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Sökning: WFRF:(Werner Johannes)

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1.
  • Kattge, Jens, et al. (författare)
  • TRY plant trait database - enhanced coverage and open access
  • 2020
  • Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
  • Tidskriftsartikel (refereegranskat)abstract
    • Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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2.
  • Abelev, Betty, et al. (författare)
  • Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
  • 2013
  • Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
  • Tidskriftsartikel (refereegranskat)abstract
    • Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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3.
  • Abelev, Betty, et al. (författare)
  • Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
  • 2012
  • Ingår i: Journal of High Energy Physics. - 1029-8479. ; :11
  • Tidskriftsartikel (refereegranskat)abstract
    • The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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4.
  • Abelev, Betty, et al. (författare)
  • Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
  • 2012
  • Ingår i: Journal of High Energy Physics. - 1029-8479. ; :7
  • Tidskriftsartikel (refereegranskat)abstract
    • We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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5.
  • Altomonte, Sergio, et al. (författare)
  • Evaluating integrated lighting projects - A Procedure to Post-Occupancy Evaluation of Daylight and Electrical Lighting Integrated Projects
  • 2021
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • This report presents tools for post-occupancy evaluation (POE) to evaluate indoor lighting of commissioned projects (‘case studies’) under a common framework. In this report, POE includes technical environmental assessment (TEA) and observer-based environmental assessment (OBEA). The framework proposed in this report evaluates four key aspects of the case study:1. Energy use (electrical lighting systems),2. Visual effects (Indoor lighting environment /photometry)3. Non-visual effects (circadian potential), and4. The user (subjective/surveys and observations)The report targets industry professionals, building designers, lighting designers, building managers, researchers and/or owners wishing to evaluate projects where lighting is supplied by a combination of electrical lighting, daylighting systems (e.g., fenestrations) and assisted technologies (e.g., smart sensors). The framework in this report makes available methods and procedures related to the evaluation of integrated lighting performance in residential and non-residential buildings and its impact on users, and it summarises and categorize methods and procedures in an accessible and industry-oriented language.The content of this document is based on methods and procedures used by participating experts in IEA SHC Task 61 for monitoring twenty-five worldwide integrated daylighting and electric lighting case studies. Since integrated lighting projects are different in type and scopes, the methods and procedures included in the framework do not follow a rigid protocol. Practitioners should use the framework to define the scope of POE monitoring in terms of the aims of the project, context, and resources available. The document is thus a toolbox for planning and executing the monitoring of their integrated lighting projects.
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6.
  • Brütt, Katharina, et al. (författare)
  • Competition and moral behavior: A meta-analysis of forty-five crowd-sourced experimental designs
  • 2023
  • Ingår i: Proceedings of the National Academy of Sciences - PNAS. - : National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 120:23
  • Tidskriftsartikel (refereegranskat)abstract
    • Does competition affect moral behavior? This fundamental question has been debated among leading scholars for centuries, and more recently, it has been tested in experimental studies yielding a body of rather inconclusive empirical evidence. A potential source of ambivalent empirical results on the same hypothesis is design heterogeneity-variation in true effect sizes across various reasonable experimental research protocols. To provide further evidence on whether competition affects moral behavior and to examine whether the generalizability of a single experimental study is jeopardized by design heterogeneity, we invited independent research teams to contribute experimental designs to a crowd-sourced project. In a large-scale online data collection, 18,123 experimental participants were randomly allocated to 45 randomly selected experimental designs out of 95 submitted designs. We find a small adverse effect of competition on moral behavior in a meta-analysis of the pooled data. The crowd-sourced design of our study allows for a clean identification and estimation of the variation in effect sizes above and beyond what could be expected due to sampling variance. We find substantial design heterogeneity-estimated to be about 1.6 times as large as the average standard error of effect size estimates of the 45 research designs-indicating that the informativeness and generalizability of results based on a single experimental design are limited. Drawing strong conclusions about the underlying hypotheses in the presence of substantive design heterogeneity requires moving toward much larger data collections on various experimental designs testing the same hypothesis.
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7.
  • Janssen, Rene, et al. (författare)
  • Machine Learning Predicts the Presence of 2,4,6-Trinitrotoluene in Sediments of a Baltic Sea Munitions Dumpsite Using Microbial Community Compositions
  • 2021
  • Ingår i: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • Bacteria are ubiquitous and live in complex microbial communities. Due to differences in physiological properties and niche preferences among community members, microbial communities respond in specific ways to environmental drivers, potentially resulting in distinct microbial fingerprints for a given environmental state. As proof of the principle, our goal was to assess the opportunities and limitations of machine learning to detect microbial fingerprints indicating the presence of the munition compound 2,4,6-trinitrotoluene (TNT) in southwestern Baltic Sea sediments. Over 40 environmental variables including grain size distribution, elemental composition, and concentration of munition compounds (mostly at pmol.g(-1) levels) from 150 sediments collected at the near-to-shore munition dumpsite Kolberger Heide by the German city of Kiel were combined with 16S rRNA gene amplicon sequencing libraries. Prediction was achieved using Random Forests (RFs); the robustness of predictions was validated using Artificial Neural Networks (ANN). To facilitate machine learning with microbiome data we developed the R package phyloseq2ML. Using the most classification-relevant 25 bacterial genera exclusively, potentially representing a TNT-indicative fingerprint, TNT was predicted correctly with up to 81.5% balanced accuracy. False positive classifications indicated that this approach also has the potential to identify samples where the original TNT contamination was no longer detectable. The fact that TNT presence was not among the main drivers of the microbial community composition demonstrates the sensitivity of the approach. Moreover, environmental variables resulted in poorer prediction rates than using microbial fingerprints. Our results suggest that microbial communities can predict even minor influencing factors in complex environments, demonstrating the potential of this approach for the discovery of contamination events over an integrated period of time. Proven for a distinct environment future studies should assess the ability of this approach for environmental monitoring in general.
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8.
  • Soliveres, Santiago, et al. (författare)
  • Biodiversity at multiple trophic levels is needed for ecosystem multifunctionality
  • 2016
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7617, s. 456-459
  • Tidskriftsartikel (refereegranskat)abstract
    • Many experiments have shown that loss of biodiversity reduces the capacity of ecosystems to provide the multiple services on which humans depend. However, experiments necessarily simplify the complexity of natural ecosystems and will normally control for other important drivers of ecosystem functioning, such as the environment or land use. In addition, existing studies typically focus on the diversity of single trophic groups, neglecting the fact that biodiversity loss occurs across many taxa and that the functional effects of any trophic group may depend on the abundance and diversity of others. Here we report analysis of the relationships between the species richness and abundance of nine trophic groups, including 4,600 above- and below-ground taxa, and 14 ecosystem services and functions and with their simultaneous provision (or multifunctionality) in 150 grasslands. We show that high species richness in multiple trophic groups (multitrophic richness) had stronger positive effects on ecosystem services than richness in any individual trophic group; this includes plant species richness, the most widely used measure of biodiversity. On average, three trophic groups influenced each ecosystem service, with each trophic group influencing at least one service. Multitrophic richness was particularly beneficial for 'regulating' and 'cultural' services, and for multifunctionality, whereas a change in the total abundance of species or biomass in multiple trophic groups (the multitrophic abundance) positively affected supporting services. Multitrophic richness and abundance drove ecosystem functioning as strongly as abiotic conditions and land-use intensity, extending previous experimental results to real-world ecosystems. Primary producers, herbivorous insects and microbial decomposers seem to be particularly important drivers of ecosystem functioning, as shown by the strong and frequent positive associations of their richness or abundance with multiple ecosystem services. Our results show that multitrophic richness and abundance support ecosystem functioning, and demonstrate that a focus on single groups has led to researchers to greatly underestimate the functional importance of biodiversity.
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9.
  • Soliveres, Santiago, et al. (författare)
  • Locally rare species influence grassland ecosystem multifunctionality
  • 2016
  • Ingår i: Philosophical Transactions of the Royal Society B: Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 371:1694
  • Tidskriftsartikel (refereegranskat)abstract
    • Species diversity promotes the delivery of multiple ecosystem functions (multifunctionality). However, the relative functional importance of rare and common species in driving the biodiversity-multifunctionality relationship remains unknown. We studied the relationship between the diversity of rare and common species (according to their local abundances and across nine different trophic groups), and multifunctionality indices derived from 14 ecosystem functions on 150 grasslands across a land-use intensity (LUI) gradient. The diversity of above-and below-ground rare species had opposite effects, with rare above-ground species being associated with high levels of multifunctionality, probably because their effects on different functions did not trade off against each other. Conversely, common species were only related to average, not high, levels of multifunctionality, and their functional effects declined with LUI. Apart from the community-level effects of diversity, we found significant positive associations between the abundance of individual species and multifunctionality in 6% of the species tested. Species-specific functional effects were best predicted by their response to LUI: species that declined in abundance with land use intensification were those associated with higher levels of multifunctionality. Our results highlight the importance of rare species for ecosystem multifunctionality and help guiding future conservation priorities.
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10.
  • Wetter, Oliver, et al. (författare)
  • The year-long unprecedented European heat and drought of 1540-a worst case
  • 2014
  • Ingår i: Climatic Change. - : Springer Science and Business Media LLC. - 0165-0009 .- 1573-1480. ; 125:3-4, s. 349-363
  • Tidskriftsartikel (refereegranskat)abstract
    • The heat waves of 2003 in Western Europe and 2010 in Russia, commonly labelled as rare climatic anomalies outside of previous experience, are often taken as harbingers of more frequent extremes in the global warming-influenced future. However, a recent reconstruction of spring-summer temperatures for WE resulted in the likelihood of significantly higher temperatures in 1540. In order to check the plausibility of this result we investigated the severity of the 1540 drought by putting forward the argument of the known soil desiccation-temperature feedback. Based on more than 300 first-hand documentary weather report sources originating from an area of 2 to 3 million km(2), we show that Europe was affected by an unprecedented 11-month-long Megadrought. The estimated number of precipitation days and precipitation amount for Central and Western Europe in 1540 is significantly lower than the 100-year minima of the instrumental measurement period for spring, summer and autumn. This result is supported by independent documentary evidence about extremely low river flows and Europe-wide wild-, forest- and settlement fires. We found that an event of this severity cannot be simulated by state-of-the-art climate models.
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12.
  • Averfalk, Helge, 1988-, et al. (författare)
  • Low-Temperature District Heating Implementation Guidebook : Final Report of IEA DHC Annex TS2. Implementation of Low-Temperature District Heating Systems
  • 2021
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • This guidebook was written between 2018 and 2021 by seventeen authors that used approximately 15 000 hours of work within the IEA DHC TS2 annex. The content is based on more than 250 literature references and 165 inspiration initiatives to obtain lower temperatures in buildings and heat distribution networks. The author group wrote 40 internal documents about early implementations of low-temperature district heating. Fifteen of these early implementations are presented in this guidebook.The guidebook contains aggregated information about the main economic drivers for low-temperature district heating. It shows how to obtain lower temperatures in heating systems inside existing and new buildings, as well as in existing and new heat distribution networks. An applied study of a campus system in Darmstadt shows the possibility of reducing temperatures in an existing heat distribution network with rather high temperatures. The competitiveness of low-temperature district heating is explored by analysing business models and heat distribution costs. Early adopters of low-temperature district heating are presented by examples and by identified transition strategies. Five groups of network configurations with fourteen variants are presented to be used for low-temperature district heating. Finally, all 165 identified inspiration initiatives and all 137 locations mentioned are listed.
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13.
  • Bergsten, Johannes, 1975-, et al. (författare)
  • Entomologmötet på Gotland 2017: temaexkursion med fokus på vattenlevande skalbaggar, skinnbaggar och trollsländor i Äskåkersvät.
  • 2017
  • Ingår i: Entomologisk Tidskrift. - 0013-886X. ; 139:1, s. 39-49
  • Tidskriftsartikel (refereegranskat)abstract
    • The yearly Swedish entomology meeting 2017 was organized by the local entomologysociety of Gotland, on the northern part of the Baltic island Gotland near Bunge, 4-6 August.One thematic excursion was focused on aquatic insects, especiallly aquatic beetles,bugs and dragonflies. A shallow pond, Äskåkersvät, with Characeae in an open grazedlandscape with high natural values was studied. Äskåkersvät lies just adjacent to the largerarea around lake Bästeträsk which is the focus of a pilot study evaluating its potential asa future national park. The pilot study is undertaken by Gotland County AdministrativeBoard, the Swedish Environmental Protection Agency, Region Gotland and the SwedishAgency for Marine and Water Management. Here we give an annotated report of the 103species found: 69 species of water beetles (out of which 34 were Dytiscidae), 20 speciesof aquatic or semiaquatic bugs (out of which 10 were Corixidae), and 14 species of dragonflies.These include Hydrophilus piceus and H. aterrimus redlisted in Sweden (both asNT), and Dytiscus latissimus, globally redlisted (VU). We also noted the noble crayfish,Astacus astacus (redlisted as CR in Sweden) and the European medicinal leech Hirudomedicinalis (redlisted as NT globally). The blue emperor dragonfly (Anax imperator) wasnoted, a species first recorded from Gotland in 2002 and we present a graph on its increaseand spreading on the island since. The number of species found in spite of a relativelymodest collecting effort at a suboptimal time when many species may be in pupal stage outof water as witnessed by many teneral individuals, indicates a species rich locality withhigh natural value. The stoneworts (Characeae) vegetation certainly contributes to this, forinstance vouched for by the occurrence of specialists as Haliplus confinis and H. obliquuswhose larvae feed on stoneworts.
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14.
  • Bernhard, Jürg, et al. (författare)
  • Clinical benefit and quality of life in patients with advanced pancreatic cancer receiving gemcitabine plus capecitabine versus gemcitabine alone : a randomized multicenter phase III clinical trial--SAKK 44/00-CECOG/PAN.1.3.001
  • 2008
  • Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 26:22, s. 3695-3701
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: To compare clinical benefit response (CBR) and quality of life (QOL) in patients receiving gemcitabine (Gem) plus capecitabine (Cap) versus single-agent Gem for advanced/metastatic pancreatic cancer. PATIENTS AND METHODS: Patients were randomly assigned to receive GemCap (oral Cap 650 mg/m(2) twice daily on days 1 through 14 plus Gem 1,000 mg/m(2) in a 30-minute infusion on days 1 and 8 every 3 weeks) or Gem (1,000 mg/m(2) in a 30-minute infusion weekly for 7 weeks, followed by a 1-week break, and then weekly for 3 weeks every 4 weeks) for 24 weeks or until progression. CBR criteria and QOL indicators were assessed over this period. CBR was defined as improvement from baseline for >or= 4 consecutive weeks in pain (pain intensity or analgesic consumption) and Karnofsky performance status, stability in one but improvement in the other, or stability in pain and performance status but improvement in weight. RESULTS: Of 319 patients, 19% treated with GemCap and 20% treated with Gem experienced a CBR, with a median duration of 9.5 and 6.5 weeks, respectively (P < .02); 54% of patients treated with GemCap and 60% treated with Gem had no CBR (remaining patients were not assessable). There was no treatment difference in QOL (n = 311). QOL indicators were improving under chemotherapy (P < .05). These changes differed by the time to failure, with a worsening 1 to 2 months before treatment failure (all P < .05). CONCLUSION: There is no indication of a difference in CBR or QOL between GemCap and Gem. Regardless of their initial condition, some patients experience an improvement in QOL on chemotherapy, followed by a worsening before treatment failure.
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15.
  • Breznau, Nate, et al. (författare)
  • Observing many researchers using the same data and hypothesis reveals a hidden universe of uncertainty
  • 2022
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:44
  • Tidskriftsartikel (refereegranskat)abstract
    • This study explores how researchers analytical choices affect the reliability of scientific findings. Most discussions of reliability problems in science focus on systematic biases. We broaden the lens to emphasize the idiosyncrasy of conscious and unconscious decisions that researchers make during data analysis. We coordinated 161 researchers in 73 research teams and observed their research decisions as they used the same data to independently test the same prominent social science hypothesis: that greater immigration reduces support for social policies among the public. In this typical case of social science research, research teams reported both widely diverging numerical findings and substantive conclusions despite identical start conditions. Researchers expertise, prior beliefs, and expectations barely predict the wide variation in research outcomes. More than 95% of the total variance in numerical results remains unexplained even after qualitative coding of all identifiable decisions in each teams workflow. This reveals a universe of uncertainty that remains hidden when considering a single study in isolation. The idiosyncratic nature of how researchers results and conclusions varied is a previously underappreciated explanation for why many scientific hypotheses remain contested. These results call for greater epistemic humility and clarity in reporting scientific findings.
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18.
  • Campbell, Bruce C V, et al. (författare)
  • Extending thrombolysis to 4·5-9 h and wake-up stroke using perfusion imaging: a systematic review and meta-analysis of individual patient data.
  • 2019
  • Ingår i: Lancet (London, England). - 1474-547X. ; 394:10193, s. 139-147
  • Tidskriftsartikel (refereegranskat)abstract
    • Stroke thrombolysis with alteplase is currently recommended 0-4·5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4·5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis.In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials.gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged ≥18 years) with ischaemic stroke treated more than 4·5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036.We identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1·86, 95% CI 1·15-2·99, p=0·011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten [5%] of 213 patients vs one [<1%] of 201 patients in the placebo group; adjusted OR 9·7, 95% CI 1·23-76·55, p=0·031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1·55, 0·81-2·96, p=0·66).Patients with ischaemic stroke 4·5-9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis.None.
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19.
  • Cavinato, Maria, et al. (författare)
  • Targeting cellular senescence based on interorganelle communication, multilevel proteostasis, and metabolic control
  • 2021
  • Ingår i: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 228:12, s. 3834-3854
  • Forskningsöversikt (refereegranskat)abstract
    • Cellular senescence, a stable cell division arrest caused by severe damage and stress, is a hallmark of aging in vertebrates including humans. With progressing age, senescent cells accumulate in a variety of mammalian tissues, where they contribute to tissue aging, identifying cellular senescence as a major target to delay or prevent aging. There is an increasing demand for the discovery of new classes of small molecules that would either avoid or postpone cellular senescence by selectively eliminating senescent cells from the body (i.e., 'senolytics') or inactivating/switching damage-inducing properties of senescent cells (i.e., 'senostatics/senomorphics'), such as the senescence-associated secretory phenotype. Whereas compounds with senolytic or senostatic activity have already been described, their efficacy and specificity has not been fully established for clinical use yet. Here, we review mechanisms of senescence that are related to mitochondria and their interorganelle communication, and the involvement of proteostasis networks and metabolic control in the senescent phenotype. These cellular functions are associated with cellular senescence in in vitro and in vivo models but have not been fully exploited for the search of new compounds to counteract senescence yet. Therefore, we explore possibilities to target these mechanisms as new opportunities to selectively eliminate and/or disable senescent cells with the aim of tissue rejuvenation. We assume that this research will provide new compounds from the chemical space which act as mimetics of caloric restriction, modulators of calcium signaling and mitochondrial physiology, or as proteostasis optimizers, bearing the potential to counteract cellular senescence, thereby allowing healthy aging.
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20.
  • Delsing, Per, 1959, et al. (författare)
  • The 2019 surface acoustic waves roadmap
  • 2019
  • Ingår i: Journal of Physics D: Applied Physics. - : IOP Publishing. - 1361-6463 .- 0022-3727. ; 52:35
  • Forskningsöversikt (refereegranskat)abstract
    • Today, surface acoustic waves (SAWs) and bulk acoustic waves are already two of the very few phononic technologies of industrial relevance and can been found in a myriad of devices employing these nanoscale earthquakes on a chip. Acoustic radio frequency filters, for instance, are integral parts of wireless devices. SAWs in particular find applications in life sciences and microfluidics for sensing and mixing of tiny amounts of liquids. In addition to this continuously growing number of applications, SAWs are ideally suited to probe and control elementary excitations in condensed matter at the limit of single quantum excitations. Even collective excitations, classical or quantum are nowadays coherently interfaced by SAWs. This wide, highly diverse, interdisciplinary and continuously expanding spectrum literally unites advanced sensing and manipulation applications. Remarkably, SAW technology is inherently multiscale and spans from single atomic or nanoscopic units up even to the millimeter scale. The aim of this Roadmap is to present a snapshot of the present state of surface acoustic wave science and technology in 2019 and provide an opinion on the challenges and opportunities that the future holds from a group of renown experts, covering the interdisciplinary key areas, ranging from fundamental quantum effects to practical applications of acoustic devices in life science.
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21.
  • Delva, Pacôme, et al. (författare)
  • GENESIS: co-location of geodetic techniques in space
  • 2023
  • Ingår i: Earth, Planets and Space. - : Springer Science and Business Media LLC. - 1880-5981 .- 1343-8832. ; 75:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Improving and homogenizing time and space reference systems on Earth and, more specifically, realizing the Terrestrial Reference Frame (TRF) with an accuracy of 1 mm and a long-term stability of 0.1 mm/year are relevant for many scientific and societal endeavors. The knowledge of the TRF is fundamental for Earth and navigation sciences. For instance, quantifying sea level change strongly depends on an accurate determination of the geocenter motion but also of the positions of continental and island reference stations, such as those located at tide gauges, as well as the ground stations of tracking networks. Also, numerous applications in geophysics require absolute millimeter precision from the reference frame, as for example monitoring tectonic motion or crustal deformation, contributing to a better understanding of natural hazards. The TRF accuracy to be achieved represents the consensus of various authorities, including the International Association of Geodesy (IAG), which has enunciated geodesy requirements for Earth sciences. Moreover, the United Nations Resolution 69/266 states that the full societal benefits in developing satellite missions for positioning and Remote Sensing of the Earth are realized only if they are referenced to a common global geodetic reference frame at the national, regional and global levels. Today we are still far from these ambitious accuracy and stability goals for the realization of the TRF. However, a combination and co-location of all four space geodetic techniques on one satellite platform can significantly contribute to achieving these goals. This is the purpose of the GENESIS mission, a component of the FutureNAV program of the European Space Agency. The GENESIS platform will be a dynamic space geodetic observatory carrying all the geodetic instruments referenced to one another through carefully calibrated space ties. The co-location of the techniques in space will solve the inconsistencies and biases between the different geodetic techniques in order to reach the TRF accuracy and stability goals endorsed by the various international authorities and the scientific community. The purpose of this paper is to review the state-of-the-art and explain the benefits of the GENESIS mission in Earth sciences, navigation sciences and metrology. This paper has been written and supported by a large community of scientists from many countries and working in several different fields of science, ranging from geophysics and geodesy to time and frequency metrology, navigation and positioning. As it is explained throughout this paper, there is a very high scientific consensus that the GENESIS mission would deliver exemplary science and societal benefits across a multidisciplinary range of Navigation and Earth sciences applications, constituting a global infrastructure that is internationally agreed to be strongly desirable. Graphical Abstract: [Figure not available: see fulltext.]
  •  
22.
  • du Plessis, Hester Esna, et al. (författare)
  • In situ reduction study of cobalt model Fischer-Tropsch synthesis catalysts
  • 2013
  • Ingår i: Physical Chemistry Chemical Physics. - : Royal Society of Chemistry (RSC). - 1463-9084 .- 1463-9076. ; 15:28, s. 11640-11645
  • Tidskriftsartikel (refereegranskat)abstract
    • Fischer-Tropsch (FT) synthesis is an important process to manufacture hydrocarbons and oxygenated hydrocarbons from mixtures of carbon monoxide and hydrogen (syngas). The catalysis process occurs on, for example, cobalt metal surfaces at elevated temperatures and pressures. A fundamental understanding of the reduction pathway of supported cobalt oxides, and the intermediate species present during the activation, can assist in developing improved industrial supported cobalt catalysts. Hard synchrotron X-rays have the unique ability to probe atomic processes both in terms of phases present as well as the crystallographic and local structure (using the pair distribution function approach) under realistic conditions. In this manuscript we present results from measurements during in situ hydrogen activation of a model Co/alumina catalyst using in situ synchrotron X-ray powder diffraction and pair-distribution function (PDF) analysis on beam line ID31 at the ESRF in Grenoble, France. The PDF analysis showed a substantially improved understanding of the reduction of cobalt oxides, as for the first time all cobalt could be accounted for by using total scattering analysis.
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23.
  • Eriksson, Johannes, et al. (författare)
  • Probing growth defects inside nanowires
  • 2006
  • Ingår i: Book of abstracts: Intl Conf on Nanosci and Technol, Basel, Switzerland (2006).
  • Konferensbidrag (refereegranskat)
  •  
24.
  • Esper, Jan, et al. (författare)
  • Environmental drivers of historical grain price variations in Europe
  • 2017
  • Ingår i: Climate Research (CR). - : Inter-Research Science Center. - 0936-577X .- 1616-1572. ; 72:1, s. 39-52
  • Tidskriftsartikel (refereegranskat)abstract
    • Grain price (GP) volatility has been a central constituent of European commerce, with fluctuations in barley, rye and wheat prices having been carefully documented over centuries. However, a thorough understanding of the climatic and environmental drivers of long-term GP variations is still lacking. Here, we present a network of historical GP records from 19 cities in central and southern Europe for the 14th to 18th centuries. Spatial variability at interannual to multidecadal scales within this network was compared with reconstructed warm-season temperatures and hydro climatic conditions. We show that European GPs are tightly coupled with historical famines and that food shortages coincide with regional summer drought anomalies. Direct correlations between historical GP and reconstructed drought indices are low, hardly exceeding r = -0.2. Yet if the analysis is focused on extreme events, the climatic controls on high-frequency price variations become obvious: GPs were exceptionally high during dry periods and exceptionally low during wet periods. In addition, we find that GP variations were affected by temperature fluctuations at multidecadal timescales. The influence of summer temperatures is particularly strong over the 1650-1750 period, subsequent to the Thirty Years' War, reaching r = -0.40 at the European scale. This observation is supported by the lack of correlation among regional GP clusters during the period of hostilities and increased inter-regional correlation thereafter. These results demonstrate that the exchange of goods and spatial coherence of GP data in Europe were controlled both by socio-political and environmental factors, with environmental factors being more influential during peacetime.
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25.
  • Greuel, Selina, et al. (författare)
  • Online measurement of oxygen enables continuous noninvasive evaluation of human-induced pluripotent stem cell (hiPSC) culture in a perfused 3D hollow-fiber bioreactor
  • 2019
  • Ingår i: Journal of Tissue Engineering and Regenerative Medicine. - : WILEY. - 1932-6254 .- 1932-7005. ; 13:7, s. 1203-1216
  • Tidskriftsartikel (refereegranskat)abstract
    • For clinical and/or pharmaceutical use of human-induced pluripotent stem cells (hiPSCs), large cell quantities of high quality are demanded. Therefore, we combined the expansion of hiPSCs in closed, perfusion-based 3D bioreactors with noninvasive online monitoring of oxygen as culture control mechanism. Bioreactors with a cell compartment volume of 3 or 17 ml were inoculated with either 10 x 10(6) or 50 x 10(6) cells, and cells were expanded over 15 days with online oxygen and offline glucose and lactate measurements being performed. The CellTiter-Blue (R) Assay was performed at the end of the bioreactor experiments for indirect cell quantification. Model simulations enabled an estimation of cell numbers based on kinetic equations and experimental data during the 15-day bioreactor cultures. Calculated oxygen uptake rates (OUR), glucose consumption rates (GCR), and lactate production rates (LPR) revealed a highly significant correlation (p amp;lt; 0.0001). Oxygen consumption, which was measured at the beginning and the end of the experiment, showed a strong culture growth in line with the OUR and GCR data. Furthermore, the yield coefficient of lactate from glucose and the OUR to GCR ratio revealed a shift from nonoxidative to oxidative metabolism. The presented results indicate that oxygen is equally as applicable as parameter for hiPSC expansion as glucose while providing an accurate real-time impression of hiPSC culture development. Additionally, oxygen measurements inform about the metabolic state of the cells. Thus, the use of oxygen online monitoring for culture control facilitates the translation of hiPSC use to the clinical setting.
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26.
  • Haak, Wolfgang, et al. (författare)
  • Massive migration from the steppe was a source for Indo-European languages in Europe
  • 2015
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 522:7555, s. 207-
  • Tidskriftsartikel (refereegranskat)abstract
    • We generated genome-wide data from 69 Europeans who lived between 8,000-3,000 years ago by enriching ancient DNA libraries for a target set of almost 400,000 polymorphisms. Enrichment of these positions decreases the sequencing required for genome-wide ancient DNA analysis by a median of around 250-fold, allowing us to study an order of magnitude more individuals than previous studies(1-8) and to obtain new insights about the past. We show that the populations of Western and Far Eastern Europe followed opposite trajectories between 8,000-5,000 years ago. At the beginning of the Neolithic period in Europe, similar to 8,000-7,000 years ago, closely related groups of early farmers appeared in Germany, Hungary and Spain, different from indigenous hunter-gatherers, whereas Russia was inhabited by a distinctive population of hunter-gatherers with high affinity to a similar to 24,000-year-old Siberian(6). By similar to 6,000-5,000 years ago, farmers throughout much of Europe had more hunter-gatherer ancestry than their predecessors, but in Russia, the Yamnaya steppe herders of this time were descended not only from the preceding eastern European hunter-gatherers, but also from a population of Near Eastern ancestry. Western and Eastern Europe came into contact similar to 4,500 years ago, as the Late Neolithic Corded Ware people from Germany traced similar to 75% of their ancestry to the Yamnaya, documenting a massive migration into the heartland of Europe from its eastern periphery. This steppe ancestry persisted in all sampled central Europeans until at least similar to 3,000 years ago, and is ubiquitous in present-day Europeans. These results provide support for a steppe origin(9) of at least some of the Indo-European languages of Europe.
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27.
  • Herrmann, Richard, et al. (författare)
  • Gemcitabine plus capecitabine compared with gemcitabine alone in advanced pancreatic cancer : a randomized, multicenter, phase III trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group
  • 2007
  • Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 25:16, s. 2212-2217
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: This phase III trial compared the efficacy and safety of gemcitabine (Gem) plus capecitabine (GemCap) versus single-agent Gem in advanced/metastatic pancreatic cancer. Patients and Methods: Patients were randomly assigned to receive GemCap (oral capecitabine 650 mg/m2 twice daily on days 1 to 14 plus Gem 1,000 mg/m2 by 30-minute infusion on days 1 and 8 every 3 weeks) or Gem (1,000 mg/m2 by 30-minute infusion weekly for 7 weeks, followed by a 1-week break, and then weekly for 3 weeks every 4 weeks). Patients were stratified according to center, Kamofsky performance score (KPS), presence of pain, and disease extent. Results: A total of 319 patients were enrolled between June 2001 and June 2004. Median overall survival (OS) time, the primary end point, was 8.4 and 7.2 months in the GemCap and Gem arms, respectively (P = .234). Post hoc analysis in patients with good KPS (score of 90 to 100) showed a significant prolongation of median OS time in the GemCap arm compared with the Gem arm (10.1 v 7.4 months, respectively; P = .014). The overall frequency of grade 3 or 4 adverse events was similar in each arm. Neutropenia was the most frequent grade 3 or 4 adverse event in both arms. Conclusion: GemCap failed to improve OS at a statistically significant level compared with standard Gem treatment. The safety of GemCap and Gem was similar. In the subgroup of patients with good performance status, median OS was improved significantly. GemCap is a practical regimen that may be considered as an alternative to single-agent Gem for the treatment of advanced/metastatic pancreatic cancer patients with a good performance status.
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28.
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29.
  • Höglinger, Günter U, et al. (författare)
  • Clinical diagnosis of progressive supranuclear palsy : The movement disorder society criteria
  • 2017
  • Ingår i: Movement Disorders. - : Wiley. - 0885-3185. ; 32:6, s. 853-864
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: PSP is a neuropathologically defined disease entity. Clinical diagnostic criteria, published in 1996 by the National Institute of Neurological Disorders and Stroke/Society for PSP, have excellent specificity, but their sensitivity is limited for variant PSP syndromes with presentations other than Richardson's syndrome. Objective: We aimed to provide an evidence- and consensus-based revision of the clinical diagnostic criteria for PSP. Methods: We searched the PubMed, Cochrane, Medline, and PSYCInfo databases for articles published in English since 1996, using postmortem diagnosis or highly specific clinical criteria as the diagnostic standard. Second, we generated retrospective standardized clinical data from patients with autopsy-confirmed PSP and control diseases. On this basis, diagnostic criteria were drafted, optimized in two modified Delphi evaluations, submitted to structured discussions with consensus procedures during a 2-day meeting, and refined in three further Delphi rounds. Results: Defined clinical, imaging, laboratory, and genetic findings serve as mandatory basic features, mandatory exclusion criteria, or context-dependent exclusion criteria. We identified four functional domains (ocular motor dysfunction, postural instability, akinesia, and cognitive dysfunction) as clinical predictors of PSP. Within each of these domains, we propose three clinical features that contribute different levels of diagnostic certainty. Specific combinations of these features define the diagnostic criteria, stratified by three degrees of diagnostic certainty (probable PSP, possible PSP, and suggestive of PSP). Clinical clues and imaging findings represent supportive features. Conclusions: Here, we present new criteria aimed to optimize early, sensitive, and specific clinical diagnosis of PSP on the basis of currently available evidence.
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30.
  • Jones, Geraint H., et al. (författare)
  • The Comet Interceptor Mission
  • 2024
  • Ingår i: Space Science Reviews. - : Springer Nature. - 0038-6308 .- 1572-9672. ; 220:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Here we describe the novel, multi-point Comet Interceptor mission. It is dedicated to the exploration of a little-processed long-period comet, possibly entering the inner Solar System for the first time, or to encounter an interstellar object originating at another star. The objectives of the mission are to address the following questions: What are the surface composition, shape, morphology, and structure of the target object? What is the composition of the gas and dust in the coma, its connection to the nucleus, and the nature of its interaction with the solar wind? The mission was proposed to the European Space Agency in 2018, and formally adopted by the agency in June 2022, for launch in 2029 together with the Ariel mission. Comet Interceptor will take advantage of the opportunity presented by ESA’s F-Class call for fast, flexible, low-cost missions to which it was proposed. The call required a launch to a halo orbit around the Sun-Earth L2 point. The mission can take advantage of this placement to wait for the discovery of a suitable comet reachable with its minimum Δ V capability of 600 ms − 1 . Comet Interceptor will be unique in encountering and studying, at a nominal closest approach distance of 1000 km, a comet that represents a near-pristine sample of material from the formation of the Solar System. It will also add a capability that no previous cometary mission has had, which is to deploy two sub-probes – B1, provided by the Japanese space agency, JAXA, and B2 – that will follow different trajectories through the coma. While the main probe passes at a nominal 1000 km distance, probes B1 and B2 will follow different chords through the coma at distances of 850 km and 400 km, respectively. The result will be unique, simultaneous, spatially resolved information of the 3-dimensional properties of the target comet and its interaction with the space environment. We present the mission’s science background leading to these objectives, as well as an overview of the scientific instruments, mission design, and schedule.
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31.
  • Kapferer-Seebacher, Ines, et al. (författare)
  • Periodontal Ehlers-Danlos Syndrome Is Caused by Mutations in C1R and C1S, which Encode Subcomponents C1r and C1s of Complement
  • 2016
  • Ingår i: American Journal of Human Genetics. - : Cell Press. - 0002-9297 .- 1537-6605. ; 99:5, s. 1005-1014
  • Tidskriftsartikel (refereegranskat)abstract
    • Periodontal Ehlers-Danlos syndrome (pEDS) is an autosomal-dominant disorder characterized by early-onset periodontitis leading to premature loss of teeth, joint hypermobility, and mild skin findings. A locus was mapped to an approximately 5.8 Mb region at 12p13.1 but no candidate gene was identified. In an international consortium we recruited 19 independent families comprising 107 individuals with pEDS to identify the locus, characterize the clinical details in those with defined genetic causes, and try to understand the physiological basis of the condition. In 17 of these families, we identified heterozygous missense or in-frame insertion/deletion mutations in C1R (15 families) or C1S (2 families), contiguous genes in the mapped locus that encode subunits C1r and C1s of the first component of the classical complement pathway. These two proteins form a heterotetramer that then combines with six C1q subunits. Pathogenic variants involve the subunit interfaces or inter-domain hinges of C1r and C1s and are associated with intracellular retention and mild endoplasmic reticulum enlargement. Clinical features of affected individuals in these families include rapidly progressing periodontitis with onset in the teens or childhood, a previously unrecognized lack of attached gingiva, pretibial hyperpigmentation, skin and vascular fragility, easy bruising, and variable musculoskeletal symptoms. Our findings open a connection between the inflammatory classical complement pathway and connective tissue homeostasis.
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32.
  • Kern, Ralph, et al. (författare)
  • Coulomb Excitation of Proton-rich N = 80 Isotones at HIE-ISOLDE
  • 2020
  • Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 1555:1
  • Tidskriftsartikel (refereegranskat)abstract
    • A projectile Coulomb-excitation experiment was performed at the radioactive ion beam facility HIE-ISOLDE at CERN. The radioactive 140Nd and 142Sm ions were post accelerated to the energy of 4.62 MeV/A and impinged on a 1.45 mg/cm2-thin 208Pb target. The γ rays depopulating the Coulomb-excited states were recorded by the HPGe-array MINIBALL. The scattered charged particles were detected by a double-sided silicon strip detector in forward direction. Experimental γ-ray intensities were used for the determination of electromagnetic transition matrix elements. Preliminary results for the reduced transition strength of the B(M1 23+ to 21+)=0.35(19) μN2 of 140Nd and a first estimation for 142Sm have been deduced using the Coulomb-excitation calculation software GOSIA. The 23+ states of 140Nd and 142Sm show indications of being the main fragment of the proton-neutron mixed-symmetry 21, ms+ state.
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33.
  • Kern, Ralph, et al. (författare)
  • Search for Isovector Valence-Shell Excitations in 140Nd and 142Sm via Coulomb excitation reactions of radioactive ion beams
  • 2018
  • Ingår i: International Conference on Nuclear Structure and Related Topics (NSRT18). - : EDP Sciences. - 2101-6275. ; 194
  • Konferensbidrag (refereegranskat)abstract
    • Projectile Coulomb excitation experiments were performed at HIE-ISOLDE at CERN with the radioactive ion beams of 140Nd and 142Sm. Ions with an energy of 4:62 MeV/A were impinging on a 1.45 mg/cm2 thick 208Pb target. The γ-rays depopulating the Coulomb-excited states were recorded by the HPGe-array MINIBALL and scattered particles were detected by a double-sided silicon strip detector. Experimental intensities were used for the determination of electromagnetic transition matrix elements. A preliminary result of the B(M1; 2+ 3 → 2+ 1) of 140Nd and an upper limit for the case of 142Sm are revealing the main fragments of the proton-neutron mixed-symmetry 2+ 1;ms states.
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34.
  • Koos, Björn, et al. (författare)
  • Platelet-derived growth factor receptor expression and activation in choroid plexus tumors
  • 2009
  • Ingår i: American Journal of Pathology. - : Elsevier BV. - 0002-9440 .- 1525-2191. ; 175:4, s. 1631-1637
  • Tidskriftsartikel (refereegranskat)abstract
    • Choroid plexus tumors are intraventricular neoplasms predominantly affecting young children. In contrast to choroid plexus papillomas, choroid plexus carcinomas progress frequently, necessitating the development of adjuvant treatment concepts. Platelet derived growth factor (PDGF) signaling has been shown to support growth in a variety of tumors. The finding of PDGF receptor expression in choroid plexus tumors prompted us to elucidate PDGF receptor activation state using a novel method, in situ proximity ligation assay, on formalin-fixed, paraffin-embedded, archival samples of 19 choroid plexus tumors. As assessed by in situ proximity ligation assay, the proportion of phosphorylated PDGF receptor alpha was low in choroid plexus papillomas and choroid plexus carcinomas, whereas phosphorylated PDGF receptor beta was found to be significantly higher in choroid plexus carcinomas. In the immortalized choroid plexus epithelial cell line Z310 expressing PDGF receptor beta, PDGF-BB exhibited a time- and dose-dependent proliferative response, which was significantly attenuated by imatinib (gleevec). In conclusion, our findings suggest that PDGF receptor beta is functionally involved in the biology of choroid plexus tumors and may represent a molecular target for therapy. In addition, this study demonstrates the feasibility and usefulness of in situ proximity ligation assay for monitoring receptor tyrosine kinase activation in formalin-fixed, paraffin-embedded, archival tissues.
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35.
  • Lacas, Benjamin, et al. (författare)
  • Role of radiotherapy fractionation in head and neck cancers (MARCH) : an updated meta-analysis
  • 2017
  • Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 18:9, s. 1221-1237
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The Meta-Analysis of Radiotherapy in squamous cell Carcinomas of Head and neck (MARCH) showed that altered fractionation radiotherapy is associated with improved overall and progression-free survival compared with conventional radiotherapy, with hyperfractionated radiotherapy showing the greatest benefit. This update aims to confirm and explain the superiority of hyperfractionated radiotherapy over other altered fractionation radiotherapy regimens and to assess the benefit of altered fractionation within the context of concomitant chemotherapy with the inclusion of new trials. Methods For this updated meta-analysis, we searched bibliography databases, trials registries, and meeting proceedings for published or unpublished randomised trials done between Jan 1, 2009, and July 15, 2015, comparing primary or postoperative conventional fractionation radiotherapy versus altered fractionation radiotherapy (comparison 1) or conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone (comparison 2). Eligible trials had to start randomisation on or after Jan 1, 1970, and completed accrual before Dec 31, 2010; had to have been randomised in a way that precluded prior knowledge of treatment assignment; and had to include patients with non-metastatic squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx undergoing first-line curative treatment. Trials including a non-conventional radiotherapy control group, investigating hypofractionated radiotherapy, or including mostly nasopharyngeal carcinomas were excluded. Trials were grouped in three types of altered fractionation: hyperfractionated, moderately accelerated, and very accelerated. Individual patient data were collected and combined with a fixed-effects model based on the intention-to-treat principle. The primary endpoint was overall survival. Findings Comparison 1 (conventional fractionation radiotherapy vs altered fractionation radiotherapy) included 33 trials and 11 423 patients. Altered fractionation radiotherapy was associated with a significant benefit on overall survival (hazard ratio [HR] 0·94, 95% CI 0·90–0·98; p=0·0033), with an absolute difference at 5 years of 3·1% (95% CI 1·3–4·9) and at 10 years of 1·2% (−0·8 to 3·2). We found a significant interaction (p=0·051) between type of fractionation and treatment effect, the overall survival benefit being restricted to the hyperfractionated group (HR 0·83, 0·74–0·92), with absolute differences at 5 years of 8·1% (3·4 to 12·8) and at 10 years of 3·9% (−0·6 to 8·4). Comparison 2 (conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone) included five trials and 986 patients. Overall survival was significantly worse with altered fractionation radiotherapy compared with concomitant chemoradiotherapy (HR 1·22, 1·05–1·42; p=0·0098), with absolute differences at 5 years of −5·8% (−11·9 to 0·3) and at 10 years of −5·1% (−13·0 to 2·8). Interpretation This update confirms, with more patients and a longer follow-up than the first version of MARCH, that hyperfractionated radiotherapy is, along with concomitant chemoradiotherapy, a standard of care for the treatment of locally advanced head and neck squamous cell cancers. The comparison between hyperfractionated radiotherapy and concomitant chemoradiotherapy remains to be specifically tested. Funding Institut National du Cancer; and Ligue Nationale Contre le Cancer.
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36.
  • Linderholm, Hans W., 1968, et al. (författare)
  • Arctic hydroclimate variability during the last 2000 years – current understanding and research challenges
  • 2018
  • Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 14, s. 473-514
  • Forskningsöversikt (refereegranskat)abstract
    • Reanalysis data show an increasing trend in Arctic precipitation over the 20th century, but changes are not homogenous across seasons or space. The observed hydroclimate changes are expected to continue and possibly accelerate in the coming century, not only affecting pan-Arctic natural ecosystems and human activities, but also lower latitudes through the atmospheric and ocean circulations. However, a lack of spatiotemporal observational data makes reliable quantification of Arctic hydroclimate change difficult, especially in a long-term context. To understand Arctic hydroclimate and its variability prior to the instrumental record, climate proxy records are needed. The purpose of this review is to summarise the current understanding of Arctic hydroclimate during the past 2000 years. First, the paper reviews the main natural archives and proxies used to infer past hydroclimate variations in this remote region and outlines the difficulty of disentangling the moisture from the temperature signal in these records. Second, a comparison of two sets of hydroclimate records covering the Common Era from two data-rich regions, North America and Fennoscan-dia, reveals inter- and intra-regional differences. Third, building on earlier work, this paper shows the potential for providing a high-resolution hydroclimate reconstruction for the Arctic and a comparison with last-millennium simulations from fully coupled climate models. In general, hydroclimate proxies and simulations indicate that the Medieval Climate Anomaly tends to have been wetter than the Little Ice Age (LIA), but there are large regional differences. However, the regional coverage of the proxy data is inadequate, with distinct data gaps in most of Eurasia and parts of North America, making robust assessments for the whole Arctic impossible at present. To fully assess pan-Arctic hydroclimate variability for the last 2 millennia, additional proxy records are required.
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37.
  • Merbold, Lutz, et al. (författare)
  • Opportunities for an African greenhouse gas observation system
  • 2021
  • Ingår i: Regional Environmental Change. - : Springer Science and Business Media LLC. - 1436-3798 .- 1436-378X. ; 21:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Global population projections foresee the biggest increase to occur in Africa with most of the available uncultivated land to ensure food security remaining on the continent. Simultaneously, greenhouse gas emissions are expected to rise due to ongoing land use change, industrialisation, and transport amongst other reasons with Africa becoming a major emitter of greenhouse gases globally. However, distinct knowledge on greenhouse gas emissions sources and sinks as well as their variability remains largely unknown caused by its vast size and diversity and an according lack of observations across the continent. Thus, an environmental research infrastructure—as being setup in other regions—is more needed than ever. Here, we present the results of a design study that developed a blueprint for establishing such an environmental research infrastructure in Africa. The blueprint comprises an inventory of already existing observations, the spatial disaggregation of locations that will enable to reduce the uncertainty in climate forcing’s in Africa and globally as well as an overall estimated cost for such an endeavour of about 550 M€ over the next 30 years. We further highlight the importance of the development of an e-infrastructure, the necessity for capacity development and the inclusion of all stakeholders to ensure African ownership.
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38.
  • Nickless, Alecia, et al. (författare)
  • Greenhouse gas observation network design for Africa
  • 2020
  • Ingår i: Tellus. Series B: Chemical and Physical Meteorology. - : Stockholm University Press. - 1600-0889 .- 0280-6509. ; 72:1, s. 1-30
  • Tidskriftsartikel (refereegranskat)abstract
    • An optimal network design was carried out to prioritise the installation or refurbishment of greenhouse gas (GHG) monitoring stations around Africa. The network was optimised to reduce the uncertainty in emissions across three of the most important GHGs: CO2, CH4, and N2O. Optimal networks were derived using incremental optimisation of the percentage uncertainty reduction achieved by a Gaussian Bayesian atmospheric inversion. The solution for CO2 was driven by seasonality in net primary productivity. The solution for N2O was driven by activity in a small number of soil flux hotspots. The optimal solution for CH4 was consistent over different seasons. All solutions for CO2 and N2O placed sites in central Africa at places such as Kisangani, Kinshasa and Bunia (Democratic Republic of Congo), Dundo and Lubango (Angola), Zoétélé (Cameroon), Am Timan (Chad), and En Nahud (Sudan). Many of these sites appeared in the CH4 solutions, but with a few sites in southern Africa as well, such as Amersfoort (South Africa). The multi-species optimal network design solutions tended to have sites more evenly spread-out, but concentrated the placement of new tall-tower stations in Africa between 10ºN and 25ºS. The uncertainty reduction achieved by the multi-species network of twelve stations reached 47.8% for CO2, 34.3% for CH4, and 32.5% for N2O. The gains in uncertainty reduction diminished as stations were added to the solution, with an expected maximum of less than 60%. A reduction in the absolute uncertainty in African GHG emissions requires these additional measurement stations, as well as additional constraint from an integrated GHG observatory and a reduction in uncertainty in the prior biogenic fluxes in tropical Africa.
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39.
  • Richards, Stephen, et al. (författare)
  • The genome of the model beetle and pest Tribolium castaneum.
  • 2008
  • Ingår i: Nature. - 1476-4687. ; 452:7190, s. 949-55
  • Tidskriftsartikel (refereegranskat)abstract
    • Tribolium castaneum is a representative of earth’s most numerous eukaryotic order, a powerful model organism for the study of generalized insect development, and also an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved an ability to interact with a diverse chemical environment as evidenced by large expansions in odorant and gustatory receptors, as well as p450 and other detoxification enzymes. Developmental patterns in Tribolium are more representative of other arthropods than those found in Drosophila, a fact represented in gene content and function. For one, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, and some are expressed in the growth zone crucial for axial elongation in short germ development. Systemic RNAi in T. castaneum appears to use mechanisms distinct from those found in C. elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control.
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40.
  • Ryon, Krista A., et al. (författare)
  • A history of the MetaSUB consortium : Tracking urban microbes around the globe
  • 2022
  • Ingår i: iScience. - : Cell Press. - 2589-0042. ; 25:11
  • Tidskriftsartikel (refereegranskat)abstract
    • The MetaSUB Consortium, founded in 2015, is a global consortium with an interdisciplinary team of clinicians, scientists, bioinformaticians, engineers, and designers, with members from more than 100 countries across the globe. This network has continually collected samples from urban and rural sites including subways and transit systems, sewage systems, hospitals, and other environmental sampling. These collections have been ongoing since 2015 and have continued when possible, even throughout the COVID-19 pandemic. The consortium has optimized their workflow for the collection, isolation, and sequencing of DNA and RNA collected from these various sites and processing them for metagenomics analysis, including the identification of SARS-CoV-2 and its variants. Here, the Consortium describes its foundations, and its ongoing work to expand on this network and to focus its scope on the mapping, annotation, and prediction of emerging pathogens, mapping microbial evolution and antibiotic resistance, and the discovery of novel organisms and biosynthetic gene clusters.
  •  
41.
  • Sumaila, U. Rashid, et al. (författare)
  • WTO must ban harmful fisheries subsidies
  • 2021
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 374:6567, s. 544-544
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
  •  
42.
  • Tomás Graça, André, 1994- (författare)
  • Light’EM up! : structural characterization of light-driven membrane protein complexes by cryogenic electron microscopy
  • 2024
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Photosynthesis is probably the most important process for allowing life to develop into the diverse forms we see today. In this process, solar radiation is used to convert CO2 into biomass. From this process, we obtain oxygen to breathe, sources of food (plant biomass), and the potential for clean and sustainable energy. Photosystem II (PSII) – a key enzyme in photosynthesis –, is a protein complex located in the thylakoid membrane of photosynthetic organisms. PSII and its light-harvesting antennae capture light energy, driving a charge separation process, which leads to the extraction of electrons from water molecules, forming and releasing molecular oxygen. A PSII dimer is composed of more than 20 unique proteins and hundreds of cofactors which fine-tune the mechanisms of light-harvesting and water oxidation, and stabilize the whole complex. While the arrangement of most (but not all!) of these proteins and cofactors is known, their dynamics and individual contributions are not yet fully understood.In my thesis work, I took on the challenge of resolving the structure of large protein complexes, such as PSII complexes from various photosynthetic organisms, using a technique called cryogenic electron microscopy (cryo-EM). This PhD dissertation focuses on structurally describing these macromolecular assemblies and how their components (protein, cofactors, and substrate) interact with each other or with their immediate cellular environment.Among the several outcomes of my research on PSII, I would like to highlight the following findings: 1) the usage of digitonin as a detergent to solubilize PSII destroys the catalytic activity and changes LHCII pigment content, among other consequences; 2) PSII does not seem to incorporate chlorophyll (Chl) a molecules with a farnesyl tail, and the Chl tails’ flexibility justifies not resolving the full-length of some of these molecules in PSII structures. We concluded that flexibility may be an advantage to PSII function; 3) cryo-EM is a technique with the potential to reveal information about electron/proton transfer processes within PSII, and provided us with data, for instance, to suggest a pathway for the protonation of QB, the final electron acceptor in PSII.In another project, also using cryo-EM, I studied the structure of the S-layer Deinoxanthin Binding Complex (SDBC), a membrane protein complex from Deinococcus radiodurans. This complex is an essential part of the cell envelope, the outermost barrier of this bacterium, and it is known to bind a carotenoid called deinoxanthin, which has significant spectroscopic and antioxidant properties. Additionally, we studied the function of this complex and showed that the SDBC is a quencher of UVC-UVB radiation and reactive oxygen species, with superoxide dismutase activity. This complex has an α-β coiled-coil stalk long enough to reach the inner membrane of the cell envelope.In summary, visualizing the structural organization and chemistry within these complexes allowed us to gain a new understanding of their function and diversity. Furthermore, this work demonstrates the potential of cryo-EM as a method to render complementary information at resolution superior to state-of-the-art X-ray diffraction methods.
  •  
43.
  • van der Bilt, Willem G. M., et al. (författare)
  • Late Holocene glacier reconstruction reveals retreat behind present limits and two-stage Little Ice Age on subantarctic South Georgia
  • 2017
  • Ingår i: Journal of Quaternary Science. - : Wiley. - 0267-8179 .- 1099-1417. ; 32:6, s. 888-901
  • Tidskriftsartikel (refereegranskat)abstract
    • Observational data show that climate in the Southern Ocean region is rapidly changing. However, past the instrumental period, our understanding of climate variability in the region is limited by a scarcity of highresolution palaeoclimate records. Alpine glaciers, present on many Southern Ocean islands, may provide such data because changes in their mass balance, extent and erosion rates often mark a response to climate shifts. Rock flour, the fine-grained fraction of the glacial erosion process, is suspended in meltwater streams and transferred into the sediments of downstream lakes, continuously recording glacier variations. Here, we utilize this relationship to present a reconstruction of the Late Holocene glacier history of subantarctic South Georgia, using sediments from the glacier-fed Middle Hamberg Lake. To fingerprint a glacial erosion/size signal, we used titanium counts, validated against changes in sediment density and grain size, allowing a continuous reconstruction of glacier variations over the past similar to 1250 years. Together with local moraine evidence and supporting evidence from other Southern Hemisphere glaciers on New Zealand and in Patagonia, our findings reveal a series of consecutively diminishing Late Holocene advances. In addition to a glacier maximum before 1250 cal a BP, these include a twostage Litle Ice Age with advances around 300 and 120 cal a BP, in line with evidence from southern Patagonia. In addition, we present evidence for an unreported retreat behind present limits around 500 cal BP.
  •  
44.
  • Werner, Johannes P., et al. (författare)
  • Spatio-temporal variability of Arctic summer temperatures over the past 2 millennia
  • 2018
  • Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 14:4, s. 527-557
  • Tidskriftsartikel (refereegranskat)abstract
    • In this article, the first spatially resolved and millennium-length summer (June August) temperature reconstruction over the Arctic and sub-Arctic domain (north of 60 degrees N) is presented. It is based on a set of 44 annually dated temperature-sensitive proxy archives of various types from the revised PAGES2k database supplemented with six new recently updated proxy records. As a major advance, an extension of the Bayesian BARCAST climate field (CF) reconstruction technique provides a means to treat climate archives with dating uncertainties. This results not only in a more precise reconstruction but additionally enables joint probabilistic constraints to be imposed on the chronologies of the used archives. The new seasonal CF reconstruction for the Arctic region can be shown to be skilful for the majority of the terrestrial nodes. The decrease in the proxy data density back in time, however, limits the analyses in the spatial domain to the period after 750 CE, while the spatially averaged reconstruction covers the entire time interval of 1-2002 CE. The centennial to millennial evolution of the reconstructed temperature is in good agreement with a general pattern that was inferred in recent studies for the Arctic and its subregions. In particular, the reconstruction shows a pronounced Medieval Climate Anomaly (MCA; here ca. 920-1060 CE), which was characterised by a sequence of extremely warm decades over the whole domain The medieval warming was followed by a gradual cooling into the Little Ice Age (LIA), with 1766-1865 CE as the longest centennial -scale cold period, culminating around 1811-1820 CE for most of the target region. In total over 600 independent realisations of the temperature CF were generated. As showcased for local and regional trends and temperature anomalies, operating in a probabilistic framework directly results in comprehensive uncertainty estimates, even for complex analyses. For the presented multi -scale trend analysis, for example, the spread in different paths across the reconstruction ensemble prevents a robust analysis of features at timescales shorter than ca. 30 years. For the spatial reconstruction, the benefit of using the spatially resolved reconstruction ensemble is demonstrated by focusing on the regional expression of the recent warming and the MCA. While our analysis shows that the peak MCA summer temperatures were as high as in the late 20th and early 21st centuries, the spatial coherence of extreme years over the last decades of the reconstruction (1980s onwards) seems unprecedented at least back until 750 CE. However, statistical testing could not provide conclusive support of the contemporary warming to exceed the peak of the MCA in terms of the pan-Arctic mean summer temperatures: the reconstruction cannot be extended reliably past 2002 CE due to lack of proxy data and thus the most recent warming is not captured.
  •  
45.
  • Werner, Yvonne Maria, et al. (författare)
  • Gustav III, Enlightenment and Religion : Ecumenical visions and Catholicizing Strategies
  • 2023
  • Ingår i: Religious enlightenment in the eighteenth-century Nordic countries : Reason and orthodoxy - Reason and orthodoxy. - 9789198740400 ; , s. 230-259
  • Bokkapitel (refereegranskat)abstract
    • As part of the “enlightened” reform activity, Gustav III issued a Tolerance Edict for “foreign believers” in 1781. This law allowed Catholic immigrants to publicly practice their religion. The members of the Reformed communities had already been granted the same rights, and in 1782 the ban on Jewish immigration was abolished. According to previous research, these edicts of toleration, in addition to the purpose of displaying an “enlightened spirit”, were issued mainly for economic reasons with the purpose to facilitate non-Lutheran foreigners to establish themselves in the country. This was undoubtedly the main reason regarding the Jews and the Reformed believers. Yet, as for the Catholics, I would argue that there was also another reason that came into play, namely Gustav III’s fascination for Catholic liturgy and culture, expressed not least in connection with his stay in Rome 1783/84. That he, a Protestant monarch, was received by the Pope on several occasions, and participated in religious services in the same way as Catholic believers, is a clear testimony of his Catholic sympathies.In my article, I am showing how the king's Catholic sympathies came to shape his church policy in a direction that ran counter to the religious ideals of Enlightenment. In line with this, I also critically question the tendency in previous research to contrast the “enlightened” Gustav III with a backward-looking Lutheran clergy. In several cases, the leading representatives of the clerical estate proved to be far more influenced by Enlightenment ideals than the king.
  •  
46.
  • Wortel, Meike T., et al. (författare)
  • Towards evolutionary predictions : current promises and challenges
  • 2023
  • Ingår i: Evolutionary Applications. - : John Wiley & Sons. - 1752-4571. ; 16:1, s. 3-21
  • Forskningsöversikt (refereegranskat)abstract
    • Evolution has traditionally been a historical and descriptive science, and predicting future evolutionary processes has long been considered impossible. However, evolutionary predictions are increasingly being developed and used in medicine, agriculture, biotechnology and conservation biology. Evolutionary predictions may be used for different purposes, such as to prepare for the future, to try and change the course of evolution or to determine how well we understand evolutionary processes. Similarly, the exact aspect of the evolved population that we want to predict may also differ. For example, we could try to predict which genotype will dominate, the fitness of the population or the extinction probability of a population. In addition, there are many uses of evolutionary predictions that may not always be recognized as such. The main goal of this review is to increase awareness of methods and data in different research fields by showing the breadth of situations in which evolutionary predictions are made. We describe how diverse evolutionary predictions share a common structure described by the predictive scope, time scale and precision. Then, by using examples ranging from SARS-CoV2 and influenza to CRISPR-based gene drives and sustainable product formation in biotechnology, we discuss the methods for predicting evolution, the factors that affect predictability and how predictions can be used to prevent evolution in undesirable directions or to promote beneficial evolution (i.e. evolutionary control). We hope that this review will stimulate collaboration between fields by establishing a common language for evolutionary predictions.
  •  
47.
  • Zhang, Huan, et al. (författare)
  • East Asian warm season temperature variations over the past two millennia
  • 2018
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • East Asia has experienced strong warming since the 1960s accompanied by an increased frequency of heat waves and shrinking glaciers over the Tibetan Plateau and the Tien Shan. Here, we place the recent warmth in a long-term perspective by presenting a new spatially resolved warm-season (May-September) temperature reconstruction for the period 1-2000 CE using 59 multiproxy records from a wide range of East Asian regions. Our Bayesian Hierarchical Model (BHM) based reconstructions generally agree with earlier shorter regional temperature reconstructions but are more stable due to additional temperature sensitive proxies. We find a rather warm period during the first two centuries CE, followed by a multi-century long cooling period and again a warm interval covering the 900-1200 CE period (Medieval Climate Anomaly, MCA). The interval from 1450 to 1850 CE (Little Ice Age, LIA) was characterized by cooler conditions and the last 150 years are characterized by a continuous warming until recent times. Our results also suggest that the 1990s were likely the warmest decade in at least 1200 years. The comparison between an ensemble of climate model simulations and our summer reconstructions since 850 CE shows good agreement and an important role of internal variability and external forcing on multi-decadal time-scales.
  •  
48.
  • 2019
  • Tidskriftsartikel (refereegranskat)
  •  
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