| 1. |
- Shultz, M. E., et al.
(författare)
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Ultraviolet spectropolarimetry with Polstar : using Polstar to test magnetospheric mass-loss quenching
- 2022
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Ingår i: Astrophysics and Space Science. - : Springer Nature. - 0004-640X .- 1572-946X. ; 367:12
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Tidskriftsartikel (refereegranskat)abstract
- Polstar is a proposed NASA MIDEX space telescope that will provide high-resolution, simultaneous full-Stokes spectropolarimetry in the far ultraviolet, together with low-resolution linear polarimetry in the near ultraviolet. This observatory offers unprecedented capabilities to obtain unique information on the magnetic and plasma properties of the magnetospheres of hot stars. We describe an observing program making use of the known population of magnetic hot stars to test the fundamental hypothesis that magnetospheres should act to rapidly drain angular momentum, thereby spinning the star down, whilst simultaneously reducing the net mass-loss rate. Both effects are expected to lead to dramatic differences in the evolution of magnetic vs. non-magnetic stars.
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| 2. |
- Wade, G. A., et al.
(författare)
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The MiMeS survey of magnetism in massive stars : introduction and overview
- 2016
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 456:1, s. 2-22
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The MiMeS (Magnetism in Massive Stars) project is a large-scale, high-resolution, sensitive spectropolarimetric investigation of the magnetic properties of O- and early B-type stars. Initiated in 2008 and completed in 2013, the project was supported by three Large Program allocations, as well as various programmes initiated by independent principal investigators, and archival resources. Ultimately, over 4800 circularly polarized spectra of 560 O and B stars were collected with the instruments ESPaDOnS (Echelle SpectroPolarimetric Device for the Observation of Stars) at the Canada-France-Hawaii Telescope, Narval at the Telescope Bernard Lyot and HARPSpol at the European Southern Observatory La Silla 3.6 m telescope, making MiMeS by far the largest systematic investigation of massive star magnetism ever undertaken. In this paper, the first in a series reporting the general results of the survey, we introduce the scientific motivation and goals, describe the sample of targets, review the instrumentation and observational techniques used, explain the exposure time calculation designed to provide sensitivity to surface dipole fields above approximately 100 G, discuss the polarimetric performance, stability and uncertainty of the instrumentation, and summarize the previous and forthcoming publications.
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| 3. |
- Alecian, E., et al.
(författare)
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First HARPSpol discoveries of magnetic fields in massive stars
- 2011
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 536, s. L6-
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Tidskriftsartikel (refereegranskat)abstract
- In the framework of the Magnetism in Massive Stars (MiMeS) project, a HARPSpol Large Program at the 3.6m-ESO telescope has recently started to collect high-resolution spectropolarimetric data of a large number of Southern massive OB stars in the field of the Galaxy and in many young clusters and associations. We report on the first discoveries of magnetic fields in two massive stars with HARPSpol - HD 130807 and HD 122451, and confirm the presence of a magnetic field at the surface of HD 105382 that was previously observed with a low spectral resolution device. The longitudinal magnetic field measurements strongly vary for HD 130807 from similar to-100 G to similar to 700 G. Those of HD 122451 and HD 105382 are less variable with values ranging from similar to-40 to -80 G, and from similar to-300 to -600 G, respectively. The discovery and confirmation of three new magnetic massive stars, including at least two He-weak stars, is an important contribution to one of MiMeS objectives: the understanding of the origin of magnetic fields in massive stars and their impact on stellar structure and evolution.
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| 4. |
- Alvarado-Gomez, J. D., et al.
(författare)
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Activity and magnetic field structure of the Sun-like planet-hosting star HD 1237
- 2015
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 582
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Tidskriftsartikel (refereegranskat)abstract
- We analyse the magnetic activity characteristics of the planet-hosting Sun-like star, HD 1237, using HARPS spectro-polarimetric time-series data. We find evidence of rotational modulation of the magnetic longitudinal field measurements that is consistent with our ZDI analysis with a period of 7 days. We investigate the effect of customising the LSD mask to the line depths of the observed spectrum and find that it has a minimal effect on the shape of the extracted Stokes V profile but does result in a small increase in the S/N (similar to 7%). We find that using a Milne-Eddington solution to describe the local line profile provides a better fit to the LSD profiles in this slowly rotating star, which also affects the recovered ZDI field distribution. We also introduce a fit-stopping criterion based on the information content (entropy) of the ZDI map solution set. The recovered magnetic field maps show a strong (+90 G) ring-like azimuthal field distribution and a complex radial field dominating at mid latitudes (similar to 45 degrees). Similar magnetic field maps are recovered from data acquired five months apart. Future work will investigate how this surface magnetic field distribution affeccts the coronal magnetic field and extended environment around this planet-hosting star.
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| 5. |
- Traylor, Matthew, et al.
(författare)
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A Novel MMP12 Locus Is Associated with Large Artery Atherosclerotic Stroke Using a Genome-Wide Age-at-Onset Informed Approach.
- 2014
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have begun to identify the common genetic component to ischaemic stroke (IS). However, IS has considerable phenotypic heterogeneity. Where clinical covariates explain a large fraction of disease risk, covariate informed designs can increase power to detect associations. As prevalence rates in IS are markedly affected by age, and younger onset cases may have higher genetic predisposition, we investigated whether an age-at-onset informed approach could detect novel associations with IS and its subtypes; cardioembolic (CE), large artery atherosclerosis (LAA) and small vessel disease (SVD) in 6,778 cases of European ancestry and 12,095 ancestry-matched controls. Regression analysis to identify SNP associations was performed on posterior liabilities after conditioning on age-at-onset and affection status. We sought further evidence of an association with LAA in 1,881 cases and 50,817 controls, and examined mRNA expression levels of the nearby genes in atherosclerotic carotid artery plaques. Secondly, we performed permutation analyses to evaluate the extent to which age-at-onset informed analysis improves significance for novel loci. We identified a novel association with an MMP12 locus in LAA (rs660599; p = 2.5×10-7), with independent replication in a second population (p = 0.0048, OR(95% CI) = 1.18(1.05-1.32); meta-analysis p = 2.6×10-8). The nearby gene, MMP12, was significantly overexpressed in carotid plaques compared to atherosclerosis-free control arteries (p = 1.2×10-15; fold change = 335.6). Permutation analyses demonstrated improved significance for associations when accounting for age-at-onset in all four stroke phenotypes (p<0.001). Our results show that a covariate-informed design, by adjusting for age-at-onset of stroke, can detect variants not identified by conventional GWAS.
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| 6. |
- Huhtaniemi, R., et al.
(författare)
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Adrenals Contribute to Growth of Castration-Resistant VCaP Prostate Cancer Xenografts
- 2018
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Ingår i: American Journal of Pathology. - : Elsevier BV. - 0002-9440. ; 188:12, s. 2890-2901
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Tidskriftsartikel (refereegranskat)abstract
- The role of adrenal androgens as drivers for castration-resistant prostate cancer (CRPC) growth in humans is generally accepted; however, the value of preclinical mouse models of CRPC is debatable, because mouse adrenals do not produce steroids activating the androgen receptor. In this study, we confirmed the expression of enzymes essential for de novo synthesis of androgens in mouse adrenals, with high intratissue concentration of progesterone (P4) and moderate levels of androgens, such as androstenedione, testosterone, and dihydrotestosterone, in the adrenal glands of both intact and orchectomized (ORX) mice. ORX alone had no effect on serum P4 concentration, whereas orchectomized and adrenalectomized (ORX + ADX) resulted in a significant decrease in serum P4 and in a further reduction in the low levels of serum androgens (androstenedione, testosterone, and dihydrotestosterone), measured by mass spectrometry. In line with this, the serum prostate-specific antigen and growth of VCaP xenografts in mice after ORX + ADX were markedly reduced compared with ORX alone, and the growth difference was not abolished by a glucocorticoid treatment. Moreover, ORX + ADX altered the androgen-dependent gene expression in the tumors, similar to that recently shown for the enzalutamide treatment. These data indicate that in contrast to the current view, and similar to humans, mouse adrenals synthesize significant amounts of steroids that contribute to the androgen receptor–dependent growth of CRPC. © 2018 American Society for Investigative Pathology
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| 7. |
- Huhtaniemi, R., et al.
(författare)
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High intratumoral dihydrotestosterone is associated with antiandrogen resistance in VCaP prostate cancer xenografts in castrated mice
- 2022
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Ingår i: iScience. - : Elsevier BV. - 2589-0042. ; 25:5
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Tidskriftsartikel (refereegranskat)abstract
- Antiandrogen treatment resistance is a major clinical concern in castration-resistant prostate cancer (CRPC) treatment. Using xenografts of VCaP cells we showed that growth of antiandrogen resistant CRPC tumors were characterized by a higher intratumor dihydrotestosterone (DHT) concentration than that of treatment responsive tumors. Furthermore, the slow tumor growth after adrenalectomy was associated with a low intratumor DHT concentration. Reactivation of androgen signaling in enzalutamide-resistant tumors was further shown by the expression of several androgen-dependent genes. The data indicate that intratumor DHT concentration and expression of several androgen-dependent genes in CRPC lesions is an indication of enzalutamide treatment resistance and an indication of the need for further androgen blockade. The presence of an androgen synthesis, independent of CYP17A1 activity, has been shown to exist in prostate cancer cells, and thus, novel androgen synthesis inhibitors are needed for the treatment of enzalutamide-resistant CRPC tumors that do not respond to abiraterone.
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| 8. |
- Knuuttila, M., et al.
(författare)
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Castration Induces Up-Regulation of Intratumoral Androgen Biosynthesis and Androgen Receptor Expression in an Orthotopic VCaP Human Prostate Cancer Xenograft Model
- 2014
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Ingår i: American Journal of Pathology. - : Elsevier BV. - 0002-9440. ; 184:8, s. 2163-2173
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Tidskriftsartikel (refereegranskat)abstract
- Androgens are key factors involved in the development and progression of prostate cancer (PCa), and PCa growth can be suppressed by androgen deprivation therapy. In a considerable proportion of men receiving androgen deprivation therapy, however, PCa progresses to castration-resistant PCa (CRPC), making the development of efficient therapies challenging. We used an orthotopic VCaP human PCa xenograft model to study cellular and molecular changes in tumors after androgen deprivation therapy (castration). Tumor growth was monitored through weekly serum prostate-specific antigen measurements, and mice with recurrent tumors after castration were randomized to treatment groups. Serum prostate-specific antigen concentrations showed significant correlation with tumor volume. Castration-resistant tumors retained concentrations of intratumoral androgen (androstenedione, testosterone, and 5 alpha-dihydrotestosterone) at Levels similar to tumors growing in intact hosts. Accordingly, castration induced up-regulation of enzymes involved in androgen synthesis (CYP17A1, AKR1C3, and HSD17B6), as well as expression of full-length androgen receptor (AR) and AR splice variants (AR-V1 and AR-V7). Furthermore, AR target gene expression was maintained in castration-resistant xenografts. The AR antagonists enzalutamide (MDV3100) and ARN-509 suppressed PSA production of castration-resistant tumors, confirming the androgen dependency of these tumors. Taken together, the findings demonstrate that our VCaP xenograft model exhibits the key characteristics of clinical CRPC and thus provides a valuable tool for identifying druggable targets and for testing therapeutic strategies targeting AR signaling in CRPC.
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| 9. |
- Laajala, T. D., et al.
(författare)
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Optimized design and analysis of preclinical intervention studies in vivo
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Recent reports have called into question the reproducibility, validity and translatability of the preclinical animal studies due to limitations in their experimental design and statistical analysis. To this end, we implemented a matching-based modelling approach for optimal intervention group allocation, randomization and power calculations, which takes full account of the complex animal characteristics at baseline prior to interventions. In prostate cancer xenograft studies, the method effectively normalized the confounding baseline variability, and resulted in animal allocations which were supported by RNA-seq profiling of the individual tumours. The matching information increased the statistical power to detect true treatment effects at smaller sample sizes in two castration-resistant prostate cancer models, thereby leading to saving of both animal lives and research costs. The novel modelling approach and its open-source and web-based software implementations enable the researchers to conduct adequately-powered and fully-blinded preclinical intervention studies, with the aim to accelerate the discovery of new therapeutic interventions.
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| 10. |
- Oksala, M. E., et al.
(författare)
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Revisiting the rigidly rotating magnetosphere model for sigma Ori E - II. Magnetic Doppler imaging, arbitrary field RRM, and light variability
- 2015
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 451:2, s. 2015-2029
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Tidskriftsartikel (refereegranskat)abstract
- The initial success of the Rigidly Rotating Magnetosphere (RRM) model application to the B2Vp star sigma Ori E by Townsend, Owocki & Groote triggered a renewed era of observational monitoring of this archetypal object. We utilize high-resolution spectropolarimetry and the magnetic Doppler imaging (MDI) technique to simultaneously determine the magnetic configuration, which is predominately dipolar, with a polar strength B-d = 7.3-7.8 kG and a smaller non-axisymmetric quadrupolar contribution, as well as the surface distribution of abundance of He, Fe, C, and Si. We describe a revised RRM model that now accepts an arbitrary surface magnetic field configuration, with the field topology from the MDI models used as input. The resulting synthetic Ha emission and broad-band photometric observations generally agree with observations, however, several features are poorly fit. To explore the possibility of a photospheric contribution to the observed photometric variability, the MDI abundance maps were used to compute a synthetic photospheric light curve to determine the effect of the surface inhomogeneities. Including the computed photospheric brightness modulation fails to improve the agreement between the observed and computed photometry. We conclude that the discrepancies cannot be explained as an effect of inhomogeneous surface abundance. Analysis of the UV light variability shows good agreement between observed variability and computed light curves, supporting the accuracy of the photospheric light variation calculation. We thus conclude that significant additional physics is necessary for the RRM model to acceptably reproduce observations of not only sigma Ori E, but also other similar stars with significant stellar wind-magnetic field interactions.
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