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- Abdalla, H., et al.
(författare)
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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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Ingår i: Journal of Cosmology and Astroparticle Physics. - : Institute of Physics Publishing (IOPP). - 1475-7516. ; :2
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Tidskriftsartikel (refereegranskat)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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- Sliz, E., et al.
(författare)
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Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
- 2023
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)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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- Abdo, A. A., et al.
(författare)
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Multi-wavelength observations of the flaring gamma-ray blazar 3C 66A in 2008 October
- 2011
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 726:1, s. 43-
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Tidskriftsartikel (refereegranskat)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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- Abdo, A. A., et al.
(författare)
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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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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 730:2, s. 101-
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Tidskriftsartikel (refereegranskat)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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- Ackermann, M., et al.
(författare)
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MULTIWAVELENGTH EVIDENCE FOR QUASI-PERIODIC MODULATION IN THE GAMMA-RAY BLAZAR PG 1553+113
- 2015
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Ingår i: Astrophysical Journal Letters. - : Institute of Physics (IOP). - 2041-8205 .- 2041-8213. ; 813:2
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Tidskriftsartikel (refereegranskat)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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- Albalushi, H, et al.
(författare)
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Laminin 521 Stabilizes the Pluripotency Expression Pattern of Human Embryonic Stem Cells Initially Derived on Feeder Cells
- 2018
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Ingår i: Stem cells international. - : Hindawi Limited. - 1687-966X .- 1687-9678. ; 2018, s. 7127042-
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Tidskriftsartikel (refereegranskat)abstract
- Human embryonic stem (hES) cells represent an important tool to study early cell development. The previously described use of human recombinant laminin (LN) 521 represented a step forward in generating clinically safe culture conditions. To test the short-term effect of LN521 on cultured hES cells, five male hES cell lines were cultured on human foreskin fibroblasts (hFFs), Matrigel, LN521, and LN121 and characterized by qPCR, immunofluorescence analysis, as well as their potential for three-germ layer differentiation. Variations in gene expression related to pluripotency, stemness, and testicular cells at different passages and culture conditions were evaluated by qPCR. All cell lines expressed pluripotency markers at protein and RNA level and were able to differentiate into cell types of the three germ layers after being cultured on LN521 for nine passages. Reduction in variation of pluripotency marker expression could be observed after culturing the cells on LN521 for nine passages. hES cells cultured on LN521 exhibited less differentiation, faster cell growth, and attachment when compared to hES cells cultured on LN121 or Matrigel. Our results indicate a positive effect of LN521 in stabilizing pluripotency gene expression and might be the first step towards more controllable and robust culture conditions for hES cells.
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- Carlsson, IB, et al.
(författare)
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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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Ingår i: Reproduction (Cambridge, England). - : Bioscientifica. - 1470-1626 .- 1741-7899. ; 131:4, s. 641-649
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Tidskriftsartikel (refereegranskat)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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- Wedenoja, S, et al.
(författare)
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A missense mutation in SLC26A3 is associated with human male subfertility and impaired activation of CFTR
- 2017
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1, s. 14208-
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Tidskriftsartikel (refereegranskat)abstract
- Chloride absorption and bicarbonate excretion through exchange by the solute carrier family 26 member 3 (SLC26A3) and cystic fibrosis transmembrane conductance regulator (CFTR) are crucial for many tissues including sperm and epithelia of the male reproductive tract. Homozygous SLC26A3 mutations cause congenital chloride diarrhea with male subfertility, while homozygous CFTR mutations cause cystic fibrosis with male infertility. Some homozygous or heterozygous CFTR mutations only manifest as male infertility. Accordingly, we studied the influence of SLC26A3 on idiopathic infertility by sequencing exons of SLC26A3 in 283 infertile and 211 control men. A heterozygous mutation c.2062 G > C (p.Asp688His) appeared in nine (3.2%) infertile men, and additionally, in two (0.9%) control men, whose samples revealed a sperm motility defect. The p.Asp688His mutation is localized in the CFTR-interacting STAS domain of SLC26A3 and enriched in Finland, showing a significant association with male infertility in comparison with 6,572 Finnish (P < 0.05) and over 120,000 global alleles (P < 0.0001) (ExAC database). Functional studies showed that while SLC26A3 is a strong activator of CFTR-dependent anion transport, SLC26A3-p.Asp688His mutant retains normal Cl−/HCO3− exchange activity but suppresses CFTR, despite unaffected domain binding and expression. These results suggest a novel mechanism for human male infertility─impaired anion transport by the coupled SLC26A3 and CFTR.
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- Altmäe, Signe, 1978-, et al.
(författare)
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Genetic predictors of controlled ovarian hyperstimulation : where do we stand today?
- 2011
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Ingår i: Human Reproduction Update. - : Oxford University Press (OUP). - 1355-4786 .- 1460-2369. ; 17:6, s. 813-828
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUNDNowadays, the use of IVF has improved the prospects of infertility treatment. The expected outcome of IVF depends greatly on the effectiveness of controlled ovarian hyperstimulation (COH), where exogenous gonadotrophins are used to induce folliculogenesis. The response to stimulation varies substantially among women and is difficult to predict. Several predictive markers of COH outcome have been proposed (e.g. maternal age and ovarian reserve), but the search for optimal predictors is ongoing. Pharmacogenetic studies demonstrate the effects of individual genetic variability on COH outcome and the potential for customizing therapy based on the patient's genome.METHODSMEDLINE, EMBASE, DARE, CINAHL and the Cochrane Library, and references from relevant articles were investigated up to February 2011 regarding any common genetic variation and COH/IVF outcome.RESULTSSeveral polymorphisms in genes involved in FSH signalling, estrogen biosynthesis, folliculogenesis, folate metabolism and other aspects influence the response to exogenous gonadotrophin administration, resulting in differences in COH and IVF outcomes. Nevertheless, the most studied polymorphism FSHR Asn680Ser is practically the only genetic marker, together with ESR1 PvuII T/C, that could be applied in clinical tests.CONCLUSIONSAlthough data are accumulating with evidence suggesting that the ovarian response to COH is mediated by various polymorphisms, the optimal biomarkers and the efficacy of the tests still remain to be evaluated.
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