| 1. |
- Freischmidt, Axel, et al.
(författare)
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Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia
- 2015
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Ingår i: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1097-6256 .- 1546-1726. ; 18:5, s. 631-
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a genetically heterogeneous neurodegenerative syndrome hallmarked by adult-onset loss of motor neurons. We performed exome sequencing of 252 familial ALS (fALS) and 827 control individuals. Gene-based rare variant analysis identified an exome-wide significant enrichment of eight loss-of-function (LoF) mutations in TBK1 (encoding TANK-binding kinase 1) in 13 fALS pedigrees. No enrichment of LoF mutations was observed in a targeted mutation screen of 1,010 sporadic ALS and 650 additional control individuals. Linkage analysis in four families gave an aggregate LOD score of 4.6. In vitro experiments confirmed the loss of expression of TBK1 LoF mutant alleles, or loss of interaction of the C-terminal TBK1 coiled-coil domain (CCD2) mutants with the TBK1 adaptor protein optineurin, which has been shown to be involved in ALS pathogenesis. We conclude that haploinsufficiency of TBK1 causes ALS and fronto-temporal dementia.
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| 2. |
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| 3. |
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| 4. |
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| 5. |
- Engert, Andreas, et al.
(författare)
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The European Hematology Association Roadmap for European Hematology Research : a consensus document
- 2016
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Ingår i: Haematologica. - Pavia, Italy : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 101:2, s. 115-208
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Tidskriftsartikel (refereegranskat)abstract
- The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
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| 6. |
- Kaschina, Elena, et al.
(författare)
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Angiotensin II type 2 receptor stimulation : a novel option of therapeutic interference with the renin-angiotensin system in myocardial infarction?
- 2008
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 118:24, s. 2523-32
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: This study is the first to examine the effect of direct angiotensin II type 2 (AT(2)) receptor stimulation on postinfarct cardiac function with the use of the novel nonpeptide AT(2) receptor agonist compound 21 (C21). METHODS AND RESULTS: Myocardial infarction (MI) was induced in Wistar rats by permanent ligation of the left coronary artery. Treatment with C21 (0.01, 0.03, 0.3 mg/kg per day IP) was started 24 hours after MI and was continued until euthanasia (7 days after MI). Infarct size was assessed by magnetic resonance imaging, and hemodynamic measurements were performed via transthoracic Doppler echocardiography and intracardiac Millar catheter. Cardiac tissues were analyzed for inflammation and apoptosis markers with immunoblotting and real-time reverse transcription polymerase chain reaction. C21 significantly improved systolic and diastolic ventricular function. Scar size was smallest in the C21-treated rats. In regard to underlying mechanisms, C21 diminished MI-induced Fas-ligand and caspase-3 expression in the peri-infarct zone, indicating an antiapoptotic effect. Phosphorylation of the p44/42 and p38 mitogen-activated protein kinases, both involved in the regulation of cell survival, was strongly reduced after MI but almost completely rescued by C21 treatment. Furthermore, C21 decreased MI-induced serum monocyte chemoattractant protein-1 and myeloperoxidase as well as cardiac interleukin-6, interleukin-1beta, and interleukin-2 expression, suggesting an antiinflammatory effect. CONCLUSIONS: Direct AT(2) receptor stimulation may be a novel therapeutic approach to improve post-MI systolic and diastolic function by antiapoptotic and antiinflammatory mechanisms.
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| 7. |
- Lorenzen, Eline D., et al.
(författare)
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Species-specific responses of Late Quaternary megafauna to climate and humans
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 479:7373, s. 359-364
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Tidskriftsartikel (refereegranskat)abstract
- Despite decades of research, the roles of climate and humans in driving the dramatic extinctions of large-bodied mammals during the Late Quaternary period remain contentious. Here we use ancient DNA, species distribution models and the human fossil record to elucidate how climate and humans shaped the demographic history of woolly rhinoceros, woolly mammoth, wild horse, reindeer, bison and musk ox. We show that climate has been a major driver of population change over the past 50,000 years. However, each species responds differently to the effects of climatic shifts, habitat redistribution and human encroachment. Although climate change alone can explain the extinction of some species, such as Eurasian musk ox and woolly rhinoceros, a combination of climatic and anthropogenic effects appears to be responsible for the extinction of others, including Eurasian steppe bison and wild horse. We find no genetic signature or any distinctive range dynamics distinguishing extinct from surviving species, emphasizing the challenges associated with predicting future responses of extant mammals to climate and human-mediated habitat change.
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| 8. |
- Persiani, Michele, 1989-, et al.
(författare)
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Traveling Drinksman : A mobile service robot for people in care-homes
- 2020
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Ingår i: 52nd International Symposium on Robotics, ISR 2020. - : VDE Verlag GmbH. - 9783800754298 ; , s. 31-36
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- This paper describes ongoing work on the development of a service robot for serving drinks to people sitting at tables, for example in the recreation room of a care-house. The robot, denoted the Traveling Drinksman, should be able to detect theoccupied tables, navigate safely according to defined policies, and interact with the humans sitting to serve them a drink. We present initial results addressing all of these problems with different sub-modules, including numerical results for the human head detection module.
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| 9. |
- Raghavan, Maanasa, et al.
(författare)
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Upper Palaeolithic Siberian genome reveals dual ancestry of Native Americans
- 2014
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 505:7481, s. 87-
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Tidskriftsartikel (refereegranskat)abstract
- The origins of the First Americans remain contentious. Although Native Americans seem to be genetically most closely related to east Asians(1-3), there is no consensus with regard to which specific Old World populations they are closest to(4-8). Here we sequence the draft genome of an approximately 24,000-year-old individual (MA-1), from Mal'ta in south-central Siberia(9), to an average depth of 1x. To our knowledge this is the oldest anatomically modern human genome reported to date. The MA-1 mitochondrial genome belongs to haplogroup U, which has also been found at high frequency among Upper Palaeolithic and Mesolithic European hunter-gatherers(10-12), and the Y chromosome of MA-1 is basal to modern-day western Eurasians and near the root of most Native American lineages(5). Similarly, we find autosomal evidence that MA-1 is basal to modern-day western Eurasians and genetically closely related to modern-day Native Americans, with no close affinity to east Asians. This suggests that populations related to contemporary western Eurasians had a more north-easterly distribution 24,000 years ago than commonly thought. Furthermore, we estimate that 14 to 38% of Native American ancestry may originate through gene flow from this ancient population. This is likely to have occurred after the divergence of Native American ancestors from east Asian ancestors, but before the diversification of Native American populations in the New World. Gene flow from the MA-1 lineage into Native American ancestors could explain why several crania from the First Americans have been reported as bearing morphological characteristics that do not resemble those of east Asians(2,13). Sequencing of another south-central Siberian, Afontova Gora-2 dating to approximately 17,000 years ago(14), revealed similar autosomal genetic signatures as MA-1, suggesting that the region was continuously occupied by humans throughout the Last Glacial Maximum. Our findings reveal that western Eurasian genetic signatures in modern-day Native Americans derive not only from post-Columbian admixture, as commonly thought, but also from a mixed ancestry of the First Americans.
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| 10. |
- Adrian-Martinez, S., et al.
(författare)
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A first search for coincident gravitational waves and high energy neutrinos using LIGO, Virgo and ANTARES data from 2007
- 2013
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :6
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of the first search for gravitational wave bursts associated with high energy neutrinos. Together, these messengers could reveal new, hidden sources that are not observed by conventional photon astronomy, particularly at high energy. Our search uses neutrinos detected by the underwater neutrino telescope ANTARES in its 5 line configuration during the period January - September 2007, which coincided with the fifth and first science runs of LIGO and Virgo, respectively. The LIGO-Virgo data were analysed for candidate gravitational-wave signals coincident in time and direction with the neutrino events. No significant coincident events were observed. We place limits on the density of joint high energy neutrino - gravitational wave emission events in the local universe, and compare them with densities of merger and core-collapse events.
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| 11. |
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| 12. |
- Auffray, Charles, et al.
(författare)
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Making sense of big data in health research: Towards an EU action plan
- 2016
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Ingår i: Genome Medicine. - : BIOMED CENTRAL LTD. - 1756-994X. ; 8:71
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Tidskriftsartikel (refereegranskat)abstract
- Medicine and healthcare are undergoing profound changes. Whole-genome sequencing and high-resolution imaging technologies are key drivers of this rapid and crucial transformation. Technological innovation combined with automation and miniaturization has triggered an explosion in data production that will soon reach exabyte proportions. How are we going to deal with this exponential increase in data production? The potential of "big data" for improving health is enormous but, at the same time, we face a wide range of challenges to overcome urgently. Europe is very proud of its cultural diversity; however, exploitation of the data made available through advances in genomic medicine, imaging, and a wide range of mobile health applications or connected devices is hampered by numerous historical, technical, legal, and political barriers. European health systems and databases are diverse and fragmented. There is a lack of harmonization of data formats, processing, analysis, and data transfer, which leads to incompatibilities and lost opportunities. Legal frameworks for data sharing are evolving. Clinicians, researchers, and citizens need improved methods, tools, and training to generate, analyze, and query data effectively. Addressing these barriers will contribute to creating the European Single Market for health, which will improve health arid healthcare for all Europearis.
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| 13. |
- Birner, Regina, et al.
(författare)
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‘We would rather die from Covid-19 than from hunger’ - Exploring lockdown stringencies in five African countries
- 2021
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Ingår i: Global Food Security. - : Elsevier BV. - 2211-9124. ; 31
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Tidskriftsartikel (refereegranskat)abstract
- Facing COVID-19, African countries were confronted with a dilemma: enacting strict lockdowns to “flatten the curve” could potentially have large effects on food security. Given this catch-22 situation, there was widespread concern that Africa would suffer most from the pandemic. Yet, emerging evidence in early 2021 showed that COVID-19 morbidity remained low, while “biblical famines” have been avoided so far. This paper explores how five African countries maneuvered around the potentially large trade-offs between public health and food security when designing their policy responses to COVID-19 based on a content analysis of 1188 newspaper articles. The findings show that food security concerns played an important role in the public policy debate and influenced the stringency of lockdowns, especially in more democratic countries.
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| 14. |
- Chng, Kern Rei, et al.
(författare)
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Cartography of opportunistic pathogens and antibiotic resistance genes in a tertiary hospital environment
- 2020
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 26, s. 941-951
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Tidskriftsartikel (refereegranskat)abstract
- Although disinfection is key to infection control, the colonization patterns and resistomes of hospital-environment microbes remain underexplored. We report the first extensive genomic characterization of microbiomes, pathogens and antibiotic resistance cassettes in a tertiary-care hospital, from repeated sampling (up to 1.5 years apart) of 179 sites associated with 45 beds. Deep shotgun metagenomics unveiled distinct ecological niches of microbes and antibiotic resistance genes characterized by biofilm-forming and human-microbiome-influenced environments with corresponding patterns of spatiotemporal divergence. Quasi-metagenomics with nanopore sequencing provided thousands of high-contiguity genomes, phage and plasmid sequences (>60% novel), enabling characterization of resistome and mobilome diversity and dynamic architectures in hospital environments. Phylogenetics identified multidrug-resistant strains as being widely distributed and stably colonizing across sites. Comparisons with clinical isolates indicated that such microbes can persist in hospitals for extended periods (>8 years), to opportunistically infect patients. These findings highlight the importance of characterizing antibiotic resistance reservoirs in hospitals and establish the feasibility of systematic surveys to target resources for preventing infections. Spatiotemporal characterization of microbial diversity and antibiotic resistance in a tertiary-care hospital reveals broad distribution and persistence of antibiotic-resistant organisms that could cause opportunistic infections in a healthcare setting.
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| 15. |
- Da Silva, Adrien
(författare)
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Aspects of material and heat transfer in drop- and powder-based laser additive manufacturing
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Additive Manufacturing became a major research topic and part of industrial production in the past years. Numerous techniques now allow to build 3D structures with a wide choice of materials. When it comes to processing of metals, a laser beam is often used as a heat source to melt either a wire or powder. Novel approaches of material deposition are also developed, such as Laser Droplet Generation, which could potentially be applied to Additive Manufacturing. During the process, the laser beam light is partly absorbed by the material, and is then converted to heat, which can induce melting and even vaporization. Additive Manufacturing presents several processing challenges, such as the recoil pressure acting on the drops and powder particles that affects their trajectory. Storage and recycling of the powders is also an important aspect since the powder properties are changed through aging. Another challenge is the adjustment of process parameters according to varying deposition conditions, where the use of process monitoring techniques is crucial.Therefore, this thesis aims at better understanding (i) the effects of recoil pressureon metal drops and powder particles, (ii) powder aging and its effects on the process, and (iii) process optimisation and stability via monitoring. In the six adjoined papers, high-speed imaging and thermal imaging were used to observe laser Additive Manufacturing processes involving both metal drops and powders. The videos enabled to observe drop detachments, measure trajectories, plot powder density maps, quantify powder catchment in the melt pool, measure themelt pool geometry, detect oxides, and extract cooling rates. The experimental results were supplemented with material analysis and theoretical calculations of thermodynamics, recoil pressure and surface tension.These studies allowed to conclude that the recoil pressure induced by laser irradiation on a drop or a powder particle can have some significant effect such as acceleration, change of trajectory, or disintegration. However, these effects seem to be considerably lower than what theoretical models predict. It was also found that the recoil pressure can be used to accurately detach drops from a wire, which was utilised as a new material deposition method for Additive Manufacturing. In Directed Energy deposition, it was showed that aging of the aluminium powder feedstock should be avoided since it induces high porosity, high dilution and decreased mechanical properties. Finally, to guarantee a defect-free deposition during the whole process, it was demonstrated that a thermal camera can be used to monitor the melt pool size, which allows to apply appropriate laser power adjustments to compensate for changing building conditions.
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| 16. |
- Danko, David, et al.
(författare)
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A global metagenomic map of urban microbiomes and antimicrobial resistance
- 2021
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Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 184:13, s. 3376-3393
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Tidskriftsartikel (refereegranskat)abstract
- We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities over 3 years, representing the first systematic, worldwide catalog of the urban microbial ecosystem. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics, antimicrobial resistance (AMR) markers, and genetic elements, including 10,928 viruses, 1,302 bacteria, 2 archaea, and 838,532 CRISPR arrays not found in reference databases. We identified 4,246 known species of urban microorganisms and a consistent set of 31 species found in 97% of samples that were distinct from human commensal organisms. Profiles of AMR genes varied widely in type and density across cities. Cities showed distinct microbial taxonomic signatures that were driven by climate and geographic differences. These results constitute a high-resolution global metagenomic atlas that enables discovery of organisms and genes, highlights potential public health and forensic applications, and provides a culture-independent view of AMR burden in cities.
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| 17. |
- Deering, Thomas F., et al.
(författare)
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Expert Consensus on Comprehensive Early Rhythm Control in Addition to Guideline-Based Care for Atrial Fibrillation : A Modified Delphi Survey
- 2023
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Ingår i: American Journal of Cardiology. - : Elsevier. - 0002-9149 .- 1879-1913. ; 207, s. 328-335
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Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation (AF) practice guidelines recommend a rhythm-control strategy to improve symptoms and quality of life, noting the side effects of antiarrhythmic drugs and catheter ablation. Emerging evidence indicates that comprehensive early rhythm control with antiarrhythmic drugs or catheter ablation is associated with a lower risk of adverse cardiovascular outcomes versus the usual care. Using an online modified Delphi survey approach, perspectives and expert consensus among electrophysiologists were examined through a series of ranking and likelihood questions around treatment decision-making on (1) the use of comprehensive early rhythm-control strategies in patients with AF based on guidelines and emerging research and (2) treatment selection factors. A panel of 17 electrophysiologists reached a consensus on using early rhythm control (median 90, interquartile range 14) based on the view that early intervention improved cardiovascular outcomes (mean rank 1.6 of 3, 82% within 1 SD) and symptoms (1.8 of 3, 41%). AF-related symptoms were identified as the most important in making a treat-ment initiation decision (1.1 of 7, 88%), followed by AF type (2.5 of 7, 82%). Participants were most likely to initiate treatment at AF symptom onset (median 80; interquartile range 6). In making treatment selection decisions, participants ranked short-term/long-term safety (1.9 of 7, 88%) and efficacy (1.8 of 7, 53%) as the top 2 considerations. In conclusion, experts were in favor of early rhythm control; however, additional research is needed to address the role that early rhythm-control strategies play in current AF treatment management algorithms.
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| 18. |
- Dengler, Jürgen, et al.
(författare)
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Ecological Indicator Values for Europe (EIVE) 1.0
- 2023
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Ingår i: Vegetation Classification and Survey. - 2683-0671. ; 4, s. 7-29
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To develop a consistent ecological indicator value system for Europe for five of the main plant niche dimensions: soil moisture (M), soil nitrogen (N), soil reaction (R), light (L) and temperature (T). Study area: Europe (and closely adjacent regions). Methods: We identified 31 indicator value systems for vascular plants in Europe that contained assessments on at least one of the five aforementioned niche dimensions. We rescaled the indicator values of each dimension to a continuous scale, in which 0 represents the minimum and 10 the maximum value present in Europe. Taxon names were harmonised to the Euro+Med Plantbase. For each of the five dimensions, we calculated European values for niche position and niche width by combining the values from the individual EIV systems. Using T values as an example, we externally validated our European indicator values against the median of bioclimatic conditions for global occurrence data of the taxa. Results: In total, we derived European indicator values of niche position and niche width for 14,835 taxa (14,714 for M, 13,748 for N, 14,254 for R, 14,054 for L, 14,496 for T). Relating the obtained values for temperature niche position to the bioclimatic data of species yielded a higher correlation than any of the original EIV systems (r = 0.859). The database: The newly developed Ecological Indicator Values for Europe (EIVE) 1.0, together with all source systems, is available in a flexible, harmonised open access database. Conclusions: EIVE is the most comprehensive ecological indicator value system for European vascular plants to date. The uniform interval scales for niche position and niche width provide new possibilities for ecological and macroecological analyses of vegetation patterns. The developed workflow and documentation will facilitate the future release of updated and expanded versions of EIVE, which may for example include the addition of further taxonomic groups, additional niche dimensions, external validation or regionalisation.
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| 19. |
- Di Tullio, Alessandro, et al.
(författare)
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CCAAT/enhancer binding protein alpha (C/EBP alpha)-induced transdifferentiation of pre-B cells into macrophages involves no overt retrodifferentiation
- 2011
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 108:41, s. 17016-17021
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Tidskriftsartikel (refereegranskat)abstract
- Earlier work has shown that pre-B cells can be converted into macrophages by the transcription factor CCAAT/enhancer binding protein a at very high frequencies. Using this system, we performed a systematic analysis of whether during transdifferentiation the cells transiently reactivate progenitor-restricted genes or even retrodifferentiate. A transcriptome analysis of transdifferentiating cells showed that most genes are up-or down-regulated continuously, acquiring a macrophage phenotype within 5 d. In addition, we observed the transient reactivation of a subset of immature myeloid markers, as well as low levels of the progenitor markers Kit and FMS-like tyrosine kinase 3 and a few lineage-inappropriate genes. Importantly, however, we were unable to observe the reexpression of cell-surface marker combinations that characterize hematopoietic stem and progenitor cells, including c-Kit and FMS-like tyrosine kinase 3, even when CAAT/enhancer binding protein a was activated in pre-B cells under culture conditions that favor growth of hematopoietic stem and progenitor cells or when the transcription factor was activated in a time-limited fashion. Together, our findings are consistent with the notion that the conversion from pre-B cells to macrophages is mostly direct and does not involve overt retrodifferentiation.
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| 20. |
- Friede, Tim, et al.
(författare)
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Recent advances in methodology for clinical trials in small populations : the InSPiRe project
- 2018
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Ingår i: Orphanet Journal of Rare Diseases. - : Springer Science and Business Media LLC. - 1750-1172. ; 13
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Forskningsöversikt (refereegranskat)abstract
- Where there are a limited number of patients, such as in a rare disease, clinical trials in these small populations present several challenges, including statistical issues. This led to an EU FP7 call for proposals in 2013. One of the three projects funded was the Innovative Methodology for Small Populations Research (InSPiRe) project. This paper summarizes the main results of the project, which was completed in 2017. The InSPiRe project has led to development of novel statistical methodology for clinical trials in small populations in four areas. We have explored new decision-making methods for small population clinical trials using a Bayesian decision-theoretic framework to compare costs with potential benefits, developed approaches for targeted treatment trials, enabling simultaneous identification of subgroups and confirmation of treatment effect for these patients, worked on early phase clinical trial design and on extrapolation from adult to pediatric studies, developing methods to enable use of pharmacokinetics and pharmacodynamics data, and also developed improved robust meta-analysis methods for a small number of trials to support the planning, analysis and interpretation of a trial as well as enabling extrapolation between patient groups. In addition to scientific publications, we have contributed to regulatory guidance and produced free software in order to facilitate implementation of the novel methods.
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| 21. |
- Graf, Alexander, et al.
(författare)
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Altered energy partitioning across terrestrial ecosystems in the European drought year 2018 : Energy partitioning in the drought 2018
- 2020
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Ingår i: Philosophical Transactions of the Royal Society B: Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 375:1810
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Tidskriftsartikel (refereegranskat)abstract
- Drought and heat events, such as the 2018 European drought, interact with the exchange of energy between the land surface and the atmosphere, potentially affecting albedo, sensible and latent heat fluxes, as well as CO 2 exchange. Each of these quantities may aggravate or mitigate the drought, heat, their side effects on productivity, water scarcity and global warming. We used measurements of 56 eddy covariance sites across Europe to examine the response of fluxes to extreme drought prevailing most of the year 2018 and how the response differed across various ecosystem types (forests, grasslands, croplands and peatlands). Each component of the surface radiation and energy balance observed in 2018 was compared to available data per site during a reference period 2004-2017. Based on anomalies in precipitation and reference evapotranspiration, we classified 46 sites as drought affected. These received on average 9% more solar radiation and released 32% more sensible heat to the atmosphere compared to the mean of the reference period. In general, drought decreased net CO 2 uptake by 17.8%, but did not significantly change net evapotranspiration. The response of these fluxes differed characteristically between ecosystems; in particular, the general increase in the evaporative index was strongest in peatlands and weakest in croplands. This article is part of the theme issue 'Impacts of the 2018 severe drought and heatwave in Europe: from site to continental scale'.
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| 22. |
- Graf, Alexander, et al.
(författare)
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Joint optimization of land carbon uptake and albedo can help achieve moderate instantaneous and long-term cooling effects
- 2023
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Ingår i: Communications Earth and Environment. - 2662-4435. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- Both carbon dioxide uptake and albedo of the land surface affect global climate. However, climate change mitigation by increasing carbon uptake can cause a warming trade-off by decreasing albedo, with most research focusing on afforestation and its interaction with snow. Here, we present carbon uptake and albedo observations from 176 globally distributed flux stations. We demonstrate a gradual decline in maximum achievable annual albedo as carbon uptake increases, even within subgroups of non-forest and snow-free ecosystems. Based on a paired-site permutation approach, we quantify the likely impact of land use on carbon uptake and albedo. Shifting to the maximum attainable carbon uptake at each site would likely cause moderate net global warming for the first approximately 20 years, followed by a strong cooling effect. A balanced policy co-optimizing carbon uptake and albedo is possible that avoids warming on any timescale, but results in a weaker long-term cooling effect.
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| 23. |
- Grossmann, Igor, et al.
(författare)
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Insights into the accuracy of social scientists' forecasts of societal change
- 2023
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Ingår i: Nature Human Behaviour. - : Springer Nature. - 2397-3374. ; 7, s. 484-501
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Tidskriftsartikel (refereegranskat)abstract
- How well can social scientists predict societal change, and what processes underlie their predictions? To answer these questions, we ran two forecasting tournaments testing the accuracy of predictions of societal change in domains commonly studied in the social sciences: ideological preferences, political polarization, life satisfaction, sentiment on social media, and gender-career and racial bias. After we provided them with historical trend data on the relevant domain, social scientists submitted pre-registered monthly forecasts for a year (Tournament 1; N = 86 teams and 359 forecasts), with an opportunity to update forecasts on the basis of new data six months later (Tournament 2; N = 120 teams and 546 forecasts). Benchmarking forecasting accuracy revealed that social scientists' forecasts were on average no more accurate than those of simple statistical models (historical means, random walks or linear regressions) or the aggregate forecasts of a sample from the general public (N = 802). However, scientists were more accurate if they had scientific expertise in a prediction domain, were interdisciplinary, used simpler models and based predictions on prior data. How accurate are social scientists in predicting societal change, and what processes underlie their predictions? Grossmann et al. report the findings of two forecasting tournaments. Social scientists' forecasts were on average no more accurate than those of simple statistical models.
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| 24. |
- Göndör, Anita, 1977-
(författare)
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Epigenetic Regulation of Higher Order Chromatin Conformations and Gene Transcription
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Epigenetic states constitute heritable features of the chromatin to regulate when, where and how genes are expressed in the developing conceptus. A special case of epigenetic regulation, genomic imprinting, is defined as parent of origin-dependent monoallelic expression. The Igf2-H19 locus is considered as paradigm of genomic imprinting with a growth-promoting gene, Igf2, expressed paternally and a growth antagonist, H19 encoding a non-coding transcript, expressed only from the maternal allele. The monoallelic expression patterns are regulated by the epigenetic status at an imprinting control region (ICR) in the 5´-flank of the H19 gene. The chromatin insulator protein CTCF interacts with only the maternal H19 ICR allele to prevent downstream enhancers to communicate with the Igf2 promoters. Mutations of these CTCF binding sites lead to biallelic Igf2 expression, increased size of the conceptus and predisposition for cancer. Reasoning that these effects cannot be explained by the regulation of Igf2 expression alone, a technique was invented to examine long-range chromatin interactions without prior knowledge of the interacting partners. Applying the circular chromosomal conformation capture (4C) technique to mouse neonatal liver cells, it was observed that 114 unique sequences interacted with the H19 ICR. A majority of these interactors was in complex with only the maternal H19 ICR allele and depended on the presence of functional CTCF binding sites. The functional consequence of chromosomal networks was demonstrated by the observation that the maternal H19 ICR allele regulated the transcription of two genes on another chromosome. As the chromosomal networks underwent reprogramming during the maturation of embryonic stem cells, attention was turned to human cancer cells, displaying features common with mouse embryonic stem cells. Subsequently, chromatin folding at the human H19 ICR suggested that stable chromatin loops were organized by synergistic interactions within and between baits and interactors. The presence of these interactions was linked to DNA methylation patterns involving repeat elements. A "flower" model of chromatin networks was formulated to explain these observations. This thesis has unravealed a novel feature of the epigenome and its functions to regulate gene expression in trans. The identified roles for CTCF as an architectural factor in the organization of higher order chromatin conformations may be of importance in understanding development and disease ontogeny from novel perspectives.
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| 25. |
- Johnson, David, et al.
(författare)
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Dealing with Diversity in Computational Cancer Modeling
- 2013
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Ingår i: Cancer Informatics. - : Libertas Academica Ltd. - 1176-9351. ; 12, s. 115-124
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Tidskriftsartikel (refereegranskat)abstract
- This paper discusses the need for interconnecting computational cancer models from different sources and scales within clinically relevant scenarios to increase the accuracy of the models and speed up their clinical adaptation, validation, and eventual translation. We briefly review current interoperability efforts drawing upon our experiences with the development of in silico models for predictive oncology within a number of European Commission Virtual Physiological Human initiative projects on cancer. A clinically relevant scenario, addressing brain tumor modeling that illustrates the need for coupling models from different sources and levels of complexity, is described. General approaches to enabling interoperability using XML-based markup languages for biological modeling are reviewed, concluding with a discussion on efforts towards developing cancer-specific XML markup to couple multiple component models for predictive in silico oncology.
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