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- 2019
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Tidskriftsartikel (refereegranskat)
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- Mahajan, Anubha, et al.
(författare)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Tidskriftsartikel (refereegranskat)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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- Kato, Norihiro, et al.
(författare)
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Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
- 2015
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
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Tidskriftsartikel (refereegranskat)abstract
- We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
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- Zhang, Xiao-Tong, et al.
(författare)
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Congenital unilateral pulmonary malformation misdiagnosed as bronchial foreign body : A review of 14 cases
- 2010
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Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 130:8, s. 971-976
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Tidskriftsartikel (refereegranskat)abstract
- Conclusion: Congenital unilateral pulmonary malformation can easily be misdiagnosed as a bronchial foreign body. Although rigid bronchoscopy helps the proper diagnosis, high risks associated with anesthesia and operative complications may limit its application. However, high-resolution computed tomography (CT) and three-dimensional lung reconstruction provide a non-invasive tool to improve the diagnosis of congenital unilateral pulmonary malformation. Objectives: To compare clinical manifestations, physical signs, and radiological examinations of congenital unilateral pulmonary malformation and bronchial foreign body, and summarize the characteristics and methods for diagnosis of congenital unilateral pulmonary malformation. Methods: Fourteen patients (five males and nine females, aged from 3 months to 14 years) with congenital unilateral pulmonary malformation, who were misdiagnosed or suspected as having bronchial foreign body or bronchial foreign body with pulmonary atelectasis, were analyzed retrospectively. Three typical cases are presented in detail. Results: All patients were previously misdiagnosed and treated as having pneumonia. From onset to final diagnosis, the longest misdiagnosis time was 10 years, and the shortest was 2 days. Only three patients presented with a history of foreign body inhalation. Six cases were finally diagnosed as having unilateral pulmonary malformation by rigid bronchoscope, five cases by X-ray and high-resolution CT scan, two cases by CT and three-dimensional lung reconstruction, and one case by autopsy. The malformation of left and right lungs was present in five and nine cases, respectively. Among these patients, four patients also had congenital cardiovascular diseases and other malformations, two patients underwent tracheotomy, and one patient died during salvage surgery.
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- Bjelic, Sinisa, et al.
(författare)
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Exploration of Alternate Catalytic Mechanisms and Optimization Strategies for Retroaldolase Design
- 2014
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 426:1, s. 256-271
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Tidskriftsartikel (refereegranskat)abstract
- Designed retroaldolases have utilized a nucleophilic lysine to promote carbon-carbon bond cleavage of β-hydroxy-ketones via a covalent Schiff base intermediate. Previous computational designs have incorporated a water molecule to facilitate formation and breakdown of the carbinolamine intermediate to give the Schiff base and to function as a general acid/base. Here we investigate an alternative active-site design in which the catalytic water molecule was replaced by the side chain of a glutamic acid. Five out of seven designs expressed solubly and exhibited catalytic efficiencies similar to previously designed retroaldolases for the conversion of 4-hydroxy-4-(6-methoxy-2-naphthyl)-2-butanone to 6-methoxy-2-naphthaldehyde and acetone. After one round of site-directed saturation mutagenesis, improved variants of the two best designs, RA114 and RA117, exhibited among the highest kcat (>10(-3)s(-1)) and kcat/KM (11-25M(-1)s(-1)) values observed for retroaldolase designs prior to comprehensive directed evolution. In both cases, the >10(5)-fold rate accelerations that were achieved are within 1-3 orders of magnitude of the rate enhancements reported for the best catalysts for related reactions, including catalytic antibodies (kcat/kuncat=10(6) to 10(8)) and an extensively evolved computational design (kcat/kuncat>10(7)). The catalytic sites, revealed by X-ray structures of optimized versions of the two active designs, are in close agreement with the design models except for the catalytic lysine in RA114. We further improved the variants by computational remodeling of the loops and yeast display selection for reactivity of the catalytic lysine with a diketone probe, obtaining an additional order of magnitude enhancement in activity with both approaches.
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- Hickstein, Daniel D., et al.
(författare)
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Direct Visualization of Laser-Driven Electron Multiple Scattering and Tunneling Distance in Strong-Field Ionization
- 2012
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Ingår i: Physical Review Letters. - 1079-7114. ; 109:7
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Tidskriftsartikel (refereegranskat)abstract
- Using a simple model of strong-field ionization of atoms that generalizes the well-known 3-step model from 1D to 3D, we show that the experimental photoelectron angular distributions resulting from laser ionization of xenon and argon display prominent structures that correspond to electrons that pass by their parent ion more than once before strongly scattering. The shape of these structures can be associated with the specific number of times the electron is driven past its parent ion in the laser field before scattering. Furthermore, a careful analysis of the cutoff energy of the structures allows us to experimentally measure the distance between the electron and ion at the moment of tunnel ionization. This work provides new physical insight into how atoms ionize in strong laser fields and has implications for further efforts to extract atomic and molecular dynamics from strong-field physics.
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- Reitsma, Marissa B., et al.
(författare)
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Smoking prevalence and attributable disease burden in 195 countries and territories, 1990-2015 : a systematic analysis from the Global Burden of Disease Study 2015
- 2017
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 389:10082, s. 1885-1906
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Tidskriftsartikel (refereegranskat)abstract
- Background The scale-up of tobacco control, especially after the adoption of the Framework Convention for Tobacco Control, is a major public health success story. Nonetheless, smoking remains a leading risk for early death and disability worldwide, and therefore continues to require sustained political commitment. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) offers a robust platform through which global, regional, and national progress toward achieving smoking-related targets can be assessed. Methods We synthesised 2818 data sources with spatiotemporal Gaussian process regression and produced estimates of daily smoking prevalence by sex, age group, and year for 195 countries and territories from 1990 to 2015. We analysed 38 risk-outcome pairs to generate estimates of smoking-attributable mortality and disease burden, as measured by disability-adjusted life-years (DALYs). We then performed a cohort analysis of smoking prevalence by birth-year cohort to better understand temporal age patterns in smoking. We also did a decomposition analysis, in which we parsed out changes in all-cause smoking-attributable DALYs due to changes in population growth, population ageing, smoking prevalence, and risk-deleted DALY rates. Finally, we explored results by level of development using the Socio-demographic Index (SDI). Findings Worldwide, the age-standardised prevalence of daily smoking was 25.0% (95% uncertainty interval [UI] 24.2-25.7) for men and 5.4% (5.1-5.7) for women, representing 28.4% (25.8-31.1) and 34.4% (29.4-38.6) reductions, respectively, since 1990. A greater percentage of countries and territories achieved significant annualised rates of decline in smoking prevalence from 1990 to 2005 than in between 2005 and 2015; however, only four countries had significant annualised increases in smoking prevalence between 2005 and 2015 (Congo [Brazzaville] and Azerbaijan for men and Kuwait and Timor-Leste for women). In 2015, 11.5% of global deaths (6.4 million [95% UI 5.7-7.0 million]) were attributable to smoking worldwide, of which 52.2% took place in four countries (China, India, the USA, and Russia). Smoking was ranked among the five leading risk factors by DALYs in 109 countries and territories in 2015, rising from 88 geographies in 1990. In terms of birth cohorts, male smoking prevalence followed similar age patterns across levels of SDI, whereas much more heterogeneity was found in age patterns for female smokers by level of development. While smoking prevalence and risk-deleted DALY rates mostly decreased by sex and SDI quintile, population growth, population ageing, or a combination of both, drove rises in overall smoking-attributable DALYs in low-SDI to middle-SDI geographies between 2005 and 2015. Interpretation The pace of progress in reducing smoking prevalence has been heterogeneous across geographies, development status, and sex, and as highlighted by more recent trends, maintaining past rates of decline should not be taken for granted, especially in women and in low-SDI to middle-SDI countries. Beyond the effect of the tobacco industry and societal mores, a crucial challenge facing tobacco control initiatives is that demographic forces are poised to heighten smoking's global toll, unless progress in preventing initiation and promoting cessation can be substantially accelerated. Greater success in tobacco control is possible but requires effective, comprehensive, and adequately implemented and enforced policies, which might in turn require global and national levels of political commitment beyond what has been achieved during the past 25 years.
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- Sun, Yifan, et al.
(författare)
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Sensitive parameters affecting dark current characteristics of SCD
- 2021
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 12061
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Konferensbidrag (refereegranskat)abstract
- The sensitive parameters affecting the dark current characteristics are further studied by using InAs/GaSb type II superlattice (T2SL) pBpp structure long wavelength Infrared photodetectors. Generation of recombination (G-R), surface leakage current and tunneling current are the main components of dark current. Using pBpp structure can suppress them effectively, thereby decreasing dark current. Based on the k · p method, the band structure of InAs/GaSb T2SL and InAs/AlSb T2SL can be obtained by solving the 8-band k · p model. We have calculated different doping levels of pBpp detector and different layer thicknesses of pBpp detector. For pBpp device, we consider the dark current for different contact layer doping and different absorber layer doping. We also study the influence of different contact layer thicknesses and different absorber layer thicknesses on dark current. The dark current of pBpp detector is dominant by tunneling current at low temperature, and diffusion is the main limiting mechanism in dark current at high temperature, for barrier layer inhibits generation-recombination contribution. Eventually, the dark current of a pBpp structure has been calculated for versus voltage at 77 K.
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- Ueda, Kiyoshi, et al.
(författare)
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Roadmap on photonic, electronic and atomic collision physics : I. Light-matter interaction
- 2019
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Ingår i: Journal of Physics B. - : IOP PUBLISHING LTD. - 0953-4075 .- 1361-6455. ; 52:17
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Tidskriftsartikel (refereegranskat)abstract
- We publish three Roadmaps on photonic, electronic and atomic collision physics in order to celebrate the 60th anniversary of the ICPEAC conference. In Roadmap I, we focus on the light-matter interaction. In this area, studies of ultrafast electronic and molecular dynamics have been rapidly growing, with the advent of new light sources such as attosecond lasers and x-ray free electron lasers. In parallel, experiments with established synchrotron radiation sources and femtosecond lasers using cutting-edge detection schemes are revealing new scientific insights that have never been exploited. Relevant theories are also being rapidly developed. Target samples for photon-impact experiments are expanding from atoms and small molecules to complex systems such as biomolecules, fullerene, clusters and solids. This Roadmap aims to look back along the road, explaining the development of these fields, and look forward, collecting contributions from twenty leading groups from the field.
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- Zhang, Lu, et al.
(författare)
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Toward terabit digital radio over fiber systems : Architecture and key technologies
- 2019
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Ingår i: IEEE Communications Magazine. - : Institute of Electrical and Electronics Engineers Inc.. - 0163-6804 .- 1558-1896. ; 57:4, s. 131-137
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Tidskriftsartikel (refereegranskat)abstract
- To support massive deployment of broadband radio applications, such as 5G and high-definition videos for terrestrial televisions, large system capacity and high spectrum efficiency are highly demanded in radio over fiber (RoF) systems. In this article, we propose a terabit digital RoF system capable of providing high-speed transmission, where multicore fiber (MCF) is introduced for the access segment between the central unit and remote unit. Two key technologies that greatly enhance system capacity and spectrum efficiency, namely MCF enabled self-homodyne detection and compressed quantization, are demonstrated.
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