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- Loza, M. J., et al.
(författare)
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Validated and longitudinally stable asthma phenotypes based on cluster analysis of the ADEPT study
- 2016
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Ingår i: Respiratory Research. - : Springer Nature. - 1465-9921 .- 1465-993X. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Asthma is a disease of varying severity and differing disease mechanisms. To date, studies aimed at stratifying asthma into clinically useful phenotypes have produced a number of phenotypes that have yet to be assessed for stability and to be validated in independent cohorts. The aim of this study was to define and validate, for the first time ever, clinically driven asthma phenotypes using two independent, severe asthma cohorts: ADEPT and U-BIOPRED. Methods: Fuzzy partition-around-medoid clustering was performed on pre-specified data from the ADEPT participants (n = 156) and independently on data from a subset of U-BIOPRED asthma participants (n = 82) for whom the same variables were available. Models for cluster classification probabilities were derived and applied to the 12-month longitudinal ADEPT data and to a larger subset of the U-BIOPRED asthma dataset (n = 397). High and low type-2 inflammation phenotypes were defined as high or low Th2 activity, indicated by endobronchial biopsies gene expression changes downstream of IL-4 or IL-13. Results: Four phenotypes were identified in the ADEPT (training) cohort, with distinct clinical and biomarker profiles. Phenotype 1 was "mild, good lung function, early onset", with a low-inflammatory, predominantly Type-2, phenotype. Phenotype 2 had a "moderate, hyper-responsive, eosinophilic" phenotype, with moderate asthma control, mild airflow obstruction and predominant Type-2 inflammation. Phenotype 3 had a "mixed severity, predominantly fixed obstructive, non-eosinophilic and neutrophilic" phenotype, with moderate asthma control and low Type-2 inflammation. Phenotype 4 had a "severe uncontrolled, severe reversible obstruction, mixed granulocytic" phenotype, with moderate Type-2 inflammation. These phenotypes had good longitudinal stability in the ADEPT cohort. They were reproduced and demonstrated high classification probability in two subsets of the U-BIOPRED asthma cohort. Conclusions: Focusing on the biology of the four clinical independently-validated easy-to-assess ADEPT asthma phenotypes will help understanding the unmet need and will aid in developing tailored therapies. Trial registration:NCT01274507(ADEPT), registered October 28, 2010 and NCT01982162(U-BIOPRED), registered October 30, 2013.
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| 3. |
- Jin, S. Y., et al.
(författare)
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Spectroscopy of 98Cd by two-nucleon removal from 100In
- 2021
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Ingår i: Physical Review C: covering nuclear physics. - 2469-9985. ; 104:2
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Tidskriftsartikel (refereegranskat)abstract
- Low-lying states of Cd-98 have been populated by the two-nucleon removal reaction (In-100, Cd-98+gamma) and studied using in-beam gamma-ray spectroscopy at the Radioactive Isotope Beam Factory at RIKEN. Two new gamma transitions were identified and assigned as decays from a previously unknown state. This state is suggested to be based on a pi 1g(/9/2)(-1)2p(1/2)(-2) configuration with J(pi) = 5(-). The present observation extends the systematics of the excitation energies of the first 5(-) state in N = 50 isotones toward Sn-100. The determined energy of the 5(- )state in Cd-98 continues a smooth trend along the N = 50 isotones. The systematics are compared with shell-model calculations in different model spaces. Good agreement is achieved when considering a model space consisting of the pi(1f(5/2), 2p(3/2), 2p(1/2), 1g(9/2)) orbitals. The calculations with a smaller model space omitting the orbitals below the Z = 38 subshell could not reproduce the experimental energy difference between the ground and first 5(-) states in N = 50 isotones, because proton excitations across Z = 38 subshell yield a large amount of correlation energy that lowers the ground states.
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- Wuttke, Matthias, et al.
(författare)
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A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
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Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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| 5. |
- Gorski, Mathias, et al.
(författare)
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Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline
- 2021
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Ingår i: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 99:4, s. 926-939
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Tidskriftsartikel (refereegranskat)abstract
- Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m2/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m2 at follow-up among those with eGFRcrea 60 mL/min/1.73m2 or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or LARP4B. Individuals at high compared to those at low genetic risk (8-14 vs 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
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| 6. |
- Lv, Jiezhao, et al.
(författare)
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Numerical Investigation of the Stimulated Growth of Single-Crystal Fibers by Point-Effect-Induced Fluid Dynamics
- 2022
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Ingår i: Crystal Growth & Design. - : AMER CHEMICAL SOC. - 1528-7483 .- 1528-7505. ; 22:12, s. 7031-7039
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Tidskriftsartikel (refereegranskat)abstract
- Using molecular dynamics analysis and a two-component diffusion model that accounts for the time-dependent crystal surface chemical reaction, we show by extensive numerical simulations that the recently observed prismatic facet growth suppression in single-crystal fibers is the combined action of self-shielding by crystal surface selectivity and self-channeling arising from a point effect due to fibers small diameters and large aspect ratios. We further show that the self-channeling leads to a pyramidal-face-aiming solute flow, resulting in accelerated single-crystal fiber growth. This mesoscopic stimulated matter growth acceleration theory can satisfactorily explain all experimental results reported to date. This new crystal fiber growth technology opens a realm of application possibilities for single-crystal fiber architectures in chip-size photonics.
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| 7. |
- Maklar, J., et al.
(författare)
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A quantitative comparison of time-of-flight momentum microscopes and hemispherical analyzers for time- and angle-resolved photoemission spectroscopy experiments
- 2020
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Ingår i: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 91:12
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Tidskriftsartikel (refereegranskat)abstract
- Time-of-flight-based momentum microscopy has a growing presence in photoemission studies, as it enables parallel energy- and momentum-resolved acquisition of the full photoelectron distribution. Here, we report table-top extreme ultraviolet time- and angle-resolved photoemission spectroscopy (trARPES) featuring both a hemispherical analyzer and a momentum microscope within the same setup. We present a systematic comparison of the two detection schemes and quantify experimentally relevant parameters, including pump- and probe-induced space-charge effects, detection efficiency, photoelectron count rates, and depth of focus. We highlight the advantages and limitations of both instruments based on exemplary trARPES measurements of bulk WSe2. Our analysis demonstrates the complementary nature of the two spectrometers for time-resolved ARPES experiments. Their combination in a single experimental apparatus allows us to address a broad range of scientific questions with trARPES.
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| 8. |
- Parkinson, Dilworth Y., et al.
(författare)
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Real-Time Data-Intensive Computing
- 2016
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Ingår i: Proceedings Of The 12Th International Conference On Synchrotron Radiation Instrumentation (SRI2015). - : Author(s). - 9780735413986
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Konferensbidrag (refereegranskat)abstract
- Today users visit synchrotrons as sources of understanding and discovery-not as sources of just light, and not as sources of data. To achieve this, the synchrotron facilities frequently provide not just light but often the entire end station and increasingly, advanced computational facilities that can reduce terabytes of data into a form that can reveal a new key insight. The Advanced Light Source (ALS) has partnered with high performance computing, fast networking, and applied mathematics groups to create a "super-facility", giving users simultaneous access to the experimental, computational, and algorithmic resources to make this possible. This combination forms an efficient closed loop, where data-despite its high rate and volume-is transferred and processed immediately and automatically on appropriate computing resources, and results are extracted, visualized, and presented to users or to the experimental control system, both to provide immediate insight and to guide decisions about subsequent experiments during beamtime. We will describe our work at the ALS ptychography, scattering, micro-diffraction, and micro-tomography beamlines.
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