| 1. |
- Kanoni, Stavroula, et al.
(author)
-
Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
-
In: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
-
Journal article (peer-reviewed)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
|
|
| 2. |
- Chown, Ryan, et al.
(author)
-
PDRs4All: IV. An embarrassment of riches: Aromatic infrared bands in the Orion Bar
- 2024
-
In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 685
-
Journal article (peer-reviewed)abstract
- Context. Mid-infrared observations of photodissociation regions (PDRs) are dominated by strong emission features called aromatic infrared bands (AIBs). The most prominent AIBs are found at 3.3, 6.2, 7.7, 8.6, and 11.2 µm. The most sensitive, highest-resolution infrared spectral imaging data ever taken of the prototypical PDR, the Orion Bar, have been captured by JWST. These high-quality data allow for an unprecedentedly detailed view of AIBs. Aims. We provide an inventory of the AIBs found in the Orion Bar, along with mid-IR template spectra from five distinct regions in the Bar: the molecular PDR (i.e. the three H2 dissociation fronts), the atomic PDR, and the H II region. Methods. We used JWST NIRSpec IFU and MIRI MRS observations of the Orion Bar from the JWST Early Release Science Program, PDRs4All (ID: 1288). We extracted five template spectra to represent the morphology and environment of the Orion Bar PDR. We investigated and characterised the AIBs in these template spectra. We describe the variations among them here. Results. The superb sensitivity and the spectral and spatial resolution of these JWST observations reveal many details of the AIB emission and enable an improved characterization of their detailed profile shapes and sub-components. The Orion Bar spectra are dominated by the well-known AIBs at 3.3, 6.2, 7.7, 8.6, 11.2, and 12.7 µm with well-defined profiles. In addition, the spectra display a wealth of weaker features and sub-components. The widths of many AIBs show clear and systematic variations, being narrowest in the atomic PDR template, but showing a clear broadening in the H II region template while the broadest bands are found in the three dissociation front templates. In addition, the relative strengths of AIB (sub-)components vary among the template spectra as well. All AIB profiles are characteristic of class A sources as designated by Peeters (2022, A&A, 390, 1089), except for the 11.2 µm AIB profile deep in the molecular zone, which belongs to class B11.2. Furthermore, the observations show that the sub-components that contribute to the 5.75, 7.7, and 11.2 µm AIBs become much weaker in the PDR surface layers. We attribute this to the presence of small, more labile carriers in the deeper PDR layers that are photolysed away in the harsh radiation field near the surface. The 3.3/11.2 AIB intensity ratio decreases by about 40% between the dissociation fronts and the H II region, indicating a shift in the polycyclic aromatic hydrocarbon (PAH) size distribution to larger PAHs in the PDR surface layers, also likely due to the effects of photochemistry. The observed broadening of the bands in the molecular PDR is consistent with an enhanced importance of smaller PAHs since smaller PAHs attain a higher internal excitation energy at a fixed photon energy. Conclusions. Spectral-imaging observations of the Orion Bar using JWST yield key insights into the photochemical evolution of PAHs, such as the evolution responsible for the shift of 11.2 µm AIB emission from class B11.2 in the molecular PDR to class A11.2 in the PDR surface layers. This photochemical evolution is driven by the increased importance of FUV processing in the PDR surface layers, resulting in a “weeding out” of the weakest links of the PAH family in these layers. For now, these JWST observations are consistent with a model in which the underlying PAH family is composed of a few species: the so-called ‘grandPAHs’.
|
|
| 3. |
- Habart, Emilie, et al.
(author)
-
PDRs4All II. JWST’s NIR and MIR imaging view of the Orion Nebula
- 2024
-
In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 685
-
Journal article (peer-reviewed)abstract
- Context. The James Webb Space Telescope (JWST) has captured the most detailed and sharpest infrared (IR) images ever taken of the inner region of the Orion Nebula, the nearest massive star formation region, and a prototypical highly irradiated dense photo-dissociation region (PDR). Aims. We investigate the fundamental interaction of far-ultraviolet (FUV) photons with molecular clouds. The transitions across the ionization front (IF), dissociation front (DF), and the molecular cloud are studied at high-angular resolution. These transitions are relevant to understanding the effects of radiative feedback from massive stars and the dominant physical and chemical processes that lead to the IR emission that JWST will detect in many Galactic and extragalactic environments. Methods. We utilized NIRCam and MIRI to obtain sub-arcsecond images over ∼150′′ and 42′′ in key gas phase lines (e.g., Pa α, Br α, [FeII] 1.64 µm, H2 1–0 S(1) 2.12 µm, 0–0 S(9) 4.69 µm), aromatic and aliphatic infrared bands (aromatic infrared bands at 3.3–3.4 µm, 7.7, and 11.3 µm), dust emission, and scattered light. Their emission are powerful tracers of the IF and DF, FUV radiation field and density distribution. Using NIRSpec observations the fractional contributions of lines, AIBs, and continuum emission to our NIRCam images were estimated. A very good agreement is found for the distribution and intensity of lines and AIBs between the NIRCam and NIRSpec observations. Results. Due to the proximity of the Orion Nebula and the unprecedented angular resolution of JWST, these data reveal that the molecular cloud borders are hyper structured at small angular scales of ∼0.1–1′′ (∼0.0002–0.002 pc or ∼40–400 au at 414 pc). A diverse set of features are observed such as ridges, waves, globules and photoevaporated protoplanetary disks. At the PDR atomic to molecular transition, several bright features are detected that are associated with the highly irradiated surroundings of the dense molecular condensations and embedded young star. Toward the Orion Bar PDR, a highly sculpted interface is detected with sharp edges and density increases near the IF and DF. This was predicted by previous modeling studies, but the fronts were unresolved in most tracers. The spatial distribution of the AIBs reveals that the PDR edge is steep and is followed by an extensive warm atomic layer up to the DF with multiple ridges. A complex, structured, and folded H0/H2 DF surface was traced by the H2 lines. This dataset was used to revisit the commonly adopted 2D PDR structure of the Orion Bar as our observations show that a 3D “terraced” geometry is required to explain the JWST observations. JWST provides us with a complete view of the PDR, all the way from the PDR edge to the substructured dense region, and this allowed us to determine, in detail, where the emission of the atomic and molecular lines, aromatic bands, and dust originate. Conclusions. This study offers an unprecedented dataset to benchmark and transform PDR physico-chemical and dynamical models for the JWST era. A fundamental step forward in our understanding of the interaction of FUV photons with molecular clouds and the role of FUV irradiation along the star formation sequence is provided.
|
|
| 4. |
- Peeters, Els, et al.
(author)
-
PDRs4All: III. JWST's NIR spectroscopic view of the Orion Bar
- 2024
-
In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 685
-
Journal article (peer-reviewed)abstract
- Context. JWST has taken the sharpest and most sensitive infrared (IR) spectral imaging observations ever of the Orion Bar photodis-sociation region (PDR), which is part of the nearest massive star-forming region the Orion Nebula, and often considered to be the 'prototypical'strongly illuminated PDR. Aims. We investigate the impact of radiative feedback from massive stars on their natal cloud and focus on the transition from the H II region to the atomic PDR -crossing the ionisation front (IF) -, and the subsequent transition to the molecular PDR -crossing the dissociation front (DF). Given the prevalence of PDRs in the interstellar medium and their dominant contribution to IR radiation, understanding the response of the PDR gas to far-ultraviolet (FUV) photons and the associated physical and chemical processes is fundamental to our understanding of star and planet formation and for the interpretation of any unresolved PDR as seen by JWST. Methods. We used high-resolution near-IR integral field spectroscopic data from NIRSpec on JWST to observe the Orion Bar PDR as part of the PDRs4All JWST Early Release Science programme. We constructed a 3″ × 25″ spatio-spectral mosaic covering 0.97-5.27 μm at a spectral resolution R of ~2700 and an angular resolution of 0.075″-0.173″. To study the properties of key regions captured in this mosaic, we extracted five template spectra in apertures centred on the three H2 dissociation fronts, the atomic PDR, and the H II region. This wealth of detailed spatial-spectral information was analysed in terms of variations in the physical conditions-incident UV field, density, and temperature -of the PDR gas. Results. The NIRSpec data reveal a forest of lines including, but not limited to, He I, H I, and C I recombination lines; ionic lines (e.g. Fe III and Fe II); O I and N I fluorescence lines; aromatic infrared bands (AIBs, including aromatic CH, aliphatic CH, and their CD counterparts); pure rotational and ro-vibrational lines from H2; and ro-vibrational lines from HD, CO, and CH+, with most of them having been detected for the first time towards a PDR. Their spatial distribution resolves the H and He ionisation structure in the Huygens region, gives insight into the geometry of the Bar, and confirms the large-scale stratification of PDRs. In addition, we observed numerous smaller-scale structures whose typical size decreases with distance from θ1 Ori C and IR lines from C I, if solely arising from radiative recombination and cascade, reveal very high gas temperatures (a few 1000 K) consistent with the hot irradiated surface of small-scale dense clumps inside the PDR. The morphology of the Bar, in particular that of the H2 lines, reveals multiple prominent filaments that exhibit different characteristics. This leaves the impression of a 'terraced'transition from the predominantly atomic surface region to the CO-rich molecular zone deeper in. We attribute the different characteristics of the H2 filaments to their varying depth into the PDR and, in some cases, not reaching the C+/C/CO transition. These observations thus reveal what local conditions are required to drive the physical and chemical processes needed to explain the different characteristics of the DFs and the photochemical evolution of the AIB carriers. Conclusions. This study showcases the discovery space created by JWST to further our understanding of the impact radiation from young stars has on their natal molecular cloud and proto-planetary disk, which touches on star and planet formation as well as galaxy evolution.
|
|
| 5. |
- Butterworth, J., et al.
(author)
-
Les Houches 2013: Physics at TeV Colliders: Standard Model Working Group Report
- 2014
-
Conference paper (peer-reviewed)abstract
- This Report summarizes the proceedings of the 2013 Les Houches workshop on Physics at TeV Colliders. Session 1 dealt primarily with (1) the techniques for calculating standard model multi-leg NLO and NNLO QCD and NLO EW cross sections and (2) the comparison of those cross sections with LHC data from Run 1, and projections for future measurements in Run 2.
|
|
| 6. |
- Laguzzi, F., et al.
(author)
-
Role of Polyunsaturated Fat in Modifying Cardiovascular Risk Associated With Family History of Cardiovascular Disease : Pooled De Novo Results From 15 Observational Studies
- 2024
-
In: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 149:4, s. 305-316
-
Journal article (peer-reviewed)abstract
- BACKGROUND: It is unknown whether dietary intake of polyunsaturated fatty acids (PUFA) modifies the cardiovascular disease (CVD) risk associated with a family history of CVD. We assessed interactions between biomarkers of low PUFA intake and a family history in relation to long-term CVD risk in a large consortium.METHODS: Blood and tissue PUFA data from 40 885 CVD-free adults were assessed. PUFA levels ≤25th percentile were considered to reflect low intake of linoleic, alpha-linolenic, and eicosapentaenoic/docosahexaenoic acids (EPA/DHA). Family history was defined as having ≥1 first-degree relative who experienced a CVD event. Relative risks with 95% CI of CVD were estimated using Cox regression and meta-analyzed. Interactions were assessed by analyzing product terms and calculating relative excess risk due to interaction.RESULTS: After multivariable adjustments, a significant interaction between low EPA/DHA and family history was observed (product term pooled RR, 1.09 [95% CI, 1.02-1.16]; P=0.01). The pooled relative risk of CVD associated with the combined exposure to low EPA/DHA, and family history was 1.41 (95% CI, 1.30-1.54), whereas it was 1.25 (95% CI, 1.16-1.33) for family history alone and 1.06 (95% CI, 0.98-1.14) for EPA/DHA alone, compared with those with neither exposure. The relative excess risk due to interaction results indicated no interactions.CONCLUSIONS: A significant interaction between biomarkers of low EPA/DHA intake, but not the other PUFA, and a family history was observed. This novel finding might suggest a need to emphasize the benefit of consuming oily fish for individuals with a family history of CVD.
|
|
| 7. |
|
|
| 8. |
- Amare, Azmeraw T, et al.
(author)
-
Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.
- 2023
-
In: Molecular psychiatry. - 1476-5578. ; 28, s. 5251-5261
-
Journal article (peer-reviewed)abstract
- Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental healthdisorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P=9.8×10-12, R2=1.9%) and continuous (P=6.4×10-9, R2=2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P=3.9×10-4, R2=0.9%), but not for the continuous outcome (P=0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.
|
|
| 9. |
- Di Nitto, A., et al.
(author)
-
Study of Non-fusion Products in the 50Ti+249Cf Reaction
- 2018
-
In: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 784, s. 199-205
-
Journal article (peer-reviewed)abstract
- The isotopic distribution of nuclei produced in the 50Ti + 249Cf reaction has been studied at the gas-filled recoil separator TASCA at GSI Darmstadt, which separates ions according to differences in magnetic rigidity. The bombardment was performed at an energy around the Bass barrier and with the TASCA magnetic fields set for collecting fusion-evaporation reaction products. Fifty-three isotopes located “north-east” of 208Pb were identified as recoiling products formed in non-fusion channels of the reaction. These recoils were implanted with energies in two distinct ranges; besides one with higher energy, a significant low-energy contribution was identified. The latter observation was not expected to occur according to kinematics of the known types of reactions, namely quasi-elastic, multi-nucleon transfer, deep-inelastic collisions or quasifission. The present observations are discussed within the framework of two-body kinematics passing through the formation of a composite system.
|
|
| 10. |
- Khuyagbaatar, J., et al.
(author)
-
48Ca+249Bk Fusion Reaction Leading to Element Z=117: Long-Lived α-Decaying 270Db and Discovery of 266Lr
- 2014
-
In: Physical Review Letters. - 1079-7114. ; 112:17
-
Journal article (peer-reviewed)abstract
- The superheavy element with atomic number Z=117 was produced as an evaporation residue in the 48Ca+249Bk fusion reaction at the gas-filled recoil separator TASCA at GSI Darmstadt, Germany. The radioactive decay of evaporation residues and their α-decay products was studied using a detection setup that allowed measuring decays of single atomic nuclei with half-lives between sub-μs and a few days. Two decay chains comprising seven α decays and a spontaneous fission each were identified and are assigned to the isotope 294-117 and its decay products. A hitherto unknown α-decay branch in 270Db (Z=105) was observed, which populated the new isotope 266Lr (Z=103). The identification of the long-lived (T1/2=1.0+1.9−0.4 h) α-emitter 270Db marks an important step towards the observation of even more long-lived nuclei of superheavy elements located on an “island of stability.”
|
|
| 11. |
- Khuyagbaatar, J., et al.
(author)
-
Fusion reaction 48Ca + 249Bk leading to formation of the element Ts (Z=117)
- 2019
-
In: Physical Review C. - 2469-9985. ; 99:5
-
Journal article (peer-reviewed)abstract
- The heaviest currently known nuclei, which have up to 118 protons, have been produced in 48Ca induced reactions with actinide targets. Among them, the element tennessine (Ts), which has 117 protons, has been synthesized by fusing 48Ca with the radioactive target 249Bk, which has a half-life of 327 d. The experiment was performed at the gas-filled recoil separator TASCA. Two long and two short α decay chains were observed. The long chains were attributed to the decay of 294Ts. The possible origin of the short-decay chains is discussed in comparison with the known experimental data. They are found to fit with the decay chain patterns attributed to 293Ts. The present experimental results confirm the previous findings at the Dubna Gas-Filled Recoil Separator on the decay chains originating from the nuclei assigned to Ts.
|
|
| 12. |
- Khuyagbaatar, J., et al.
(author)
-
Search for elements 119 and 120
- 2020
-
In: Physical Review C. - 2469-9985. ; 102:6
-
Journal article (peer-reviewed)abstract
- A search for production of the superheavy elements with atomic numbers 119 and 120 was performed in the 50Ti+249Bk and 50Ti+249Cf fusion-evaporation reactions, respectively, at the gas-filled recoil separator TASCA at GSI Darmstadt, Germany. Over four months of irradiation, the 249Bk target partially decayed into 249Cf, which allowed for a simultaneous search for both elements. Neither was detected at cross-section sensitivity levels of 65 and 200 fb for the 50Ti+249Bk and 50Ti+249Cf reactions, respectively, at a midtarget beam energy of Elab = 281.5 MeV. The nonobservation of elements 119 and 120 is discussed within the concept of fusion-evaporation reactions including various theoretical predictions on the fission-barrier heights of superheavy nuclei in the region of the island of stability.
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
- Buunen, M, et al.
(author)
-
COLOR II. A randomized clinical trial comparing laparoscopic and open surgery for rectal cancer.
- 2009
-
In: Danish medical bulletin. - 1603-9629 .- 0907-8916. ; 56:2, s. 89-91
-
Journal article (peer-reviewed)abstract
- INTRODUCTION: Laparoscopic resection of rectal cancer has been proven efficacious but morbidity and oncological outcome need to be investigated in a randomized clinical trial. Trial design: Non-inferiority randomized clinical trial. METHODS: The COLOR II trial is an ongoing international randomized clinical trial. Currently 27 hospitals from Europe, South Korea and Canada are including patients. The primary endpoint is loco-regional recurrence rate three years post-operatively. Secondary endpoints cover quality of life, overall and disease free survival, post-operative morbidity and health economy analysis. RESULTS: By July 2008, 27 hospitals from the Netherlands, Belgium, Germany, Sweden, Spain, Denmark, South Korea and Canada had included 739 patients. The intra-operative conversion rate in the laparoscopic group was 17%. Distribution of age, location of the tumor and radiotherapy were equal in both treatment groups. Most tumors are located in the mid-rectum (41%). CONCLUSION: Laparoscopic surgery in the treatment of rectal cancer is feasible. The results and safety of laparoscopic surgery in the treatment of rectal cancer remain unknown, but are subject of interim analysis within the COLOR II trial. Completion of inclusion is expected by the end of 2009. Trial registration: Clinicaltrials.gov, identifier: NCT00297791 (www.clinicaltrials.gov).
|
|
| 18. |
- Cox, D. M., et al.
(author)
-
Spectroscopy along flerovium decay chains. II. Fine structure in odd-A 289Fl
- 2023
-
In: Physical Review C. - 2469-9985. ; 107:2
-
Journal article (peer-reviewed)abstract
- Fifteen correlated α-decay chains starting from the odd-A superheavy nucleus 289Fl were observed following the fusion-evaporation reaction 48Ca+244Pu. The results call for at least two parallel α-decay sequences starting from at least two different states of 289Fl. This implies that close-lying levels in nuclei along these chains have quite different spin-parity assignments. Further, observed α-electron and α-photon coincidences, as well as the α-decay fine structure along the decay chains, suggest a change in the ground-state spin assignment between 285Cn and 281Ds. Our experimental results, on the excited level structure of the heaviest odd-N nuclei to date, provide a direct testing ground for theory. This is illustrated by comparison with new nuclear structure calculations based on the symmetry-conserving configuration mixing theory.
|
|
| 19. |
- Götz, S., et al.
(author)
-
Rapid extraction of short-lived isotopes from a buffer gas cell for use in gas-phase chemistry experiments, Part II : On-line studies with short-lived accelerator-produced radionuclides
- 2021
-
In: Nuclear Instruments and Methods in Physics Research, Section B: Beam Interactions with Materials and Atoms. - : Elsevier BV. - 0168-583X. ; 507, s. 27-35
-
Journal article (peer-reviewed)abstract
- A novel combination of advanced gas-chromatography and detection systems coupled to a buffer-gas cell was characterized on-line to allow gas-phase chemical studies of accelerator-produced short-lived α-decaying mercury, francium, and astatine isotopes. These were produced in 40Ar- and 48Ca-induced nuclear fusion–evaporation reactions, subsequently isolated in the recoil separators MARS at Texas A&M University, USA, and TASCA at GSI Darmstadt, Germany, before being thermalized in a buffer-gas-stopping cell. From the latter, the nuclear reaction products were extracted into gas-phase chromatographic systems, suitable for registering α-decaying short-lived radionuclides, such as isotopes of superheavy elements. Efficiencies of 21(3)% for 204-209Fr were reached for the extraction into the optimized miniCOMPACT gas-chromatography setup, indicating that this technique enables the identification of isotopes of volatile as well as non-volatile elements. These studies guide the path towards chemical investigations of superheavy elements beyond flerovium, which are out of reach with currently used setups.
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
- Kalman, Janos L, et al.
(author)
-
Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study.
- 2019
-
In: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 21:1, s. 68-75
-
Journal article (peer-reviewed)abstract
- Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients.A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18years] vs adulthood [>18years]) or considered as a continuous measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with regression models.BD- and SCZ-PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment.The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype.
|
|
| 23. |
- Såmark-Roth, A., et al.
(author)
-
Spectroscopy along flerovium decay chains. III. Details on experiment, analysis, 282Cn, and spontaneous fission branches
- 2023
-
In: Physical Review C. - 2469-9985. ; 107:2
-
Journal article (peer-reviewed)abstract
- Flerovium isotopes (element Z = 114) were produced in the fusion-evaporation reactions 48Ca+242,244Pu and studied with an upgraded TASISpec decay station placed in the focal plane of the gas-filled separator TASCA at the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt, Germany. Twenty-nine flerovium decay chains were identified by means of correlated implantation, α decay, and spontaneous fission events. Data analysis aspects and statistical assessments, primarily based on measured rates of various events, which laid the foundation for the comprehensive spectroscopic information on the flerovium decay chains, are presented in detail. Various decay scenarios of an excited state observed in 282Cn are examined in depth with the help of GEANT4 simulations and assessed by predictions of beyond mean-field calculations including triaxial shape degrees of freedom. Previous, revised, and newly derived fission probabilities of even-even superheavy nuclei are compared with various theoretical predictions.
|
|
| 24. |
- Thust, S. C., et al.
(author)
-
Glioma imaging in Europe : A survey of 220 centres and recommendations for best clinical practice
- 2018
-
In: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 28:8, s. 3306-3317
-
Journal article (peer-reviewed)abstract
- Objectives: At a European Society of Neuroradiology (ESNR) Annual Meeting 2015 workshop, commonalities in practice, current controversies and technical hurdles in glioma MRI were discussed. We aimed to formulate guidance on MRI of glioma and determine its feasibility, by seeking information on glioma imaging practices from the European Neuroradiology community. Methods: Invitations to a structured survey were emailed to ESNR members (n=1,662) and associates (n=6,400), European national radiologists’ societies and distributed via social media. Results: Responses were received from 220 institutions (59% academic). Conventional imaging protocols generally include T2w, T2-FLAIR, DWI, and pre- and post-contrast T1w. Perfusion MRI is used widely (85.5%), while spectroscopy seems reserved for specific indications. Reasons for omitting advanced imaging modalities include lack of facility/software, time constraints and no requests. Early postoperative MRI is routinely carried out by 74% within 24–72 h, but only 17% report a percent measure of resection. For follow-up, most sites (60%) issue qualitative reports, while 27% report an assessment according to the RANO criteria. A minority of sites use a reporting template (23%). Conclusion: Clinical best practice recommendations for glioma imaging assessment are proposed and the current role of advanced MRI modalities in routine use is addressed. Key Points: • We recommend the EORTC-NBTS protocol as the clinical standard glioma protocol.• Perfusion MRI is recommended for diagnosis and follow-up of glioma.• Use of advanced imaging could be promoted with increased education activities.• Most response assessment is currently performed qualitatively.• Reporting templates are not widely used, and could facilitate standardisation.
|
|
| 25. |
- Yakushev, A., et al.
(author)
-
On the adsorption and reactivity of element 114, flerovium
- 2022
-
In: Frontiers in Chemistry. - : Frontiers Media SA. - 2296-2646. ; 10
-
Journal article (peer-reviewed)abstract
- Flerovium (Fl, element 114) is the heaviest element chemically studied so far. To date, its interaction with gold was investigated in two gas-solid chromatography experiments, which reported two different types of interaction, however, each based on the level of a few registered atoms only. Whereas noble-gas-like properties were suggested from the first experiment, the second one pointed at a volatile-metal-like character. Here, we present further experimental data on adsorption studies of Fl on silicon oxide and gold surfaces, accounting for the inhomogeneous nature of the surface, as it was used in the experiment and analyzed as part of the reported studies. We confirm that Fl is highly volatile and the least reactive member of group 14. Our experimental observations suggest that Fl exhibits lower reactivity towards Au than the volatile metal Hg, but higher reactivity than the noble gas Rn.
|
|
| 26. |
- Cox, D. M., et al.
(author)
-
Spectroscopic Tools Applied to Flerovium Decay Chains
- 2020
-
In: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 1643
-
Journal article (peer-reviewed)abstract
- An upgraded TASISpec setup, with the addition of a veto DSSD and the new Compex detector-germanium array, has been employed with the gas-filled recoil separator TASCA at the GSI Helmholtzzentrum für Schwerionenforschung Darmstadt, to study flerovium (element 114) decay chains. The detector upgrades along with development of new analytical techniques have improved the sensitivity of the TASISpec setup for measuring α-photon coincidences. These improvements have been assessed with test reactions. The reaction 48Ca+206,207Pb was used for verification of experimental parameters such as transmission to implantation DSSD and target-segment to α-decay correlations. The reaction 48Ca+ natHf was used to produce several short-lived nuclei with multiple-α decay chains to investigate pile-up event deconvolution.
|
|
| 27. |
- Düllmann, Ch. E., et al.
(author)
-
Production and Decay of Element 114: High Cross Sections and the New Nucleus 277Hs
- 2010
-
In: Physical Review Letters. - 1079-7114. ; 104:25
-
Journal article (peer-reviewed)abstract
- The fusion-evaporation reaction 244Pu(48Ca, 3-4n)288,289114 was studied at the new gas-filled recoil separator TASCA. Thirteen correlated decay chains were observed and assigned to the production and decay of 288,289114. At a compound nucleus excitation energy of E* = 39.8-43.9 MeV, the 4n evaporation channel cross section was 9.8(-3.1)(+3.9) pb. At E* = 36.1-39.5 MeV, that of the 3n evaporation channel was 8.0-(+7.4)(4.5) pb. In one of the 3n evaporation channel decay chains, a previously unobserved alpha branch in 281Ds was observed ( probability to be of random origin from background: 0.1%). This alpha decay populated the new nucleus 277Hs, which decayed by spontaneous fission after a lifetime of 4.5 ms.
|
|
| 28. |
- Ertel, D., et al.
(author)
-
Ultrastable, high-repetition-rate attosecond beamline for time-resolved XUV-IR coincidence spectroscopy
- 2023
-
In: Review of Scientific Instruments. - 0034-6748. ; 94:7
-
Journal article (peer-reviewed)abstract
- The implementation of attosecond photoelectron-photoion coincidence spectroscopy for the investigation of atomic and molecular dynamics calls for a high-repetition-rate driving source combined with experimental setups characterized by excellent stability for data acquisition over time intervals ranging from a few hours up to a few days. This requirement is crucial for the investigation of processes characterized by low cross sections and for the characterization of fully differential photoelectron(s) and photoion(s) angular and energy distributions. We demonstrate that the implementation of industrial-grade lasers, combined with a careful design of the delay line implemented in the pump-probe setup, allows one to reach ultrastable experimental conditions leading to an error in the estimation of the time delays of only 12 as over an acquisition time of 6.5 h. This result opens up new possibilities for the investigation of attosecond dynamics in simple quantum systems.
|
|
| 29. |
- Fisher, Michael J., et al.
(author)
-
Integrated molecular and clinical analysis of low-grade gliomas in children with neurofibromatosis type 1 (NF1)
- 2021
-
In: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 141:4, s. 605-617
-
Journal article (peer-reviewed)abstract
- Low-grade gliomas (LGGs) are the most common childhood brain tumor in the general population and in individuals with the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome. Surgical biopsy is rarely performed prior to treatment in the setting of NF1, resulting in a paucity of tumor genomic information. To define the molecular landscape of NF1-associated LGGs (NF1-LGG), we integrated clinical data, histological diagnoses, and multi-level genetic/genomic analyses on 70 individuals from 25 centers worldwide. Whereas, most tumors harbored bi-allelic NF1 inactivation as the only genetic abnormality, 11% had additional mutations. Moreover, tumors classified as non-pilocytic astrocytoma based on DNA methylation analysis were significantly more likely to harbor these additional mutations. The most common secondary alteration was FGFR1 mutation, which conferred an additional growth advantage in multiple complementary experimental murine Nf1 models. Taken together, this comprehensive characterization has important implications for the management of children with NF1-LGG, distinct from their sporadic counterparts.
|
|
| 30. |
- Forsberg, Ulrika, et al.
(author)
-
First Experiment at TASCA Towards X-Ray Fingerprinting of Element 115 Decay Chains
- 2012
-
In: Acta Physica Polonica. Series B: Elementary Particle Physics, Nuclear Physics, Statistical Physics, Theory of Relativity, Field Theory. - 0587-4254. ; 43:2, s. 305-311
-
Journal article (peer-reviewed)abstract
- To identify the atomic number of superheavy nuclei produced in Ca-48-induced fusion-evaporation reactions, an experiment aiming at measuring characteristic X-rays is being prepared at GSI, Darmstadt, Germany. The gas-filled separator TASCA will be employed, sending the residues towards the multi-coincidence detector setup TASISpec. Two ion-optical modes relying on differing magnetic polarities of the quadrupole magnets can be used at TASCA. New simulations and experimental tests of transmission and background suppression for these two focusing modes into TASISpec are presented.
|
|
| 31. |
- Forsberg, Ulrika, et al.
(author)
-
Spectroscopic Tools Applied to Element Z = 115 Decay Chains
- 2014
-
In: EPJ Web of Conferences. - : EDP Sciences. - 2100-014X .- 2101-6275. - 9782759811755 - 9782759811762 ; 66, s. 02036-02036
-
Conference paper (peer-reviewed)abstract
- Nuclides that are considered to be isotopes of element Z = 115 were produced in the reaction 48Ca + 243Am at the GSI Helmholtzzentrum für Schwerionenforschung Darmstadt. The detector setup TASISpec was used. It was mounted behind the gas-filled separator TASCA. Thirty correlated α-decay chains were found, and the energies of the particles were determined with high precision. Two important spectroscopic aspects of the offline data analysis are discussed in detail: the handling of digitized preamplified signals from the silicon strip detectors, and the energy reconstruction of particles escaping to upstream detectors relying on pixel-by-pixel dead-layer thicknesses.
|
|
| 32. |
- Khuyagbaatar, J., et al.
(author)
-
Fission in the landscape of heaviest elements: Some recent examples
- 2016
-
In: Nobel Symposium NS 160 – Chemistry and Physics of Heavy and Superheavy Elements. - : EDP Sciences. - 9782759890118 ; 131
-
Conference paper (peer-reviewed)abstract
- The fission process still remains a main factor that determines the stability of the atomic nucleus of heaviest elements. Fission half-lives vary over a wide range, 10^−19 to 10^24 s. Present experimental techniques for the synthesis of the superheavy elements that usually measure α-decay chains are sensitive only in a limited range of half-lives, often 10^5 to 10^3 s. In the past years, measurement techniques for very short-lived and very long-lived nuclei were significantly improved at the gas-filled recoil separator TASCA at GSI Darmstadt. Recently, several experimental studies of fission-related phenomena have successfully been performed. In this paper, results on 254−256Rf and 266Lr are presented and corresponding factors for retarding the fission process are discussed.
|
|
| 33. |
- Khuyagbaatar, J., et al.
(author)
-
New Short-Lived Isotope 221U and the Mass Surface Near N=126
- 2015
-
In: Physical Review Letters. - 1079-7114. ; 115:24
-
Journal article (peer-reviewed)abstract
- Two short-lived isotopes 221U and 222U were produced as evaporation residues in the fusion reaction 50Ti+176Yb at the gas-filled recoil separator TASCA. An α decay with an energy of Eα=9.31(5) MeV and half-life T1/2=4.7(7) μs was attributed to 222U. The new isotope 221U was identified in α-decay chains starting with Eα=9.71(5) MeV and T1/2=0.66(14) μs leading to known daughters. Synthesis and detection of these unstable heavy nuclei and their descendants were achieved thanks to a fast data readout system. The evolution of the N=126 shell closure and its influence on the stability of uranium isotopes are discussed within the framework of α-decay reduced width.
|
|
| 34. |
- Lindner, Thomas, et al.
(author)
-
Current state and guidance on arterial spin labeling perfusion MRI in clinical neuroimaging.
- 2023
-
In: Magnetic Resonance in Medicine. - : John Wiley & Sons. - 0740-3194 .- 1522-2594. ; 89:5, s. 2024-2047
-
Journal article (peer-reviewed)abstract
- This article focuses on clinical applications of arterial spin labeling (ASL) and is part of a wider effort from the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group to update and expand on the recommendations provided in the 2015 ASL consensus paper. Although the 2015 consensus paper provided general guidelines for clinical applications of ASL MRI, there was a lack of guidance on disease-specific parameters. Since that time, the clinical availability and clinical demand for ASL MRI has increased. This position paper provides guidance on using ASL in specific clinical scenarios, including acute ischemic stroke and steno-occlusive disease, arteriovenous malformations and fistulas, brain tumors, neurodegenerative disease, seizures/epilepsy, and pediatric neuroradiology applications, focusing on disease-specific considerations for sequence optimization and interpretation. We present several neuroradiological applications in which ASL provides unique information essential for making the diagnosis. This guidance is intended for anyone interested in using ASL in a routine clinical setting (i.e., on a single-subject basis rather than in cohort studies) building on the previous ASL consensus review.
|
|
| 35. |
- Mehlgarten, Constance, et al.
(author)
-
Elongator function in tRNA wobble uridine modification is conserved between yeast and plants
- 2010
-
In: Molecular Microbiology. - : Wiley. - 0950-382X .- 1365-2958. ; 76:5, s. 1082-1094
-
Journal article (peer-reviewed)abstract
- Based on studies in yeast and mammalian cells the Elongator complex has been implicated in functions as diverse as histone acetylation, polarized protein trafficking and tRNA modification. Here we show that Arabidopsis mutants lacking the Elongator subunit AtELP3/ELO3 have a defect in tRNA wobble uridine modification. Moreover, we demonstrate that yeast elp3 and elp1 mutants expressing the respective Arabidopsis Elongator homologues AtELP3/ELO3 and AtELP1/ELO2 assemble integer Elongator complexes indicating a high degree of structural conservation. Surprisingly, in vivo complementation studies based on Elongator-dependent tRNA nonsense suppression and zymocin tRNase toxin assays indicated that while AtELP1 rescued defects of a yeast elp1 mutant, the most conserved Elongator gene AtELP3, failed to complement an elp3 mutant. This lack of complementation is due to incompatibility with yeast ELP1 as coexpression of both plant genes in an elp1 elp3 yeast mutant restored Elongator’s tRNA modification function in vivo. Similarly, AtELP1, not ScELP1 also supported partial complementation by yeast-plant Elp3 hybrids suggesting that AtElp1 has less stringent sequence requirements for Elp3 than ScElp1. We conclude that yeast and plant Elongator share tRNA modification roles and propose that this function might be conserved in Elongator from all eukaryotic kingdoms of life.
|
|
| 36. |
|
|
| 37. |
- Paterson, Ross W, et al.
(author)
-
Serum and cerebrospinal fluid biomarker profiles in acute SARS-CoV-2-associated neurological syndromes.
- 2021
-
In: Brain communications. - : Oxford University Press (OUP). - 2632-1297. ; 3:3
-
Journal article (peer-reviewed)abstract
- Preliminary pathological and biomarker data suggest that SARS-CoV-2 infection can damage the nervous system. To understand what, where and how damage occurs, we collected serum and CSF from patients with COVID-19 and characterized neurological syndromes involving the PNS and CNS (n=34). We measured biomarkers of neuronal damage and neuroinflammation, and compared these with non-neurological control groups, which included patients with (n=94) and without (n=24) COVID-19. We detected increased concentrations of neurofilament light, a dynamic biomarker of neuronal damage, in the CSF of those with CNS inflammation (encephalitis and acute disseminated encephalomyelitis) [14800pg/ml (400, 32400)], compared to those with encephalopathy [1410pg/ml (756, 1446)], peripheral syndromes (Guillain-Barré syndrome) [740pg/ml (507, 881)] and controls [872pg/ml (654, 1200)]. Serum neurofilament light levels were elevated across patients hospitalized with COVID-19, irrespective of neurological manifestations. There was not the usual close correlation between CSF and serum neurofilament light, suggesting serum neurofilament light elevation in the non-neurological patients may reflect peripheral nerve damage in response to severe illness. We did not find significantly elevated levels of serum neurofilament light in community cases of COVID-19 arguing against significant neurological damage. Glial fibrillary acidic protein, a marker of astrocytic activation, was not elevated in the CSF or serum of any group, suggesting astrocytic activation is not a major mediator of neuronal damage in COVID-19.
|
|
| 38. |
- Prank, Marje, et al.
(author)
-
An operational model for forecasting ragweed pollen release and dispersion in Europe.
- 2013
-
In: Agricultural and Forest Meteorology. - : Elsevier BV. - 0168-1923. ; 182-183, s. 43-53
-
Journal article (peer-reviewed)abstract
- The paper considers the possibilities of modelling the release and dispersion of the pollen of common ragweed (Ambrosia artemisiifolia L.), a highly allergenic invasive weed, which is spreading through southern and central Europe. In order to provide timely warnings for the allergy sufferers, a model was developed for forecasting ragweed pollen concentrations in the air. The development was based on the system for integrated modelling of atmospheric composition (SILAM) and concentrated on spatio-temporal modelling of ragweed flowering season and pollen release, which constitutes the emission term. Evaluation of the new model against multi-annual ragweed pollen observations demonstrated that the model reproduces well the main ragweed pollen season in the areas with major plant presence, such as the Pannonian Plain, the Lyon area in France, the Milan region in Italy, Ukraine and southern Russia. The predicted start of the season is mostly within 3 days of the observed for the majority of stations in these areas. The temporal correlation between modelled and observed concentrations exceeds 0.6 for the bulk of the stations. Model application to the seasons of 2005–2011 indicated the regions with high ragweed pollen concentrations, in particular the areas where allergenic thresholds are exceeded. It is demonstrated that, due to long-range transport of pollen, high-concentration areas are substantially more extensive than the heavily infested territories.
|
|
| 39. |
|
|
| 40. |
- Ulfendahl, M., et al.
(author)
-
Mechanical response characteristics of the hearing organ in the low-frequency regions of the cochlea
- 1996
-
In: Journal of Neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 76:6, s. 3850-3862
-
Journal article (peer-reviewed)abstract
- 1. With the use of an in vitro preparation of the guinea pig temporal bone, in which the apical turns of the cochlea are exposed, the mechanical and electrical responses of the cochlea in the low-frequency regions were studied during sound stimulation. 2. The mechanical characteristics were investigated in the fourth and third turns of the cochlea with the use of laser heterodyne interferometry, which allows the vibratory responses of both sensory and supporting cells to be recorded. The electrical responses, which can be maintained for several hours, were recorded only in the most apical turn. 3. In the most apical turn, the frequency locations and shapes of the mechanical and electrical responses were very similar. 4. The shapes of the tuning curves and the spatial locations of the frequency maxima in the temporal bone preparation compared very favorably with published results from in vivo recordings of hair cell receptor potentials and sound-induced vibrations of the Reissner's membrane. 5. Compressive nonlinearities were present in both the mechanical and the electrical responses at moderate sound pressure levels. 6. The mechanical tuning changed along the length of the cochlea, the center frequencies in the fourth and third turns being approximately 280 and 570 Hz, respectively. 7. The mechanical responses of sensory and supporting cells were almost identical in shape but differed significantly in amplitude radially across the reticular lamina.
|
|
| 41. |
|
|
| 42. |
- Yakushev, A., et al.
(author)
-
First Study on Nihonium (Nh, Element 113) Chemistry at TASCA
- 2021
-
In: Frontiers in Chemistry. - : Frontiers Media SA. - 2296-2646. ; 9
-
Journal article (peer-reviewed)abstract
- Nihonium (Nh, element 113) and flerovium (Fl, element 114) are the first superheavy elements in which the 7p shell is occupied. High volatility and inertness were predicted for Fl due to the strong relativistic stabilization of the closed 7p1/2 sub-shell, which originates from a large spin-orbit splitting between the 7p1/2 and 7p3/2 orbitals. One unpaired electron in the outermost 7p1/2 sub-shell in Nh is expected to give rise to a higher chemical reactivity. Theoretical predictions of Nh reactivity are discussed, along with results of the first experimental attempts to study Nh chemistry in the gas phase. The experimental observations verify a higher chemical reactivity of Nh atoms compared to its neighbor Fl and call for the development of advanced setups. First tests of a newly developed detection device miniCOMPACT with highly reactive Fr isotopes assure that effective chemical studies of Nh are within reach.
|
|
