| 1. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 2. |
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| 3. |
- Hyde, K. D., et al.
(författare)
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Global consortium for the classification of fungi and fungus-like taxa
- 2023
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Ingår i: MYCOSPHERE. - : Mushroom Research Foundation. - 2077-7000 .- 2077-7019. ; 14:1, s. 1960-2012
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Tidskriftsartikel (refereegranskat)abstract
- The Global Consortium for the Classification of Fungi and fungus-like taxa is an international initiative of more than 550 mycologists to develop an electronic structure for the classification of these organisms. The members of the Consortium originate from 55 countries/regions worldwide, from a wide range of disciplines, and include senior, mid-career and early-career mycologists and plant pathologists. The Consortium will publish a biannual update of the Outline of Fungi and fungus-like taxa, to act as an international scheme for other scientists. Notes on all newly published taxa at or above the level of species will be prepared and published online on the Outline of Fungi website (https://www.outlineoffungi.org/), and these will be finally published in the biannual edition of the Outline of Fungi and fungus-like taxa. Comments on recent important taxonomic opinions on controversial topics will be included in the biannual outline. For example, 'to promote a more stable taxonomy in Fusarium given the divergences over its generic delimitation', or 'are there too many genera in the Boletales?' and even more importantly, 'what should be done with the tremendously diverse 'dark fungal taxa?' There are undeniable differences in mycologists' perceptions and opinions regarding species classification as well as the establishment of new species. Given the pluralistic nature of fungal taxonomy and its implications for species concepts and the nature of species, this consortium aims to provide a platform to better refine and stabilise fungal classification, taking into consideration views from different parties. In the future, a confidential voting system will be set up to gauge the opinions of all mycologists in the Consortium on important topics. The results of such surveys will be presented to the International Commission on the Taxonomy of Fungi (ICTF) and the Nomenclature Committee for Fungi (NCF) with opinions and percentages of votes for and against. Criticisms based on scientific evidence with regards to nomenclature, classifications, and taxonomic concepts will be welcomed, and any recommendations on specific taxonomic issues will also be encouraged; however, we will encourage professionally and ethically responsible criticisms of others' work. This biannual ongoing project will provide an outlet for advances in various topics of fungal classification, nomenclature, and taxonomic concepts and lead to a community-agreed classification scheme for the fungi and fungus-like taxa. Interested parties should contact the lead author if they would like to be involved in future outlines.
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| 4. |
- Kristan, Matej, et al.
(författare)
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The first visual object tracking segmentation VOTS2023 challenge results
- 2023
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Ingår i: 2023 IEEE/CVF International conference on computer vision workshops (ICCVW). - : Institute of Electrical and Electronics Engineers Inc.. - 9798350307443 - 9798350307450 ; , s. 1788-1810
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Konferensbidrag (refereegranskat)abstract
- The Visual Object Tracking Segmentation VOTS2023 challenge is the eleventh annual tracker benchmarking activity of the VOT initiative. This challenge is the first to merge short-term and long-term as well as single-target and multiple-target tracking with segmentation masks as the only target location specification. A new dataset was created; the ground truth has been withheld to prevent overfitting. New performance measures and evaluation protocols have been created along with a new toolkit and an evaluation server. Results of the presented 47 trackers indicate that modern tracking frameworks are well-suited to deal with convergence of short-term and long-term tracking and that multiple and single target tracking can be considered a single problem. A leaderboard, with participating trackers details, the source code, the datasets, and the evaluation kit are publicly available at the challenge website1
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| 5. |
- Zhu, RJ, et al.
(författare)
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Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms
- 2021
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Ingår i: Cell research. - : Springer Science and Business Media LLC. - 1748-7838 .- 1001-0602. ; 31:12, s. 1244-1262
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Tidskriftsartikel (refereegranskat)abstract
- The infusion of coronavirus disease 2019 (COVID-19) patients with mesenchymal stem cells (MSCs) potentially improves clinical symptoms, but the underlying mechanism remains unclear. We conducted a randomized, single-blind, placebo-controlled (29 patients/group) phase II clinical trial to validate previous findings and explore the potential mechanisms. Patients treated with umbilical cord-derived MSCs exhibited a shorter hospital stay (P = 0.0198) and less time required for symptoms remission (P = 0.0194) than those who received placebo. Based on chest images, both severe and critical patients treated with MSCs showed improvement by day 7 (P = 0.0099) and day 21 (P = 0.0084). MSC-treated patients had fewer adverse events. MSC infusion reduced the levels of C-reactive protein, proinflammatory cytokines, and neutrophil extracellular traps (NETs) and promoted the maintenance of SARS-CoV-2-specific antibodies. To explore how MSCs modulate the immune system, we employed single-cell RNA sequencing analysis on peripheral blood. Our analysis identified a novel subpopulation of VNN2+ hematopoietic stem/progenitor-like (HSPC-like) cells expressing CSF3R and PTPRE that were mobilized following MSC infusion. Genes encoding chemotaxis factors — CX3CR1 and L-selectin — were upregulated in various immune cells. MSC treatment also regulated B cell subsets and increased the expression of costimulatory CD28 in T cells in vivo and in vitro. In addition, an in vivo mouse study confirmed that MSCs suppressed NET release and reduced venous thrombosis by upregulating kindlin-3 signaling. Together, our results underscore the role of MSCs in improving COVID-19 patient outcomes via maintenance of immune homeostasis.
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| 6. |
- Abbafati, Cristiana, et al.
(författare)
-
- 2020
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Tidskriftsartikel (refereegranskat)
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| 7. |
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| 8. |
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| 9. |
- Chen, DS, et al.
(författare)
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Single cell atlas for 11 non-model mammals, reptiles and birds
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 7083-
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Tidskriftsartikel (refereegranskat)abstract
- The availability of viral entry factors is a prerequisite for the cross-species transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Large-scale single-cell screening of animal cells could reveal the expression patterns of viral entry genes in different hosts. However, such exploration for SARS-CoV-2 remains limited. Here, we perform single-nucleus RNA sequencing for 11 non-model species, including pets (cat, dog, hamster, and lizard), livestock (goat and rabbit), poultry (duck and pigeon), and wildlife (pangolin, tiger, and deer), and investigated the co-expression of ACE2 and TMPRSS2. Furthermore, cross-species analysis of the lung cell atlas of the studied mammals, reptiles, and birds reveals core developmental programs, critical connectomes, and conserved regulatory circuits among these evolutionarily distant species. Overall, our work provides a compendium of gene expression profiles for non-model animals, which could be employed to identify potential SARS-CoV-2 target cells and putative zoonotic reservoirs.
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| 10. |
- Fenstermacher, M.E., et al.
(författare)
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DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy
- 2022
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4
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Tidskriftsartikel (refereegranskat)abstract
- DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.
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| 11. |
- Han, L., et al.
(författare)
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Cell transcriptomic atlas of the non-human primate Macaca fascicularis
- 2022
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 604:7907, s. 723-731
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Tidskriftsartikel (refereegranskat)abstract
- Studying tissue composition and function in non-human primates (NHPs) is crucial to understand the nature of our own species. Here we present a large-scale cell transcriptomic atlas that encompasses over 1 million cells from 45 tissues of the adult NHP Macaca fascicularis. This dataset provides a vast annotated resource to study a species phylogenetically close to humans. To demonstrate the utility of the atlas, we have reconstructed the cell–cell interaction networks that drive Wnt signalling across the body, mapped the distribution of receptors and co-receptors for viruses causing human infectious diseases, and intersected our data with human genetic disease orthologues to establish potential clinical associations. Our M. fascicularis cell atlas constitutes an essential reference for future studies in humans and NHPs.
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| 12. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)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.
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| 13. |
- Kristan, Matej, et al.
(författare)
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The Ninth Visual Object Tracking VOT2021 Challenge Results
- 2021
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Ingår i: 2021 IEEE/CVF INTERNATIONAL CONFERENCE ON COMPUTER VISION WORKSHOPS (ICCVW 2021). - : IEEE COMPUTER SOC. - 9781665401913 ; , s. 2711-2738
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Konferensbidrag (refereegranskat)abstract
- The Visual Object Tracking challenge VOT2021 is the ninth annual tracker benchmarking activity organized by the VOT initiative. Results of 71 trackers are presented; many are state-of-the-art trackers published at major computer vision conferences or in journals in recent years. The VOT2021 challenge was composed of four sub-challenges focusing on different tracking domains: (i) VOT-ST2021 challenge focused on short-term tracking in RGB, (ii) VOT-RT2021 challenge focused on "real-time" short-term tracking in RGB, (iii) VOT-LT2021 focused on long-term tracking, namely coping with target disappearance and reappearance and (iv) VOT-RGBD2021 challenge focused on long-term tracking in RGB and depth imagery. The VOT-ST2021 dataset was refreshed, while VOT-RGBD2021 introduces a training dataset and sequestered dataset for winner identification. The source code for most of the trackers, the datasets, the evaluation kit and the results along with the source code for most trackers are publicly available at the challenge website(1).
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| 14. |
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| 15. |
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| 16. |
- Zhang, Wei, et al.
(författare)
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Critical Role of Phosphorus in Hollow Structures Cobalt-Based Phosphides as Bifunctional Catalysts for Water Splitting
- 2022
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Ingår i: Small. - : Wiley. - 1613-6810 .- 1613-6829. ; 18:4
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Tidskriftsartikel (refereegranskat)abstract
- Cobalt phosphides electrocatalysts have great potential for water splitting, but the unclear active sides hinder the further development of cobalt phosphides. Wherein, three different cobalt phosphides with the same hollow structure morphology (CoP-HS, CoP2-HS, CoP3-HS) based on the same sacrificial template of ZIF-67 are prepared. Surprisingly, these cobalt phosphides exhibit similar OER performances but quite different HER performances. The identical OER performance of these CoPx-HS in alkaline solution is attributed to the similar surface reconstruction to CoOOH. CoP-HS exhibits the best catalytic activity for HER among these CoPx-HS in both acidic and alkaline media, originating from the adjusted electronic density of phosphorus to affect absorption–desorption process on H. Moreover, the calculated ΔGH* based on P-sites of CoP-HS follows a quite similar trend with the normalized overpotential and Tafel slope, indicating the important role of P-sites for the HER process. Moreover, CoP-HS displays good performance (cell voltage of 1.67 V at a current density of 50 mA cm−2) and high stability in 1 M KOH. For the first time, this work detailly presents the critical role of phosphorus in cobalt-based phosphides for water splitting, which provides the guidance for future investigations on transition metal phosphides from material design to mechanism understanding.
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| 17. |
- Zhang, Xiao-Jie, et al.
(författare)
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Auto-suppression of Tet dioxygenases protects the mouse oocyte genome from oxidative demethylation
- 2024
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Ingår i: Nature Structural & Molecular Biology. - : NATURE PORTFOLIO. - 1545-9993 .- 1545-9985. ; 31:1
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Tidskriftsartikel (refereegranskat)abstract
- DNA cytosine methylation plays a vital role in repressing retrotransposons, and such derepression is linked with developmental failure, tumorigenesis and aging. DNA methylation patterns are formed by precisely regulated actions of DNA methylation writers (DNA methyltransferases) and erasers (TET, ten-eleven translocation dioxygenases). However, the mechanisms underlying target-specific oxidation of 5mC by TET dioxygenases remain largely unexplored. Here we show that a large low-complexity domain (LCD), located in the catalytic part of Tet enzymes, negatively regulates the dioxygenase activity. Recombinant Tet3 lacking LCD is shown to be hyperactive in converting 5mC into oxidized species in vitro. Endogenous expression of the hyperactive Tet3 mutant in mouse oocytes results in genome-wide 5mC oxidation. Notably, the occurrence of aberrant 5mC oxidation correlates with a consequent loss of the repressive histone mark H3K9me3 at ERVK retrotransposons. The erosion of both 5mC and H3K9me3 causes ERVK derepression along with upregulation of their neighboring genes, potentially leading to the impairment of oocyte development. These findings suggest that Tet dioxygenases use an intrinsic auto-regulatory mechanism to tightly regulate their enzymatic activity, thus achieving spatiotemporal specificity of methylome reprogramming, and highlight the importance of methylome integrity for development. Here the authors show that TET dioxygenases, the erasers of DNA methylation, use a self-limiting mechanism via their LCD domain to ensure adaptable methylome status and protect the genome from excessive oxidative methylation.
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| 18. |
- Abe, K., et al.
(författare)
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Neutron tagging following atmospheric neutrino events in a water Cherenkov detector
- 2022
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Ingår i: Journal of Instrumentation. - : Institute of Physics (IOP). - 1748-0221. ; 17:10
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Tidskriftsartikel (refereegranskat)abstract
- We present the development of neutron-tagging techniques in Super-Kamiokande IV using a neural network analysis. The detection efficiency of neutron capture on hydrogen is estimated to be 26%, with a mis-tag rate of 0.016 per neutrino event. The uncertainty of the tagging efficiency is estimated to be 9.0%. Measurement of the tagging efficiency with data from an Americium-Beryllium calibration agrees with this value within 10%. The tagging procedure was performed on 3,244.4 days of SK-IV atmospheric neutrino data, identifying 18,091 neutrons in 26,473 neutrino events. The fitted neutron capture lifetime was measured as 218 +/- 9 mu s.
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| 19. |
- Abou Ghayda, Ramy, et al.
(författare)
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The global case fatality rate of coronavirus disease 2019 by continents and national income: A meta-analysis
- 2022
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Ingår i: Journal of Medical Virology. - : WILEY. - 0146-6615 .- 1096-9071. ; 94:6, s. 2402-2413
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study is to provide a more accurate representation of COVID-19s case fatality rate (CFR) by performing meta-analyses by continents and income, and by comparing the result with pooled estimates. We used multiple worldwide data sources on COVID-19 for every country reporting COVID-19 cases. On the basis of data, we performed random and fixed meta-analyses for CFR of COVID-19 by continents and income according to each individual calendar date. CFR was estimated based on the different geographical regions and levels of income using three models: pooled estimates, fixed- and random-model. In Asia, all three types of CFR initially remained approximately between 2.0% and 3.0%. In the case of pooled estimates and the fixed model results, CFR increased to 4.0%, by then gradually decreasing, while in the case of random-model, CFR remained under 2.0%. Similarly, in Europe, initially, the two types of CFR peaked at 9.0% and 10.0%, respectively. The random-model results showed an increase near 5.0%. In high-income countries, pooled estimates and fixed-model showed gradually increasing trends with a final pooled estimates and random-model reached about 8.0% and 4.0%, respectively. In middle-income, the pooled estimates and fixed-model have gradually increased reaching up to 4.5%. in low-income countries, CFRs remained similar between 1.5% and 3.0%. Our study emphasizes that COVID-19 CFR is not a fixed or static value. Rather, it is a dynamic estimate that changes with time, population, socioeconomic factors, and the mitigatory efforts of individual countries.
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| 20. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 21. |
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| 22. |
- Chen, Yuqian, et al.
(författare)
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Experimental and numerical study of flow and ignition and lean blowout characteristics of jet-cooled wall flameholder in a dual-mode combustor
- 2022
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Ingår i: Aerospace Science and Technology. - : Elsevier BV. - 1270-9638. ; 122
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Tidskriftsartikel (refereegranskat)abstract
- The wall flameholder is one of the credible alternatives to realize pilot ignition in augmented/ramjet combustors. To overcome the ablation for a long-term operation, two types of jet cooling, external-inhaled air and pressure-driven jet cooling, are proposed for the wall flameholder. In this work, the flow and combustion process in a laboratory scale rig is studied for different cooling schemes and cooling conditions using experimental and numerical methods. Flow analysis in pressure-driven jet cooling scheme shows that the flow field of flameholder is influenced significantly by the cooling hole angle on the oblique plate α and on the rear plate β. In particular, the cooling jet angle combinations (α=30o, β=30o) and (α=90o, β=150o) are the two schemes with the most different characteristics. To investigate the effects of jet cooling type and cooling jet angle on the flow, ignition, and lean blowout (LBO) characteristics, the two distinctively different angle combinations are applied to form two kinds of jet cooling schemes mentioned above. Results suggest that the jet cooling type has less impact on the flow field but more influence on the flow loss than the cooling jet angle. The ignition performance of cooling schemes with α=30o and β=30o is better than that of those with α=90o and β=150o, but it has a more significant flow loss. The LBO limits of external-inhaled air cooling are lower than that of pressure-driven jet cooling. Moreover, the ignition and LBO limits decrease gradually with the increased mainstream temperature and they are only slightly affected by the mainstream velocity. Notably, the pressure-driven jet cooling scheme can slightly reduce the flow loss but it leads to a deteriorated ignition and LBO performance. The external-inhaled air cooling scheme with α=30o and β=30o has an excellent ignition and LBO performance, and the ignition and LBO limits increase with the increasing cooling air flow rate and the decreasing cooling air temperature.
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| 23. |
- Chen, Yuqian, et al.
(författare)
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Experimental study on combustion and flow resistance characteristics of an afterburner with air-cooled bluff-body flameholder
- 2022
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Ingår i: Aerospace Science and Technology. - : Elsevier BV. - 1270-9638. ; 123
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Tidskriftsartikel (refereegranskat)abstract
- In the afterburner assembled with an air-cooled bluff-body flameholder, cooling air is directly injected into the recirculation zone behind the bluff-body, which can reduce the local temperature and increase the oxygen concentration of the gas mixture in the wake of the bluff-body, thereby affecting the total pressure loss and combustion characteristics. To better understand the flow and combustion process of the system, the exhaust gas temperature, cold and hot total pressure losses in a rectangular premixed combustor are investigated under different cooling air jet conditions. Experimental results show that the added cooling air could improve the combustion efficiency and widen the blowout limit, whereas it could also give rise to an extra total pressure loss. However, when the cooling air flow rate was higher than a critical value, i.e., after the blowing ratio reached 2.5, the recirculation zone could be blown away, resulting in a failed ignition in the afterburner. Notably, the decreased temperature difference between the mainstream and the cooling air could improve the combustion efficiency and reduce the thermal resistance loss but enlarge the cold flow loss and hot total pressure loss. Moreover, since the oxygen content declined and autoignition appeared after the mainstream temperature reached 1100 K, the exhaust gas temperature and combustion efficiency declined rapidly, and the hot total pressure loss also decreased. In addition, with the fuel-gas ratio increasing, the combustion efficiency significantly dropped, the exhaust gas temperature and thermal resistance loss firstly increased to a peak value (at the equivalence ratio of 1.14) and then decreased for excessively fuel-rich combustion.
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| 24. |
- Chen, Zhibin, et al.
(författare)
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Summary of the 3rd International Workshop on Gas-Dynamic Trap based Fusion Neutron Source (GDT-FNS)
- 2022
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:6
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Tidskriftsartikel (refereegranskat)abstract
- The 3rd International Workshop on Gas-Dynamic Trap-based Fusion Neutron Source (GDT-FNS) was held through the hybrid mode on 13-14 September 2021 in Hefei, China, jointly organized by the Hefei Institutes of Physical Science (HFIPS), Chinese Academy of Sciences (CAS), and the Budker Institute of Nuclear Physics (BINP), Russian Academy of Sciences (RAS). It followed the 1st GDT-FNS Workshop held in November 2018 in Hefei, China, and the 2nd taking place in November 2019 in Novosibirsk, Russian Federation. With the financial support from CAS and China Association for Science and Technology (CAST), this workshop was attended by more than 80 participants representing 20 institutes and universities from seven countries, with oral presentations broadcast via the Zoom conferencing system. Twenty-two presentations were made with topics covering design and key technologies, simulation and experiments, steady-state operation, status of the ALIANCE project, multi applications of neutron sources, and other concepts (Tokamaks, Mirrors, FRC, Plasma Focus, etc). The workshop consensus was made including the establishment of the ALIANCE International Working Group. The next GDT-FNS workshop is planned to be held in May 2022 in Novosibirsk.
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| 25. |
- Han, Jianhua, et al.
(författare)
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Understanding photochemical degradation mechanisms in photoactive layer materials for organic solar cells
- 2024
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Ingår i: Chemical Society Reviews. - 1460-4744 .- 0306-0012. ; 53:14, s. 7426-7454
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Forskningsöversikt (refereegranskat)abstract
- Over the past decades, the field of organic solar cells (OSCs) has witnessed a significant evolution in materials chemistry, which has resulted in a remarkable enhancement of device performance, achieving efficiencies of over 19%. The photoactive layer materials in OSCs play a crucial role in light absorption, charge generation, transport and stability. To facilitate the scale-up of OSCs, it is imperative to address the photostability of these electron acceptor and donor materials, as their photochemical degradation process remains a challenge during the photo-to-electric conversion. In this review, we present an overview of the development of electron acceptor and donor materials, emphasizing the crucial aspects of their chemical stability behavior that are linked to the photostability of OSCs. Throughout each section, we highlight the photochemical degradation pathways for electron acceptor and donor materials, and their link to device degradation. We also discuss the existing interdisciplinary challenges and obstacles that impede the development of photostable materials. Finally, we offer insights into strategies aimed at enhancing photochemical stability and discuss future directions for developing photostable photo-active layers, facilitating the commercialization of OSCs.
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| 26. |
- Han, Zheng, et al.
(författare)
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Dynamic contrast-enhanced CEST MRI using a low molecular weight dextran
- 2022
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Ingår i: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 35:3
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Tidskriftsartikel (refereegranskat)abstract
- Natural and synthetic sugars have great potential for developing highly biocompatible and translatable chemical exchange saturation transfer (CEST) MRI contrast agents. In this study, we aimed to develop the smallest clinically available form of dextran, Dex1 (molecular weight, MW ~ 1 kDa), as a new CEST agent. We first characterized the CEST properties of Dex1 in vitro at 11.7 T and showed that the Dex1 had a detectable CEST signal at ~1.2 ppm, attributed to hydroxyl protons. In vivo CEST MRI studies were then carried out on C57BL6 mice bearing orthotopic GL261 brain tumors (n = 5) using a Bruker BioSpec 11.7 T MRI scanner. Both steady-state full Z-spectral images and single offset (1.2 ppm) dynamic dextran-enhanced (DDE) images were acquired before and after the intravenous injection of Dex1 (2 g/kg). The steady-state Z-spectral analysis showed a significantly higher CEST contrast enhancement in the tumor than in contralateral brain (∆MTRasym 1.2 ppm = 0.010 ± 0.006 versus 0.002 ± 0.008, P = 0.0069) at 20 min after the injection of Dex1. Pharmacokinetic analyses of DDE were performed using the area under the curve (AUC) in the first 10 min after Dex1 injection, revealing a significantly higher uptake of Dex1 in the tumor than in brain tissue for tumor-bearing mice (AUC[0-10 min] = 21.9 ± 4.2 versus 5.3 ± 6.4%·min, P = 0.0294). In contrast, no Dex1 uptake was foundling in the brains of non-tumor-bearing mice (AUC[0-10 min] = -1.59 ± 2.43%·min). Importantly, the CEST MRI findings were consistent with the measurements obtained using DCE MRI and fluorescence microscopy, demonstrating the potential of Dex1 as a highly translatable CEST MRI contrast agent for assessing tumor hemodynamics.
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| 27. |
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| 28. |
- Kang, Nai-xin, et al.
(författare)
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Anemoside B4 inhibits enterovirus 71 propagation in mice through upregulating 14-3-3 expression and type I interferon responses
- 2022
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Ingår i: Acta Pharmacologica Sinica. - : Springer Nature. - 1671-4083 .- 1745-7254. ; 43, s. 977-991
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Tidskriftsartikel (refereegranskat)abstract
- Enterovirus 71 (EV71) is the major pathogens of human hand, foot, and mouth disease (HFMD). EV71 efficiently escapes innate immunity responses of the host to cause infection. At present, no effective antiviral drugs for EV71 are available. Anemoside B4 (B4) is a natural saponin isolated from the roots of Pulsatilla chinensis (Bunge) Regel. P. chinensis extracts that shows a wide variety of biological activities. In this study, we investigated the antiviral activities of B4 against EV71 both in cell culture and in suckling mice. We showed that B4 (12.5-200 mu M) dose dependently increased the viability of EV71-infected RD cells with an IC50 value of 24.95 +/- 0.05 mu M against EV71. The antiviral activity of B4 was associated with enhanced interferon (IFN)-beta response, since knockdown of IFN-beta abolished its antiviral activity. We also confirmed that the enhanced IFN response was mediated via activation of retinoic acid-inducible gene I (RIG-I) like receptors (RLRs) pathway, and it was executed by upregulation of 14-3-3 protein, which disrupted the interaction between yes-associated protein (YAP) and interferon regulatory factor 3 (IRF3). By using amino acids in cell culture (SILAC)-based proteomics profiling, we identified the Hippo pathway as the top-ranking functional cluster in B4-treated EV71-infected cells. In vivo experiments were conducted in suckling mice (2-day-old) infected with EV71 and subsequently B4 (200 mg center dot kg(-1) center dot d(-1), i.p.) was administered for 16 days. We showed that B4 administration effectively suppressed EV71 replication and improved muscle inflammation and limb activity. Meanwhile, B4 administration regulated the expressions of HFMD biomarkers IL-10 and IFN-gamma, attenuating complications of EV71 infection. Collectively, our results suggest that B4 could enhance the antiviral effect of IFN-beta by orchestrating Hippo and RLRs pathway, and B4 would be a potential lead compound for developing an anti-EV71 drug.
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| 29. |
- Karlsson, Max, et al.
(författare)
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Genome-wide annotation of protein-coding genes in pig
- 2022
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Ingår i: BMC Biology. - : Springer Nature. - 1741-7007. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is a need for functional genome-wide annotation of the protein-coding genes to get a deeper understanding of mammalian biology. Here, a new annotation strategy is introduced based on dimensionality reduction and density-based clustering of whole-body co-expression patterns. This strategy has been used to explore the gene expression landscape in pig, and we present a whole-body map of all protein-coding genes in all major pig tissues and organs. Results: An open-access pig expression map (www.rnaatlas.org ) is presented based on the expression of 350 samples across 98 well-defined pig tissues divided into 44 tissue groups. A new UMAP-based classification scheme is introduced, in which all protein-coding genes are stratified into tissue expression clusters based on body-wide expression profiles. The distribution and tissue specificity of all 22,342 protein-coding pig genes are presented. Conclusions: Here, we present a new genome-wide annotation strategy based on dimensionality reduction and density-based clustering. A genome-wide resource of the transcriptome map across all major tissues and organs in pig is presented, and the data is available as an open-access resource (www.rnaatlas.org), including a comparison to the expression of human orthologs.
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| 30. |
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| 31. |
- Li, Sirui, et al.
(författare)
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Glioma grading, molecular feature classification, and microstructural characterization using MR diffusional variance decomposition (DIVIDE) imaging
- 2021
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Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 31:11, s. 8197-8207
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate the potential of diffusional variance decomposition (DIVIDE) for grading, molecular feature classification, and microstructural characterization of gliomas. Materials and methods: Participants with suspected gliomas underwent DIVIDE imaging, yielding parameter maps of fractional anisotropy (FA), mean diffusivity (MD), anisotropic mean kurtosis (MKA), isotropic mean kurtosis (MKI), total mean kurtosis (MKT), MKA/MKT, and microscopic fractional anisotropy (μFA). Tumor type and grade, isocitrate dehydrogenase (IDH) 1/2 mutant status, and the Ki-67 labeling index (Ki-67 LI) were determined after surgery. Statistical analysis included 33 high-grade gliomas (HGG) and 17 low-grade gliomas (LGG). Tumor diffusion metrics were compared between HGG and LGG, among grades, and between wild and mutated IDH types using appropriate tests according to normality assessment results. Receiver operating characteristic and Spearman correlation analysis were also used for statistical evaluations. Results: FA, MD, MKA, MKI, MKT, μFA, and MKA/MKT differed between HGG and LGG (FA: p = 0.047; MD: p = 0.037, others p < 0.001), and among glioma grade II, III, and IV (FA: p = 0.048; MD: p = 0.038, others p < 0.001). All diffusion metrics differed between wild-type and mutated IDH tumors (MKI: p = 0.003; others: p < 0.001). The metrics that best discriminated between HGG and LGGs and between wild-type and mutated IDH tumors were MKT and FA respectively (area under the curve 0.866 and 0.881). All diffusion metrics except FA showed significant correlation with Ki-67 LI, and MKI had the highest correlation coefficient (rs = 0.618). Conclusion: DIVIDE is a promising technique for glioma characterization and diagnosis. Key Points: • DIVIDE metrics MKIis related to cell density heterogeneity while MKAand μFA are related to cell eccentricity. • DIVIDE metrics can effectively differentiate LGG from HGG and IDH mutation from wild-type tumor, and showed significant correlation with the Ki-67 labeling index. • MKIwas larger than MKAwhich indicates predominant cell density heterogeneity in gliomas. • MKAand MKIincreased with grade or degree of malignancy, however with a relatively larger increase in the cell eccentricity metric MKAin relation to the cell density heterogeneity metric MKI.
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| 32. |
- Lin, Zhen, et al.
(författare)
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Worse Outcomes After Readmission to a Different Hospital After Sepsis : A Nationwide Cohort Study
- 2022
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Ingår i: Journal of Emergency Medicine. - : Elsevier. - 0736-4679 .- 1090-1280. ; 63:4, s. 569-581
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In the United States, sepsis accounts for 13% of the total hospital expenses and > 50% of hospital deaths. Moreover, people with sepsis are more likely to be readmitted.OBJECTIVE: The aim of this study was to assess the prevalence and outcomes of different hospital readmissions (DHRs) in patients with sepsis, and the factors associated with DHR.METHODS: We used data from the Nationwide Readmissions Database of the United States in 2017 to identify patients admitted for sepsis. Multivariable logistic regression analysis was used to evaluate the factors associated with DHR; five models were constructed to elucidate the relationship between DHR and in-hospital outcomes.RESULTS: In 2017, 85,120 (21.97%) of all patients with sepsis readmitted within 30 days in the United States were readmitted to a different hospital. The most common reason for readmission was infection irrespective of hospital status. Compared with the patients with sepsis who were readmitted to the same hospital, DHR was associated with higher hospitalization costs ($2264; 95% CI $1755-$2772; p < 0.001), longer length of stay (0.58 days; 95% CI 0.44-0.71 days; p < 0.001), and higher risk of in-hospital mortality (odds ratio 1.63; 95% CI 1.55-1.72; p < 0.001).CONCLUSIONS: DHR occurred in one-fifth of patients with sepsis in the United States. Our findings suggest that patients readmitted to a different hospital within 30 days may experience higher in-hospital mortality, longer length of stay, and higher hospitalization costs. Future studies need to examine whether continuity of care can improve the prognosis of patients with sepsis.
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| 33. |
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| 34. |
- Lu, WS, et al.
(författare)
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PDGFD switches on stem cell endothelial commitment
- 2022
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Ingår i: Angiogenesis. - : Springer Science and Business Media LLC. - 1573-7209 .- 0969-6970. ; 25:4, s. 517-533
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Tidskriftsartikel (refereegranskat)abstract
- The critical factors regulating stem cell endothelial commitment and renewal remain not well understood. Here, using loss- and gain-of-function assays together with bioinformatic analysis and multiple model systems, we show that PDGFD is an essential factor that switches on endothelial commitment of embryonic stem cells (ESCs). PDGFD genetic deletion or knockdown inhibits ESC differentiation into EC lineage and increases ESC self-renewal, and PDGFD overexpression activates ESC differentiation towards ECs. RNA sequencing reveals a critical requirement of PDGFD for the expression of vascular-differentiation related genes in ESCs. Importantly, PDGFD genetic deletion or knockdown increases ESC self-renewal and decreases blood vessel densities in both embryonic and neonatal mice and in teratomas. Mechanistically, we reveal that PDGFD fulfills this function via the MAPK/ERK pathway. Our findings provide new insight of PDGFD as a novel regulator of ESC fate determination, and suggest therapeutic implications of modulating PDGFD activity in stem cell therapy.
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| 35. |
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| 36. |
- Paleti, Sri Harish Kumar, et al.
(författare)
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Hexanary blends : a strategy towards thermally stable organic photovoltaics
- 2023
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Non-fullerene based organic solar cells display a high initial power conversion efficiency but continue to suffer from poor thermal stability, especially in case of devices with thick active layers. Mixing of five structurally similar acceptors with similar electron affinities, and blending with a donor polymer is explored, yielding devices with a power conversion efficiency of up to 17.6%. The hexanary device performance is unaffected by thermal annealing of the bulk-heterojunction active layer for at least 23 days at 130 °C in the dark and an inert atmosphere. Moreover, hexanary blends offer a high degree of thermal stability for an active layer thickness of up to 390 nm, which is advantageous for high-throughput processing of organic solar cells. Here, a generic strategy based on multi-component acceptor mixtures is presented that permits to considerably improve the thermal stability of non-fullerene based devices and thus paves the way for large-area organic solar cells.
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| 37. |
- Wang, Kui, et al.
(författare)
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Efficient electro-demulsification of O/W emulsions and simultaneous oil removal enabled by a multiscale porous biocarbon electrode
- 2024
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Ingår i: Chemical Engineering Journal. - : Elsevier BV. - 1385-8947 .- 1873-3212. ; 481
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Tidskriftsartikel (refereegranskat)abstract
- Emulsion wastewater contain substantial amounts of oil and various additives, which pose threats to the environment and human health. Demulsification is a crucial pretreatment stage for wastewater. This study aims to identify a novel electro-demulsification method with high oil removal efficiency and low energy consumption. Modified carbonized birch wood with a unique isotropic multiscale pore structure is used as a self-standing electrode to treat a toluene oil-in-water (O/W) emulsion. The electrode must have a highly porous structure to facilitate efficient water diffusion and oil adsorption. It must also have high electronic conductivity to expedite polarized molecular electrophoresis to realize penetration into the pores and, subsequently, demulsification. Guided by an applied electric field force, polarized O/W droplets are drawn toward the electrode, revealing electrical characteristics distinct from those of polarized organic molecules. This electric field force augments the capture and adhesion of droplets by the electric double layer at the electrode interface. Consequently, adsorbed droplets in close proximity to the electrode rupture due to the combined influence of the electric field force and the electrostatic effects stemming from the electrode's multiscale porous structure. This synergistic action enables demulsification to occur efficiently at low energy consumption levels. This study has revealed that electro-demulsification can effectively treat toluene emulsions stabilized by various surfactants and microemulsion containing toluene. Therefore, this electro-demulsification technology can be further developed for various types of water pollution.
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| 38. |
- Wang, Ning, et al.
(författare)
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Boride-derived oxygen-evolution catalysts
- 2021
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- Metal borides/borates have been considered promising as oxygen evolution reaction catalysts; however, to date, there is a dearth of evidence of long-term stability at practical current densities. Here we report a phase composition modulation approach to fabricate effective borides/borates-based catalysts. We find that metal borides in-situ formed metal borates are responsible for their high activity. This knowledge prompts us to synthesize NiFe-Boride, and to use it as a templating precursor to form an active NiFe-Borate catalyst. This boride-derived oxide catalyzes oxygen evolution with an overpotential of 167 mV at 10 mA/cm2 in 1 M KOH electrolyte and requires a record-low overpotential of 460 mV to maintain water splitting performance for over 400 h at current density of 1 A/cm2. We couple the catalyst with CO reduction in an alkaline membrane electrode assembly electrolyser, reporting stable C2H4 electrosynthesis at current density 200 mA/cm2 for over 80 h.
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| 39. |
- Wang, Si-Yu, et al.
(författare)
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Kaempferia galanga L. : Progresses in Phytochemistry, Pharmacology, Toxicology and Ethnomedicinal Uses
- 2021
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Ingår i: Frontiers in Pharmacology. - : Frontiers Media S.A.. - 1663-9812. ; 12
-
Forskningsöversikt (refereegranskat)abstract
- K. galanga is an aromatic medicinal herb. It is locally to India and distributed in China, Myanmar, Indonesia, Malaysia, and Thailand. K. galanga is a Traditional Chinese Herb Medicine (TCHM), which has been applied to treat cold, dry cough, toothaches, rheumatism, hypertension and so on. In addition, it has been used widely as spices since its highly aromas. The aim of this review is to compile and update the current progresses of ethnomedicinal uses, phytochemistry, pharmacology and toxicology of K. galanga. All the data on K. galanga were based on different classical literary works, multiple electronic databases including SciFinder, Web of Science, PubMed, etc. The results showed that ninety-seven compounds have been identified from rhizome of K. galanga, including terpenoids, phenolics, cyclic dipeptides, flavonoids, diarylheptanoids, fatty acids and esters. Modern pharmacology studies revealed that extracts or secondary metabolites of the herb possessed anti-inflammatory, anti-oxidant, anti-tumorous, anti-bacterial, and anti-angiogenesis effects, which were closely related to its abundant ethnomedicinal uses. In conclusion, although previous research works have provided various information of K. galanga, more in-depth studies are still necessary to systemically evaluate phytochemistry, pharmacological activities, toxicity and quality control of this herb.
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| 40. |
- Xu, Han, et al.
(författare)
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Dissecting the structure-stability relationship of Y-series electron acceptors for real-world solar cell applications
- 2023
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Ingår i: Joule. - 2542-4351. ; 7:9, s. 2135-2151
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Tidskriftsartikel (refereegranskat)abstract
- Despite striking progress toward improving the photovoltaic (PV) performance of organic solar cells (OSCs) with recent Y-series non-fullerene acceptors (Y-NFAs), knowledge about their outdoor performance under real-world conditions and photodegradation mechanisms remains elusive, which is urgently needed to close the lab-to-fab gap of OSCs. Herein, for the first time, we study the structure-outdoor-stability relationship of Y-NFAs. We show that Y-NFAs with long internal side-chains exhibit high energy barriers for photoisomerization, and fluorinated end-groups can enhance the structural confinement to inhibit the photodegradation pathway and thereby improve device stability. Furthermore, the performance loss of Y-NFA-based OSCs under illumination is mainly driven by increased trap-assisted recombination over time. The structure-stability correlation and demonstration of outdoor performance of these state-of-the-art Y-NFA cells provided in this study highlight molecular engineering of device stability control to minimize power output losses in real-world climates.
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| 41. |
- Xu, Huan, et al.
(författare)
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Osteoconductive and Antibacterial Poly(lactic acid) Fibrous Membranes Impregnated with Biobased Nanocarbons for Biodegradable Bone Regenerative Scaffolds
- 2021
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Ingår i: Industrial & Engineering Chemistry Research. - : American Chemical Society (ACS). - 0888-5885 .- 1520-5045. ; 60:32, s. 12021-12031
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Tidskriftsartikel (refereegranskat)abstract
- Carbonaceous nanostructures featuring unique structural characteristics and high cytocompatibility offer a wealth of possibilities to impart enhancements of mechanical properties and biological activities for osteogenic tissue scaffolds. Here, we unveil the fabrication of osteoconductive and antibacterial porous poly(lactic acid) (PLA) membranes by direct electrospinning of microfibers impregnated with coffee-ground-derived quantum dots (QDs). It enabled a straightforward pathway to regulate the diameter and its distribution for the electrospun PLA microfibers, as well as the improved hydrophilicity. The QDs exhibited high affinity to the PLA matrix, permitting remarkable promotion of tensile strength and elastic modulus for the QD-modified PLA membranes while maintaining comparable extensibility. More importantly, osteoblast adhesion and stretching on the electrospun membranes were significantly enhanced with the existence of QDs, as exemplified by the nearly 1.8-fold increase in cell viability cultured onto the composite membrane loaded with 1.5% QDs compared to that of pure PLA. This was accompanied by rapid biomimetic mineralization and uniform apatite formation in an osteofriendly manner. Unexpectedly, immediate and broad-spectrum antibacterial performance was achieved for the composite membranes, likely arising from the synergistic effects of QD-imparted membrane stress and oxidative stress. The unusual combination of mechanical, biomineralization, biological, and antibacterial performances makes the biodegradable membrane scaffolds promising for guided bone/tissue regeneration therapy.
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| 42. |
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| 43. |
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| 44. |
- Xu, Xiao-Ye, et al.
(författare)
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Experimental extraction of nonlocal weak values for demonstrating the failure of a product rule
- 2020
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Ingår i: Optics Letters. - 0146-9592 .- 1539-4794. ; 45:7, s. 1715-1718
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Tidskriftsartikel (refereegranskat)abstract
- We experimentally demonstrate an alternative method for measuring nonlocal weak values in linear optics, avoiding the use of second-order interaction. The method is based on the concept of modular values. The paths of two photons, initialized in hyperentangled states, are adopted as the meter with the polarization acting as the system. The modular values are read out through the reconstructed final states of the meter. The weak value of nonlocal observables is given through its connection to the modular value. Comparing the weak values of local and nonlocal observables, we demonstrate the failure of product rules for an entangled system. Our results significantly simplify the task of measuring nonloral weak values and will play an important role in the application of weak measurement.
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| 45. |
- Yuan, Shuai, et al.
(författare)
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Mendelian randomization and clinical trial evidence supports TYK2 inhibition as a therapeutic target for autoimmune diseases
- 2023
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 89
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Tidskriftsartikel (refereegranskat)abstract
- Background: To explore the associations of genetically proxied TYK2 inhibition with a wide range of disease outcomes and biomarkers to identify therapeutic repurposing opportunities, adverse effects, and biomarkers of efficacy.Methods: The loss-of-function missense variant rs34536443 in TYK2 gene was used as a genetic instrument to proxy the effect of TYK2 inhibition. A phenome-wide Mendelian randomization (MR) study was conducted to explore the associations of genetically-proxied TYK2 inhibition with 1473 disease outcomes in UK Biobank (N = 339,197). Identified associations were examined for replication in FinnGen (N = 260,405). We further performed tissue -specific gene expression MR, colocalization analyses, and MR with 247 blood biomarkers. A systematic review of randomized controlled trials (RCTs) on TYK2 inhibitor was performed to complement the genetic evidence.Findings: PheWAS-MR found that genetically-proxied TYK2 inhibition was associated with lower risk of a wide range of autoimmune diseases. The associations with hypothyroidism and psoriasis were confirmed in MR analysis of tissue-specific TYK2 gene expression and the associations with systemic lupus erythematosus, psoriasis, and rheumatoid arthritis were observed in colocalization analysis. There were nominal associations of genetically-proxied TYK2 inhibition with increased risk of prostate and breast cancer but not in tissue-specific expression MR or colocalization analyses. Thirty-seven blood biomarkers were associated with the TYK2 loss-of-function mutation. Evidence from RCTs confirmed the effectiveness of TYK2 inhibitors on plaque psoriasis and reported several adverse effects.Interpretation: This study supports TYK2 inhibitor as a potential treatment for psoriasis and several other autoim-mune diseases. Increased pharmacovigilance is warranted in relation to the potential adverse effects.
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| 46. |
- Yuan, Yuan, et al.
(författare)
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Comprehensive molecular characterization of mitochondrial genomes in human cancers
- 2020
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 52:3, s. 342-352
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondria are essential cellular organelles that play critical roles in cancer. Here, as part of the International Cancer Genome Consortium/The Cancer Genome Atlas Pan-Cancer Analysis of Whole Genomes Consortium, which aggregated whole-genome sequencing data from 2,658 cancers across 38 tumor types, we performed a multidimensional, integrated characterization of mitochondrial genomes and related RNA sequencing data. Our analysis presents the most definitive mutational landscape of mitochondrial genomes and identifies several hypermutated cases. Truncating mutations are markedly enriched in kidney, colorectal and thyroid cancers, suggesting oncogenic effects with the activation of signaling pathways. We find frequent somatic nuclear transfers of mitochondrial DNA, some of which disrupt therapeutic target genes. Mitochondrial copy number varies greatly within and across cancers and correlates with clinical variables. Co-expression analysis highlights the function of mitochondrial genes in oxidative phosphorylation, DNA repair and the cell cycle, and shows their connections with clinically actionable genes. Our study lays a foundation for translating mitochondrial biology into clinical applications.
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| 47. |
- Zhao, Xue-Ke, et al.
(författare)
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Focal amplifications are associated with chromothripsis events and diverse prognoses in gastric cardia adenocarcinoma
- 2021
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- The role of focal amplifications and extrachromosomal DNA (ecDNA) is unknown in gastric cardia adenocarcinoma (GCA). Here, we identify frequent focal amplifications and ecDNAs in Chinese GCA patient samples, and find focal amplifications in the GCA cohort are associated with the chromothripsis process and may be induced by accumulated DNA damage due to local dietary habits. We observe diverse correlations between the presence of oncogene focal amplifications and prognosis, where ERBB2 focal amplifications positively correlate with prognosis and EGFR focal amplifications negatively correlate with prognosis. Large-scale ERBB2 immunohistochemistry results from 1668 GCA patients show survival probability of ERBB2 positive patients is lower than that of ERBB2 negative patients when their surviving time is under 2 years, however, the tendency is opposite when their surviving time is longer than 2 years. Our observations indicate that the ERBB2 focal amplifications may represent a good prognostic marker in GCA patients.
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| 48. |
- Zheng, TY, et al.
(författare)
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Systematical analysis reveals a strong cancer relevance of CREB1-regulated genes
- 2021
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Ingår i: Cancer cell international. - : Springer Science and Business Media LLC. - 1475-2867. ; 21:1, s. 530-
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Tidskriftsartikel (refereegranskat)abstract
- The transcription factor cyclic-AMP response element-binding protein 1 (CREB1) responds to cAMP level and controls the expression of target genes, which regulates nutrition partitioning. The promoters of CREB1-targeted genes responsive to cAMP have been extensively investigated and characterized with the presence of both cAMP response element and TATA box. Compelling evidence demonstrates that CREB1 also plays an essential role in promoting tumor development. However, only very few genes required for cell survival, proliferation and migration are known to be constitutively regulated by CREB1 in tumors. Their promoters mostly do not harbor any cAMP response element. Thus, it is very likely that CREB1 regulates the expressions of distinct sets of target genes in normal tissues and tumors. The whole gene network constitutively regulated by CREB1 in tumors has remained unrevealed. Here, we employ a systematical and integrative approach to decipher this gene network in the context of both tissue cultured cancer cells and patient samples. We combine transcriptomic, Rank-Rank Hypergeometric Overlap, and Chipseq analysis, to define and characterize CREB1-regulated genes in a multidimensional fashion. A strong cancer relevance of those top-ranked targets, which meet the most stringent criteria, is eventually verified by overall survival analysis of cancer patients. These findings strongly suggest the importance of genes constitutively regulated by CREB1 for their implicative involvement in promoting tumorigenesis.
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| 49. |
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| 50. |
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