1. |
- Kehoe, Laura, et al.
(author)
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Make EU trade with Brazil sustainable
- 2019
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Journal article (other academic/artistic)
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2. |
- Abelev, Betty, et al.
(author)
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Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
- 2013
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In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
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Journal article (peer-reviewed)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.
(author)
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Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
- 2012
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In: Journal of High Energy Physics. - 1029-8479. ; :11
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Journal article (peer-reviewed)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.
(author)
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Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
- 2012
-
In: Journal of High Energy Physics. - 1029-8479. ; :7
-
Journal article (peer-reviewed)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. |
- Demichev, Vadim, et al.
(author)
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A proteomic survival predictor for COVID-19 patients in intensive care
- 2022
-
In: PLOS Digital Health. - : Public Library of Science (PLoS). - 2767-3170. ; 1:1 January
-
Journal article (peer-reviewed)abstract
- Global healthcare systems are challenged by the COVID-19 pandemic. There is a need to optimize allocation of treatment and resources in intensive care, as clinically established risk assessments such as SOFA and APACHE II scores show only limited performance for predicting the survival of severely ill COVID-19 patients. Additional tools are also needed to monitor treatment, including experimental therapies in clinical trials. Comprehensively capturing human physiology, we speculated that proteomics in combination with new data-driven analysis strategies could produce a new generation of prognostic discriminators. We studied two independent cohorts of patients with severe COVID-19 who required intensive care and invasive mechanical ventilation. SOFA score, Charlson comorbidity index, and APACHE II score showed limited performance in predicting the COVID-19 outcome. Instead, the quantification of 321 plasma protein groups at 349 timepoints in 50 critically ill patients receiving invasive mechanical ventilation revealed 14 proteins that showed trajectories different between survivors and non-survivors. A predictor trained on proteomic measurements obtained at the first time point at maximum treatment level (i.e. WHO grade 7), which was weeks before the outcome, achieved accurate classification of survivors (AUROC 0.81). We tested the established predictor on an independent validation cohort (AUROC 1.0). The majority of proteins with high relevance in the prediction model belong to the coagulation system and complement cascade. Our study demonstrates that plasma proteomics can give rise to prognostic predictors substantially outperforming current prognostic markers in intensive care.
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6. |
- Algaba, Juan-Carlos, et al.
(author)
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Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign
- 2021
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In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 911:1
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Research review (peer-reviewed)abstract
- In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M o˙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87's spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded.
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7. |
- Bjerner, Johan, et al.
(author)
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Baseline Serum Prostate-specific Antigen Value Predicts the Risk of Subsequent Prostate Cancer Death-Results from the Norwegian Prostate Cancer Consortium.
- 2024
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In: European Urology. - 0302-2838. ; 86:1, s. 20-26
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Journal article (peer-reviewed)abstract
- Prostate-specific antigen (PSA) levels in midlife are strongly associated with the long-term risk of lethal prostate cancer in cohorts not subject to screening. This is the first study evaluating the association between PSA levels drawn as part of routine medical care in the Norwegian population and prostate cancer incidence and mortality.To determine the association between midlife PSA levels <4.0 ng/ml, drawn as part of routine medical care, and long-term risk of prostate cancer death.The Norwegian Prostate Cancer Consortium collected >8 million PSA results from >1 million Norwegian males ≥40 yr of age. We studied 176099 men (predefined age strata: 40-54 and 55-69 yr) without a prior prostate cancer diagnosis who had a nonelevated baseline PSA level (<4.0 ng/ml) between January 1, 1995 and December 31, 2005.Baseline PSA.We assessed the 16-yr risk of prostate cancer mortality. We calculated the discrimination (C-index) between predefined PSA strata (<0.5, 0.5-0.9, 1.0-1.9, 2.0-2.9, and 3.0-3.9 ng/ml) and subsequent prostate cancer death. Survival curves were plotted using the Kaplan-Meier method.The median follow-up time of men who did not get prostate cancer was 17.9 yr. Overall, 84% of men had a baseline PSA level of <2.0 ng/ml and 1346 men died from prostate cancer, with 712 deaths (53%) occurring in the 16% of men with the highest baseline PSA of 2.0-3.9 ng/ml. Baseline PSA levels were associated with prostate cancer mortality (C-index 0.72 for both age groups, 40-54 and 55-69 yr). The fact that the reason for any given PSA measurement remains unknown represents a limitation.We replicated prior studies that baseline PSA at age 40-69 yr can be used to stratify a man's risk of dying from prostate cancer within the next 15-20 yr.A prostate-specific antigen level obtained as part of routine medical care is strongly associated with a man's risk of dying from prostate cancer in the next two decades.
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8. |
- Carsten, Hobohm, et al.
(author)
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Land Use Change and the Future of Biodiversity
- 2021
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In: Perspectives for Biodiversity and Ecosystems. - Cham : Springer. - 2214-2827 .- 2214-2835. - 9783030577094 ; , s. 451-483
-
Book chapter (other academic/artistic)abstract
- This synthesis report is a meta-analysis of perspectives for biodiversity and ecosystems, with a strong focus on human impacts on the environment, and a work order to enable and manage the protection, survival and evolution of all species on Earth. The goal is to protect nature without any further species loss (Zero Extinction). With this report, we assess alarming signals from the environment; determine the needs of threatened biota and the required actions to manage and protect landscapes and ecosystems; and identify some inescapable tendencies, challenges but also possibilities. The story of humans on Earth is at a critical juncture. Human behaviour is inherently dependent on physical and societal relations, including orientation and positioning within the physical environment. There is no single cultural benefit that is independent of provisioning through ecosystem services. Humans are part of the environment, acquire all needs from it and, as such, depend on its integrity and management for life and well-being. Moreover, if human impacts to the environment continue to increase the risk of rebound effects impacting human life and health will increase as well. Whenever a biome, ecosystem, habitat or species is heavily impacted or threatened with irreversible transformation or extinction, prevailing environmental conditions are relevant and should be observed, analysed and remedied as necessary and where possible. Ecology examines the evolutionary, historical and more recent interplay between biological life and the abiotic environment, while the role of social science and the humanities is to question the physical and social landscape, and how and why it should be protected or influenced, e.g. by nature conservation measures under political and economic, ethical and legal considerations. Thus, for all inter-relationships between natural and sociocultural processes, a joint venture in the form of social-ecological thinking is necessary to combine natural sciences and the humanities. With this contribution, we combine ecological knowledge with social science knowledge (s.l.) through the participation of scientists of many different disciplines. We analyse history and current processes to assess risks, threats and possibilities, and call for an array of regulations and measures that can contribute to halting of biodiversity loss and that assist in achieving a sustainable future. Regulations comprise creativity, cultural incentives, social norms, environmental education and economic investments—such as payments for sustainable agriculture, forestry, and fishery; investments in water, soil and air purity; and much clearer and stronger legal restrictions and consequences around waste streams and environmental degradation. Moreover, a gradual change from profit-oriented economies in the short-run to environmentally-sensitive policies that include systematic environmental programmes in the long term might help to decrease pressure on ecosystems and biota. Such economics might also include the real costs of consumerism, including the impacts of particular products on the environment and on human health. The greatest hurdle for the continued existence of many critically endangered species is the impact of widespread anthropogenic-driven change in the usage of water, air and land, and industry intensification in agriculture, aquaculture, forestry, urbanisation, transportation and mining sectors. However, there is not one simple solution to solve these issues. We conclude that many of the current developments have to be adjusted or gradually altered in a step-wise manner, especially with respect to existing sociocultural behaviours. Therefore, various concepts, decisions and measures should be discussed and implemented at all scales from local to supranational and among researchers, practitioners and politicians.
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9. |
- Demichev, Vadim, et al.
(author)
-
A time-resolved proteomic and prognostic map of COVID-19
- 2021
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In: Cell Systems. - : Elsevier BV. - 2405-4712 .- 2405-4720. ; 12:8, s. 780-794.e7
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Journal article (peer-reviewed)abstract
- COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease.
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10. |
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11. |
- Schewe, Jacob, et al.
(author)
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State-of-the-art global models underestimate impacts from climate extremes
- 2019
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
-
Journal article (peer-reviewed)abstract
- Global impact models represent process-level understanding of how natural and human systems may be affected by climate change. Their projections are used in integrated assessments of climate change. Here we test, for the first time, systematically across many important systems, how well such impact models capture the impacts of extreme climate conditions. Using the 2003 European heat wave and drought as a historical analogue for comparable events in the future, we find that a majority of models underestimate the extremeness of impacts in important sectors such as agriculture, terrestrial ecosystems, and heat-related human mortality, while impacts on water resources and hydropower are overestimated in some river basins; and the spread across models is often large. This has important implications for economic assessments of climate change impacts that rely on these models. It also means that societal risks from future extreme events may be greater than previously thought.
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12. |
- Wartenburger, Richard, et al.
(author)
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Evapotranspiration simulations in ISIMIP2a-Evaluation of spatio-temporal characteristics with a comprehensive ensemble of independent datasets
- 2018
-
In: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 13:7
-
Journal article (peer-reviewed)abstract
- Actual land evapotranspiration (ET) is a key component of the global hydrological cycle and an essential variable determining the evolution of hydrological extreme events under different climate change scenarios. However, recently available ET products show persistent uncertainties that are impeding a precise attribution of human-induced climate change. Here, we aim at comparing a range of independent global monthly land ET estimates with historical model simulations from the global water, agriculture, and biomes sectors participating in the second phase of the Inter-Sectoral Impact Model Intercomparison Project (ISIMIP2a). Among the independent estimates, we use the EartH2Observe Tier-1 dataset (E2O), two commonly used reanalyses, a pre-compiled ensemble product (LandFlux-EVAL), and an updated collection of recently published datasets that algorithmically derive ET from observations or observations-based estimates (diagnostic datasets). A cluster analysis is applied in order to identify spatio-temporal differences among all datasets and to thus identify factors that dominate overall uncertainties. The clustering is controlled by several factors including the model choice, the meteorological forcing used to drive the assessed models, the data category (models participating in the different sectors of ISIMIP2a, E2O models, diagnostic estimates, reanalysis-based estimates or composite products), the ET scheme, and the number of soil layers in the models. By using these factors to explain spatial and spatio-temporal variabilities in ET, we find that the model choice mostly dominates (24%-40% of variance explained), except for spatio-temporal patterns of total ET, where the forcing explains the largest fraction of the variance (29%). The most dominant clusters of datasets are further compared with individual diagnostic and reanalysis-based estimates to assess their representation of selected heat waves and droughts in the Great Plains, Central Europe and western Russia. Although most of the ET estimates capture these extreme events, the generally large spread among the entire ensemble indicates substantial uncertainties.
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13. |
- Witjes, J. Alfred, et al.
(author)
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EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer – An International Collaborative Multistakeholder Effort : Under the Auspices of the EAU-ESMO Guidelines Committees
- 2020
-
In: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 77:2, s. 223-250
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference.SETTING: Online Delphi survey and consensus conference.PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), and 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease.CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time when further evidence is available to guide our approach.PATIENT SUMMARY: This report summarises findings from an international, multistakeholder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available.
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14. |
- Amagat, Jordi, et al.
(author)
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Injectable 2D flexible hydrogel sheets for optoelectrical/biochemical dual stimulation of neurons
- 2023
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In: Biomaterials Advances. - : Elsevier BV. - 2772-9516 .- 2772-9508. ; 146
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Journal article (peer-reviewed)abstract
- Major challenges in developing implanted neural stimulation devices are the invasiveness, complexity, and cost of the implantation procedure. Here, we report an injectable, nanofibrous 2D flexible hydrogel sheet-based neural stimulation device that can be non-invasively implanted via syringe injection for optoelectrical and biochemical dual stimulation of neuron. Specifically, methacrylated gelatin (GelMA)/alginate hydrogel nanofibers were mechanically reinforced with a poly(lactide-co-ε-caprolactone) (PLCL) core by coaxial electrospinning. The lubricant hydrogel shell enabled not only injectability, but also facile incorporation of functional nanomaterials and bioactives. The nanofibers loaded with photocatatlytic g-C3N4/GO nanoparticles were capable of stimulating neural cells via blue light, with a significant 36.3 % enhancement in neurite extension. Meanwhile, the nerve growth factor (NGF) loaded nanofibers supported a sustained release of NGF with well-maintained function to biochemically stimulate neural differentiation. We have demonstrated the capability of an injectable, hydrogel nanofibrous, neural stimulation system to support neural stimulation both optoelectrically and biochemically, which represents crucial early steps in a larger effort to create a minimally invasive system for neural stimulation.
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15. |
- Andresen, Louise C., 1974, et al.
(author)
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Shifting Impacts of Climate Change: Long-Term Patterns of Plant Response to Elevated CO2, Drought, and Warming Across Ecosystems
- 2016
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In: Large-Scale Ecology: Model Systems to Global Perspectives. - : Elsevier. - 9780081009352 ; , s. 437-473
-
Book chapter (peer-reviewed)abstract
- Field experiments that expose terrestrial ecosystems to climate change factors by manipulations are expensive to maintain, and typically only last a few years. Plant biomass is commonly used to assess responses to climate treatments and to predict climate change impacts. However, response to the treatments might be considerably different between the early years and a decade later. The aim of this data analysis was to develop and apply a method for evaluating changes in plant biomass responses through time, in order to provide a firm basis for discussing how the ‘short-term’ response might differ from the ‘long-term’ response. Across 22 sites situated in the northern hemisphere, which covered three continents, and multiple ecosystems (grasslands, shrublands, moorlands, forests, and deserts), we evaluated biomass datasets from long-term experiments with exposure to elevated CO2 (eCO2), warming, or drought. We developed methods for assessing biomass response patterns to the manipulations using polynomial and linear (piecewise) model analysis and linked the responses to sitespecific variables such as temperature and rainfall. Polynomial patterns across sites indicated changes in response direction over time under eCO2, warming, and drought. In addition, five distinct pattern types were confirmed within sites: ‘no response’, ‘delayed response’, ‘directional response’, ‘dampening response’, and ‘altered response’ patterns. We found that biomass response direction was as likely to change over time as it was to be consistent, and therefore suggest that climate manipulation experiments should be carried out over timescales covering both short- and long-term responses, in order to realistically assess future impacts of climate change.
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16. |
- Attié, David, et al.
(author)
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A time projection chamber with GEM-based readout
- 2017
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In: Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. - : Elsevier BV. - 0168-9002. ; 856, s. 109-118
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Journal article (peer-reviewed)abstract
- For the International Large Detector concept at the planned International Linear Collider, the use of time projection chambers (TPC) with micro-pattern gas detector readout as the main tracking detector is investigated. In this paper, results from a prototype TPC, placed in a 1. T solenoidal field and read out with three independent Gas Electron Multiplier (GEM) based readout modules, are reported. The TPC was exposed to a 6. GeV electron beam at the DESY II synchrotron. The efficiency for reconstructing hits, the measurement of the drift velocity, the space point resolution and the control of field inhomogeneities are presented.
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17. |
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18. |
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19. |
- Bergmann, René, et al.
(author)
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Prominent Binding of Human and Equine Fibrinogen to Streptococcus equi subsp. zooepidemicus Is Mediated by Specific SzM Types and Is a Distinct Phenotype of Zoonotic Isolates
- 2020
-
In: Infection and Immunity. - 1098-5522. ; 88:1
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Journal article (peer-reviewed)abstract
- Streptococcus equi subsp. zooepidemicus is an important pathogen in horses that causes severe diseases such as pneumonia and abortion. Furthermore, it is a zoonotic agent, and contact with horses is a known risk factor. In this study, we investigated the working hypothesis that the zoonotic potential varies among S. equi subsp. zooepidemicus strains in association with differences in M-like protein-mediated binding of host plasma proteins. We demonstrate via in-frame deletion mutagenesis of two different S. equi subsp. zooepidemicus strains that the M-like protein SzM is crucial for the binding of fibrinogen to the bacterial surface and for survival in equine and human blood. S. equi subsp. zooepidemicus isolates of equine and human origins were compared with regard to SzM sequences and binding of equine and human fibrinogens. The N-terminal 216 amino acids of the mature SzM were found to exhibit a high degree of diversity, but the majority of human isolates grouped in three distinct SzM clusters. Plasma protein absorption assays and flow cytometry analysis revealed that pronounced binding of human fibrinogen is a common phenotype of human S. equi subsp. zooepidemicus isolates but much less so in equine S. equi subsp. zooepidemicus isolates. Furthermore, binding of human fibrinogen is associated with specific SzM types. These results suggest that SzM-mediated binding of human fibrinogen is an important virulence mechanism of zoonotic S. equi subsp. zooepidemicus isolates.
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20. |
- Brenner, David, et al.
(author)
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Hot-spot KIF5A mutations cause familial ALS
- 2018
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In: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 141, s. 688-697
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Journal article (peer-reviewed)abstract
- Heterozygous missense mutations in the N-terminal motor or coiled-coil domains of the kinesin family member 5A (KIF5A) gene cause monogenic spastic paraplegia (HSP10) and Charcot-Marie-Tooth disease type 2 (CMT2). Moreover, heterozygous de novo frame-shift mutations in the C-terminal domain of KIF5A are associated with neonatal intractable myoclonus, a neurodevelopmental syndrome. These findings, together with the observation that many of the disease genes associated with amyotrophic lateral sclerosis disrupt cytoskeletal function and intracellular transport, led us to hypothesize that mutations in KIF5A are also a cause of amyotrophic lateral sclerosis. Using whole exome sequencing followed by rare variant analysis of 426 patients with familial amyotrophic lateral sclerosis and 6137 control subjects, we detected an enrichment of KIF5A splice-site mutations in amyotrophic lateral sclerosis (2/426 compared to 0/6137 in controls; P = 4.2 x 10-3), both located in a hot-spot in the C-terminus of the protein and predicted to affect splicing exon 27. We additionally show co-segregation with amyotrophic lateral sclerosis of two canonical splice-site mutations in two families. Investigation of lymphoblast cell lines from patients with KIF5A splice-site mutations revealed the loss of mutant RNA expression and suggested haploinsufficiency as the most probable underlying molecular mechanism. Furthermore, mRNA sequencing of a rare non-synonymous missense mutation (predicting p. Arg1007Gly) located in the C-terminus of the protein shortly upstream of the splice donor of exon 27 revealed defective KIF5A pre-mRNA splicing in respective patient-derived cell lines owing to abrogation of the donor site. Finally, the non-synonymous single nucleotide variant rs113247976 (minor allele frequency = 1.00% in controls, n = 6137), also located in the C-terminal region [p.(Pro986Leu) in exon 26], was significantly enriched in familial amyotrophic lateral sclerosis patients (minor allele frequency = 3.40%; P = 1.28 x 10-7). Our study demonstrates that mutations located specifically in a C-terminal hotspot of KIF5A can cause a classical amyotrophic lateral sclerosis phenotype, and underline the involvement of intracellular transport processes in amyotrophic lateral sclerosis pathogenesis.
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21. |
- Brockmann, Sarah J., et al.
(author)
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CHCHD10 mutations p.R15L and p.G66V cause motoneuron disease by haploinsufficiency
- 2018
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In: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 27:4, s. 706-715
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Journal article (peer-reviewed)abstract
- Mutations in the mitochondrially located protein CHCHD10 cause motoneuron disease by an unknown mechanism. In this study, we investigate the mutations p. R15L and p. G66V in comparison to wild-type CHCHD10 and the non-pathogenic variant p. P34S in vitro, in patient cells as well as in the vertebrate in vivo model zebrafish. We demonstrate a reduction of CHCHD10 protein levels in p. R15L and p. G66V mutant patient cells to approximately 50%. Quantitative real-time PCR revealed that expression of CHCHD10 p. R15L, but not of CHCHD10 p. G66V, is already abrogated at the mRNA level. Altered secondary structure and rapid protein degradation are observed with regard to the CHCHD10 p. G66V mutant. In contrast, no significant differences in expression, degradation rate or secondary structure of non-pathogenic CHCHD10 p. P34S are detected when compared with wild-type protein. Knockdown of CHCHD10 expression in zebrafish to about 50% causes motoneuron pathology, abnormal myofibrillar structure and motility deficits in vivo. Thus, our data show that the CHCHD10 mutations p. R15L and p. G66V cause motoneuron disease primarily based on haploinsufficiency of CHCHD10.
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22. |
- Brueckner, Frank, et al.
(author)
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Enhanced manufacturing possibilities using multi-materials in laser metal deposition
- 2018
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In: Journal of laser applications. - : American Institute of Physics (AIP). - 1042-346X .- 1938-1387. ; 26:2, s. 10-12
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Journal article (peer-reviewed)abstract
- Additive manufacturing (AM) addresses various benefits as the buildup of complex shaped parts, the possibility of functional integration, reduced lead times or the use of difficult machinable materials compared to conventional manufacturing possibilities. Beside these advantages, the use of more than one material in a component would strongly increase the field of applications in typical AM branches as energy, aerospace, or medical technology. By means of multi-material buildups, cost-intensive alloys could be only used in high-loaded areas of the part, whereas the remaining part could be fabricated with cheaper compositions. The selection of combined materials strongly depends on the requested thermophysical but also mechanical properties. Within this contribution, examples (e.g., used in the turbine business) show how alloys can be arranged to fit together, e.g., in terms of a well-chosen coefficient of thermal expansion. As can be seen in nature, the multi-material usage can be characterized by sharp intersections from one material to the other (e.g., in case of a thin corrosion protection), but also by graded structures enabling a smoother material transition (e.g., in case of dissimilar materials which are joined together without defects). The latter is shown for an example from aerospace within this paper. Another possibility is the simultaneous placement of several materials, e.g., hard carbide particles placed in a more ductile matrix composition. These particles can be varied in size (e.g., TiC versus WC). Also the ratio between carbides and matrix alloy can be adjusted depending on its application. Especially, nozzle-based free form fabrication technologies, e.g., laser metal deposition, enable the utilization of more than one material. Within this contribution, possibilities to feed more than one filler material are demonstrated. In addition, results of multi-material processes are shown. Finally, this work focuses on different (potential) applications, mainly on power generation, but also for medical technology or wear resistant components.
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23. |
- Brueckner, Frank, et al.
(author)
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Phenomena in multi-material fabrication using laser metal deposition
- 2019
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In: Laser 3D Manufacturing VI. - : SPIE - The International Society for Optics and Photonics.
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Conference paper (peer-reviewed)abstract
- Additive Manufacturing (AM) processes as Laser Metal Deposition (LMD) addresses various benefits such as the build-up of complex shaped parts, the possibility of functional integration, reduced lead times or the use of difficult machinable materials compared to conventional manufacturing possibilities. Beside mentioned advantages, the use of more than one material in a component strongly increases the field of applications. Similar to structures in nature, multi-material arrangements can be realized by (I) sharp intersections from one material to the other (e. g. in the case of a thin corrosion protection), (II) graded structures enabling smoother material transitions (e. g. dissimilar materials joined together without defects), (III) composite structures with enclosed particles in a matrix material as well as by (IV) in-situ alloying of different material compositions. Due to varying material properties (e.g. thermo-physical, mechanical, optical), the combination of materials often requires a detailed investigation of occurring process phenomena and well-chosen modifications of the process regimes. Within this paper, (a) the right material feeding as well as powder interaction between various materials in Laser Metal Deposition, (b) the suitable selection of laser wavelengths for different materials, (c) process window adjustments by means of additional sensor equipment, (d) limitations of material combinations as well as (e) results and material characterization of multi-material parts are discussed. Phenomena are discussed by means of exemplary industrial applications, e.g. from the jet engine or medical business.
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24. |
- Cao, Jun, et al.
(author)
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Whole-genome sequencing of multiple Arabidopsis thaliana populations.
- 2011
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:10, s. 956-63
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Journal article (peer-reviewed)abstract
- The plant Arabidopsis thaliana occurs naturally in many different habitats throughout Eurasia. As a foundation for identifying genetic variation contributing to adaptation to diverse environments, a 1001 Genomes Project to sequence geographically diverse A. thaliana strains has been initiated. Here we present the first phase of this project, based on population-scale sequencing of 80 strains drawn from eight regions throughout the species' native range. We describe the majority of common small-scale polymorphisms as well as many larger insertions and deletions in the A. thaliana pan-genome, their effects on gene function, and the patterns of local and global linkage among these variants. The action of processes other than spontaneous mutation is identified by comparing the spectrum of mutations that have accumulated since A. thaliana diverged from its closest relative 10 million years ago with the spectrum observed in the laboratory. Recent species-wide selective sweeps are rare, and potentially deleterious mutations are more common in marginal populations.
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25. |
- Chen, Z, et al.
(author)
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Importance of heterotrophic nitrification and dissimilatory nitrate reduction to ammonium in a cropland soil: Evidences from a 15N tracing study to literature synthesis
- 2015
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In: Soil Biology and Biochemistry. - : Elsevier BV. - 0038-0717 .- 1879-3428. ; 91, s. 65-75
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Journal article (peer-reviewed)abstract
- Future climate change is predicted to influence soil moisture regime, a key factor regulating soil nitrogen (N) cycling. To elucidate how soil moisture affects gross N transformation in a cultivated black soil, a 15N tracing study was conducted at 30%, 50% and 70% water-filled pore space (WFPS). While gross mineralization rate of recalcitrant organic N (Nrec) increased from 0.56 to 2.47 mg N kg−1 d−1, the rate of labile organic N mineralization declined from 4.23 to 2.41 mg N kg−1 d−1 with a WFPS increase from 30% to 70%. Similar to total mineralization, no distinct moisture effect was found on total immobilization of ammonium, which primarily entered the Nrec pool. Nitrate (NO3−) was mainly produced via autotrophic nitrification, which was significantly stimulated by increasing WFPS. Unexpectedly, heterotrophic nitrification was observed, with the highest rate of 1.06 mg N kg−1 d−1 at 30% WFPS, contributing 31.8% to total NO3− production, and decreased with WFPS. Dissimilatory nitrate reduction to ammonium (DNRA) increased from near zero (30% WFPS) to 0.26 mg N kg−1 d−1 (70% WFPS), amounting to 16.7–92.9% of NO3− consumption. A literature synthetic analysis from global multiple ecosystems showed that the rates of heterotrophic nitrification and DNRA in test soil were comparative to the forest and grassland ecosystems, and that heterotrophic nitrification was positively correlated with precipitation, soil organic carbon (SOC) and C/N, but negatively with pH and bulk density, while DNRA showed positive relationships with precipitation, clay, SOC, C/NO3− and WFPS. We suggested that low pH and bulk density and high SOC and C/N in test soil might favor heterotrophic nitrification, and that C and NO3− availability together with anaerobic condition were crucial for DNRA. Overall, our study highlights the role of moisture in regulating gross N turnover and the importance of heterotrophic nitrification for NO3− production under low moisture and DNRA for NO3− retention under high moisture in cropland.
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