| 1. |
- Alkhazov, GD, et al.
(author)
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SPES4-pi: installation for exclusive study of nuclear reactions
- 2005
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In: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002. ; 551:2-3, s. 290-311
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Journal article (peer-reviewed)abstract
- The paper describes the spectrometric system "SPES4-pi" used at the National Laboratory Saturne (CE Saclay, France) for the exclusive study of the baryon resonance excitation in inelastic alpha and d scattering on the proton, as well as coherent pion production in charge exchange reactions. The system consists of the magnetic spectrometer SPES4 and two wide-aperture position-sensitive detector arrays, equipped with wire chambers and scintillator hodoscopes, installed around a large-gap C-shape dipole magnet.
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| 2. |
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| 3. |
- Bevilacqua, R., et al.
(author)
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Neutron induced light-ion production from Iron and Bismuth at 175 MeV
- 2010
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In: CNR*09 - Second International Workshop on Compound Nuclear Reactions and Related Topics. - : EDP Sciences. - 9782759805211 ; , s. 05005-
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Conference paper (peer-reviewed)abstract
- We have measured light-ion (p, d, t, 3He and α) production in the interaction of 175 MeV neutrons with iron and bismuth, using the MEDLEY setup. A large set of measurements at 96 MeV has been recently completed and published, and now higher energy region is under investigation. MEDLEY is a conventional spectrometer system that allows low-energy thresholds and offers measurements over a wide angular range. The system consists of eight telescopes, each of them composed of two silicon surface barrier detectors, to perform particle identification, and a CsI(Tl) scintillator to fully measure the kinetic energy of the produced light-ions. The telescopes are placed at angles from 20° to 160°, in steps of 20°. Measurements have been performed at The Svedberg Laboratory, Uppsala (Sweden), where a quasi mono-energetic neutron beam is available and well characterized. Time of flight techniques are used to select light-ion events induced by neutrons in the main peak of the source neutron spectrum. We report preliminary double differential cross sections for production of protons, deuterons and tritons in comparison with model calculations using TALYS-1.0 code.
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| 4. |
- Forsgård, Richard A., 1987-, et al.
(author)
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Deoxycholic acid induced changes in electrophysiological parameters and macromolecular permeability in murine small intestine with and without functional enteric nervous system plexuses
- 2014
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In: Neurogastroenterology and Motility. - : Wiley-Blackwell. - 1350-1925 .- 1365-2982. ; 26:8, s. 1179-1187
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Journal article (peer-reviewed)abstract
- Background: We have previously shown in mice that the fecal proportion and concentration of the hydrophobic bile acid deoxycholic acid (DCA) is elevated with high-fat feeding and that these changes are able to disrupt the intestinal barrier function. The aim of this study was to investigate whether these changes are mediated by the enteric nervous system (ENS).Methods: The function of the ENS in the small intestinal tissues of mice was compromised by two different methods: by removing the seromuscular layer and by incubating the intact tissues with tetrodotoxin (TTX), a neural conduction blocker, before DCA treatment. Tissues with or without functional plexuses were mounted into a Ussing chamber system and treated with 3 mM DCA for 20 min. After DCA treatment, the intestinal permeability to fluorescein was assessed. Short-circuit current (I-sc) and transepithelial resistance (TER) were recorded throughout the experiment.Key Results: DCA increased intestinal fluorescein permeability only in tissues where the seromuscular layer was removed. In tissues with intact seromuscular layer, DCA induced a significant increase in TER, which was attenuated by blocking of the neural function by TTX.Conclusions & Inferences: The results of this study suggest that the DCA-induced increase observed in fluorescein permeability is not mediated through neural pathways, but more due to a direct effect on the epithelium. However, as TTX was able to attenuate the DCA-induced increase in TER, it can be speculated that DCA is also able to elicit responses through neural pathways.
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| 5. |
- Gunnarsson, L., et al.
(author)
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Pharmacology beyond the patient - The environmental risks of human drugs
- 2019
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In: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 129, s. 320-332
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Journal article (peer-reviewed)abstract
- Background: The presence of pharmaceuticals in the environment is a growing global concern and although environmental risk assessment is required for approval of new drugs in Europe and the USA, the adequacy of the current triggers and the effects-based assessments has been questioned. Objective: To provide a comprehensive analysis of all regulatory compliant aquatic ecotoxicity data and evaluate the current triggers and effects-based environmental assessments to facilitate the development of more efficient approaches for pharmaceuticals toxicity testing. Methods: Publicly-available regulatory compliant ecotoxicity data for drugs targeting human proteins was compiled together with pharmacological information including drug targets, Cmax and lipophilicity. Possible links between these factors and the ecotoxicity data for effects on, growth, mortality and/or reproduction, were evaluated. The environmental risks were then assessed based on a combined analysis of drug toxicity and predicted environmental concentrations based on European patient consumption data. Results: For most (88%) of the of 975 approved small molecule drugs targeting human proteins a complete set of regulatory compliant ecotoxicity data in the public domain was lacking, highlighting the need for both intelligent approaches to prioritize legacy human drugs for a tailored environmental risk assessment and a transparent database that captures environmental data. We show that presence/absence of drug-target orthologues are predictive of susceptible species for the more potent drugs. Drugs that target the endocrine system represent the highest potency and greatest risk. However, for most drugs ( > 80%) with a full set of ecotoxicity data, risk quotients assuming worst-case exposure assessments were below one in all European countries indicating low environmental risks for the endpoints assessed. Conclusion: We believe that the presented analysis can guide improvements to current testing procedures, and provide valuable approaches for prioritising legacy drugs (i.e. those registered before 2006) for further ecotoxicity testing. For drugs where effects of possible concern (e.g. behaviour) are not captured in regulatory tests, additional mechanistic testing may be required to provide the highest confidence for avoiding environmental impacts.
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| 8. |
- Sahin, Cagla, et al.
(author)
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Structural Basis for Dityrosine-Mediated Inhibition of α-Synuclein Fibrillization
- 2022
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In: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 144:27, s. 11949-11954
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Journal article (peer-reviewed)abstract
- α-Synuclein (α-Syn) is an intrinsically disordered protein which self-assembles into highly organized β-sheet structures that accumulate in plaques in brains of Parkinson’s disease patients. Oxidative stress influences α-Syn structure and self-assembly; however, the basis for this remains unclear. Here we characterize the chemical and physical effects of mild oxidation on monomeric α-Syn and its aggregation. Using a combination of biophysical methods, small-angle X-ray scattering, and native ion mobility mass spectrometry, we find that oxidation leads to formation of intramolecular dityrosine cross-linkages and a compaction of the α-Syn monomer by a factor of √2. Oxidation-induced compaction is shown to inhibit ordered self-assembly and amyloid formation by steric hindrance, suggesting an important role of mild oxidation in preventing amyloid formation.
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| 9. |
- Simutkin, Vasily D., et al.
(author)
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Experimental Neutron-induced Fission Fragment Mass Yields of Th-232 and U-238 at Energies from 10 to 33 MeV
- 2014
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In: Nuclear Data Sheets. - : Elsevier BV. - 0090-3752 .- 1095-9904. ; 119, s. 331-333
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Journal article (peer-reviewed)abstract
- Development of nuclear energy applications requires data for neutron-induced reactions for actinides in a wide neutron energy range. Here we describe measurements of pre-neutron emission fission fragment mass yields of Th-232 and U-238 at incident neutron energies from 10 to 33 MeV. The measurements were done at the quasi-monoenergetic neutron beam of the Louvain-la-Neuve cyclotron facility CYCLONE; a multi-section twin Frisch-gridded ionization chamber was used to detect fission fragments. For the peak neutron energies at 33, 45 and 60 MeV, the details of the data analysis and the experimental results were published in Ref. [1]. In this work we present data analysis in the low-energy tail of the neutron energy spectra. The preliminary measurement results are compared with available experimental data and theoretical predictions.
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| 10. |
- Verbruggen, B., et al.
(author)
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ECOdrug: A database connecting drugs and conservation of their targets across species
- 2018
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In: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 46:D1
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Journal article (peer-reviewed)abstract
- Pharmaceuticals are designed to interact with specific molecular targets in humans and these targets generally have orthologs in other species. This provides opportunities for the drug discovery community to use alternative model species for drug development. It also means, however, there is potential for mode of action related effects in non-target wildlife species as many pharmaceuticals reach the environment through patient use and manufacturing wastes. Acquiring insight in drug target ortholog predictions across species and taxonomic groups has proven difficult because of the lack of an optimal strategy and because necessary information is spread across multiple and diverse sources and platforms. We introduce a new research platform tool, ECOdrug, that reliably connects drugs to their protein targets across divergent species. It harmonizes ortholog predictions from multiple sources via a simple user interface underpinning critical applications for a wide range of studies in pharmacology, ecotoxicology and comparative evolutionary biology. ECOdrug can be used to identify species with drug targets and identify drugs that interact with those targets. As such, it can be applied to support intelligent targeted drug safety testing by ensuring appropriate and relevant species are selected in ecological risk assessments. ECOdrug is freely accessible and available at: Http://www.ecodrug.org. © 2017 The Author(s).
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