| 1. |
- Mercuri, E., et al.
(författare)
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Safety and effectiveness of ataluren: comparison of results from the STRIDE Registry and CINRG DMD Natural History Study
- 2020
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Ingår i: Journal of Comparative Effectiveness Research. - : Becaris Publishing Limited. - 2042-6305 .- 2042-6313. ; 9:5, s. 341-360
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Strategic Targeting of Registries and International Database of Excellence (STRIDE) is an ongoing, multicenter registry providing real-world evidence regarding ataluren use in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD). We examined the effectiveness of ataluren + standard of care (SoC) in the registry versus SoC alone in the Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study (DNHS), DMD genotype-phenotype/-ataluren benefit correlations and ataluren safety. Patients & methods: Propensity score matching was performed to identify STRIDE and CINRG DNHS patients who were comparable in established disease progression predictors (registry cut-off date, 9 July 2018). Results & conclusion: Kaplan-Meier analyses demonstrated that ataluren + SoC significantly delayed age at loss of ambulation and age at worsening performance in timed function tests versus SoC alone (p <= 0.05). There were no DMD genotype-phenotype/ataluren benefit correlations. Ataluren was well tolerated. These results indicate that ataluren + SoC delays functional milestones of DMD progression in patients with nmDMD in routine clinical practice. ClinicalTrials.gov identifier: NCT02369731. ClinicalTrials.gov identifier: NCT02369731.
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| 2. |
- Lacour, S., et al.
(författare)
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The mass of β Pictoris c from β Pictoris b orbital motion
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 654
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Tidskriftsartikel (refereegranskat)abstract
- Aims. We aim to demonstrate that the presence and mass of an exoplanet can now be effectively derived from the astrometry of another exoplanet.Methods. We combined previous astrometry of β Pictoris b with a new set of observations from the GRAVITY interferometer. The orbital motion of β Pictoris b is fit using Markov chain Monte Carlo simulations in Jacobi coordinates. The inner planet, β Pictoris c, was also reobserved at a separation of 96 mas, confirming the previous orbital estimations.Results. From the astrometry of planet b only, we can (i) detect the presence of β Pictoris c and (ii) constrain its mass to 10.04(-3.10)(+4.53) M-Jup. If one adds the astrometry of β Pictoris c, the mass is narrowed down to 9.15(-1.06)(+1.08) M-Jup. The inclusion of radial velocity measurements does not affect the orbital parameters significantly, but it does slightly decrease the mass estimate to 8.89(-0.75)(+0.75) M-Jup. With a semimajor axis of 2.68 +/- 0.02 au, a period of 1221 +/- 15 days, and an eccentricity of 0.32 +/- 0.02, the orbital parameters of β Pictoris c are now constrained as precisely as those of β Pictoris b. The orbital configuration is compatible with a high-order mean-motion resonance (7:1). The impact of the resonance on the planets' dynamics would then be negligible with respect to the secular perturbations, which might have played an important role in the eccentricity excitation of the outer planet.
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| 3. |
- Ashizawa, T., et al.
(författare)
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Consensus-based care recommendations for adults with myotonic dystrophy type 1
- 2018
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Ingår i: Neurology-Clinical Practice. - : Ovid Technologies (Wolters Kluwer Health). - 2163-0402 .- 2163-0933. ; 8:6, s. 507-520
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Forskningsöversikt (refereegranskat)abstract
- Purpose of review Myotonic dystrophy type 1 (DM1) is a severe, progressive genetic disease that affects between 1 in 3,000 and 8,000 individuals globally. No evidence-based guideline exists to inform the care of these patients, and most do not have access to multidisciplinary care centers staffed by experienced professionals, creating a clinical care deficit. Recent findings The Myotonic Dystrophy Foundation (MDF) recruited 66 international clinicians experienced in DM1 patient care to develop consensus-based care recommendations. MDF created a 2-step methodology for the project using elements of the Single Text Procedure and the Nominal Group Technique. The process generated a 4-page Quick Reference Guide and a comprehensive, 55-page document that provides clinical care recommendations for 19 discrete body systems and/or care considerations. The resulting recommendations are intended to help standardize and elevate care for this patient population and reduce variability in clinical trial and study environments.
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| 4. |
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| 5. |
- Ayeni, O. R., et al.
(författare)
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Clinical and Radiographic Criteria Define "Acceptable" Surgical Correction of Hip Femoroacetabular Impingement Syndrome as Well as Postoperative Complications: An International Modified Delphi Study
- 2023
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Ingår i: Arthroscopy-the Journal of Arthroscopic and Related Surgery. - : Elsevier BV. - 0749-8063. ; 39:5, s. 1198-1210
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To develop recommendations for clinical and radiographic criteria to help define the "acceptable" surgical correction of femoroacetabular impingement syndrome (FAIS) and identify/define complications postoperatively. Methods: A 3-phase modified Delphi study was conducted involving a case-based survey; a Likert/multiple choice-based survey concerning radiographic and physical examination characteristics to help define FAIS correction, as well as the prevalence and definition of potential postoperative complications; and 2 consensus meetings. Results: Of the 75 experts invited, 54 completed the Phase I survey, 50 completed the Phase II survey (72% and 67% response rate), and 50 participated in the Phase III consensus meetings. For both typical and atypical (complex) cases, there was consensus that fluoroscopy with multiple views and dynamic hip assessment should be used intraoperatively (96% and 100%, respectively). For typical FAIS cases, the Expert Panel agreed that Dunn lateral and anteroposterior radiographs were the most important radiographs to evaluate the hip postoperatively (88%, consensus). When asked about evaluating the correction of cam impingement postoperatively, 87% voted that they use subjective evaluation of the "sphericity" of the femoral head. In the case of focal and global pincer-type FAIS, there was consensus that the reduction or elimination of the crossover sign (84%) and lateral center-edge angle (91%) were important to inform the extent of the FAIS correction. There was consensus for recommending further investigation at 6 months postoperatively if hip pain had increased/plateaued (92% agreed); that additional investigation and treatment should occur between 6 and 12 months (90% agreed); and that a reoperation may be recommended at 12 months or later following this investigation period (89% agreed). Conclusions: This consensus project identified the importance of using fluoroscopy and dynamic hip assessment intraoperatively; Dunn lateral and anteroposterior view radiographs postoperatively; evaluating the "sphericity" of the femoral head for cam-type correction and the use of dynamic hip assessment; reducing/eliminating the crossover sign for focal pincertype FAIS; evaluating the lateral center-edge angle for global pincer-type FAIS; and avoiding overcorrection of pincer-type FAIS. In cases in which postoperative hip pain increased/plateaued, further investigation and treatment is warranted between 6 and 12 months, and a reoperation may be recommended at a minimum of 12 months depending on the cause of the hip pain. Clinical Relevance: Hip arthroscopy surgeons have yet to reach a firm agreement on what constitutes an "acceptable" or "good" surgery radiographically and how they can achieve desired clinical outcomes. Although this was a comprehensive effort, more study is needed to determine therapeutic thresholds that can be universally applied.
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| 6. |
- Jones, G., et al.
(författare)
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Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition: n=48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease (HLA-DQA1p=4x10(-17)), arthritis (GDF5p=4x10(-13)), cell cycle control and cancer protection, regulation of transcription, and others involved in the development and maintenance of the musculoskeletal system. Using Mendelian randomization we report possible overlapping causal pathways, including diabetes susceptibility, haematological parameters, and the immune system. We conclude that muscle weakness in older adults has distinct mechanisms from continuous strength, including several pathways considered to be hallmarks of ageing. Muscle weakness has been associated with morbidity and mortality in older people. Here, the authors have investigated this trait further by performing a genome-wide meta-analysis of grip strength and Mendelian randomization to discover causal relationships between muscle weakness and other diseases.
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| 7. |
- Schoch, CL, et al.
(författare)
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Nuclear ribosomal internal transcribed spacer (ITS) region as a universal DNA barcode marker for Fungi
- 2012
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 109:16, s. 6241-6246
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Tidskriftsartikel (refereegranskat)abstract
- Six DNA regions were evaluated as potential DNA barcodes for Fungi, the second largest kingdom of eukaryotic life, by a multinational, multilaboratory consortium. The region of the mitochondrial cytochrome c oxidase subunit 1 used as the animal barcode was excluded as a potential marker, because it is difficult to amplify in fungi, often includes large introns, and can be insufficiently variable. Three subunits from the nuclear ribosomal RNA cistron were compared together with regions of three representative protein-coding genes (largest subunit of RNA polymerase II, second largest subunit of RNA polymerase II, and minichromosome maintenance protein). Although the protein-coding gene regions often had a higher percent of correct identification compared with ribosomal markers, low PCR amplification and sequencing success eliminated them as candidates for a universal fungal barcode. Among the regions of the ribosomal cistron, the internal transcribed spacer (ITS) region has the highest probability of successful identification for the broadest range of fungi, with the most clearly defined barcode gap between inter- and intraspecific variation. The nuclear ribosomal large subunit, a popular phylogenetic marker in certain groups, had superior species resolution in some taxonomic groups, such as the early diverging lineages and the ascomycete yeasts, but was otherwise slightly inferior to the ITS. The nuclear ribosomal small subunit has poor species-level resolution in fungi. ITS will be formally proposed for adoption as the primary fungal barcode marker to the Consortium for the Barcode of Life, with the possibility that supplementary barcodes may be developed for particular narrowly circumscribed taxonomic groups.
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| 8. |
- Sungnak, W., et al.
(författare)
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SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes
- 2020
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Ingår i: Nature Medicine. - : Nature Research. - 1078-8956 .- 1546-170X. ; 26:5, s. 681-687
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Tidskriftsartikel (refereegranskat)abstract
- We investigated SARS-CoV-2 potential tropism by surveying expression of viral entry-associated genes in single-cell RNA-sequencing data from multiple tissues from healthy human donors. We co-detected these transcripts in specific respiratory, corneal and intestinal epithelial cells, potentially explaining the high efficiency of SARS-CoV-2 transmission. These genes are co-expressed in nasal epithelial cells with genes involved in innate immunity, highlighting the cells’ potential role in initial viral infection, spread and clearance. The study offers a useful resource for further lines of inquiry with valuable clinical samples from COVID-19 patients and we provide our data in a comprehensive, open and user-friendly fashion at www.covid19cellatlas.org.
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| 9. |
- Woitowich, N. C., et al.
(författare)
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Structural basis for light control of cell development revealed by crystal structures of a myxobacterial phytochrome
- 2018
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Ingår i: Iucrj. - : International Union of Crystallography (IUCr). - 2052-2525. ; 5:Part 5, s. 619-634
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Tidskriftsartikel (refereegranskat)abstract
- Phytochromes are red-light photoreceptors that were first characterized in plants, with homologs in photosynthetic and non-photosynthetic bacteria known as bacteriophytochromes (BphPs). Upon absorption of light, BphPs interconvert between two states denoted Pr and Pfr with distinct absorption spectra in the red and far-red. They have recently been engineered as enzymatic photoswitches for fluorescent-marker applications in non-invasive tissue imaging of mammals. This article presents cryo- and room-temperature crystal structures of the unusual phytochrome from the non-photosynthetic myxobacterium Stigmatella aurantiaca (SaBphP1) and reveals its role in the fruitingbody formation of this photomorphogenic bacterium. SaBphP1 lacks a conserved histidine (His) in the chromophore-binding domain that stabilizes the Pr state in the classical BphPs. Instead it contains a threonine (Thr), a feature that is restricted to several myxobacterial phytochromes and is not evolutionarily understood. SaBphP1 structures of the chromophore binding domain (CBD) and the complete photosensory core module (PCM) in wild-type and Thr-to-His mutant forms reveal details of the molecular mechanism of the Pr/Pfr transition associated with the physiological response of this myxobacterium to red light. Specifically, key structural differences in the CBD and PCM between the wild-type and the Thr-to-His mutant involve essential chromophore contacts with proximal amino acids, and point to how the photosignal is transduced through the rest of the protein, impacting the essential enzymatic activity in the photomorphogenic response of this myxobacterium.
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| 10. |
- Tinetti, G., et al.
(författare)
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A chemical survey of exoplanets with ARIEL
- 2018
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Ingår i: Experimental Astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 46:1, s. 135-209
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Tidskriftsartikel (refereegranskat)abstract
- Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.
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| 11. |
- Young, William J., et al.
(författare)
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Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways
- 2022
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease. The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.
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| 12. |
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| 13. |
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| 14. |
- Henricson, E. K., et al.
(författare)
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The cooperative international neuromuscular research group Duchenne natural history study: Glucocorticoid treatment preserves clinically meaningful functional milestones and reduces rate of disease progression as measured by manual muscle testing and other commonly used clinical trial outcome measures
- 2013
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Ingår i: Muscle & Nerve. - : Wiley. - 0148-639X. ; 48:1, s. 55-67
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Glucocorticoid (GC) therapy in Duchenne muscular dystrophy (DMD) has altered disease progression, necessitating contemporary natural history studies. Methods: The Cooperative Neuromuscular Research Group (CINRG) DMD Natural History Study (DMD-NHS) enrolled 340 DMD males, ages 2-28 years. A comprehensive battery of measures was obtained. Results: A novel composite functional milestone scale scale showed clinically meaningful mobility and upper limb abilities were significantly preserved in GC-treated adolescents/young adults. Manual muscle test (MMT)-based calculations of global strength showed that those patients <10 years of age treated with steroids declined by 0.4 +/- 0.39 MMT unit/year, compared with -0.4 +/- 0.39 MMT unit/year in historical steroid-naive subjects. Pulmonary function tests (PFTs) were relatively preserved in steroid-treated adolescents. The linearity and magnitude of decline in measures were affected by maturational changes and functional status. Conclusions: In DMD, long-term use of GCs showed reduced strength loss and preserved functional capabilities and PFTs compared with previous natural history studies performed prior to the widespread use of GC therapy.
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| 15. |
- Sikkema, Lisa, et al.
(författare)
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An integrated cell atlas of the lung in health and disease
- 2023
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Ingår i: Nature Medicine. - : Springer Nature. - 1078-8956 .- 1546-170X. ; 29:6, s. 1563-1577
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Tidskriftsartikel (refereegranskat)abstract
- Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations of individual studies and capture the variability present in the population. Here we present the integrated Human Lung Cell Atlas (HLCA), combining 49 datasets of the human respiratory system into a single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents a consensus cell type re-annotation with matching marker genes, including annotations of rare and previously undescribed cell types. Leveraging the number and diversity of individuals in the HLCA, we identify gene modules that are associated with demographic covariates such as age, sex and body mass index, as well as gene modules changing expression along the proximal-to-distal axis of the bronchial tree. Mapping new data to the HLCA enables rapid data annotation and interpretation. Using the HLCA as a reference for the study of disease, we identify shared cell states across multiple lung diseases, including SPP1 + profibrotic monocyte-derived macrophages in COVID-19, pulmonary fibrosis and lung carcinoma. Overall, the HLCA serves as an example for the development and use of large-scale, cross-dataset organ atlases within the Human Cell Atlas.
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| 16. |
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| 17. |
- Young, WJ, et al.
(författare)
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Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease
- 2023
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1, s. 1411-
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Tidskriftsartikel (refereegranskat)abstract
- The 3-dimensional spatial and 2-dimensional frontal QRS-T angles are measures derived from the vectorcardiogram. They are independent risk predictors for arrhythmia, but the underlying biology is unknown. Using multi-ancestry genome-wide association studies we identify 61 (58 previously unreported) loci for the spatial QRS-T angle (N = 118,780) and 11 for the frontal QRS-T angle (N = 159,715). Seven out of the 61 spatial QRS-T angle loci have not been reported for other electrocardiographic measures. Enrichments are observed in pathways related to cardiac and vascular development, muscle contraction, and hypertrophy. Pairwise genome-wide association studies with classical ECG traits identify shared genetic influences with PR interval and QRS duration. Phenome-wide scanning indicate associations with atrial fibrillation, atrioventricular block and arterial embolism and genetically determined QRS-T angle measures are associated with fascicular and bundle branch block (and also atrioventricular block for the frontal QRS-T angle). We identify potential biology involved in the QRS-T angle and their genetic relationships with cardiovascular traits and diseases, may inform future research and risk prediction.
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| 18. |
- Abarenkov, Kessy, et al.
(författare)
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The UNITE database for molecular identification and taxonomic communication of fungi and other eukaryotes: sequences, taxa and classifications reconsidered
- 2024
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Ingår i: Nucleic Acids Research. - 0305-1048 .- 1362-4962. ; 52:D1, s. D791-D797
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Tidskriftsartikel (refereegranskat)abstract
- UNITE (https://unite.ut.ee) is a web-based database and sequence management environment for molecular identification of eukaryotes. It targets the nuclear ribosomal internal transcribed spacer (ITS) region and offers nearly 10 million such sequences for reference. These are clustered into similar to 2.4M species hypotheses (SHs), each assigned a unique digital object identifier (DOI) to promote unambiguous referencing across studies. UNITE users have contributed over 600 000 third-party sequence annotations, which are shared with a range of databases and other community resources. Recent improvements facilitate the detection of cross-kingdom biological associations and the integration of undescribed groups of organisms into everyday biological pursuits. Serving as a digital twin for eukaryotic biodiversity and communities worldwide, the latest release of UNITE offers improved avenues for biodiversity discovery, precise taxonomic communication and integration of biological knowledge across platforms. Graphical Abstract
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| 19. |
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| 20. |
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| 21. |
- Buder, S., et al.
(författare)
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The GALAH survey : An abundance, age, and kinematic inventory of the solar neighbourhood made with TGAS
- 2019
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Ingår i: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 624
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Tidskriftsartikel (refereegranskat)abstract
- The overlap between the spectroscopic Galactic Archaeology with HERMES (GALAH) survey and Gaia provides a high-dimensional chemodynamical space of unprecedented size. We present a first analysis of a subset of this overlap, of 7066 dwarf, turn-off, and subgiant stars. These stars have spectra from the GALAH survey and high parallax precision from the Gaia DR1 Tycho-Gaia Astrometric Solution. We investigate correlations between chemical compositions, ages, and kinematics for this sample. Stellar parameters and elemental abundances are derived from the GALAH spectra with the spectral synthesis code SPECTROSCOPY MADE EASY. We determine kinematics and dynamics, including action angles, from the Gaia astrometry and GALAH radial velocities. Stellar masses and ages are determined with Bayesian isochrone matching, using our derived stellar parameters and absolute magnitudes. We report measurements of Li, C, O, Na, Mg, Al, Si, K, Ca, Sc, Ti, V, Cr, Mn, Co, Ni, Cu, Zn, Y, as well as Ba and we note that we have employed non-LTE calculations for Li, O, Al, and Fe. We show that the use of astrometric and photometric data improves the accuracy of the derived spectroscopic parameters, especially log g. Focusing our investigation on the correlations between stellar age, iron abundance [Fe/H], and mean alpha-enhancement [alpha/Fe] of the magnitude-selected sample, we recover the result that stars of the high-a sequence are typically older than stars in the low-a sequence, the latter spanning iron abundances of -0.7 < [Fe/H] < +0.5. While these two sequences become indistinguishable in [alpha/Fe] vs. [Fe/H] at the metal-rich regime, we find that age can be used to separate stars from the extended high-a and the low-a sequence even in this regime. When dissecting the sample by stellar age, we find that the old stars (>8 Gyr) have lower angular momenta L-z than the Sun, which implies that they are on eccentric orbits and originate from the inner disc. Contrary to some previous smaller scale studies we find a continuous evolution in the high-alpha-sequence up to super-solar [Fe/H] rather than a gap, which has been interpreted as a separate "high-alpha metal-rich" population. Stars in our sample that are younger than 10 Gyr, are mainly found on the low alpha-sequence and show a gradient in L-z from low [Fe/H] > (L-z > L-z,L-circle dot) towards higher [Fe/H] (L-z < L-z,L-circle dot), which implies that the stars at the ends of this sequence are likely not originating from the close solar vicinity.
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| 22. |
- Duong, T. C., et al.
(författare)
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A hierarchical computational thermodynamic and kinetic approach to discontinuous precipitation in the U-Nb system
- 2015
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Ingår i: PTM 2015 - Proceedings of the International Conference on Solid-Solid Phase Transformations in Inorganic Materials 2015. - : International Conference on Solid-Solid Phase Transformations in Inorganic Materials. - 9780692437360 ; , s. 887-894
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Konferensbidrag (refereegranskat)abstract
- U-Nb alloys decompose via discontinuous precipitation (DP) over a broad range of aging conditions, adversely affecting their properties. The growth kinetics, lamellar spacing, and Nb partitioning have been measured, but the thermodynamic and kinetic factors underlying these specific transformation characteristics and reaction paths, vis-a-vis the monotectoid reaction, are not fully resolved. In this work, a hierarchical computational thermodynamic and kinetic approach was carried out to investigate DP. The hierarchical approach started with density-functional theory (DFT) investigations of ground-state formation energies of bcc-based U-Nb alloys. The estimated energetic data was then utilized as an imposed first-principles-based constraint to improve the consistency of the CALPHAD thermodynamic and, subsequently, kinetic assessments of U-Nb. Phasefield simulations were then carried out to study DP's microstructure evolution using the assessed CALPHAD thermodynamic and kinetic representations. Good agreement with experiments on different physical/length scales was achieved, which validates the present theoretical contributions to a better understanding of DP in U-Nb alloys.
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| 23. |
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| 24. |
- Muus, Christoph, et al.
(författare)
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Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics
- 2021
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:3, s. 546-559
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Tidskriftsartikel (refereegranskat)abstract
- Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2(+)TMPRSS2(+) cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention. An integrated analysis of over 100 single-cell and single-nucleus transcriptomics studies illustrates severe acute respiratory syndrome coronavirus 2 viral entry gene coexpression patterns across different human tissues, and shows association of age, smoking status and sex with viral entry gene expression in respiratory cell populations.
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| 25. |
- Sanchez, J. C., et al.
(författare)
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High-resolution crystal structures of amyxobacterial phytochrome at cryo and roomtemperatures
- 2019
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Ingår i: Structural Dynamics-Us. - : AIP Publishing. - 2329-7778. ; 6:5
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Tidskriftsartikel (refereegranskat)abstract
- Phytochromes (PHYs) are photoreceptor proteins first discovered in plants, where they control a variety of photomorphogenesis events. PHYs as photochromic proteins can reversibly switch between two distinct states: a red light (Pr) and a far-red light (Pfr) absorbing form. The discovery of Bacteriophytochromes (BphPs) in nonphotosynthetic bacteria has opened new frontiers in our understanding of the mechanisms by which these natural photoswitches can control single cell development, although the role of BphPs in vivo remains largely unknown. BphPs are dimeric proteins that consist of a photosensory core module (PCM) and an enzymatic domain, often a histidine kinase. The PCM is composed of three domains (PAS, GAF, and PHY). It holds a covalently bound open-chain tetrapyrrole (biliverdin, BV) chromophore. Upon absorption of light, the double bond between BV rings C and D isomerizes and reversibly switches the protein between Pr and Pfr states. We report crystal structures of the wild-type and mutant (His275Thr) forms of the canonical BphP from the nonphotosynthetic myxobacterium Stigmatella aurantiaca (SaBphP2) in the Pr state. Structures were determined at 1.65A degrees and 2.2A degrees (respectively), the highest resolution of any PCM construct to date. We also report the room temperature wild-type structure of the same protein determined at 2.1A degrees at the SPring-8 Angstrom Compact free electron LAser (SACLA), Japan. Our results not only highlight and confirm important amino acids near the chromophore that play a role in Pr-Pfr photoconversion but also describe the signal transduction into the PHY domain which moves across tens of angstroms after the light stimulus. (C) 2019 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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| 26. |
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| 27. |
- Björling, Alexander, 1983, et al.
(författare)
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Ubiquitous Structural Signaling in Bacterial Phytochromes
- 2015
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Ingår i: Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185. ; 6:17, s. 3379-3383
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Tidskriftsartikel (refereegranskat)abstract
- The phytochrome family of light-switchable proteins has long been studied by biochemical, spectroscopic and crystallographic means, while a direct probe for global conformational signal propagation has been lacking. Using solution X-ray scattering, we find that the photosensory cores of several bacterial phytochromes undergo similar large-scale structural changes upon red-light excitation. The data establish that phytochromes with ordinary and inverted photocycles share a structural signaling mechanism and that a particular conserved histidine, previously proposed to be involved in signal propagation, in fact tunes photoresponse.
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| 28. |
- Börjesson, Karl, 1982, et al.
(författare)
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Optically switchable transistors comprising a hybrid photochromic molecule/n-type organic active layer
- 2015
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Ingår i: Journal of Materials Chemistry C. - : Royal Society of Chemistry (RSC). - 2050-7534 .- 2050-7526. ; 3:16, s. 4156-4161
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Tidskriftsartikel (refereegranskat)abstract
- Organic semiconductors can be easily combined with other molecular building blocks in order to fabricate multifunctional devices, in which each component conveys a specific (opto)electronic function. We have fabricated photoswitchable hybrid thin-film transistors based on an active bi-component material, consisting of an n-type fullerene derivative and a photochromic diarylethene that possesses light-tunable energy levels. The devices can be gated in two independent ways by either using an electrical stimulus via the application of a voltage to the gate electrode or an optical stimulus causing interconversion of the diarylethene molecules between their two isomers. Fine control over the device output current is achieved by engineering the diarylethenes' LUMO that can act as an intra-gap state controlled by a distinct wavelength in the UV or in the visible range. Importantly, the devices based on a mixed diarylethene/fullerene active layer preserve the high mobility of the pristine semiconductor. This journal is
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| 29. |
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| 30. |
- Duong, G.K., et al.
(författare)
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Blowup solutions for the nonlocal shadow limit model of a singular Gierer-Meinhardt system with critical parameters
- 2022
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Ingår i: Journal of Differential Equations. - : Elsevier. - 0022-0396 .- 1090-2732. ; 336, s. 73-125
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Tidskriftsartikel (refereegranskat)abstract
- We consider a nonlocal parabolic PDE, which may be regarded as the standard semilinear heat equation with power nonlinearity, where the nonlinear term is divided by some Sobolev norm of the solution. Unlike the earlier work in [13] where we consider a subcritical regime of parameters, we focus here on the critical regime, which is much more complicated. Our main result concerns the construction of a blow-up solution with the description of its asymptotic behavior. Our method relies on a formal approach, where we find an approximate solution. Then, adopting a rigorous approach, we linearize the equation around that approximate solution, and reduce the question to a finite dimensional problem. Using an argument based on index theory, we solve that finite-dimensional problem, and derive an exact solution to the full problem. We would like to point out that our constructed solution has a new blowup speed with a log correction term, which makes it different from the speed in the subcritical range of parameters and the standard heat equation.
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| 31. |
- Duong, L., et al.
(författare)
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The GALAH survey : properties of the Galactic disc(s) in the solar neighbourhood
- 2018
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Ingår i: Monthly notices of the Royal Astronomical Society. - : OXFORD UNIV PRESS. - 0035-8711 .- 1365-2966. ; 476:4, s. 5216-5232
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Tidskriftsartikel (refereegranskat)abstract
- Using data from the GALAH pilot survey, we determine properties of the Galactic thin and thick discs near the solar neighbourhood. The data cover a small range of Galactocentric radius (7.9 less than or similar to R-GC less than or similar to 9.5 kpc), but extend up to 4 kpc in height from the Galactic plane, and several kpc in the direction of Galactic anti-rotation (at longitude 260 degrees <= l <= 280 degrees). This allows us to reliably measure the vertical density and abundance profiles of the chemically and kinematically defined 'thick' and 'thin' discs of the Galaxy. The thin disc (low-alpha population) exhibits a steep negative vertical metallicity gradient, at d[M/H]/dz = -0.18 +/- 0.01 dex kpc(-1), which is broadly consistent with previous studies. In contrast, its vertical alpha-abundance profile is almost flat, with a gradient of d[alpha/M]/dz = 0.008 +/- 0.002 dex kpc(-1). The steep vertical metallicity gradient of the low-a population is in agreement with models where radial migration has a major role in the evolution of the thin disc. The thick disc (high-alpha population) has a weaker vertical metallicity gradient d[M/H]/dz = -0.058 +/- 0.003 dex kpc(-1). The aabundance of the thick disc is nearly constant with height, d[alpha/M]/dz = 0.007 +/- 0.002 dex kpc(-1). The negative gradient in metallicity and the small gradient in [alpha/M] indicate that the high-alpha population experienced a settling phase, but also formed prior to the onset of major Type I alpha supernova enrichment. We explore the implications of the distinct alpha-enrichments and narrow [alpha/M] range of the sub-populations in the context of thick disc formation.
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| 32. |
- Duong, M., et al.
(författare)
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Global differences in lung function by region (PURE): An international, community-based prospective study
- 2013
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Ingår i: The Lancet Respiratory Medicine. - 2213-2600. ; 1:8, s. 599-609
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite the rising burden of chronic respiratory diseases, global data for lung function are not available. We investigated global variation in lung function in healthy populations by region to establish whether regional factors contribute to lung function. Methods: In an international, community-based prospective study, we enrolled individuals from communities in 17 countries between Jan 1, 2005, and Dec 31, 2009 (except for in Karnataka, India, where enrolment began on Jan 1, 2003). Trained local staff obtained data from participants with interview-based questionnaires, measured weight and height, and recorded forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC). We analysed data from participants 130-190 cm tall and aged 34-80 years who had a 5 pack-year smoking history or less, who were not affected by specified disorders and were not pregnant, and for whom we had at least two FEV1 and FVC measurements that did not vary by more than 200 mL. We divided the countries into seven socioeconomic and geographical regions: south Asia (India, Bangladesh, and Pakistan), east Asia (China), southeast Asia (Malaysia), sub-Saharan Africa (South Africa and Zimbabwe), South America (Argentina, Brazil, Colombia, and Chile), the Middle East (Iran, United Arab Emirates, and Turkey), and North America or Europe (Canada, Sweden, and Poland). Data were analysed with non-linear regression to model height, age, sex, and region. Findings: 153 996 individuals were enrolled from 628 communities. Data from 38 517 asymptomatic, healthy non-smokers (25 614 women; 12 903 men) were analysed. For all regions, lung function increased with height non-linearly, decreased with age, and was proportionately higher in men than women. The quantitative effect of height, age, and sex on lung function differed by region. Compared with North America or Europe, FEV1 adjusted for height, age, and sex was 31·3% (95% CI 30·8-31·8%) lower in south Asia, 24·2% (23·5-24·9%) lower in southeast Asia, 12·8% (12·4-13·4%) lower in east Asia, 20·9% (19·9-22·0%) lower in sub-Saharan Africa, 5·7% (5·1-6·4%) lower in South America, and 11·2% (10·6-11·8%) lower in the Middle East. We recorded similar but larger differences in FVC. The differences were not accounted for by variation in weight, urban versus rural location, and education level between regions. Interpretation: Lung function differs substantially between regions of the world. These large differences are not explained by factors investigated in this study; the contribution of socioeconomic, genetic, and environmental factors and their interactions with lung function and lung health need further clarification. Funding: Full funding sources listed at end of the paper (see Acknowledgments). © 2013 Elsevier Ltd.
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| 33. |
- El Gemayel, M., et al.
(författare)
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Optically switchable transistors by simple incorporation of photochromic systems into small-molecule semiconducting matrices
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- The fabrication of multifunctional high-performance organic thin-film transistors as key elements in future logic circuits is a major research challenge. Here we demonstrate that a photoresponsive bi-functional field-effect transistor with carrier mobilities exceeding 0.2cm 2 V-1 s-1 can be developed by incorporating photochromic molecules into an organic semiconductor matrix via a single-step solution processing deposition of a two components blend. Tuning the interactions between the photochromic diarylethene system and the organic semiconductor is achieved via ad-hoc side functionalization of the diarylethene. Thereby, a large-scale phase-segregation can be avoided and superior miscibility is provided, while retaining optimal π-π stacking to warrant efficient charge transport and to attenuate the effect of photoinduced switching on the extent of current modulation. This leads to enhanced electrical performance of transistors incorporating small conjugated molecules as compared with polymeric semiconductors. These findings are of interest for the development of high-performing optically gated electronic devices.
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| 34. |
- Lyu, Xueying, et al.
(författare)
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Tau-neurodegeneration mismatch reveals vulnerability and resilience to comorbidities in Alzheimer's continuum
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Ingår i: Alzheimer's and Dementia. - 1552-5260.
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Variability in relationship of tau-based neurofibrillary tangles (T) and neurodegeneration (N) in Alzheimer's disease (AD) arises from non-specific nature of N, modulated by non-AD co-pathologies, age-related changes, and resilience factors. METHODS: We used regional T-N residual patterns to partition 184 patients within the Alzheimer's continuum into data-driven groups. These were compared with groups from 159 non-AD (amyloid “negative”) patients partitioned using cortical thickness, and groups in 98 patients with ante mortem MRI and post mortem tissue for measuring N and T, respectively. We applied the initial T-N residual model to classify 71 patients in an independent cohort into predefined groups. RESULTS: AD groups displayed spatial T-N mismatch patterns resembling neurodegeneration patterns in non-AD groups, similarly associated with non-AD factors and diverging cognitive outcomes. In the autopsy cohort, limbic T-N mismatch correlated with TDP-43 co-pathology. DISCUSSION: T-N mismatch may provide a personalized approach for determining non-AD factors associated with resilience/vulnerability in AD.
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| 35. |
- Martell, S. L., et al.
(författare)
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The GALAH survey : observational overview and Gaia DR1 companion
- 2017
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Ingår i: Monthly notices of the Royal Astronomical Society. - : OXFORD UNIV PRESS. - 0035-8711 .- 1365-2966. ; 465:3, s. 3203-3219
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Tidskriftsartikel (refereegranskat)abstract
- The Galactic Archaeology with HERMES (GALAH) survey is amassive observational project to trace the MilkyWay's history of star formation, chemical enrichment, stellar migration and minor mergers. Using high-resolution (R similar or equal to 28 000) spectra, taken with the High Efficiency and Resolution Multi- Element Spectrograph (HERMES) instrument at the Anglo-Australian Telescope, GALAH will determine stellar parameters and abundances of up to 29 elements for up to one million stars. Selecting targets from a colour-unbiased catalogue built from 2MASS, APASS and UCAC4 data, we expect to observe dwarfs at 0.3-3 kpc and giants at 1-10 kpc. This enables a thorough local chemical inventory of the Galactic thin and thick discs, and also captures smaller samples of the bulge and halo. In this paper, we present the plan, process and progress as of early 2016 for GALAH survey observations. In our first two years of survey observing we have accumulated the largest high-quality spectroscopic data set at this resolution, over 200 000 stars. We also present the first public GALAH data catalogue: stellar parameters (T-eff, log(g), [ Fe/ H], [ alpha/ Fe]), radial velocity, distance modulus and reddening for 10 680 observations of 9860 Tycho-2 stars, 7894 of which are included in the first Gaia data release.
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| 36. |
- Martell, S., et al.
(författare)
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The GALAH survey : Scientific motivation
- 2015
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 449:3
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Tidskriftsartikel (refereegranskat)abstract
- The Galactic Archaeology with HERMES (GALAH) survey is a large high-resolution spectroscopic survey using the newly commissioned High Efficiency and Resolution Multi-Element Spectrograph (HERMES) on the Anglo-Australian Telescope. The HERMES spectrograph provides high-resolution (R ~ 28 000) spectra in four passbands for 392 stars simultaneously over a 2 deg field of view. The goal of the survey is to unravel the formation and evolutionary history of the Milky Way, using fossil remnants of ancient star formation events which have been disrupted and are now dispersed throughout the Galaxy. Chemical tagging seeks to identify such dispersed remnants solely from their common and unique chemical signatures; these groups are unidentifiable from their spatial, photometric or kinematic properties. To carry out chemical tagging, the GALAH survey will acquire spectra for a million stars down to V ~ 14. The HERMES spectra of FGK stars contain absorption lines from 29 elements including light proton-capture elements, α-elements, odd-Z elements, iron-peak elements and n-capture elements from the light and heavy s-process and the r-process. This paper describes the motivation and planned execution of the GALAH survey, and presents some results on the first-light performance of HERMES.
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| 37. |
- Ngo, H. Q., et al.
(författare)
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Uplink Performance Analysis of Multicell MU-SIMO Systems With ZF Receivers
- 2013
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Ingår i: IEEE Transactions on Vehicular Technology. - : Institute of Electrical and Electronics Engineers (IEEE). - 0018-9545 .- 1939-9359. ; 62:9, s. 4471-4483
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Tidskriftsartikel (refereegranskat)abstract
- We consider the uplink of a multicell multiuser single-input multiple-output system (MU-SIMO), where the channel experiences both small-and large-scale fading. The data detection is done by using the linear zero-forcing technique, assuming the base station (BS) has perfect channel state information of all users in its cell. We derive new exact analytical expressions for the uplink rate, the symbol error rate (SER), and the outage probability per user, as well as a lower bound on the achievable rate. This bound is very tight and becomes exact in the large-number-of-antenna limit. We further study the asymptotic system performance in the regimes of high signal-to-noise ratio (SNR), large number of antennas, and large number of users per cell. We show that, at high SNRs, the system is interference limited, and hence, we cannot improve the system performance by increasing the transmit power of each user. Instead, by increasing the number of BS antennas, the effects of interference and noise can be reduced, thereby improving system performance. We demonstrate that, with very large antenna arrays at the BS, the transmit power of each user can be made inversely proportional to the number of BS antennas while maintaining a desired quality of service. Numerical results are presented to verify our analysis.
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