| 1. |
|
|
| 2. |
- Niemi, MEK, et al.
(författare)
-
- 2021
-
swepub:Mat__t
|
|
| 3. |
- Joffrin, E., et al.
(författare)
-
Overview of the JET preparation for deuterium-tritium operation with the ITER like-wall
- 2019
-
Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
-
Forskningsöversikt (refereegranskat)abstract
- For the past several years, the JET scientific programme (Pamela et al 2007 Fusion Eng. Des. 82 590) has been engaged in a multi-campaign effort, including experiments in D, H and T, leading up to 2020 and the first experiments with 50%/50% D-T mixtures since 1997 and the first ever D-T plasmas with the ITER mix of plasma-facing component materials. For this purpose, a concerted physics and technology programme was launched with a view to prepare the D-T campaign (DTE2). This paper addresses the key elements developed by the JET programme directly contributing to the D-T preparation. This intense preparation includes the review of the physics basis for the D-T operational scenarios, including the fusion power predictions through first principle and integrated modelling, and the impact of isotopes in the operation and physics of D-T plasmas (thermal and particle transport, high confinement mode (H-mode) access, Be and W erosion, fuel recovery, etc). This effort also requires improving several aspects of plasma operation for DTE2, such as real time control schemes, heat load control, disruption avoidance and a mitigation system (including the installation of a new shattered pellet injector), novel ion cyclotron resonance heating schemes (such as the three-ions scheme), new diagnostics (neutron camera and spectrometer, active Alfven eigenmode antennas, neutral gauges, radiation hard imaging systems...) and the calibration of the JET neutron diagnostics at 14 MeV for accurate fusion power measurement. The active preparation of JET for the 2020 D-T campaign provides an incomparable source of information and a basis for the future D-T operation of ITER, and it is also foreseen that a large number of key physics issues will be addressed in support of burning plasmas.
|
|
| 4. |
- Abel, I, et al.
(författare)
-
Overview of the JET results with the ITER-like wall
- 2013
-
Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:10, s. 104002-
-
Tidskriftsartikel (refereegranskat)abstract
- Following the completion in May 2011 of the shutdown for the installation of the beryllium wall and the tungsten divertor, the first set of JET campaigns have addressed the investigation of the retention properties and the development of operational scenarios with the new plasma-facing materials. The large reduction in the carbon content (more than a factor ten) led to a much lower Z(eff) (1.2-1.4) during L- and H-mode plasmas, and radiation during the burn-through phase of the plasma initiation with the consequence that breakdown failures are almost absent. Gas balance experiments have shown that the fuel retention rate with the new wall is substantially reduced with respect to the C wall. The re-establishment of the baseline H-mode and hybrid scenarios compatible with the new wall has required an optimization of the control of metallic impurity sources and heat loads. Stable type-I ELMy H-mode regimes with H-98,H-y2 close to 1 and beta(N) similar to 1.6 have been achieved using gas injection. ELM frequency is a key factor for the control of the metallic impurity accumulation. Pedestal temperatures tend to be lower with the new wall, leading to reduced confinement, but nitrogen seeding restores high pedestal temperatures and confinement. Compared with the carbon wall, major disruptions with the new wall show a lower radiated power and a slower current quench. The higher heat loads on Be wall plasma-facing components due to lower radiation made the routine use of massive gas injection for disruption mitigation essential.
|
|
| 5. |
- Romanelli, F, et al.
(författare)
-
Overview of the JET results
- 2011
-
Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 51:9
-
Tidskriftsartikel (refereegranskat)abstract
- Since the last IAEA Conference JET has been in operation for one year with a programmatic focus on the qualification of ITER operating scenarios, the consolidation of ITER design choices and preparation for plasma operation with the ITER-like wall presently being installed in JET. Good progress has been achieved, including stationary ELMy H-mode operation at 4.5 MA. The high confinement hybrid scenario has been extended to high triangularity, lower ρ*and to pulse lengths comparable to the resistive time. The steady-state scenario has also been extended to lower ρ*and ν*and optimized to simultaneously achieve, under stationary conditions, ITER-like values of all other relevant normalized parameters. A dedicated helium campaign has allowed key aspects of plasma control and H-mode operation for the ITER non-activated phase to be evaluated. Effective sawtooth control by fast ions has been demonstrated with3He minority ICRH, a scenario with negligible minority current drive. Edge localized mode (ELM) control studies using external n = 1 and n = 2 perturbation fields have found a resonance effect in ELM frequency for specific q95values. Complete ELM suppression has, however, not been observed, even with an edge Chirikov parameter larger than 1. Pellet ELM pacing has been demonstrated and the minimum pellet size needed to trigger an ELM has been estimated. For both natural and mitigated ELMs a broadening of the divertor ELM-wetted area with increasing ELM size has been found. In disruption studies with massive gas injection up to 50% of the thermal energy could be radiated before, and 20% during, the thermal quench. Halo currents could be reduced by 60% and, using argon/deuterium and neon/deuterium gas mixtures, runaway electron generation could be avoided. Most objectives of the ITER-like ICRH antenna have been demonstrated; matching with closely packed straps, ELM resilience, scattering matrix arc detection and operation at high power density (6.2 MW m-2) and antenna strap voltages (42 kV). Coupling measurements are in very good agreement with TOPICA modelling. © 2011 IAEA, Vienna.
|
|
| 6. |
- Bécoulet, A., et al.
(författare)
-
Science and technology research and development in support to ITER and the Broader Approach at CEA
- 2013
-
Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:10
-
Tidskriftsartikel (refereegranskat)abstract
- In parallel to the direct contribution to the procurement phase of ITER and Broader Approach, CEA has initiated research & development programmes, accompanied by experiments together with a significant modelling effort, aimed at ensuring robust operation, plasma performance, as well as mitigating the risks of the procurement phase. This overview reports the latest progress in both fusion science and technology including many areas, namely the mitigation of superconducting magnet quenches, disruption-generated runaway electrons, edge-localized modes (ELMs), the development of imaging surveillance, and heating and current drive systems for steady-state operation. The WEST (W Environment for Steady-state Tokamaks) project, turning Tore Supra into an actively cooled W-divertor platform open to the ITER partners and industries, is presented.
|
|
| 7. |
- de Rojas, I., et al.
(författare)
-
Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
|
|
| 8. |
|
|
| 9. |
- Bellenguez, C, et al.
(författare)
-
New insights into the genetic etiology of Alzheimer's disease and related dementias
- 2022
-
Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
-
Tidskriftsartikel (refereegranskat)abstract
- Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
|
|
| 10. |
|
|
| 11. |
- Fecchio, Alan, et al.
(författare)
-
Global drivers of avian haemosporidian infections vary across zoogeographical regions
- 2021
-
Ingår i: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 30:12, s. 2393-2406
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: Macroecological analyses provide valuable insights into factors that influence how parasites are distributed across space and among hosts. Amid large uncertainties that arise when generalizing from local and regional findings, hierarchical approaches applied to global datasets are required to determine whether drivers of parasite infection patterns vary across scales. We assessed global patterns of haemosporidian infections across a broad diversity of avian host clades and zoogeographical realms to depict hotspots of prevalence and to identify possible underlying drivers. Location: Global. Time period: 1994–2019. Major taxa studied: Avian haemosporidian parasites (genera Plasmodium, Haemoproteus, Leucocytozoon and Parahaemoproteus). Methods: We amalgamated infection data from 53,669 individual birds representing 2,445 species world-wide. Spatio-phylogenetic hierarchical Bayesian models were built to disentangle potential landscape, climatic and biotic drivers of infection probability while accounting for spatial context and avian host phylogenetic relationships. Results: Idiosyncratic responses of the three most common haemosporidian genera to climate, habitat, host relatedness and host ecological traits indicated marked variation in host infection rates from local to global scales. Notably, host ecological drivers, such as migration distance for Plasmodium and Parahaemoproteus, exhibited predominantly varying or even opposite effects on infection rates across regions, whereas climatic effects on infection rates were more consistent across realms. Moreover, infections in some low-prevalence realms were disproportionately concentrated in a few local hotspots, suggesting that regional-scale variation in habitat and microclimate might influence transmission, in addition to global drivers. Main conclusions: Our hierarchical global analysis supports regional-scale findings showing the synergistic effects of landscape, climate and host ecological traits on parasite transmission for a cosmopolitan and diverse group of avian parasites. Our results underscore the need to account for such interactions, in addition to possible variation in drivers across regions, to produce the robust inference required to predict changes in infection risk under future scenarios.
|
|
| 12. |
- Cabrera, J., et al.
(författare)
-
The planetary system around HD 190622 (TOI-1054): Measuring the gas content of low-mass planets orbiting F-stars
- 2023
-
Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 675
-
Tidskriftsartikel (refereegranskat)abstract
- Context. Giant planets are known to dominate the long-term stability of planetary systems due to their prevailing gravitational interactions, but they are also thought to play an important role in planet formation. Observational constraints improve our understanding of planetary formation processes such as the delivery of volatile-rich planetesimals from beyond the ice line into the inner planetary system. Additional constraints may come from studies of the atmosphere, but almost all such studies of the atmosphere investigate the detection of certain species, and abundances are not routinely quantitatively measured. Aims. Accurate measurements of planetary bulk parameters-that is, mass and density-provide constraints on the inner structure and chemical composition of transiting planets. This information provides insight into properties such as the amounts of volatile species, which in turn can be related to formation and evolution processes. Methods. The Transiting Exoplanet Survey Satellite (TESS) reported a planetary candidate around HD 190622 (TOI-1054), which was subsequently validated and found to merit further characterization with photometric and spectroscopic facilities. The KESPRINT collaboration used data from the High Accuracy Radial Velocity Planet Searcher (HARPS) to independently confirm the planetary candidate, securing its mass, and revealing the presence of an outer giant planet in the system. The CHEOPS consortium invested telescope time in the transiting target in order to reduce the uncertainty on the radius, improving the characterization of the planet. Results. We present the discovery and characterization of the planetary system around HD 190622 (TOI-1054). This system hosts one transiting planet, which is smaller than Neptune (3.087-0.053+0.058REarth, 7.7 ± 1.0 MEarth) but has a similar bulk density (1.43 ± 0.21 g cm-3) and an orbital period of 16 days; and a giant planet, not known to be transiting, with a minimum mass of 227.0 ± 6.7 MEarth in an orbit with a period of 315 days. Conclusions. Our measurements constrain the structure and composition of the transiting planet. HD 190622b has singular properties among the known population of transiting planets, which we discuss in detail. Among the sub-Neptune-sized planets known today, this planet stands out because of its large gas content.
|
|
| 13. |
- Munch, Marie W., et al.
(författare)
-
Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia The COVID STEROID 2 Randomized Trial
- 2021
-
Ingår i: Journal of the American Medical Association (JAMA). - : AMER MEDICAL ASSOC. - 0098-7484 .- 1538-3598. ; 326:18, s. 1807-1817
-
Tidskriftsartikel (refereegranskat)abstract
- Question What is the effect of 12 mg vs 6 mg of dexamethasone on the number of days alive without life support at 28 days in patients with COVID-19 and severe hypoxemia? Findings In this randomized trial that included 1000 patients with COVID-19 and severe hypoxemia, treatment with 12 mg/d of dexamethasone resulted in 22.0 days alive without life support at 28 days compared with 20.5 days in those receiving 6 mg/d of dexamethasone. This difference was not statistically significant. Meaning Compared with 6 mg of dexamethasone, 12 mg of dexamethasone did not statistically significantly reduce the number of days alive without life support at 28 days. This multicenter randomized clinical trial compares the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. IMPORTANCE A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease. OBJECTIVE To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. DESIGN, SETTING, AND PARTICIPANTS A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021. INTERVENTIONS Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and >= 1 serious adverse reactions at 28 days). RESULTS Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]). CONCLUSIONS AND RELEVANCE Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference.
|
|
| 14. |
- Barragan, O., et al.
(författare)
-
The young HD 73583 (TOI-560) planetary system: two 10-M-circle plus mini-Neptunes transiting a 500-Myr-old, bright, and active K dwarf
- 2022
-
Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 514:2, s. 1606-1627
-
Tidskriftsartikel (refereegranskat)abstract
- We present the discovery and characterization of two transiting planets observed by TESS in the light curves of the young and bright (V = 9.67) star HD73583 (TOI-560). We perform an intensive spectroscopic and photometric space- and ground-based follow-up in order to confirm and characterize the system. We found that HD73583 is a young (similar to 500 Myr) active star with a rotational period of 12.08 +/- 0.11 d, and a mass and radius of 0.73 +/- 0.02 M-circle dot and 0.65 +/- 0.02 R-circle dot, respectively. HD 73583 b (P-b = 6.3980420(-0.0000062)(+0.0000067 )d) has a mass and radius of 10.2(-3.1)(+3.4) M-circle plus and 2.79 +/- 0.10 R-circle plus, respectively, which gives a density of 2.58(-0.81)(+0.95) g cm(-3). HD 73583 c (P-c = 18.87974(-0.00074)(+0.00086) d) has a mass and radius of 9.7(-1.7)(+1.8) M-circle plus and 2.39(-0.09)(+0.10) R-circle plus, respectively, which translates to a density of 3.88(-0.80)(+0.91) g cm(-3). Both planets are consistent with worlds made of a solid core surrounded by a volatile envelope. Because of their youth and host star brightness, they both are excellent candidates to perform transmission spectroscopy studies. We expect ongoing atmospheric mass-loss for both planets caused by stellar irradiation. We estimate that the detection of evaporating signatures on H and He would be challenging, but doable with present and future instruments.
|
|
| 15. |
|
|
| 16. |
- Bonfanti, A., et al.
(författare)
-
TOI-1055 b: Neptunian planet characterised with HARPS, TESS, and CHEOPS
- 2023
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 671
-
Tidskriftsartikel (refereegranskat)abstract
- Context. TOI-1055 is a Sun-like star known to host a transiting Neptune-sized planet on a 17.5-day orbit (TOI-1055 b). Radial velocity (RV) analyses carried out by two independent groups using nearly the same set of HARPS spectra have provided measurements of planetary masses that differ by ∼2σ. Aims. Our aim in this work is to solve the inconsistency in the published planetary masses by significantly extending the set of HARPS RV measurements and employing a new analysis tool that is able to account and correct for stellar activity. Our further aim was to improve the precision on measurements of the planetary radius by observing two transits of the planet with the CHEOPS space telescope. Methods. We fit a skew normal function to each cross correlation function extracted from the HARPS spectra to obtain RV measurements and hyperparameters to be used for the detrending. We evaluated the correlation changes of the hyperparameters along the RV time series using the breakpoint technique. We performed a joint photometric and RV analysis using a Markov chain Monte Carlo scheme to simultaneously detrend the light curves and the RV time series. Results. We firmly detected the Keplerian signal of TOI-1055 b, deriving a planetary mass of Mb = 20.4-2.5+2.6 MO (∼12%). This value is in agreement with one of the two estimates in the literature, but it is significantly more precise. Thanks to the TESS transit light curves combined with exquisite CHEOPS photometry, we also derived a planetary radius of Rb = 3.490-0.064+0.070 RO (∼1.9%). Our mass and radius measurements imply a mean density of ρb = 2.65-0.35+0.37 g cm-3 (∼14%). We further inferred the planetary structure and found that TOI-1055 b is very likely to host a substantial gas envelope with a mass of 0.41-0.20+0.34 MO and a thickness of 1.05-0.29+0.30 RO. Conclusions. Our RV extraction combined with the breakpoint technique has played a key role in the optimal removal of stellar activity from the HARPS time series, enabling us to solve the tension in the planetary mass values published so far for TOI-1055 b.
|
|
| 17. |
|
|
| 18. |
- Douglas, K. B., et al.
(författare)
-
Complement receptor 2 polymorphisms associated with systemic lupus erythematosus modulate alternative splicing
- 2009
-
Ingår i: Genes and Immunity. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 10:5, s. 457-469
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic factors influence susceptibility to systemic lupus erythematosus (SLE). A recent family-based analysis in Caucasian and Chinese populations provided evidence for association of single-nucleotide polymorphisms (SNPs) in the complement receptor 2 (CR2/CD21) gene with SLE. Here we confirmed this result in a case-control analysis of an independent European-derived population including 2084 patients with SLE and 2853 healthy controls. A haplotype formed by the minor alleles of three CR2 SNPs (rs1048971, rs17615, rs4308977) showed significant association with decreased risk of SLE (30.4% in cases vs 32.6% in controls, P=0.016, OR=0.90 (0.82-0.98)). Two of these SNPs are in exon 10, directly 5' of an alternatively spliced exon preferentially expressed in follicular dendritic cells (FDC), and the third is in the alternatively spliced exon. Effects of these SNPs and a fourth SNP in exon 11 (rs17616) on alternative splicing were evaluated. We found that the minor alleles of these SNPs decreased splicing efficiency of exon 11 both in vitro and ex vivo. These findings further implicate CR2 in the pathogenesis of SLE and suggest that CR2 variants alter the maintenance of tolerance and autoantibody production in the secondary lymphoid tissues where B cells and FDCs interact.
|
|
| 19. |
- Kozyrev, Sergey V, et al.
(författare)
-
Functional variants in the B-cell gene BANK1 are associated with systemic lupus erythematosus
- 2008
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:2, s. 211-216
-
Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by production of autoantibodies and complex genetic inheritance(1-3). In a genome-wide scan using 85,042 SNPs, we identified an association between SLE and a nonsynonymous substitution (rs10516487, R61H) in the B-cell scaffold protein with ankyrin repeats gene, BANK1. We replicated the association in four independent case-control sets (combined P = 3.7 x 10(-10); OR = 1.38). We analyzed BANK1 cDNA and found two isoforms, one full-length and the other alternatively spliced and lacking exon 2 (Delta 2), encoding a protein without a putative IP3R-binding domain. The transcripts were differentially expressed depending on a branch point-site SNP, rs17266594, in strong linkage disequilibrium (LD) with rs10516487. A third associated variant was found in the ankyrin domain (rs3733197, A383T). Our findings implicate BANK1 as a susceptibility gene for SLE, with variants affecting regulatory sites and key functional domains. The disease-associated variants could contribute to sustained B cell-receptor signaling and B-cell hyperactivity characteristic of this disease.
|
|
| 20. |
- Magnusson, V., et al.
(författare)
-
Both risk alleles for Fc gamma RIIA and Fc gamma RIIIA are susceptibility factors for SLE : a unifying hypothesis
- 2004
-
Ingår i: Genes and Immunity. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 5:2, s. 130-137
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to analyze in families with SLE for the presence of linkage and the structure and transmission of haplotypes containing alleles for the low-affinity Fcgamma receptors. The Fcgamma receptor polymorphisms FcgammaRIIA-131R/H, FcgammaRIIIA176F/ V and FcgammaRIIIB-NA1/2 and a polymorphism in the FcgammaRIIB gene were genotyped with RFLP, allele-specific PCR or pyrosequencing. Individual SNPs and haplotypes were tested for linkage in multicase families and for association using contingency tables, transmission disequilibrium test and affected family-based control groups in Swedish and Mexican single-case families. No linkage or association could be detected using the FcgammaR polymorphisms in the multicase families. However, an association was found for both FcgammaRIIA-131R and IIIA-176F alleles in the single-case families, but not for IIIB or IIB. Allelic association to SLE was found for a haplotype that included both risk alleles, but not in haplotypes where only one or the other was present. We propose that FcgammaRIIA-131R and FcgammaRIIIA-176F are both risk alleles for SLE transmitted primarily, but not exclusively on a single major haplotype that behaves functionally in a situation similar to that of compound heterozygozity.
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
- Abellán, C., et al.
(författare)
-
Challenging Local Realism with Human Choices
- 2018
-
Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 557, s. 212-216
-
Tidskriftsartikel (refereegranskat)abstract
- A Bell test is a randomized trial that compares experimental observations against the philosophical worldview of local realism , in which the properties of the physical world are independent of our observation of them and no signal travels faster than light. A Bell test requires spatially distributed entanglement, fast and high-efficiency detection and unpredictable measurement settings. Although technology can satisfy the first two of these requirements, the use of physical devices to choose settings in a Bell test involves making assumptions about the physics that one aims to test. Bell himself noted this weakness in using physical setting choices and argued that human 'free will' could be used rigorously to ensure unpredictability in Bell tests. Here we report a set of local-realism tests using human choices, which avoids assumptions about predictability in physics. We recruited about 100,000 human participants to play an online video game that incentivizes fast, sustained input of unpredictable selections and illustrates Bell-test methodology. The participants generated 97,347,490 binary choices, which were directed via a scalable web platform to 12 laboratories on five continents, where 13 experiments tested local realism using photons, single atoms, atomic ensembles and superconducting devices. Over a 12-hour period on 30 November 2016, participants worldwide provided a sustained data flow of over 1,000 bits per second to the experiments, which used different human-generated data to choose each measurement setting. The observed correlations strongly contradict local realism and other realistic positions in bi-partite and tri-partite 12 scenarios. Project outcomes include closing the 'freedom-of-choice loophole' (the possibility that the setting choices are influenced by 'hidden variables' to correlate with the particle properties), the utilization of video-game methods for rapid collection of human-generated randomness, and the use of networking techniques for global participation in experimental science.
|
|
| 30. |
- Abelson, Anna-Karin, et al.
(författare)
-
No evidence of association between genetic variants of the PDCD1 ligands and SLE
- 2007
-
Ingår i: Genes and Immunity. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:1, s. 69-74
-
Tidskriftsartikel (refereegranskat)abstract
- PDCD1, an immunoreceptor involved in peripheral tolerance has previously been shown to be genetically associated with systemic lupus erythematosus (SLE). PDCD1 has two ligands whose genes are located in close proximity on chromosome 9p24. Our attention was drawn to these ligands after finding suggestive linkage to a marker (gata62f03, Z=2.27) located close to their genes in a genome scan of Icelandic families multiplex for SLE. Here, we analyse Swedish trios (N=149) for 23 single nucleotide polymorphisms (SNPs) within the genes of the PDCD1 ligands. Initially, indication of association to eight SNPs was observed, and these SNPs were therefore also analysed in Mexican trios (N=90), as well as independent sets of patients and controls from Sweden (152 patients, 448 controls) and Argentina (288 patients, 288 controls). We do not find support for genetic association to SLE. This is the first genetic study of SLE and the PDCD1 ligands and the lack of association in several cohorts implies that these genes are not major risk factors for SLE.
|
|
| 31. |
- Abelson, Anna-Karin, et al.
(författare)
-
STAT4 Associates with SLE through two independent effects that correlate with gene expression and act additively with IRF5 to increase risk
- 2009
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 68:11, s. 1746-1753
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To confirm and define the genetic association of STAT4 and systemic lupus erythematosus, investigate the possibility of correlations with differential splicing and/or expression levels, and genetic interaction with IRF5. METHODS: 30 tag SNPs were genotyped in an independent set of Spanish cases and controls. SNPs surviving correction for multiple tests were genotyped in 5 new sets of cases and controls for replication. STAT4 cDNA was analyzed by 5'-RACE PCR and sequencing. Expression levels were measured by quantitative PCR. RESULTS: In the fine-mapping, four SNPs were significant after correction for multiple testing, with rs3821236 and rs3024866 as the strongest signals, followed by the previously associated rs7574865, and by rs1467199. Association was replicated in all cohorts. After conditional regression analyses, two major independent signals represented by SNPs rs3821236 and rs7574865, remained significant across the sets. These SNPs belong to separate haplotype blocks. High levels of STAT4 expression correlated with SNPs rs3821236, rs3024866 (both in the same haplotype block) and rs7574865 but not with other SNPs. We also detected transcription of alternative tissue-specific exons 1, indicating presence of tissue-specific promoters of potential importance in the expression of STAT4. No interaction with associated SNPs of IRF5 was observed using regression analysis. CONCLUSIONS: These data confirm STAT4 as a susceptibility gene for SLE and suggest the presence of at least two functional variants affecting levels of STAT4. Our results also indicate that both genes STAT4 and IRF5 act additively to increase risk for SLE.
|
|
| 32. |
- Achá Alarcón, L., et al.
(författare)
-
Development and performance evaluation of an In-House ELISA for the detection of group A rotavirus in diarrheal stool samples from children and domestic South American camelids
- 2022
-
Ingår i: Journal of Virological Methods. - : Elsevier BV. - 0166-0934. ; 301
-
Tidskriftsartikel (refereegranskat)abstract
- Group A rotavirus (RVA) is a prevalent pathogen causing acute gastroenteritis (AGE) in young children and animals. We developed an in-house ELISA (ROTA-GeFeK) for RVA detection, based on the expression of native recombinant VP6 protein in E. coli. To detect the RVA antigen, rabbit polyclonal IgG antibodies, produced against rVP6,were used as capture and detector antibodies in a sandwich ELISA. To validate the ROTA-GeFeK, 252 stool samples from children with AGE, were evaluated by conventional RT-PCR and commercial ELISA. Compared to RT-PCR, the ROTAGeFeK had a sensitivity of 88.2 % and a specificity of 94.4 %. Total detection rates with the ROTA-GeFeK, commercial ELISA and RT-PCR were 58 %, 58 % and 64 % respectively. The limit of detection was equal to 2.1 × 10 4 CCID 50 of the RVA strain RIX4414. No cross-reactivity with other enteric pathogens was observed. The RVApositive samples detected by the assay belonged to a diversity of G and [P] genotypes.This assay displayed reactivity and was proved to be useful for the detection of RVA in diarrheal samples of domestic South American Camelids. We suggest that the ROTAGeFeK can be used as an epidemiologic tool for rotavirus surveillance and for RVA detection in other animal species. © 2021
|
|
| 33. |
- Acosta-Herrera, M, et al.
(författare)
-
Genome-wide meta-analysis reveals shared new loci in systemic seropositive rheumatic diseases
- 2019
-
Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:3, s. 311-319
-
Tidskriftsartikel (refereegranskat)abstract
- Immune-mediated inflammatory diseases (IMIDs) are heterogeneous and complex conditions with overlapping clinical symptoms and elevated familial aggregation, which suggests the existence of a shared genetic component. In order to identify this genetic background in a systematic fashion, we performed the first cross-disease genome-wide meta-analysis in systemic seropositive rheumatic diseases, namely, systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis and idiopathic inflammatory myopathies.MethodsWe meta-analysed ~6.5 million single nucleotide polymorphisms in 11 678 cases and 19 704 non-affected controls of European descent populations. The functional roles of the associated variants were interrogated using publicly available databases.ResultsOur analysis revealed five shared genome-wide significant independent loci that had not been previously associated with these diseases: NAB1, KPNA4-ARL14, DGQK, LIMK1 and PRR12. All of these loci are related with immune processes such as interferon and epidermal growth factor signalling, response to methotrexate, cytoskeleton dynamics and coagulation cascade. Remarkably, several of the associated loci are known key players in autoimmunity, which supports the validity of our results. All the associated variants showed significant functional enrichment in DNase hypersensitivity sites, chromatin states and histone marks in relevant immune cells, including shared expression quantitative trait loci. Additionally, our results were significantly enriched in drugs that are being tested for the treatment of the diseases under study.ConclusionsWe have identified shared new risk loci with functional value across diseases and pinpoint new potential candidate loci that could be further investigated. Our results highlight the potential of drug repositioning among related systemic seropositive rheumatic IMIDs.
|
|
| 34. |
- Alarcón, José Faúndez, et al.
(författare)
-
Role of streak secondary instabilities on free-stream turbulence-induced transition
- 2024
-
Ingår i: Journal of Fluid Mechanics. - : Cambridge University Press. - 0022-1120 .- 1469-7645. ; 988
-
Tidskriftsartikel (refereegranskat)abstract
- We study the stability of a zero-pressure gradient boundary layer subjected to free-stream disturbances by means of local stability analysis. The dataset under study corresponds to a direct numerical simulation (DNS) of a flat plate with a sharp leading edge in realistic wind tunnel conditions, with a turbulence level of 3.45 % at the leading edge. We present a method to track the convective evolution of the secondary instabilities of streaks by performing sequential stability calculations following the wave packet, connecting successive unstable eigenfunctions. A scattered nature, in time and space, of secondary instabilities is seen in the stability calculations. These instabilities can be detected before they reach finite amplitude in the DNS, preceding the nucleation of turbulent spots, and whose appearance is well correlated to the transition onset. This represents further evidence regarding the relevance of secondary instabilities of streaks in the bypass transition in realistic flow conditions. Consistent with the spatio-temporal nature of this problem, our approach allows us to integrate directly the local growth rates to obtain the spatial amplification ratio of the individual instabilities, where it is shown that instabilities reaching an -factor in the range [2.5,4] can be directly correlated to more than 65 % of the nucleation events. Interestingly, it is found that high amplification is not only attained by modes with high growth rates, but also by instabilities with sustained low growth rates for a long time.
|
|
| 35. |
|
|
| 36. |
|
|
| 37. |
- Brauko, Kalina M., et al.
(författare)
-
Marine Heatwaves, Sewage and Eutrophication Combine to Trigger Deoxygenation and Biodiversity Loss: A SW Atlantic Case Study
- 2020
-
Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Marine heatwaves (MHWs) are a major concern worldwide due to their increasing impacts in recent years, and these extreme events may trigger deoxygenation of coastal waters affected by sewage and eutrophication. Here we investigate the combined effects of MHWs and nutrient enrichment on the water quality and biodiversity of the Bay of Santa Catarina Island (Brazil). We used historical (1994–2020) sea surface temperature data from satellites and in situ physical, chemical and biological parameters to assess temporal trends. Oxygen levels have been decreasing whilst phosphorus levels have been increasing in the bay. During the austral summer of 2020 a regional sea surface heatwave was detected by satellite, lasting for 9 days and coinciding with our research cruise. During this period, seawater temperatures reached 29.8°C and anoxia was detected for the first time in the bay. A decrease in macrobenthic and phytoplankton community richness correlated with decreases in oxygen both through time and towards more urbanized areas. Overall, poor wastewater treatment is a key stressor that combined with MHWs to degrade coastal waters. Mitigation strategies are needed to minimize the impact of MHWs, including improved sewage treatment, restoration and conservation of wetlands and the use of nature-based technologies to promote coastal ecosystem recovery.
|
|
| 38. |
- Castillejo-Lopez, Casimiro, et al.
(författare)
-
Genetic and physical interaction of the B-cell systemic lupus erythematosus-associated genes BANK1 and BLK
- 2012
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 71:1, s. 136-142
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectivesAltered signalling in B cells is a predominant feature of systemic lupus erythematosus (SLE). The genes BANK1 and BLK were recently described as associated with SLE. BANK1 codes for a B-cell-specific cytoplasmic protein involved in B-cell receptor signalling and BLK codes for an Src tyrosine kinase with important roles in B-cell development. To characterise the role of BANK1 and BLK in SLE, a genetic interaction analysis was performed hypothesising that genetic interactions could reveal functional pathways relevant to disease pathogenesis.MethodsThe GPAT16 method was used to analyse the gene-gene interactions of BANK1 and BLK. Confocal microscopy was used to investigate co-localisation, and immunoprecipitation was used to verify the physical interaction of BANK1 and BLK.ResultsEpistatic interactions between BANK1 and BLK polymorphisms associated with SLE were observed in a discovery set of 279 patients and 515 controls from northern Europe. A meta-analysis with 4399 European individuals confirmed the genetic interactions between BANK1 and BLK. As BANK1 was identified as a binding partner of the Src tyrosine kinase LYN, the possibility that BANK1 and BLK could also show a protein-protein interaction was tested. The co-immunoprecipitation and co-localisation of BLK and BANK1 were demonstrated. In a Daudi cell line and primary naive B cells endogenous binding was enhanced upon B-cell receptor stimulation using anti-IgM antibodies.ConclusionsThis study shows a genetic interaction between BANK1 and BLK, and demonstrates that these molecules interact physically. The results have important consequences for the understanding of SLE and other autoimmune diseases and identify a potential new signalling pathway.
|
|
| 39. |
|
|
| 40. |
|
|
| 41. |
|
|
| 42. |
- Delgado-Vega, Angélica M., et al.
(författare)
-
Fine mapping and conditional analysis identify a new mutation in the autoimmunity susceptibility gene BLK that leads to reduced half-life of the BLK protein
- 2012
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 71:7, s. 1219-1226
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTo perform fine mapping of the autoimmunity susceptibility gene BLK and identify functional variants involved in systemic lupus erythematosus (SLE).MethodsGenotyping of 1163 European SLE patients and 1482 controls and imputation were performed covering the BLK gene with 158 single-nucleotide polymorphisms. Logistic regression analysis was done using PLINK and conditional analyses using GENABEL's test score. Transfections of BLK constructs on HEK293 cells containing the novel mutation or the wild type form were analysed for their effect on protein half-life using a protein stability assay, cycloheximide and western blot. CHiP-qPCR for detection of nuclear factor. B (NFkB) binding.ResultsFine mapping of BLK identified two independent genetic effects with functional consequences: one represented by two tightly linked associated haplotype blocks significantly enriched for NF kappa B-binding sites and numerous putative regulatory variants whose risk alleles correlated with low BLK mRNA levels. Binding of NFkBp50 and p65 to an associated 1.2 Kb haplotype segment was confirmed. A second independent genetic effect was represented by an Ala71Thr, low-frequency missense substitution with an OR = 2.31 (95% CI 1.38 to 3.86). The 71Thr decreased BLK protein half-life.ConclusionsThese results show that rare and common regulatory variants in BLK are involved in disease susceptibility and both, albeit independently, lead to reduced levels of BLK protein.
|
|
| 43. |
- Delgado-Vega, Angelica M., et al.
(författare)
-
Genetic associations in type I interferon related pathways with autoimmunity
- 2010
-
Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 12, s. S2-
-
Forskningsöversikt (refereegranskat)abstract
- Type I interferons play an outstanding role in innate and adaptive immunity by enhancing functions of dendritic cells, inducing differentiation of monocytes, promoting immunoglobulin class switching in B cells and stimulating effector functions of T cells. The increased production of IFN alpha/beta by plasmacytoid dendritic cells could be responsible for not only efficient antiviral defence, but it also may be a pathological factor in the development of various autoimmune disorders. The first evidence of a genetic link between type I interferons and autoimmune diseases was the observation that elevated IFN alpha activity is frequently detected in the sera of patients with systemic lupus erythematosus, and that this trait shows high heritability and familial aggregation in their first-degree healthy relatives. To date, a number of genes involved in interferon signalling have been associated with various autoimmune diseases. Patients with systemic lupus erythematosus, Sjogren's syndrome, dermatomyositis, psoriasis, and a fraction of patients with rheumatoid arthritis display a specific expression pattern of interferon-dependent genes in their leukocytes, termed the interferon signature. Here, in an attempt to understand the role of type I interferons in the pathogenesis of autoimmunity, we review the recent advances in the genetics of autoimmune diseases focusing on the association of genes involved in type I interferon pathways.
|
|
| 44. |
- Delgado-Vega, Angélica M., et al.
(författare)
-
Whole Exome Sequencing of Patients from Multicase Families with Systemic Lupus Erythematosus Identifies Multiple Rare Variants
- 2018
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 8775-
-
Tidskriftsartikel (refereegranskat)abstract
- In an effort to identify rare alleles associated with SLE, we have performed whole exome sequencing of the most distantly related affected individuals from two large Icelandic multicase SLE families followed by Ta targeted genotyping of additional relatives. We identified multiple rare likely pathogenic variants in nineteen genes co-segregating with the disease through multiple generations. Gene co-expression and protein-protein interaction analysis identified a network of highly connected genes comprising several loci previously implicated in autoimmune diseases. These genes were significantly enriched for immune system development, lymphocyte activation, DNA repair, and V(D)J gene recombination GO-categories. Furthermore, we found evidence of aggregate association and enrichment of rare variants at the FAM71E1/EMC10 locus in an independent set of 4,254 European SLE-cases and 4,349 controls. Our study presents evidence supporting that multiple rare likely pathogenic variants, in newly identified genes involved in known disease pathogenic pathways, segregate with SLE at the familial and population level.
|
|
| 45. |
- Farnocchia, Davide, et al.
(författare)
-
The Second International Asteroid Warning Network Timing Campaign: 2005 LW3
- 2023
-
Ingår i: The Planetary Science Journal. - : Institute of Physics (IOP). - 2632-3338. ; 4:11
-
Tidskriftsartikel (refereegranskat)abstract
- The Earth close approach of near-Earth asteroid 2005 LW3 on 2022 November 23 represented a good opportunity for a second observing campaign to test the timing accuracy of astrometric observation. With 82 participating stations, the International Asteroid Warning Network collected 1046 observations of 2005 LW3 around the time of the close approach. Compared to the previous timing campaign targeting 2019 XS, some individual observers were able to significantly improve the accuracy of their reported observation times. In particular, U.S. surveys achieved good timing performance. However, no broad, systematic improvement was achieved compared to the previous campaign, with an overall negative bias persisting among the different observers. The calibration of observing times and the mitigation of timing errors should be important future considerations for observers and orbit computers, respectively.
|
|
| 46. |
|
|
| 47. |
- Gandolfi, Davide, et al.
(författare)
-
The Transiting Multi-planet System HD 3167: A 5.7 M ⊕ Super-Earth and an 8.3 M ⊕ Mini-Neptune
- 2017
-
Ingår i: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 154:3, s. 123-
-
Tidskriftsartikel (refereegranskat)abstract
- HD 3167 is a bright (V = 8.9 mag) K0 V star observed by NASA’s K2 space mission during its Campaign 8. It has recently been found to host two small transiting planets, namely, HD 3167b, an ultra-short-period (0.96 days) super-Earth, and HD 3167c, a mini-Neptune on a relatively long-period orbit (29.85 days). Here we present an intensive radial velocity (RV) follow-up of HD 3167 performed with the FIES@NOT, HARPS@ESO-3.6 m, and HARPS-N@TNG spectrographs. We revise the system parameters and determine radii, masses, and densities of the two transiting planets by combining the K2 photometry with our spectroscopic data. With a mass of 5.69 ± 0.44 M⊕, a radius of 1.574 ± 0.054 R⊕, and a mean density of {8.00}-0.98+1.10 g cm^-3, HD 3167b joins the small group of ultra-short-period planets known to have rocky terrestrial compositions. HD 3167c has a mass of 8.33-1.85+1.79 M⊕ and a radius of 2.74}-0.100+0.106 R⊕, yielding a mean density of 2.21-0.53+0.56 g cm^-3, indicative of a planet with a composition comprising a solid core surrounded by a thick atmospheric envelope. The rather large pressure scale height (∼350 km) and the brightness of the host star make HD 3167c an ideal target for atmospheric characterization via transmission spectroscopy across a broad range of wavelengths. We found evidence of additional signals in the RV measurements but the currently available data set does not allow us to draw any firm conclusions on the origin of the observed variation.
|
|
| 48. |
- Georgoulas, George, et al.
(författare)
-
Principal component analysis of the start-up transient and hidden Markov modeling for broken rotor bar fault diagnosis in asynchronous machines
- 2013
-
Ingår i: Expert systems with applications. - : Elsevier BV. - 0957-4174 .- 1873-6793. ; 40:17, s. 7024-7033
-
Tidskriftsartikel (refereegranskat)abstract
- This article presents a novel computational method for the diagnosis of broken rotor bars in three phase asynchronous machines. The proposed method is based on Principal Component Analysis (PCA) and is applied to the stator’s three phase start-up current. The fault detection is easier in the start-up transient because of the increased current in the rotor circuit, which amplifies the effects of the fault in the stator’s current independently of the motor’s load. In the proposed fault detection methodology, PCA is initially utilized to extract a characteristic component, which reflects the rotor asymmetry caused by the broken bars. This component can be subsequently processed using Hidden Markov Models (HMMs). Two schemes, a multiclass and a one-class approach are proposed. The efficiency of the novel proposed schemes is evaluated by multiple experimental test cases. The results obtained indicate that the suggested approaches based on the combination of PCA and HMM, can be successfully utilized not only for identifying the presence of a broken bar but also for estimating the severity (number of broken bars) of the fault.
|
|
| 49. |
|
|
| 50. |
|
|
