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| 2. |
- Butler-Laporte, G, et al.
(författare)
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Exome-wide association study to identify rare variants influencing COVID-19 outcomes: Results from the Host Genetics Initiative
- 2022
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 18:11, s. e1010367-
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Tidskriftsartikel (refereegranskat)abstract
- Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75–10.05, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.
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| 3. |
- Eng, Ryan C., et al.
(författare)
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KATANIN and CLASP function at different spatial scales to mediate microtubule response to mechanical stress in Arabidopsis cotyledons
- 2021
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Ingår i: Current Biology. - : Elsevier BV. - 0960-9822. ; 31:15, s. 6-3274
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Tidskriftsartikel (refereegranskat)abstract
- Mechanical stress influences cell- and tissue-scale processes across all kingdoms. It remains challenging to delineate how mechanical stress, originating at these different length scales, impacts cell and tissue form. We combine growth tracking of cells, quantitative image analysis, as well as molecular and mechanical perturbations to address this problem in pavement cells of Arabidopsis thaliana cotyledon tissue. We show that microtubule organization based on chemical signals and cell-shape-derived mechanical stress varies during early stages of pavement cell development and is mediated by the evolutionary conserved proteins, KATANIN and CLASP. However, we find that these proteins regulate microtubule organization in response to tissue-scale mechanical stress to different extents in the cotyledon epidermis. Our results further demonstrate that regulation of cotyledon form is uncoupled from the mechanical-stress-dependent control of pavement cell shape that relies on microtubule organization governed by subcellular mechanical stress.
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| 4. |
- Bojar, Daniel, et al.
(författare)
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A Useful Guide to Lectin Binding: Machine-Learning Directed Annotation of 57 Unique Lectin Specificities
- 2022
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Ingår i: ACS Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 17:11, s. 2993-3012
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Tidskriftsartikel (refereegranskat)abstract
- Glycans are critical to every facet of biology and medicine, from viral infections to embryogenesis. Tools to study glycans are rapidly evolving; however, the majority of our knowledge is deeply dependent on binding by glycan binding proteins (e.g., lectins). The specificities of lectins, which are often naturally isolated proteins, have not been well-defined, making it difficult to leverage their full potential for glycan analysis. Herein, we use a combination of machine learning algorithms and expert annotation to define lectin specificity for this important probe set. Our analysis uses comprehensive glycan microarray analysis of commercially available lectins we obtained using version 5.0 of the Consortium for Functional Glycomics glycan microarray (CFGv5). This data set was made public in 2011. We report the creation of this data set and its use in large-scale evaluation of lectin-glycan binding behaviors. Our motif analysis was performed by integrating 68 manually defined glycan features with systematic probing of computational rules for significant binding motifs using mono- and disaccharides and linkages. Combining machine learning with manual annotation, we create a detailed interpretation of glycan-binding specificity for 57 unique lectins, categorized by their major binding motifs: mannose, complex-type N-glycan, O-glycan, fucose, sialic acid and sulfate, GlcNAc and chitin, Gal and LacNAc, and GalNAc. Our work provides fresh insights into the complex binding features of commercially available lectins in current use, providing a critical guide to these important reagents. ©
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| 5. |
- Curbis, F, et al.
(författare)
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HIGHLIGHTS FROM THE CONCEPTUAL DESIGN REPORT OF THE SOFT X-RAY LASER AT MAX IV
- 2021
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Ingår i: Proceedings of IPAC2021.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The SXL (Soft X-ray Laser) project developed a conceptual design for a soft X-ray Free Electron Laser (FEL) in the 1-5 nm wavelength range, driven by the existing MAX IV 3 GeV linac. In this contribution we will focus on the FEL operation modes developed for the first phase of the project based on two different linac modes. The design work was supported by the Knut and Alice Wallenberg foundation and by several Swedish universities and organizations (
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| 6. |
- Fu, Becky Q., et al.
(författare)
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Barriers and Facilitators to Implementing Interventions for Reducing Avoidable Hospital Readmission: Systematic Review of Qualitative Studies
- 2023
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Ingår i: International Journal of Health Policy and Management. - : KERMAN UNIV MEDICAL SCIENCES. - 2322-5939. ; 12, s. 1-17
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Forskningsöversikt (refereegranskat)abstract
- Background: Avoidable hospital readmission is a major problem among health systems. Although there are effective peri-discharge interventions for reducing avoidable hospital readmission, successful implementation is challenging. This systematic review(SR) of qualitative studies aimed to identify barriers and facilitators to implementing peri-discharge interventions from providers and service users perspectives.Methods: We searched four databases for potentially eligible qualitative studies from databases inception to Mar 2020, and updated literature search for studies published between 2020 to Oct 2021. Barriers and facilitators to implementing peri-discharge interventions were identified and mapped onto the Consolidated Framework for Implementation Research(CFIR) constructs. Inductive analysis of the CFIR constructs was performed to yield thematic areas that illustrated the relationship between various facilitators and barriers, generating practical insights to key implementation issues. Results: Thirteen qualitative studies were included in this SR. Key issues were clustered in the CFIR constructs of Design Quality and Complexity of the intervention, strength of Network and Communication, being responsive to Patient Needs with sufficient Resource support, and External Incentives. The three thematic areas were rationality of the interventions, readiness and effort of multidisciplinary implementation teams, and influence of external stakeholders. Common barriers included i) limited resources, ii) poor communication among team members, iii) incompatibility between the new intervention and existing work routine, iv) complicated implementation process, v) low practicality of supporting instruments, and vi) lack of understanding about the content and effectiveness of the new interventions. Common facilitators were i) information sharing via regular meetings on implementation issues, ii) organizational culture that values quality and accountability, iii) financial penalties for hospitals with high avoidable readmissions rates, iv) external support offered via quality improvement programs and community resources, and v) senior leadership support. Conclusions: This study synthesized commonly-presenting barriers and facilitators to implementing peri-discharge interventions among different healthcare organizations. Findings may inform development of implementation strategies in different health systems after appropriate tailoring, based on a consensus-based formative research process.
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| 7. |
- Garg, D., et al.
(författare)
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Fragmentation Dynamics of Fluorene Explored Using Ultrafast XUV-Vis Pump-Probe Spectroscopy
- 2022
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Ingår i: Frontiers in Physics. - : Frontiers Media SA. - 2296-424X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- We report on the use of extreme ultraviolet (XUV, 30.3 nm) radiation from the Free-electron LASer in Hamburg (FLASH) and visible (Vis, 405 nm) photons from an optical laser to investigate the relaxation and fragmentation dynamics of fluorene ions. The ultrashort laser pulses allow to resolve the molecular processes occurring on the femtosecond timescales. Fluorene is a prototypical small polycyclic aromatic hydrocarbon (PAH). Through their infrared emission signature, PAHs have been shown to be ubiquitous in the universe, and they are assumed to play an important role in the chemistry of the interstellar medium. Our experiments track the ionization and dissociative ionization products of fluorene through time-of-flight mass spectrometry and velocity-map imaging. Multiple processes involved in the formation of each of the fragment ions are disentangled through analysis of the ion images. The relaxation lifetimes of the excited fluorene monocation and dication obtained through the fragment formation channels are reported to be in the range of a few tens of femtoseconds to a few picoseconds.
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| 8. |
- Kockert, Hansjochen, et al.
(författare)
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UV-induced dissociation of CH2BrI probed by intense femtosecond XUV pulses
- 2022
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Ingår i: JOURNAL OF PHYSICS B-ATOMIC MOLECULAR AND OPTICAL PHYSICS. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 55:1
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Tidskriftsartikel (refereegranskat)abstract
- The ultraviolet (UV)-induced dissociation and photofragmentation of gas-phase CH2BrI molecules induced by intense femtosecond extreme ultraviolet (XUV) pulses at three different photon energies are studied by multi-mass ion imaging. Using a UV-pump-XUV-probe scheme, charge transfer between highly charged iodine ions and neutral CH2Br radicals produced by C-I bond cleavage is investigated. In earlier charge-transfer studies, the center of mass of the molecules was located along the axis of the bond cleaved by the pump pulse. In the present case of CH2BrI, this is not the case, thus inducing a rotation of the fragment. We discuss the influence of the rotation on the charge transfer process using a classical over-the-barrier model. Our modeling suggests that, despite the fact that the dissociation is slower due to the rotational excitation, the critical interatomic distance for charge transfer is reached faster. Furthermore, we suggest that charge transfer during molecular fragmentation may be modulated in a complex way.
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| 9. |
- Lee, Jason W.l., et al.
(författare)
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The Kinetic Energy of PAH Dication and Trication Dissociation Determined by Recoil-Frame Covariance Map Imaging
- 2022
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Ingår i: Physical Chemistry Chemical Physics. - 1463-9084. ; 24:38, s. 23096-23105
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the dissociation of dications and trications of three polycyclic aromatic hydrocarbons (PAHs), fluorene, phenanthrene, and pyrene. PAHs are a family of molecules ubiquitous in space and involved in much of the chemistry of the interstellar medium. In our experiments, ions are formed by interaction with 30.3 nm extreme ultraviolet (XUV) photons, and their velocity map images are recorded using a PImMS2 multi-mass imaging sensor. Application of recoil-frame covariance analysis allows the total kinetic energy release (TKER) associated with multiple fragmentation channels to be determined to high precision, ranging 1.94-2.60 eV and 2.95-5.29 eV for the dications and trications, respectively. Experimental measurements are supported by Born-Oppenheimer molecular dynamics (BOMD) simulations.
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| 10. |
- Lee, J. W. L., et al.
(författare)
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The kinetic energy of PAH dication and trication dissociation determined by recoil-frame covariance map imaging
- 2022
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Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 24:38, s. 23096-23105
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the dissociation of dications and trications of three polycyclic aromatic hydrocarbons (PAHs), fluorene, phenanthrene, and pyrene. PAHs are a family of molecules ubiquitous in space and involved in much of the chemistry of the interstellar medium. In our experiments, ions are formed by interaction with 30.3 nm extreme ultraviolet (XUV) photons, and their velocity map images are recorded using a PImMS2 multi-mass imaging sensor. Application of recoil-frame covariance analysis allows the total kinetic energy release (TKER) associated with multiple fragmentation channels to be determined to high precision, ranging 1.94-2.60 eV and 2.95-5.29 eV for the dications and trications, respectively. Experimental measurements are supported by Born-Oppenheimer molecular dynamics (BOMD) simulations.
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