1. |
- Sliz, E., et al.
(author)
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Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
- 2023
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Journal article (peer-reviewed)abstract
- Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
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2. |
- Abdalla, H., et al.
(author)
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Sensitivity of the Cherenkov Telescope Array for probing cosmology and fundamental physics with gamma-ray propagation
- 2021
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In: Journal of Cosmology and Astroparticle Physics. - : Institute of Physics Publishing (IOPP). - 1475-7516. ; :2
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Journal article (peer-reviewed)abstract
- The Cherenkov Telescope Array (CTA), the new-generation ground-based observatory for gamma-ray astronomy, provides unique capabilities to address significant open questions in astrophysics, cosmology, and fundamental physics. We study some of the salient areas of gamma-ray cosmology that can be explored as part of the Key Science Projects of CTA, through simulated observations of active galactic nuclei (AGN) and of their relativistic jets. Observations of AGN with CTA will enable a measurement of gamma-ray absorption on the extragalactic background light with a statistical uncertainty below 15% up to a redshift z = 2 and to constrain or detect gamma-ray halos up to intergalactic-magnetic-field strengths of at least 0.3 pG. Extragalactic observations with CTA also show promising potential to probe physics beyond the Standard Model. The best limits on Lorentz invariance violation from gamma-ray astronomy will be improved by a factor of at least two to three. CTA will also probe the parameter space in which axion-like particles could constitute a significant fraction, if not all, of dark matter. We conclude on the synergies between CTA and other upcoming facilities that will foster the growth of gamma-ray cosmology.
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3. |
- Abdo, A. A., et al.
(author)
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Multi-wavelength observations of the flaring gamma-ray blazar 3C 66A in 2008 October
- 2011
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 726:1, s. 43-
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Journal article (peer-reviewed)abstract
- The BL Lacertae object 3C 66A was detected in a flaring state by the Fermi Large Area Telescope (LAT) and VERITAS in 2008 October. In addition to these gamma-ray observations, F-GAMMA, GASP-WEBT, PAIRITEL, MDM, ATOM, Swift, and Chandra provided radio to X-ray coverage. The available light curves show variability and, in particular, correlated flares are observed in the optical and Fermi-LAT gamma-ray band. The resulting spectral energy distribution can be well fitted using standard leptonic models with and without an external radiation field for inverse Compton scattering. It is found, however, that only the model with an external radiation field can accommodate the intra-night variability observed at optical wavelengths.
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5. |
- Kurki, MI, et al.
(author)
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FinnGen provides genetic insights from a well-phenotyped isolated population
- 2023
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 613:7944, s. 508-
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Journal article (peer-reviewed)abstract
- Population isolates such as those in Finland benefit genetic research because deleterious alleles are often concentrated on a small number of low-frequency variants (0.1% ≤ minor allele frequency < 5%). These variants survived the founding bottleneck rather than being distributed over a large number of ultrarare variants. Although this effect is well established in Mendelian genetics, its value in common disease genetics is less explored1,2. FinnGen aims to study the genome and national health register data of 500,000 Finnish individuals. Given the relatively high median age of participants (63 years) and the substantial fraction of hospital-based recruitment, FinnGen is enriched for disease end points. Here we analyse data from 224,737 participants from FinnGen and study 15 diseases that have previously been investigated in large genome-wide association studies (GWASs). We also include meta-analyses of biobank data from Estonia and the United Kingdom. We identified 30 new associations, primarily low-frequency variants, enriched in the Finnish population. A GWAS of 1,932 diseases also identified 2,733 genome-wide significant associations (893 phenome-wide significant (PWS), P < 2.6 × 10–11) at 2,496 (771 PWS) independent loci with 807 (247 PWS) end points. Among these, fine-mapping implicated 148 (73 PWS) coding variants associated with 83 (42 PWS) end points. Moreover, 91 (47 PWS) had an allele frequency of <5% in non-Finnish European individuals, of which 62 (32 PWS) were enriched by more than twofold in Finland. These findings demonstrate the power of bottlenecked populations to find entry points into the biology of common diseases through low-frequency, high impact variants.
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6. |
- Abdo, A. A., et al.
(author)
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THE FIRST FERMI MULTIFREQUENCY CAMPAIGN ON BL LACERTAE : CHARACTERIZING THE LOW-ACTIVITY STATE OF THE EPONYMOUS BLAZAR
- 2011
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In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 730:2, s. 101-
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Journal article (peer-reviewed)abstract
- We report on observations of BL Lacertae during the first 18 months of Fermi LAT science operations and present results from a 48 day multifrequency coordinated campaign from 2008 August 19 to 2008 October 7. The radio to gamma-ray behavior of BL Lac is unveiled during a low-activity state thanks to the coordinated observations of radio-band (Metsahovi and VLBA), near-IR/optical (Tuorla, Steward, OAGH, and MDM), and X-ray (RXTE and Swift) observatories. No variability was resolved in gamma rays during the campaign, and the brightness level was 15 times lower than the level of the 1997 EGRET outburst. Moderate and uncorrelated variability has been detected in UV and X-rays. The X-ray spectrum is found to be concave, indicating the transition region between the low- and high-energy components of the spectral energy distribution (SED). VLBA observation detected a synchrotron spectrum self-absorption turnover in the innermost part of the radio jet appearing to be elongated and inhomogeneous, and constrained the average magnetic field there to be less than 3 G. Over the following months, BL Lac appeared variable in gamma rays, showing flares (in 2009 April and 2010 January). There is no evidence for the correlation of gamma rays with the optical flux monitored from the ground in 18 months. The SED may be described by a single-zone or a two-zone synchrotron self-Compton (SSC) model, but a hybrid SSC plus external radiation Compton model seems to be preferred based on the observed variability and the fact that it provides a fit closest to equipartition.
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7. |
- Arlen, T., et al.
(author)
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Rapid TeV Gamma-Ray Flaring of BL Lacertae
- 2013
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In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 762:2
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Journal article (peer-reviewed)abstract
- We report on the detection of a very rapid TeV gamma-ray flare from BL Lacertae on 2011 June 28 with the Very Energetic Radiation Imaging Telescope Array System (VERITAS). The flaring activity was observed during a 34.6 minute exposure, when the integral flux above 200 GeV reached (3.4 ± 0.6) × 10–6 photons m–2 s–1, roughly 125% of the Crab Nebula flux measured by VERITAS. The light curve indicates that the observations missed the rising phase of the flare but covered a significant portion of the decaying phase. The exponential decay time was determined to be 13 ± 4 minutes, making it one of the most rapid gamma-ray flares seen from a TeV blazar. The gamma-ray spectrum of BL Lacertae during the flare was soft, with a photon index of 3.6 ± 0.4, which is in agreement with the measurement made previously by MAGIC in a lower flaring state. Contemporaneous radio observations of the source with the Very Long Baseline Array revealed the emergence of a new, superluminal component from the core around the time of the TeV gamma-ray flare, accompanied by changes in the optical polarization angle. Changes in flux also appear to have occurred at optical, UV, and GeV gamma-ray wavelengths at the time of the flare, although they are difficult to quantify precisely due to sparse coverage. A strong flare was seen at radio wavelengths roughly four months later, which might be related to the gamma-ray flaring activities. We discuss the implications of these multiwavelength results.
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8. |
- Forstner, A. J., et al.
(author)
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Genome-wide association study of panic disorder reveals genetic overlap with neuroticism and depression
- 2021
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In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26, s. 4179-4190
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Journal article (peer-reviewed)abstract
- Panic disorder (PD) has a lifetime prevalence of 2–4% and heritability estimates of 40%. The contributory genetic variants remain largely unknown, with few and inconsistent loci having been reported. The present report describes the largest genome-wide association study (GWAS) of PD to date comprising genome-wide genotype data of 2248 clinically well-characterized PD patients and 7992 ethnically matched controls. The samples originated from four European countries (Denmark, Estonia, Germany, and Sweden). Standard GWAS quality control procedures were conducted on each individual dataset, and imputation was performed using the 1000 Genomes Project reference panel. A meta-analysis was then performed using the Ricopili pipeline. No genome-wide significant locus was identified. Leave-one-out analyses generated highly significant polygenic risk scores (PRS) (explained variance of up to 2.6%). Linkage disequilibrium (LD) score regression analysis of the GWAS data showed that the estimated heritability for PD was 28.0–34.2%. After correction for multiple testing, a significant genetic correlation was found between PD and major depressive disorder, depressive symptoms, and neuroticism. A total of 255 single-nucleotide polymorphisms (SNPs) with p < 1 × 10−4 were followed up in an independent sample of 2408 PD patients and 228,470 controls from Denmark, Iceland and the Netherlands. In the combined analysis, SNP rs144783209 showed the strongest association with PD (pcomb = 3.10 × 10−7). Sign tests revealed a significant enrichment of SNPs with a discovery p-value of <0.0001 in the combined follow up cohort (p = 0.048). The present integrative analysis represents a major step towards the elucidation of the genetic susceptibility to PD. © 2019, The Author(s), under exclusive licence to Springer Nature Limited.
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9. |
- Ackermann, M., et al.
(author)
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MULTIWAVELENGTH EVIDENCE FOR QUASI-PERIODIC MODULATION IN THE GAMMA-RAY BLAZAR PG 1553+113
- 2015
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In: Astrophysical Journal Letters. - : Institute of Physics (IOP). - 2041-8205 .- 2041-8213. ; 813:2
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Journal article (peer-reviewed)abstract
- We report for the first time a gamma-ray and multiwavelength nearly periodic oscillation in an active galactic nucleus. Using the Fermi Large Area Telescope we have discovered an apparent quasi-periodicity in the gamma-ray flux (E > 100 MeV) from the GeV/TeV BL Lac object PG 1553+113. The marginal significance of the 2.18 +/- 0.08 year period gamma-ray cycle is strengthened by correlated oscillations observed in radio and optical fluxes, through data collected in the Owens Valley Radio Observatory, Tuorla, Katzman Automatic Imaging Telescope, and Catalina Sky Survey monitoring programs and Swift-UVOT. The optical cycle appearing in similar to 10 years of data has a similar period, while the 15 GHz oscillation is less regular than seen in the other bands. Further long-term multiwavelength monitoring of this blazar may discriminate among the possible explanations for this quasi-periodicity.
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10. |
- Lister, M. L., et al.
(author)
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gamma-RAY AND PARSEC-SCALE JET PROPERTIES OF A COMPLETE SAMPLE OF BLAZARS FROM THE MOJAVE PROGRAM
- 2011
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In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 742:1, s. 27-
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Journal article (peer-reviewed)abstract
- We investigate the Fermi Large Area Telescope gamma-ray and 15 GHz Very Long Baseline Array radio properties of a joint gamma-ay and radio-selected sample of active galactic nuclei (AGNs) obtained during the first 11 months of the Fermi mission (2008 August 4-2009 July 5). Our sample contains the brightest 173 AGNs in these bands above declination -30 degrees during this period, and thus probes the full range of gamma-ray loudness (gamma-ray to radio band luminosity ratio) in the bright blazar population. The latter quantity spans at least 4 orders of magnitude, reflecting a wide range of spectral energy distribution (SED) parameters in the bright blazar population. The BL Lac objects, however, display a linear correlation of increasing gamma-ray loudness with synchrotron SED peak frequency, suggesting a universal SED shape for objects of this class. The synchrotron self-Compton model is favored for the gamma-ray emission in these BL Lac objects over external seed photon models, since the latter predict a dependence of Compton dominance on Doppler factor that would destroy any observed synchrotron SED-peak-gamma-ray-loudness correlation. The high-synchrotron peaked (HSP) BL Lac objects are distinguished by lower than average radio core brightness temperatures, and none display large radio modulation indices or high linear core polarization levels. No equivalent trends are seen for the flat-spectrum radio quasars (FSRQs) in our sample. Given the association of such properties with relativistic beaming, we suggest that the HSP BL Lac objects have generally lower Doppler factors than the lower-synchrotron peaked BL Lac objects or FSRQs in our sample.
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13. |
- D’Ammando, F., et al.
(author)
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The most powerful flaring activity from the NLSy1 PMN J0948+0022
- 2015
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 446:3, s. 2456-2467
-
Journal article (peer-reviewed)abstract
- We report on multifrequency observations performed during 2012 December–2013 August of the first narrow-line Seyfert 1 galaxy detected in γ-rays, PMN J0948+0022 (z = 0.5846). A γ-ray flare was observed by the Large Area Telescope on board Fermi during 2012 December–2013 January, reaching a daily peak flux in the 0.1–100 GeV energy range of (155 ± 31) × 10−8 ph cm−2 s−1 on 2013 January 1, corresponding to an apparent isotropic luminosity of ∼1.5 × 1048 erg s−1. The γ-ray flaring period triggered Swift and Very Energetic Radiation Imaging Telescope Array System (VERITAS) observations in addition to radio and optical monitoring by Owens Valley Radio Observatory, Monitoring Of Jets in Active galactic nuclei with VLBA Experiments, and Catalina Real-time Transient Survey. A strong flare was observed in optical, UV, and X-rays on 2012 December 30, quasi-simultaneously to the γ-ray flare, reaching a record flux for this source from optical to γ-rays. VERITAS observations at very high energy (E > 100 GeV) during 2013 January 6–17 resulted in an upper limit of F>0.2 TeV < 4.0 × 10−12 ph cm−2 s−1. We compared the spectral energy distribution (SED) of the flaring state in 2013 January with that of an intermediate state observed in 2011. The two SEDs, modelled as synchrotron emission and an external Compton scattering of seed photons from a dust torus, can be modelled by changing both the electron distribution parameters and the magnetic field.
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14. |
- Sindi, S., et al.
(author)
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Baseline telomere length and effects of a multidomain lifestyle intervention on cognition : The FINGER randomized controlled trial
- 2017
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In: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 59:4, s. 1459-1470
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Journal article (peer-reviewed)abstract
- Leukocyte telomere length (LTL) is a biomarker of aging, and it is associated with lifestyle. It is currently unknown whether LTL is associated with the response to lifestyle interventions. The goal is to assess whether baseline LTL modified the cognitive benefits of a 2-year multidomain lifestyle intervention (exploratory analyses). The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) was a 2-year randomized controlled trial including 1,260 people at risk of cognitive decline, aged 60-77 years identified from the general population. Participants were randomly assigned to the lifestyle intervention (diet, exercise, cognitive training, and vascular risk management) and control (general health advice) groups. Primary outcome was change in cognition (comprehensive neuropsychological test battery). Secondary outcomes were changes in cognitive domains: Memory, executive functioning, and processing speed. 775 participants (392 control, 383 intervention) had baseline LTL (peripheral blood DNA). Mixed effects regression models with maximum likelihood estimation were used to analyze change in cognition as a function of randomization group, time, baseline LTL, and their interaction. Intervention and control groups did not significantly differ at baseline. Shorter LTL was related to less healthy baseline lifestyle. Intervention benefits on executive functioning were more pronounced among those with shorter baseline LTL (p-value for interaction was 0.010 adjusted for age and sex, and 0.007 additionally adjusted for baseline lifestyle factors). The FINGER intervention cognitive benefits were more pronounced with shorter baseline LTL, particularly for executive functioning, indicating that the multidomain lifestyle intervention was especially beneficial among higher-risk individuals.
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15. |
- Sindi, S., et al.
(author)
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Telomere Length Change in a Multidomain Lifestyle Intervention to Prevent Cognitive Decline : A Randomized Clinical Trial
- 2021
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In: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press. - 1079-5006 .- 1758-535X. ; 76:3, s. 491-498
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Journal article (peer-reviewed)abstract
- BACKGROUND: Shorter leukocyte telomere length (LTL) is associated with aging and dementia. Impact of lifestyle changes on LTL, and relation to cognition and genetic susceptibility for dementia, has not been investigated in randomized controlled trials (RCTs). METHODS: Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability is a 2-year RCT enrolling 1260 participants at risk for dementia from the general population, aged 60-77 years, randomly assigned (1:1) to multidomain lifestyle intervention or control group. The primary outcome was cognitive change (Neuropsychological Test Battery z-score). Relative LTL was measured using quantitative real-time polymerase chain reaction (trial registration: NCT01041989). RESULTS: This exploratory LTL substudy included 756 participants (377 intervention, 379 control) with baseline and 24-month LTL measurements. The mean annual LTL change (SD) was -0.016 (0.19) in the intervention group and -0.023 (0.17) in the control group. Between-group difference was nonsignificant (unstandardized β-coefficient 0.007, 95% CI -0.015 to 0.030). Interaction analyses indicated better LTL maintenance among apolipoprotein E (APOE)-ε4 carriers versus noncarriers: 0.054 (95% CI 0.007 to 0.102); younger versus older participants: -0.005 (95% CI -0.010 to -0.001); and those with more versus less healthy lifestyle changes: 0.047 (95% CI 0.005 to 0.089). Cognitive intervention benefits were more pronounced among participants with better LTL maintenance for executive functioning (0.227, 95% CI 0.057 to 0.396) and long-term memory (0.257, 95% CI 0.024 to 0.489), with a similar trend for Neuropsychological Test Battery total score (0.127, 95% CI -0.011 to 0.264). CONCLUSIONS: This is the first large RCT showing that a multidomain lifestyle intervention facilitated LTL maintenance among subgroups of older people at risk for dementia, including APOE-ε4 carriers. LTL maintenance was associated with more pronounced cognitive intervention benefits. CLINICAL TRIALS REGISTRATION NUMBER: NCT01041989.
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16. |
- Raiteri, C. M., et al.
(author)
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WEBT and XMM-Newton observations of 3C 454.3 during the post-outburst phase - Detection of the little and big blue bumps
- 2007
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 473:3, s. 819-827
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Journal article (peer-reviewed)abstract
- Context. The quasar-type blazar 3C 454.3 was observed to undergo an unprecedented optical outburst in spring 2005, affecting the source brightness from the near-IR to the X-ray frequencies. This was first followed by a millimetric and then by a radio outburst, which peaked in February 2006. Aims. In this paper we report on follow-up observations to study the multiwavelength emission in the post-outburst phase. Methods. Radio, near-infrared, and optical monitoring was performed by the Whole Earth Blazar Telescope (WEBT) collaboration in the 2006-2007 observing season. XMM-Newton observations on July 2-3 and December 18-19, 2006 added information on the X-ray and UV states of the source. Results. The source was in a faint state. The radio flux at the higher frequencies showed a fast decreasing trend, which represents the tail of the big radio outburst. It was followed by a quiescent state, common at all radio frequencies. In contrast, moderate activity characterized the near-IR and optical light curves, with a progressive increase of the variability amplitude with increasing wavelength. We ascribe this redder-when-brighter behaviour to the presence of a ""little blue bump"" due to line emission from the broad line region, which is clearly visible in the source spectral energy distribution (SED) during faint states. Moreover, the data from the XMM- Newton Optical Monitor reveal a rise of the SED in the ultraviolet, suggesting the existence of a "" big blue bump"" due to thermal emission from the accretion disc. The X-ray spectra are well fitted with a power- law model with photoelectric absorption, possibly larger than the Galactic one. However, the comparison with previous X-ray observations would imply that the amount of absorbing matter is variable. Alternatively, the intrinsic X-ray spectrum presents a curvature, which may depend on the X-ray brightness. In this case, two scenarios are possible. i) There is no extra absorption, and the X-ray spectrum hardens at low energies, the hardening being more evident in bright states; ii) there is a constant amount of extra absorption, likely in the quasar environment, and the X-ray spectrum softens at low energies, at least in faint X-ray states. This softening might be the result of a flux contribution by the high-frequency tail of the big blue bump.
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- Blinov, D., et al.
(author)
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The RoboPol sample of optical polarimetric standards
- 2023
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In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 677
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Journal article (peer-reviewed)abstract
- Context. Optical polarimeters are typically calibrated using measurements of stars with known and stable polarization parameters. However, there is a lack of such stars available across the sky. Many of the currently available standards are not suitable for medium and large telescopes due to their high brightness. Moreover, as we find, some of the polarimetric standards used are in fact variable or have polarization parameters that differ from their cataloged values. Aims. Our goal is to establish a sample of stable standards suitable for calibrating linear optical polarimeters with an accuracy down to 10-3 in fractional polarization. Methods. For 4 yr, we have been running a monitoring campaign of a sample of standard candidates comprised of 107 stars distributed across the northern sky. We analyzed the variability of the linear polarization of these stars, taking into account the non-Gaussian nature of fractional polarization measurements. For a subsample of nine stars, we also performed multiband polarization measurements. Results. We created a new catalog of 65 stars (see Table 2) that are stable, have small uncertainties of measured polarimetric parameters, and can be used as calibrators of polarimeters at medium and large telescopes.
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21. |
- Hovatta, T., et al.
(author)
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Magnetic field at a jet base: extreme Faraday rotation in 3C 273 revealed by ALMA
- 2019
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 623
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Journal article (peer-reviewed)abstract
- Aims. We studied the polarization behavior of the quasar 3C 273 over the 1 mm wavelength band at ALMA with a total bandwidth of 7.5 GHz across 223-243 GHz at 0.8 '' resolution, corresponding to 2.1 kpc at the distance of 3C 273. With these observations we were able to probe the optically thin polarized emission close to the jet base, and constrain the magnetic field structure. Methods. We computed the Faraday rotation measure using simple linear fitting and Faraday rotation measure synthesis. In addition, we modeled the broadband behavior of the fractional Stokes Q and U parameters (qu-fitting). The systematic uncertainties in the polarization observations at ALMA were assessed through Monte Carlo simulations. Results. We find the unresolved core of 3C 273 to be 1.8% linearly polarized. We detect a very high rotation measure (RM) of (5.0 +/- 0.3) x 10(5) rad m(-2) over the 1 mm band when assuming a single polarized component and an external RM screen. This results in a rotation of >40 degrees of the intrinsic electric vector position angle, which is significantly higher than typically assumed for millimeter wavelengths. The polarization fraction increases as a function of wavelength, which according to our qu-fitting could be due to multiple polarized components of different Faraday depth within our beam or to internal Faraday rotation. With our limited wavelength coverage we cannot distinguish between the cases, and additional multi-frequency and high angular resolution observations are needed to determine the location and structure of the magnetic field of the Faraday active region. Comparing our RM estimate with values obtained at lower frequencies, the RM increases as a function of observing frequency, following a power law with an index of 2.0 +/- 0.2, consistent with a sheath surrounding a conically expanding jet. We also detect similar to 0.2% circular polarization, although further observations are needed to confirm this result.
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22. |
- Jantti, H, et al.
(author)
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Human PSEN1 Mutant Glia Improve Spatial Learning and Memory in Aged Mice
- 2022
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In: Cells. - : MDPI AG. - 2073-4409. ; 11:24
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Journal article (peer-reviewed)abstract
- The PSEN1 ΔE9 mutation causes a familial form of Alzheimer’s disease (AD) by shifting the processing of amyloid precursor protein (APP) towards the generation of highly amyloidogenic Aβ42 peptide. We have previously shown that the PSEN1 ΔE9 mutation in human-induced pluripotent stem cell (iPSC)-derived astrocytes increases Aβ42 production and impairs cellular responses. Here, we injected PSEN1 ΔE9 mutant astrosphere-derived glial progenitors into newborn mice and investigated mouse behavior at the ages of 8, 12, and 16 months. While we did not find significant behavioral changes in younger mice, spatial learning and memory were paradoxically improved in 16-month-old PSEN1 ΔE9 glia-transplanted male mice as compared to age-matched isogenic control-transplanted animals. Memory improvement was associated with lower levels of soluble, but not insoluble, human Aβ42 in the mouse brain. We also found a decreased engraftment of PSEN1 ΔE9 mutant cells in the cingulate cortex and significant transcriptional changes in both human and mouse genes in the hippocampus, including the extracellular matrix-related genes. Overall, the presence of PSEN1 ΔE9 mutant glia exerted a more beneficial effect on aged mouse brain than the isogenic control human cells likely as a combination of several factors.
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- Carlsson, IB, et al.
(author)
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Kit ligand and c-Kit are expressed during early human ovarian follicular development and their interaction is required for the survival of follicles in long-term culture
- 2006
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In: Reproduction (Cambridge, England). - : Bioscientifica. - 1470-1626 .- 1741-7899. ; 131:4, s. 641-649
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Journal article (peer-reviewed)abstract
- The receptor tyrosine c-Kit and its cognate ligand, c-Kit ligand (KL, stem cell factor, SCF), are involved in ovarian follicular development in several animal species. We studied the expression of KL and c-Kit usingin situhybridization and immunohistochemistry in donated human ovarian cortical tissue. The KL transcripts were expressed in granulosa cells of primary follicles, whereas the expression of c-Kit was confined to the oocyte and granulosa cells in primary and secondary follicles. We employed an ovarian organ culture using firstly serum-containing and then serum-free medium to study the effects of KL and an anti-c-Kit antibody, ACK2, on the development and survival of ovarian folliclesin vitro. Culture of ovarian cortical slices for 7 days resulted in a 37% increase in the number of primary follicles and a 6% increase in secondary follicles. The proportion of viable follicles decreased in all cultures. The addition of KL (1, 10 and 100 ng/ml) into the culture media did not affect the developmental stages of the follicles or the proportion of atretic follicles. Inclusion of ACK2 (800 ng/ml) in the culture medium significantly increased the proportion of atretic follicles on days 7 (49 vs 28% in control cultures) and 14 (62 vs 38%) of culture. In conclusion, c-Kit and KL are expressed in human ovaries during follicular development. Blocking the c-Kit receptor induces follicular atresia. The KL/c-Kit signaling system is likely to control the survival of human ovarian follicles during early follicular development.
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- D'Ammando, F., et al.
(author)
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Multiwavelength observations of the gamma-ray-emitting narrow-line Seyfert 1 PMN J0948+0022 in 2011
- 2014
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 438:4, s. 3521-3534
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Journal article (peer-reviewed)abstract
- We report on radio-to-gamma-ray observations during 2011 May-September of PMN J0948+0022, the first narrow-line Seyfert 1 (NLSy1) galaxy detected in gamma-rays by Fermi-Large Area Telescope. Strong variability was observed in gamma-rays, with two flaring periods peaking on 2011 June 20 and July 28. The variability observed in optical and near-infrared seems to have no counterpart in gamma-rays. This different behaviour could be related to a bending and inhomogeneous jet or a turbulent extreme multicell scenario. The radio spectra showed a variability pattern typical of relativistic jets. The XMM spectrum shows that the emission from the jet dominates above similar to 2 keV, while a soft X-ray excess is evident in the low-energy part of the X-ray spectrum. Models where the soft emission is partly produced by blurred reflection or Comptonization of the thermal disc emission provide good fits to the data. The X-ray spectral slope is similar to that found in radio-quiet NLSy1, suggesting that a standard accretion disc is present, as expected from the high accretion rate. Except for the soft X-ray excess, unusual in jet-dominated active galactic nuclei, PMN J0948+0022, shows all characteristics of the blazar class.
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- Hovatta, T., et al.
(author)
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Optical polarization of high-energy BL Lacertae objects
- 2016
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In: Monthly Notices of the Royal Astronomical Society. - : EDP Sciences. - 0035-8711 .- 1365-2966. ; 596
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Journal article (peer-reviewed)abstract
- Context. We investigate the optical polarization properties of high-energy BL Lac objects using data from the RoboPol blazar monitoring program and the Nordic Optical Telescope. Aims: We wish to understand if there are differences between the BL Lac objects that have been detected with the current-generation TeV instruments and those objects that have not yet been detected. Methods: We used a maximum-likelihood method to investigate the optical polarization fraction and its variability in these sources. In order to study the polarization position angle variability, we calculated the time derivative of the electric vector position angle (EVPA) change. We also studied the spread in the Stokes Q/I-U/I plane and rotations in the polarization plane. Results: The mean polarization fraction of the TeV-detected BL Lacs is 5%, while the non-TeV sources show a higher mean polarization fraction of 7%. This difference in polarization fraction disappears when the dilution by the unpolarized light of the host galaxy is accounted for. The TeV sources show somewhat lower fractional polarization variability amplitudes than the non-TeV sources. Also the fraction of sources with a smaller spread in the Q/I-U/I plane and a clumped distribution of points away from the origin, possibly indicating a preferred polarization angle, is larger in the TeV than in the non-TeV sources. These differences between TeV and non-TeV samples seem to arise from differences between intermediate and high spectral peaking sources instead of the TeV detection. When the EVPA variations are studied, the rate of EVPA change is similar in both samples. We detect significant EVPA rotations in both TeV and non-TeV sources, showing that rotations can occur in high spectral peaking BL Lac objects when the monitoring cadence is dense enough. Our simulations show that we cannot exclude a random walk origin for these rotations. Conclusions: These results indicate that there are no intrinsic differences in the polarization properties of the TeV-detected and non-TeV-detected high-energy BL Lac objects. This suggests that the polarization properties are not directly related to the TeV-detection, but instead the TeV loudness is connected to the general flaring activity, redshift, and the synchrotron peak location.
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