthesis of structurally related analogues and spin-off compounds as inhibitors of tubulin polymerization. The discovery that a water-soluble phosphate prodrug salt of CA4 (referred to as CA4P) is capable of imparting profound and selective damage to tumor-associated blood vessels paved the way for the development of a new therapeutic approach for cancer treatment utilizing small-molecule inhibitors of tubulin polymerization that also act as vascular disrupting agents (VDAs). Combination of salient structural features associated with colchicine and CA4 led to the design and synthesis of a variety of fused aryl-cycloalkyl and aryl-heterocyclic compounds that function as inhibitors of tubulin polymerization. Prominent among these compounds is a benzosuberene analogue (referred to as KGP18), which demonstrates sub-nM cytotoxicity against human cancer cell lines and functions (when administered as a water-soluble prodrug salt) as a VDA in mouse models. Structure activity relationship considerations led to the evaluation of benzocyclooctyl [6,8 fused] and indene [6,5 fused] ring systems. Four benzocyclooctene and four indene analogues were prepared and evaluated biologically. Three of the benzocyclooctene analogues were active as inhibitors of tubulin polymerization (IC50 < 5 μM), and benzocyclooctene phenol 23 was comparable to KGP18 in terms of potency. The analogous indene-based compound 31 also functioned as an inhibitor of tubulin polymerization (IC50 = 11 μM) with reduced potency. The most potent inhibitor of tubulin polymerization from this group was benzocyclooctene analogue 23, and it was converted to its water-soluble prodrug salt 24 to assess its potential as a VDA. Preliminary in vivo studies, which utilized the MCF7-luc-GFP-mCherry breast tumor in a SCID mouse model, demonstrated that treatment with 24 (120 mg/kg) resulted in significant vascular shutdown, as evidenced by bioluminescence imaging at 4 h post administration, and that the effect continued at both 24 and 48 h. Contemporaneous studies with CA4P, a clinically relevant VDA, were carried out as a positive control.

We present occurrence rates for rocky planets in the habitable zones (HZ) of main-sequence dwarf stars based on the Kepler DR25 planet candidate catalog and Gaia-based stellar properties. We provide the first analysis in terms of star-dependent instellation flux, which allows us to track HZ planets. We define $\eta_\oplus$ as the HZ occurrence of planets with radius between 0.5 and 1.5 $R_\oplus$ orbiting stars with effective temperatures between 4800 K and 6300 K. We find that $\eta_\oplus$ for the conservative HZ is between $0.37^{+0.48}_{-0.21}$ (errors reflect 68\% credible intervals) and $0.60^{+0.90}_{-0.36}$ planets per star, while the optimistic HZ occurrence is between $0.58^{+0.73}_{-0.33}$ and $0.88^{+1.28}_{-0.51}$ planets per star. These bounds reflect two extreme assumptions about the extrapolation of completeness beyond orbital periods where DR25 completeness data are available. The large uncertainties are due to the small number of detected small HZ planets. We find similar occurrence rates using both a Poisson likelihood Bayesian analysis and Approximate Bayesian Computation. Our results are corrected for catalog completeness and reliability. Both completeness and the planet occurrence rate are dependent on stellar effective temperature. We also present occurrence rates for various stellar populations and planet size ranges. We estimate with $95\%$ confidence that, on average, the nearest HZ planet around G and K dwarfs is about 6 pc away, and there are about 4 HZ rocky planets around G and K dwarfs within 10 pc of the Sun., Comment: To appear in The Astronomical Journal

Around the world, dairy production continues to intensify, with farmers increasing stocking rates, feeding more supplements, and transitioning into fully housed systems. Dairy production in Victoria is no exception and farmers are starting a move towards intensive (i.e. permanently housed) dairy operations. Challenges associated with these transformations have included difficulties, or failure, to obtain planning approval and public concern around the effect of intensive developments on environmental degradation, animal welfare and industry image. We examined current land-use planning provisions, environmental requirements, animal-welfare regulations, industry guidelines and codes of practice for their applicability and suitability to the implementation of intensive dairy-production operations, particularly large-scale ones, in Victoria, Australia. Our aim was to clearly identify factors that have the potential to hinder the growth and expansion of existing dairy-production systems into intensive operations, and the establishment of new intensive dairy enterprises. The majority of legislation examined posed no obstacles to the development of large-scale intensive dairy operations. New definitions for intensive livestock production and the inclusion of an intensive dairy-farm category in the State planning provisions will reduce current confusion across and within planning departments. A standard methodology to determine separation distances is required and a code for intensive dairy farming would greatly assist with the planning-approval process. Many advisory publications fall short when applied to intensive dairy operations as they are currently written for pasture-based farms with limited infrastructure for regularly feeding or housing large herds of >700 cows.

The Sun is the most studied of all stars. It is a reference for all other observed stars and a laboratory of fundamental physics helping us understand processes occuring in conditions irreproducible on Earth. However, our understanding of the Sun is currently stained by the solar modelling problem which can stem from various causes, such as the opacities, the equation of state and the mixing of chemical elements. We combine inversions of sound speed, an entropy proxy and the Ledoux discriminant with constraints such as the position of the base of the convective zone and the photospheric helium abundance. We test various combinations of standard ingredients for solar modelling such as abundance tables, equation of state, formalism for convection and diffusion and opacity tables and study the diagnostic potential of the inversions to constrain ad-hoc modifications of the opacity profile and additional mixing below the convective envelope. Combining inversions provides stringent constraints on the modifications on the models, far beyond what is achievable only from sound speed inversions. We constrain the form and amplitude of the opacity increase required and show that a 15% increase at log T=6.35 provides a significant improvement but that a more global increase of the opacity, within the uncertainties of current tables, coupled with an additional mixing at the bottom of the convective zone gives the best agreement for low metallicity models. We show that high metallicity models do not satisfy all the inversion results. We conclude that the solar problem likely occurs from various small sources, as ingredients such as the equation of state or the formalism of convection can induce small but significant changes and that using phase shift analyses combined with our approach is the next step for a better understanding of the inaccuracies of solar models just below the convective envelope., Accepted for publication in Astronomy and Astrophysics

NASA's Transiting Exoplanet Survey Satellite (TESS) has begun a two-year survey of most of the sky, which will include lightcurves for thousands of solar-like oscillators sampled at a cadence of two minutes. To prepare for this steady stream of data, we present a mock catalogue of lightcurves, designed to realistically mimic the properties of the TESS sample. In the process, we also present the first public release of the asteroFLAG Artificial Dataset Generator, which simulates lightcurves of solar-like oscillators based on input mode properties. The targets are drawn from a simulation of the Milky Way's populations and are selected in the same way as TESS's true Asteroseismic Target List. The lightcurves are produced by combining stellar models, pulsation calculations and semi-empirical models of solar-like oscillators. We describe the details of the catalogue and provide several examples. We provide pristine lightcurves to which noise can be added easily. This mock catalogue will be valuable in testing asteroseismology pipelines for TESS and our methods can be applied in preparation and planning for other observatories and observing campaigns., 14 pages, 6 figures, accepted for publication in ApJS. Archives containing the mock catalogue are available at https://doi.org/10.5281/zenodo.1470155 and the pipeline to produce it at https://github.com/warrickball/s4tess . The first public release of the asteroFLAG Artificial Dataset Generator v3 (AADG3) is described at https://warrickball.github.io/AADG3/

In this work, we have taken advantage of the most recent accurate stellar characterizations carried out using asteroseismology, eclipsing binaries and interferometry to evaluate a comprehensive set of empirical relations for the estimation of stellar masses and radii. We have gathered a total of 934 stars -- of which around two-thirds are on the Main Sequence -- that are characterized with different levels of precision, most of them having estimates of M, R, Teff, L, g, density, and [Fe/H]. We have deliberately used a heterogeneous sample (in terms of characterizing techniques and spectroscopic types) to reduce the influence of possible biases coming from the observation, reduction, and analysis methods used to obtain the stellar parameters. We have studied a total of 576 linear combinations of Teff, L, g, density, and [Fe/H] (and their logarithms) to be used as independent variables to estimate M or R. We have used an error-in-variables linear regression algorithm to extract the relations and to ensure the fair treatment of the uncertainties. We present a total of 38 new or revised relations that have an adj-R2 regression statistic higher than 0.85, and a relative accuracy and precision better than 10% for almost all the cases. The relations cover almost all the possible combinations of observables, ensuring that, whatever list of observables is available, there is at least one relation for estimating the stellar mass and radius., 49 Pages, 17 figures, 11 tables, accepted for publication in ApJS

We report the discovery and characterization of HD 89345b (K2-234b; EPIC 248777106b), a Saturn-sized planet orbiting a slightly evolved star. HD 89345 is a bright star ($V = 9.3$ mag) observed by the K2 mission with one-minute time sampling. It exhibits solar-like oscillations. We conducted asteroseismology to determine the parameters of the star, finding the mass and radius to be $1.12^{+0.04}_{-0.01}~M_\odot$ and $1.657^{+0.020}_{-0.004}~R_\odot$, respectively. The star appears to have recently left the main sequence, based on the inferred age, $9.4^{+0.4}_{-1.3}~\mathrm{Gyr}$, and the non-detection of mixed modes. The star hosts a "warm Saturn" ($P = 11.8$~days, $R_p = 6.86 \pm 0.14~R_\oplus$). Radial-velocity follow-up observations performed with the FIES, HARPS, and HARPS-N spectrographs show that the planet has a mass of $35.7 \pm 3.3~M_\oplus$. The data also show that the planet's orbit is eccentric ($e\approx 0.2$). An investigation of the rotational splitting of the oscillation frequencies of the star yields no conclusive evidence on the stellar inclination angle. We further obtained Rossiter-McLaughlin observations, which result in a broad posterior of the stellar obliquity. The planet seems to conform to the same patterns that have been observed for other sub-Saturns regarding planet mass and multiplicity, orbital eccentricity, and stellar metallicity., Comment: Submitted to MNRAS on 23 February 2018, accepted for publication, 4 May 2018

The pattern of migrating zonal flow bands associated with the solar cycle, known as the torsional oscillation, has been monitored with continuous global helioseismic observations by the Global Oscillations Network Group, together with those made by the Michelson Doppler Imager onboard the Solar and Heliosepheric Observatory and its successor the Helioseismic and Magnetic Imager onboard the Solar Dynamics Observatory, since 1995, giving us nearly two full solar cycles of observations. We report that the flows now show traces of the mid-latitude acceleration that is expected to become the main equatorward-moving branch of the zonal flow pattern for Cycle 25. Based on the current position of this branch, we speculate that the onset of widespread activity for Cycle 25 is unlikely to be earlier than the middle of 2019., Comment: 8 pages, 5 figures, accepted by ApJL 5 July 2018

In the Sun, the frequencies of the acoustic modes are observed to vary in phase with the magnetic activity level. These frequency variations are expected to be common in solar-type stars and contain information about the activity-related changes that take place in their interiors. The unprecedented duration of Kepler photometric time-series provides a unique opportunity to detect and characterize stellar magnetic cycles through asteroseismology. In this work, we analyze a sample of 87 solar-type stars, measuring their temporal frequency shifts over segments of length 90 days. For each segment, the individual frequencies are obtained through a Bayesian peak-bagging tool. The mean frequency shifts are then computed and compared with: 1) those obtained from a cross-correlation method; 2) the variation in the mode heights; 3) a photometric activity proxy; and 4) the characteristic timescale of the granulation. For each star and 90-d sub-series, we provide mean frequency shifts, mode heights, and characteristic timescales of the granulation. Interestingly, more than 60% of the stars show evidence for (quasi-)periodic variations in the frequency shifts. In the majority of the cases, these variations are accompanied by variations in other activity proxies. About 20% of the stars show mode frequencies and heights varying approximately in phase, in opposition to what is observed for the Sun., Comment: Accepted for publication in ApJS, 19(+86) pages, 11(+89) figures, 2(+87) tables

Stellar models typically use the mixing length approximation as a way to implement convection in a simplified manner. While conventionally the value of the mixing length parameter, $\alpha$, used is the solar calibrated value, many studies have shown that other values of $\alpha$ are needed to properly model stars. This uncertainty in the value of the mixing length parameter is a major source of error in stellar models and isochrones. Using asteroseismic data, we determine the value of the mixing length parameter required to properly model a set of about 450 stars ranging in $\log g$, $T_{\mathrm{eff}}$, and $\mathrm{[Fe/H]}$. The relationship between the value of $\alpha$ required and the properties of the star is then investigated. For Eddington atmosphere, non-diffusion models, we find that the value of $\alpha$ can be approximated by a linear model, in the form of $\alpha/\alpha_{\odot}=5.426 -0.101 \log (g) -1.071 \log (T_{\mathrm{eff}}) + 0.437 (\mathrm{[Fe/H]})$. This process is repeated using a variety of model physics as well as compared to previous studies and results from 3D convective simulations., Comment: 20 pages, 17 figures, accepted for publication in ApJ

Studies of stars and stellar populations, and the discovery and characterization of exoplanets, are being revolutionized by new satellite and telescope observations of unprecedented quality and scope. Some of the most significant advances have been in the field of asteroseismology, the study of stars by observation of their oscillations. This book gives a comprehensive technical introduction to this discipline. It not only helps students and researchers learn about asteroseismology; it also serves as an essential instruction manual for those entering the field. The book presents readers with the foundational techniques used in the analysis and interpretation of asteroseismic data on cool stars that show solar-like oscillations. The techniques have been refined, and in some cases developed, to analyze asteroseismic data collected by the NASA Kepler mission. Topics range from the analysis of time-series observations to extract seismic data for stars to the use of those data to determine global and internal properties of the stars. Reading lists and problem sets are provided, and data necessary for the problem sets are available online.

The last decade has seen a revolution in the field of asteroseismology - the study of stellar pulsations. It has become a powerful method to precisely characterize exoplanet host stars and as a consequence also the exoplanets themselves. This synergy between asteroseismology and exoplanet science has flourished in large part due to space missions such as Kepler, which have provided high-quality data that can be used for both types of studies. Perhaps the primary contribution from asteroseismology to the research on transiting exoplanets is the determination of very precise stellar radii that translate into precise planetary radii, but asteroseismology has also proven useful in constraining eccentricities of exoplanets as well as the dynamical architecture of planetary systems. In this chapter, we introduce some basic principles of asteroseismology and review current synergies between the two fields.

We present a catalog of stellar properties for a large sample of 6676 evolved stars with APOGEE spectroscopic parameters and \textit{Kepler} asteroseismic data analyzed using five independent techniques. Our data includes evolutionary state, surface gravity, mean density, mass, radius, age, and the spectroscopic and asteroseismic measurements used to derive them. We employ a new empirical approach for combining asteroseismic measurements from different methods, calibrating the inferred stellar parameters, and estimating uncertainties. With high statistical significance, we find that asteroseismic parameters inferred from the different pipelines have systematic offsets that are not removed by accounting for differences in their solar reference values. We include theoretically motivated corrections to the large frequency spacing ($\Delta \nu$) scaling relation, and we calibrate the zero point of the frequency of maximum power ($\nu_{\rm max}$) relation to be consistent with masses and radii for members of star clusters. For most targets, the parameters returned by different pipelines are in much better agreement than would be expected from the pipeline-predicted random errors, but 22\% of them had at least one method not return a result and a much larger measurement dispersion. This supports the usage of multiple analysis techniques for asteroseismic stellar population studies. The measured dispersion in mass estimates for fundamental calibrators is consistent with our error model, which yields median random and systematic mass uncertainties for RGB stars of order 4\%. Median random and systematic mass uncertainties are at the 9\% and 8\% level respectively for RC stars., Comment: 29 pages, 26 figures. Submitted ApJSupp. Comments welcome. For access to the main data table (Table 5) use https://www.dropbox.com/s/k33td8ukefwy5tv/APOKASC2_Table5.txt?dl=0; for access to the individual pipeline values (Table 6) use https://www.dropbox.com/s/vl9s2p3obftrv8m/APOKASC2_Table6.txt?dl=0

We aim to establish and improve the accuracy level of asteroseismic estimates of mass, radius, and age of giant stars. This can be achieved by measuring independent, accurate, and precise masses, radii, effective temperatures and metallicities of long period eclipsing binary stars with a red giant component that displays solar-like oscillations. We measured precise properties of the three eclipsing binary systems KIC 7037405, KIC 9540226, and KIC 9970396 and estimated their ages be $5.3\pm0.5$, $3.1\pm0.6$, and $4.8\pm0.5$ Gyr. The measurements of the giant stars were compared to corresponding measurements of mass, radius, and age using asteroseismic scaling relations and grid modeling. We found that asteroseismic scaling relations without corrections to $\Delta\nu$ systematically overestimate the masses of the three red giants by 11.7%, 13.7%, and 18.9%, respectively. However, by applying theoretical correction factors $f_{\Delta\nu}$ according to Rodrigues et al. (2017), we reached general agreement between dynamical and asteroseismic mass estimates, and no indications of systematic differences at the precision level of the asteroseismic measurements. The larger sample investigated by Gaulme et al. (2016) showed a much more complicated situation, where some stars show agreement between the dynamical and corrected asteroseismic measures while others suggest significant overestimates of the asteroseismic measures. We found no simple explanation for this, but indications of several potential problems, some theoretical, others observational. Therefore, an extension of the present precision study to a larger sample of eclipsing systems is crucial for establishing and improving the accuracy of asteroseismology of giant stars., Comment: Accepted for publication in MNRAS, 17 pages

The discovery of 3-methoxy-9-(3′,4′,5′-trimethoxyphenyl)-6,7-dihydro-5H-benzo[7]annulen-4-ol (a benzosuberene-based analogue referred to as KGP18) was originally inspired by the natural products colchicine and combretastatin A-4 (CA4). The relative structural simplicity and ease of synthesis of KGP18, coupled with its potent biological activity as an inhibitor of tubulin polymerization and its cytotoxicity (in vitro) against human cancer cell lines, has resulted in studies focused on new analogue design and synthesis. Our goal was to probe the relationship of structure to function in this class of anticancer agents. A series of twenty-two new benzosuberene-based analogues of KGP18 was designed and synthesized. These compounds vary in their methoxylation pattern and separately incorporate trifluoromethyl groups around the pendant aryl ring for the evaluation of the effect of functional group modifications on the fused six-membered aromatic ring. In addition, the 8,9-saturated congener of KGP18 has been synthesized to assess the necessity of unsaturation at the carbon atom bearing the pendant aryl ring. Six of the molecules from this benzosuberene-series of compounds were active (IC50 < 5 μM) as inhibitors of tubulin polymerization while four analogues were comparable (IC50 approximately 1 μM) in their tubulin inhibitory activity to CA4 and KGP18. The potency of a bis-trifluoromethyl analogue 74 and the unsaturated KGP18 derivative 73 as inhibitors of tubulin assembly along with their moderate cytotoxicity suggested the potential utility of these compounds as vascular disrupting agents (VDAs) to selectively target microvessels feeding tumors. Accordingly, water-soluble and DMSO-soluble phosphate prodrug salts of each were synthesized for preliminary in vivo studies to assess their potential efficacy as VDAs.

Combretastatin A-4 phosphate (CA4P), a tubulin depolymerizing agent, shows promise in anti-cancer therapy and is associated with dose-dependent transient hypertension. The cardiac consequence of this hypertensive effect is unknown. This study was conducted to examine the cardiotoxic effect of CA4P on a rat model of hypertension. Hypertensive rats were created by feeding a 6% high salt (HS) diet to Dahl salt sensitive (DSS) rats for 2.5 weeks. Cardiac toxicity was measured using serum troponin I levels 24 h after CA4P administration. In rats fed HS diet, there was a significant increase in mean arterial blood pressure (MAP) from baseline, which was further increased by 80% following CA4P administration with peak systolic blood pressure (BP) of 247 mm Hg. Treatment with the calcium channel blockers, diltiazem and nicardipine, completely inhibited the hypertensive effects of CA4P. Nitroglycerin or enalapril, however, failed to completely block the hypertensive effects of CA4P. CA4P injection also significantly increased the cardiac troponin I level in hypertensive rats though pretreatment with diltiazem effectively blocked troponin I increase after CA4P administration. Based on these findings, an exaggerated hypertensive response to CA4P is associated with myocardial damage in hypertensive rats. Calcium channel blockers effectively blocked both CA4P induced hypertension and cardiac damage.

Current European Commission (EC) surveillance regulations require discriminatory testing of all transmissible spongiform encephalopathy (TSE)-positive small ruminant (SR) samples in order to classify them as bovine spongiform encephalopathy (BSE) or non-BSE. This requires a range of tests, including characterization by bioassay in mouse models. Since 2005, naturally occurring BSE has been identified in two goats. It has also been demonstrated that more than one distinct TSE strain can coinfect a single animal in natural field situations. This study assesses the ability of the statutory methods as listed in the regulation to identify BSE in a blinded series of brain samples, in which ovine BSE and distinct isolates of scrapie are mixed at various ratios ranging from 99% to 1%. Additionally, these current statutory tests were compared with a new in vitro discriminatory method, which uses serial protein misfolding cyclic amplification (sPMCA). Western blotting consistently detected 50% BSE within a mixture, but at higher dilutions it had variable success. The enzyme-linked immunosorbent assay (ELISA) method consistently detected BSE only when it was present as 99% of the mixture, with variable success at higher dilutions. Bioassay and sPMCA reported BSE in all samples where it was present, down to 1%. sPMCA also consistently detected the presence of BSE in mixtures at 0.1%. While bioassay is the only validated method that allows comprehensive phenotypic characterization of an unknown TSE isolate, the sPMCA assay appears to offer a fast and cost-effective alternative for the screening of unknown isolates when the purpose of the investigation was solely to determine the presence or absence of BSE.

We present a study of 33 {\it Kepler} planet-candidate host stars for which asteroseismic observations have sufficiently high signal-to-noise ratio to allow extraction of individual pulsation frequencies. We implement a new Bayesian scheme that is flexible in its input to process individual oscillation frequencies, combinations of them, and average asteroseismic parameters, and derive robust fundamental properties for these targets. Applying this scheme to grids of evolutionary models yields stellar properties with median statistical uncertainties of 1.2\% (radius), 1.7\% (density), 3.3\% (mass), 4.4\% (distance), and 14\% (age), making this the exoplanet host-star sample with the most precise and uniformly determined fundamental parameters to date. We assess the systematics from changes in the solar abundances and mixing-length parameter, showing that they are smaller than the statistical errors. We also determine the stellar properties with three other fitting algorithms and explore the systematics arising from using different evolution and pulsation codes, resulting in 1\% in density and radius, and 2\% and 7\% in mass and age, respectively. We confirm previous findings of the initial helium abundance being a source of systematics comparable to our statistical uncertainties, and discuss future prospects for constraining this parameter by combining asteroseismology and data from space missions. Finally we compare our derived properties with those obtained using the global average asteroseismic observables along with effective temperature and metallicity, finding an excellent level of agreement. Owing to selection effects, our results show that the majority of the high signal-to-noise ratio asteroseismic {\it Kepler} host stars are older than the Sun., 25 pages, 17 figures, MNRAS accepted

We investigate the masses of "retired A stars" using asteroseismic detections on seven low-luminosity red-giant and sub-giant stars observed by the NASA Kepler and K2 Missions. Our aim is to explore whether masses derived from spectroscopy and isochrone fitting may have been systematically overestimated. Our targets have all previously been subject to long term radial velocity observations to detect orbiting bodies, and satisfy the criteria used by Johnson et al. (2006) to select survey stars that may have had A-type (or early F-type) main-sequence progenitors. The sample actually spans a somewhat wider range in mass, from $\approx 1\,\rm M_{\odot}$ up to $\approx 1.7\,\rm M_{\odot}$. Whilst for five of the seven stars the reported discovery mass from spectroscopy exceeds the mass estimated using asteroseismology, there is no strong evidence for a significant, systematic bias across the sample. Moreover, comparisons with other masses from the literature show that the absolute scale of any differences is highly sensitive to the chosen reference literature mass, with the scatter between different literature masses significantly larger than reported error bars. We find that any mass difference can be explained through use of differing constraints during the recovery process. We also conclude that underestimated uncertainties on the input parameters can significantly bias the recovered stellar masses, which may have contributed to the controversy on the mass scale for retired A stars., Comment: Accepted MNRAS, 14 pages, 7 Figures, 3 Tables

A poor understanding of the impact of convective turbulence in the outer layers of the Sun and Sun-like stars challenges the advance towards an improved understanding of their internal structure and dynamics. Assessing and calibrating these effects is therefore of great importance. Here we study the spatial coherence of granulation noise and oscillation modes in the Sun, with the aim of exploiting any incoherence to beat-down observed granulation noise, hence improving the detection of low-frequency p-modes. Using data from the BiSON 2B instrument, we assess the coherence between different atmospheric heights and between different surface regions. We find that granulation noise from the different atmospheric heights probed is largely incoherent; frequency regions dominated by oscillations are almost fully coherent. We find a randomised phase difference for the granulation noise, and a near zero difference for the evanescent oscillations. A reduction of the incoherent granulation noise is shown by application of the cross-spectrum., 8 pages, 7 figures, MNRAS in press

Observations of Sun-like stars over the last half-century have improved our understanding of how magnetic dynamos, like that responsible for the 11-year solar cycle, change with rotation, mass and age. Here we show for the first time how metallicity can affect a stellar dynamo. Using the most complete set of observations of a stellar cycle ever obtained for a Sun-like star, we show how the solar analog HD 173701 exhibits solar-like differential rotation and a 7.4-year activity cycle. While the duration of the cycle is comparable to that generated by the solar dynamo, the amplitude of the brightness variability is substantially stronger. The only significant difference between HD 173701 and the Sun is its metallicity, which is twice the solar value. Therefore, this provides a unique opportunity to study the effect of the higher metallicity on the dynamo acting in this star and to obtain a comprehensive understanding of the physical mechanisms responsible for the observed photometric variability. The observations can be explained by the higher metallicity of the star, which is predicted to foster a deeper outer convection zone and a higher facular contrast, resulting in stronger variability., Submitted to ApJ

International audience; In this erratum, we provide corrected sets of r 01,10,02 difference ratio values and associated uncertainties, which were overestimated in the original paper (as noted by Roxburgh 2017) due to a missing trimming in the post-processing of the Markov chain Monte Carlo (MCMC) chains for these values. The typical reduction in the ratio uncertainties from performing the trimming is a factor of 10 (see Figure 3). Other parameters optimized in the peak-bagging (for instance, individual mode frequencies) are unaffected, as the trimming was performed for these in the original work (Lund et al. 2017). We also provide updated values for the n D 2 values of l=3 modes. We note that the values presented here, as with those presented in the original work, are obtained from a single peak-bagging procedure (see Lund et al. 2017 for details) and have yet to be verified by independent analyses using the same input power spectra. Examples of the updated tables from the original paper are given in Tables 1-3. We note that tables with individual mode parameters (Table 2) have been added for completeness, but the parameters in these tables are unchanged compared to the original paper. In addition to the corrected values mentioned above, we provide covariance matrices for the mode frequencies, frequency difference ratios (r 01,10,02), and second differences (n D 2) for the LEGACY sample (Lund et al. 2017), which were not published with the original work. The values provided by this erratum will be available in the online version of the paper. Figure 1. Comparison between ratio distribution of = r n 01, 25 (n » m 3090 Hz) for KIC 9139151 from the full (green) and properly thinned MCMC chains (black). The dashed red line (on top of the black curve) shows the distribution obtained by sampling from the reported frequency values and corresponding uncertainties (assuming that these are normally distributed and uncorrelated). The central peak is captured by both distributions, but the wide background signal representing the ratio prior has disappeared from the thinned chains. Dotted lines indicate the distribution medians; dashed lines bound the corresponding 68% highest probability density intervals.

We present an extensive peakbagging effort on Kepler data of $\sim$50 red giant stars in the open star cluster NGC 6819. By employing sophisticated pre-processing of the time series and Markov Chain Monte Carlo techniques we extracted individual frequencies, heights and linewidths for hundreds of oscillation modes. We show that the "average" asteroseismic parameter $\delta\nu_{02}$, derived from these, can be used to distinguish the stellar evolutionary state between the red giant branch (RGB) stars and red clump (RC) stars. Masses and radii are estimated using asteroseismic scaling relations, both empirically corrected to obtain self-consistency as well as agreement with independent measures of distance, and using updated theoretical corrections. Remarkable agreement is found, allowing the evolutionary state of the giants to be determined exclusively from the empirical correction to the scaling relations. We find a mean mass of the RGB stars and RC stars in NGC 6819 to be $1.61\pm0.02\,\textrm{M}_\odot$ and $1.64{\pm}0.02\,\textrm{M}_\odot$, respectively. The difference $\Delta M=-0.03\pm0.01\,\textrm{M}_\odot$ is almost insensitive to systematics, suggesting very little RGB mass loss, if any. Stars that are outliers relative to the ensemble reveal overmassive members that likely evolved via mass-transfer in a blue straggler phase. We suggest that KIC 4937011, a low-mass Li-rich giant, is a cluster member in the RC phase that experienced very high mass-loss during its evolution. Such over- and undermassive stars need to be considered when studying field giants, since the true age of such stars cannot be known and there is currently no way to distinguish them from normal stars., Comment: 21 pages, 11 figures

We present preliminary results of our grid based modelling (GBM) of the dwarf/subgiant sample of stars observed with Kepler including global asteroseismic parameters. GBM analysis in this work is based on a large grid of stellar models that is characterized by five independent parameters: model mass and age, initial metallicity ($\zini$), initial helium ($\yini$), and mixing length parameter ($\alpha_{mlt}$). Using this grid relaxes assumptions used in all previous GBM work where the initial composition is determined by a single parameter and that $\alpha_{mlt}$ is fixed to a solar-calibrated value. The new grid allows us to study, for example, the impact of different galactic chemical enrichment models on the determination of stellar parameters such as mass radius and age. Also, it allows to include new results from stellar atmosphere models on $\alpha_{mlt}$ in the GBM analysis in a simple manner. Alternatively, it can be tested if global asteroseismology is a useful tool to constraint our ignorance on quantities such as $\yini$ and $\alpha_{mlt}$. Initial findings show that mass determination is robust with respect to freedom in the latter quantities, with a 4.4\% maximum deviation for extreme assumptions regarding prior information on $\yini-\zini$ relations and $\alpha_{mlt}$. On the other hand, tests carried out so far seem to indicate that global seismology does not have much power to constrain $\yini-\zini$ relations of $\alpha_{mlt}$ values without resourcing to additional information., Comment: To appear in the Proceedings of the joint TASC2/KASC9 workshop - SPACEINN & HELAS8 conference. 4 pages

The activity-related variations in the solar acoustic frequencies have been known for 30 years. However, the importance of the different contributions is still not well established. With this in mind, we developed an empirical model to estimate the spot-induced frequency shifts, which takes into account the sunspot properties, such as area and latitude. The comparison between the model frequency shifts obtained from the daily sunspot records and those observed suggests that the contribution from a stochastic component to the total frequency shifts is about 30%. The remaining 70% is related to a global, long-term variation. We also propose a new observable to investigate the short- and mid-term variations of the frequency shifts, which is insensitive to the long-term variations contained in the data. On the shortest time scales the variations in the frequency shifts are strongly correlated with the variations in the total area covered by sunspots. However, a significant loss of correlation is still found, which cannot be fully explained by ignoring the invisible side of the Sun when accounting for the total sunspot area. We also verify that the times when the frequency shifts and the sunspot areas do not vary in a similar way tend to coincide with the times of the maximum amplitude of the quasi-biennial variations found in the seismic data., Comment: 4 pages, 2 figures, proceedings of the Joint TASC2 - KASC9 Workshop - SPACEINN - HELAS8 Conference "Seismology of the Sun and the Distant Stars 2016: Using Today's Successes to Prepare the Future". To be published by the EPJ Web of Conferences