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| 2. |
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| 3. |
- Sonderby, Ida E., et al.
(författare)
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Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia
- 2020
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:3, s. 584-602
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Tidskriftsartikel (refereegranskat)abstract
- Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = −0.71 to −1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = −0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10−6, 1.7 × 10−9, 3.5 × 10−12 and 1.0 × 10−4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes.
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| 5. |
- Li, Jian-Yang, et al.
(författare)
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Ejecta from the DART-produced active asteroid Dimorphos
- 2023
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 616, s. 452-456
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Tidskriftsartikel (refereegranskat)abstract
- Some active asteroids have been proposed to be formed as a result of impact events1. Because active asteroids are generally discovered by chance only after their tails have fully formed, the process of how impact ejecta evolve into a tail has, to our knowledge, not been directly observed. The Double Asteroid Redirection Test (DART) mission of NASA2, in addition to having successfully changed the orbital period of Dimorphos3, demonstrated the activation process of an asteroid resulting from an impact under precisely known conditions. Here we report the observations of the DART impact ejecta with the Hubble Space Telescope from impact time T + 15 min to T + 18.5 days at spatial resolutions of around 2.1 km per pixel. Our observations reveal the complex evolution of the ejecta, which are first dominated by the gravitational interaction between the Didymos binary system and the ejected dust and subsequently by solar radiation pressure. The lowest-speed ejecta dispersed through a sustained tail that had a consistent morphology with previously observed asteroid tails thought to be produced by an impact4,5. The evolution of the ejecta after the controlled impact experiment of DART thus provides a framework for understanding the fundamental mechanisms that act on asteroids disrupted by a natural impact1,6.
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| 8. |
- Caligiore, Daniele, et al.
(författare)
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Consensus Paper: Towards a Systems-Level View of Cerebellar Function: the Interplay Between Cerebellum, Basal Ganglia, and Cortex.
- 2016
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Ingår i: Cerebellum. - : Springer Science and Business Media LLC. - 1473-4230.
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Tidskriftsartikel (refereegranskat)abstract
- Despite increasing evidence suggesting the cerebellum works in concert with the cortex and basal ganglia, the nature of the reciprocal interactions between these three brain regions remains unclear. This consensus paper gathers diverse recent views on a variety of important roles played by the cerebellum within the cerebello-basal ganglia-thalamo-cortical system across a range of motor and cognitive functions. The paper includes theoretical and empirical contributions, which cover the following topics: recent evidence supporting the dynamical interplay between cerebellum, basal ganglia, and cortical areas in humans and other animals; theoretical neuroscience perspectives and empirical evidence on the reciprocal influences between cerebellum, basal ganglia, and cortex in learning and control processes; and data suggesting possible roles of the cerebellum in basal ganglia movement disorders. Although starting from different backgrounds and dealing with different topics, all the contributors agree that viewing the cerebellum, basal ganglia, and cortex as an integrated system enables us to understand the function of these areas in radically different ways. In addition, there is unanimous consensus between the authors that future experimental and computational work is needed to understand the function of cerebellar-basal ganglia circuitry in both motor and non-motor functions. The paper reports the most advanced perspectives on the role of the cerebellum within the cerebello-basal ganglia-thalamo-cortical system and illustrates other elements of consensus as well as disagreements and open questions in the field.
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| 9. |
- Miguel-Blanco, Celia, et al.
(författare)
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The antimalarial efficacy and mechanism of resistance of the novel chemotype DDD01034957
- 2021
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- New antimalarial therapeutics are needed to ensure that malaria cases continue to be driven down, as both emerging parasite resistance to frontline chemotherapies and mosquito resistance to current insecticides threaten control programmes. Plasmodium, the apicomplexan parasite responsible for malaria, causes disease pathology through repeated cycles of invasion and replication within host erythrocytes (the asexual cycle). Antimalarial drugs primarily target this cycle, seeking to reduce parasite burden within the host as fast as possible and to supress recrudescence for as long as possible. Intense phenotypic drug screening efforts have identified a number of promising new antimalarial molecules. Particularly important is the identification of compounds with new modes of action within the parasite to combat existing drug resistance and suitable for formulation of efficacious combination therapies. Here we detail the antimalarial properties of DDD01034957—a novel antimalarial molecule which is fast-acting and potent against drug resistant strains in vitro, shows activity in vivo, and possesses a resistance mechanism linked to the membrane transporter PfABCI3. These data support further medicinal chemistry lead-optimization of DDD01034957 as a novel antimalarial chemical class and provide new insights to further reduce in vivo metabolic clearance.
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| 10. |
- Pena, FJ, et al.
(författare)
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Identification of sperm morphometric subpopulations in two different portions of the boar ejaculate and its relation to postthaw quality
- 2005
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Ingår i: Journal of Andrology. - : American Society of Andrology. - 0196-3635 .- 1939-4640. ; 26:6, s. 716-723
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Tidskriftsartikel (refereegranskat)abstract
- A statistical approach using sequentially principal component analysis (PCA), clustering, and discriminant analyses was. developed to identify sperm morphometric subpopulations in well-defined portions of the fresh boar ejaculate. Semen was obtained as 2 portions (the first 10 mL of the sperm-rich fraction and the rest of. the ejaculate, respectively) and frozen using a conventional protocol. Before freezing, an aliquot was Used for computer-assisted. sperm morphometry analysis (ASMA). Postthaw quality was evaluated using computer-assisted sperm analysis (CASA), and an annexin-V/PI assay evaluated sperm membranes. The PCA revealed that 3 variables represented more than 78% of the cumulative variance in sperm subpopulations. The clustering and discriminant analyses, based on 5780 individual spermatozoa, revealed the existence of 4 sperm subpopulations. The relative percentage of these subpopulations Varied between boar and ejaculate portions. Linear regression models based on measured morphometric characteristics could account for up to 36% of the percentage of intact sperm membranes postthaw. The ASMA protocol used in our study was useful to detect subtle morphometric differences between spermatozoa, and the combination of this analysis with a multivariate statistical procedure gave hew information on the biological characteristics of boar ejaculates that is not given by conventional sperm analysis.
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| 11. |
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| 12. |
- Yang, J, et al.
(författare)
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Guidelines and definitions for research on epithelial-mesenchymal transition
- 2020
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Ingår i: Nature reviews. Molecular cell biology. - : Springer Science and Business Media LLC. - 1471-0080 .- 1471-0072. ; 21:6, s. 341-352
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Tidskriftsartikel (refereegranskat)abstract
- Epithelial–mesenchymal transition (EMT) encompasses dynamic changes in cellular organization from epithelial to mesenchymal phenotypes, which leads to functional changes in cell migration and invasion. EMT occurs in a diverse range of physiological and pathological conditions and is driven by a conserved set of inducing signals, transcriptional regulators and downstream effectors. With over 5,700 publications indexed by Web of Science in 2019 alone, research on EMT is expanding rapidly. This growing interest warrants the need for a consensus among researchers when referring to and undertaking research on EMT. This Consensus Statement, mediated by ‘the EMT International Association’ (TEMTIA), is the outcome of a 2-year-long discussion among EMT researchers and aims to both clarify the nomenclature and provide definitions and guidelines for EMT research in future publications. We trust that these guidelines will help to reduce misunderstanding and misinterpretation of research data generated in various experimental models and to promote cross-disciplinary collaboration to identify and address key open questions in this research field. While recognizing the importance of maintaining diversity in experimental approaches and conceptual frameworks, we emphasize that lasting contributions of EMT research to increasing our understanding of developmental processes and combatting cancer and other diseases depend on the adoption of a unified terminology to describe EMT.
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| 13. |
- Chang, Heejun, et al.
(författare)
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Assessment of urban flood vulnerability using the social-ecological-technological systems framework in six US cities
- 2021
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Ingår i: Sustainable cities and society. - : Elsevier BV. - 2210-6707. ; 68
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Tidskriftsartikel (refereegranskat)abstract
- As urban populations continue to grow through the 21st century, more people are projected to be at risk of exposure to climate change-induced extreme events. To investigate the complexity of urban floods, this study applied an interlinked social-ecological-technological systems (SETS) vulnerability framework by developing an urban flood vulnerability index for six US cities. Indicators were selected to reflect and illustrate exposure, sensitivity, and adaptive capacity to flooding for each of the three domains of SETS. We quantified 18 indicators and normalized them by the cities' 500-yr floodplain area at the census block group level. Clusters of flood vulnerable areas were identified differently by each SETS domain, and some areas were vulnerable to floods in more than one domain. Results are provided to support decision-making for reducing risks to flooding, by considering social, ecological, and technological vulnerability as well as hotspots where multiple sources of vulnerability coexist. The spatially explicit urban SETS flood vulnerability framework can be transferred to other regions facing challenging urban floods and other types of environmental hazards. Mapping SETS flood vulnerability helps to reveal intersections of complex SETS interactions and inform policy-making for building more resilient cities in the face of extreme events and climate change impacts.
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| 14. |
- Fuglesang, Christer, 1957-, et al.
(författare)
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Manuscript Template And Style Guide
- 2021
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Ingår i: Proceedings of the International Astronautical Congress, IAC. - : International Astronautical Federation, IAF.
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Konferensbidrag (refereegranskat)abstract
- Space-based geoengineering has rarely been studied from a practical point of view, considered unrealistic as a near-future alternative to fight climate change. This study evaluates the feasibility of implementing a space sunshade in the vicinity of the first Lagrange point of the Sun-Earth system by the middle of the century. The analysis considers the necessary technological development, the possible trajectories for the shades, and an approximation of the size and cost of the system. The mass of the system is strongly dependent on possible optical properties of future solar sails, so a conservative assumption was made for these. To counteract a global temperature increase of 1 °C the shade would be formed by 7.5x108 sailcraft with a sail area of 2 500 m2 each and a total mass of 4x1010 kg. It is argued that the sailcraft could be launched to a 2000 km altitude orbit, from where they will travel for about 600 days to the equilibrium point using solar radiation pressure. The total cost of the mission is estimated to be around five trillion US dollars, based on a launch cost of 50 USD/kg. However, the cost to society, environment and global economy could be two to three orders of magnitude larger, if global temperature increase cannot be controlled by limiting greenhouse gas emissions. There are two main technological challenges for this to become a reality: the low TRL of the solar sails proposed and the necessary development in the launch vehicle industry given the dimensions of the mission.
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| 15. |
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| 16. |
- Herrera, A, et al.
(författare)
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Endothelial cell activation on 3D-matrices derived from PDGF-BB-stimulated fibroblasts is mediated by Snail1
- 2018
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Ingår i: Oncogenesis. - : Springer Science and Business Media LLC. - 2157-9024. ; 7:9, s. 76-
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Tidskriftsartikel (refereegranskat)abstract
- Carcinomas, such as colon cancer, initiate their invasion by rescuing the innate plasticity of both epithelial cells and stromal cells. Although Snail is a transcriptional factor involved in the Epithelial-Mesenchymal Transition, in recent years, many studies have also identified the major role of Snail in the activation of Cancer-Associated Fibroblast (CAF) cells and the remodeling of the extracellular matrix. In CAFs, Platelet-derived growth factor (PDGF) receptor signaling is a major functional determinant. High expression of both SNAI1 and PDGF receptors is associated with poor prognosis in cancer patients, but the mechanism(s) that underlie these connections are not understood. In this study, we demonstrate that PDGF-activated fibroblasts stimulate extracellular matrix (ECM) fiber remodeling and deposition. Furthermore, we describe how SNAI1, through the FAK pathway, is a necessary factor for ECM fiber organization. The parallel-oriented fibers are used by endothelial cells as “tracks”, facilitating their activation and the creation of tubular structures mimicking in vivo capillary formation. Accordingly, Snail1 expression in fibroblasts was required for the co-adjuvant effect of these cells on matrix remodeling and neoangiogenesis when co-xenografted in nude mice. Finally, in tumor samples from colorectal cancer patients a direct association between stromal SNAI1 expression and the endothelial marker CD34 was observed. In summary, our results advance the understanding of PDGF/SNAI1-activated CAFs in matrix remodeling and angiogenesis stimulation.
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| 17. |
- Martin-Brevet, S., et al.
(författare)
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Quantifying the Effects of 16p11.2 Copy Number Variants on Brain Structure: A Multisite Genetic-First Study
- 2018
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223. ; 84:4, s. 253-264
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: 16p11.2 breakpoint 4 to 5 copy number variants (CNVs) increase the risk for developing autism spectrum disorder, schizophrenia, and language and cognitive impairment. In this multisite study, we aimed to quantify the effect of 16p11.2 CNVs on brain structure. METHODS: Using voxel- and surface-based brain morphometric methods, we analyzed structural magnetic resonance imaging collected at seven sites from 78 individuals with a deletion, 71 individuals with a duplication, and 212 individuals without a CNV. RESULTS: Beyond the 16p11.2-related mirror effect on global brain morphometry, we observe regional mirror differences in the insula (deletion. control. duplication). Other regions are preferentially affected by either the deletion or the duplication: the calcarine cortex and transverse temporal gyrus (deletion > control > Cohen's d > -1), the superior and middle temporal gyri (deletion > control > Cohen's d, 21), and the caudate and hippocampus (control > duplication > -0.5 > Cohen's d > -1). Measures of cognition, language, and social responsiveness and the presence of psychiatric diagnoses do not influence these results. CONCLUSIONS: The global and regional effects on brain morphometry due to 16p11.2 CNVs generalize across site, computational method, age, and sex. Effect sizes on neuroimaging and cognitive traits are comparable. Findings partially overlap with results of meta-analyses performed across psychiatric disorders. However, the lack of correlation between morphometric and clinical measures suggests that CNV-associated brain changes contribute to clinical manifestations but require additional factors for the development of the disorder. These findings highlight the power of genetic risk factors as a complement to studying groups defined by behavioral criteria.
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| 19. |
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| 20. |
- Torres, Cynthia M., et al.
(författare)
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Cupric and Chloride Ions : Leaching of Chalcopyrite Concentrate with Low Chloride Concentration Media
- 2019
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Ingår i: Minerals. - : MDPI. - 2075-163X. ; 9:10
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, the effect of the cupric and chloride ions concentrations on copper dissolution from chalcopyrite concentrate was studied in acidified media. Variables included three different concentrations of Cu2+ (0.5, 1.5, and 2.5 g L−1), four different concentrations of Cl− (0, 5, 7, and 10 g L−1), two different pH values of 1 and 2, and a constant temperature of 60 °C. Results indicated that addition of Cl− to the system improves copper extractions, especially at higher concentrations of Cu2+. Initial copper concentrations in the leaching solution did not significantly affect the copper extraction when Cl− was not present. Better copper extractions were obtained at pH 1 as compared with pH 2. As the Cu2+ and Cl− concentrations were increased, higher values of redox potential were obtained. According to the formation constants of the chloro-complexes, the predominant species in the Cu2+/Cl− system in the studied interval were CuCl+ and Cu2+. Using a model of copper speciation in the experimental range predicted for a single copper concentration with increasing Cl− concentration, the Cu2+ concentration decreased significantly while the concentration of the chloro-complex species CuCl+ increased. In the leached residue, evidence of sulfur formation was found using SEM and corroborated by XRD analysis. When chloride is present in the medium, the amounts of copper and iron in the residue decrease, confirming a positive effect of chloride on the extraction of copper from concentrate for the studied conditions.
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