| 1. |
- Verra, L., et al.
(författare)
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Controlled Growth of the Self-Modulation of a Relativistic Proton Bunch in Plasma
- 2022
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Ingår i: Physical Review Accelerators and Beams. - : American Physical Society. - 2469-9888. ; 25:7
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Tidskriftsartikel (refereegranskat)abstract
- A long, narrow, relativistic charged particle bunch propagating in plasma is subject to the self -modulation (SM) instability. We show that SM of a proton bunch can be seeded by the wakefields driven by a preceding electron bunch. SM timing reproducibility and control are at the level of a small fraction of the modulation period. With this seeding method, we independently control the amplitude of the seed wakefields with the charge of the electron bunch and the growth rate of SM with the charge of the proton bunch. Seeding leads to larger growth of the wakefields than in the instability case.
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| 4. |
- Mikus, Maria, et al.
(författare)
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Elevated levels of circulating CDH5 and FABP1 in association with human drug-induced liver injury
- 2016
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Ingår i: Liver international. - : John Wiley & Sons. - 1478-3223 .- 1478-3231. ; 37:1, s. 132-140
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: The occurrence of drug-induced liver injury (DILI) is a major issue in all phases of drug development. To identify novel biomarker candidates associated with DILI, we utilised an affinity proteomics strategy, where antibody suspension bead arrays were applied to profile plasma and serum samples from human DILI cases and controls. Methods: An initial screening was performed using 4594 randomly selected antibodies, representing 3450 human proteins. Resulting candidate proteins together with proposed DILI biomarker candidates generated a DILI array of 251 proteins for subsequent target analysis and verifications. In total, 1196 samples from 241 individuals across four independent cohorts were profiled: healthy volunteers receiving acetaminophen, patients with human immunodeficiency virus and/or tuberculosis receiving treatment, DILI cases originating from a wide spectrum of drugs, and healthy volunteers receiving heparins. Results: We observed elevated levels of cadherin 5, type 2 (CDH5) and fatty acid-binding protein 1 (FABP1) in DILI cases. In the two longitudinal cohorts, CDH5 was elevated already at baseline. FABP1 was elevated after treatment initiation and seemed to respond more rapidly than alanine aminotransferase (ALT). The elevations were verified in the DILI cases treated with various drugs. In the heparin cohort, CDH5 was stable over time whereas FABP1 was elevated. Conclusions: These results suggest that CDH5 may have value as a susceptibility marker for DILI. FABP1 was identified as a biomarker candidate with superior characteristics regarding tissue distribution and kinetics compared to ALT but likely with limited predictive value for the development of severe DILI. Further studies are needed to determine the clinical utility of the proposed markers.
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| 5. |
- Bachmann, L., et al.
(författare)
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The role of systematics for understanding ecosystem functions: Proceedings of the Zoologica Scripta Symposium, Oslo, Norway, 25 August 2022
- 2023
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Ingår i: Zoologica Scripta. - : Wiley. - 0300-3256 .- 1463-6409. ; 52:3, s. 187-214
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Tidskriftsartikel (refereegranskat)abstract
- On 25 August 2022, the Zoologica Scripta - An International Journal of Systematic Zoology and the Norwegian Academy of Sciences and Letters arranged a symposium entitled 'The role of systematics for understanding ecosystem functions' in the Academy's premises in Oslo, Norway. The symposium aimed at offering a forum for exploring and discussing trends and future developments in the field of systematics. Eleven international experts contributed expertise on various issues related to global challenges, such as biodiversity assessments, databases, cutting-edge analysis tools, and the consequences of the taxonomic impediment. Here, we compiled a multi-author proceedings paper of the symposium contributions that are arranged in chapters and presents the content and the key conclusions of the majority of the presentations.
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| 7. |
- De Caterina, R, et al.
(författare)
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General mechanisms of coagulation and targets of anticoagulants (Section I) : Position Paper of the ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease
- 2013
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 109:4, s. 569-579
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Tidskriftsartikel (refereegranskat)abstract
- Contrary to previous models based on plasma, coagulation processes are currently believed to be mostly cell surface-based, including three overlapping phases: initiation, when tissue factor-expressing cells and microparticles are exposed to plasma; amplification, whereby small amounts of thrombin induce platelet activation and aggregation, and promote activation of factors (F)V, FVIII and FXI on platelet surfaces; and propagation, in which the Xase (tenase) and prothrombinase complexes are formed, producing a burst of thrombin and the cleavage of fibrinogen to fibrin. Thrombin exerts a number of additional biological actions, including platelet activation, amplification and self-inhibition of coagulation, clot stabilisation and anti-fibrinolysis, in processes occurring in the proximity of vessel injury, tightly regulated by a series of inhibitory mechanisms. "Classical" anticoagulants, including heparin and vitamin K antagonists, typically target multiple coagulation steps. A number of new anticoagulants, already developed or under development, target specific steps in the process, inhibiting a single coagulation factor or mimicking natural coagulation inhibitors.
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| 8. |
- Hug, S., et al.
(författare)
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High-dimensional Bayesian parameter estimation: Case study for a model of JAK2/STAT5 signaling
- 2013
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Ingår i: Mathematical Biosciences. - : Elsevier. - 0025-5564 .- 1879-3134. ; 246:2, s. 293-304
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Tidskriftsartikel (refereegranskat)abstract
- In this work we present results of a detailed Bayesian parameter estimation for an analysis of ordinary differential equation models. These depend on many unknown parameters that have to be inferred from experimental data. The statistical inference in a high-dimensional parameter space is however conceptually and computationally challenging. To ensure rigorous assessment of model and prediction uncertainties we take advantage of both a profile posterior approach and Markov chain Monte Carlo sampling. We analyzed a dynamical model of the JAK2/STAT5 signal transduction pathway that contains more than one hundred parameters. Using the profile posterior we found that the corresponding posterior distribution is bimodal. To guarantee efficient mixing in the presence of multimodal posterior distributions we applied a multi-chain sampling approach. The Bayesian parameter estimation enables the assessment of prediction uncertainties and the design of additional experiments that enhance the explanatory power of the model. This study represents a proof of principle that detailed statistical analysis for quantitative dynamical modeling used in systems biology is feasible also in high-dimensional parameter spaces.
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| 10. |
- Schulte-Oehlmann, U, et al.
(författare)
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COMPRENDO: Focus and approach.
- 2006
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Ingår i: Environmental Health Perspectives. - : Environmental Health Perspectives. - 1552-9924 .- 0091-6765. ; 114:Supplement 1, s. 98-100
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Tidskriftsartikel (refereegranskat)abstract
- Tens of thousands of man-made chemicals are in regular use and discharged into the environment. Many of them are known to interfere with the hormonal systems in humans and wildlife. Given the complexity of endocrine systems, there are many ways in which endocrine-disrupting chemicals (EDCs) can affect the body's signaling system, and this makes unraveling the mechanisms of action of these chemicals difficult. A major concern is that some of these EDCs appear to be biologically active at extremely low concentrations. There is growing evidence to indicate that the guiding principle of traditional toxicology that "the dose makes the poison" may not always be the case because some EDCs do not induce the classical dose-response relationships. The European Union project COMPRENDO (Comparative Research on Endocrine Disrupters--Phylogenetic Approach and Common Principles focussing on Androgenic/Antiandrogenic Compounds) therefore aims to develop an understanding of potential health problems posed by androgenic and antiandrogenic compounds (AACs) to wildlife and humans by focusing on the commonalities and differences in responses to AACs across the animal kingdom (from invertebrates to vertebrates) .
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