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- Godoy, Patricio, et al.
(författare)
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Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME
- 2013
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Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 87:8, s. 1315-1530
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Forskningsöversikt (refereegranskat)abstract
- This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro. In a complex architecture of nested, zonated lobules, the liver consists of approximately 80 % hepatocytes and 20 % non-parenchymal cells, the latter being involved in a secondary phase that may dramatically aggravate the initial damage. Hepatotoxicity, as well as hepatic metabolism, is controlled by a set of nuclear receptors (including PXR, CAR, HNF-4 alpha, FXR, LXR, SHP, VDR and PPAR) and signaling pathways. When isolating liver cells, some pathways are activated, e.g., the RAS/MEK/ERK pathway, whereas others are silenced (e.g. HNF-4 alpha), resulting in up- and downregulation of hundreds of genes. An understanding of these changes is crucial for a correct interpretation of in vitro data. The possibilities and limitations of the most useful liver in vitro systems are summarized, including three-dimensional culture techniques, co-cultures with non-parenchymal cells, hepatospheres, precision cut liver slices and the isolated perfused liver. Also discussed is how closely hepatoma, stem cell and iPS cell-derived hepatocyte-like-cells resemble real hepatocytes. Finally, a summary is given of the state of the art of liver in vitro and mathematical modeling systems that are currently used in the pharmaceutical industry with an emphasis on drug metabolism, prediction of clearance, drug interaction, transporter studies and hepatotoxicity. One key message is that despite our enthusiasm for in vitro systems, we must never lose sight of the in vivo situation. Although hepatocytes have been isolated for decades, the hunt for relevant alternative systems has only just begun.
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- Rossi, L., et al.
(författare)
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A European Collaboration to Investigate Superconducting Magnets for Next Generation Heavy Ion Therapy
- 2022
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Ingår i: IEEE transactions on applied superconductivity (Print). - : Institute of Electrical and Electronics Engineers (IEEE). - 1051-8223 .- 1558-2515. ; 32:4
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Tidskriftsartikel (refereegranskat)abstract
- Next generation ion therapy magnets both for gantry and for accelerator (synchrotron) are under investigation in a recently launched European collaboration that, in the frame of the European H2020 HITRIplus and I.FAST programmes, has obtained some funding for work packages on superconducting magnets. Design and technology of superconducting magnets will be developed for ion therapy synchrotron and -especially- gantry, taking as reference beams of 430 MeV/nucleon ions (C-ions) with 10(10) ions/pulse. The magnets are about 60-90 mm diameter, 4 to 5 T peak field with a field change of about 0.3 T/s and good field quality. The paper will illustrate the organization of the collaboration and the technical program. Various superconductor options (LTS, MgB2 or HTS) and different magnet shapes, like classical CosTheta or innovative Canted CosTheta (CCT), with curved multifunction (dipole and quadrupole), are under evaluation, CCT being the baseline. These studies should provide design inputs for a new superconducting gantry design for existing facilities and, on a longer time scale, for a brand-new hadron therapy centre to be placed in the South East Europe (SEEIIST project).
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- Agnini, Claudia, et al.
(författare)
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Proposal for the Global Boundary Stratotype Section and Point (GSSP) for the Priabonian Stage (Eocene) at the Alano section (Italy)
- 2021
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Ingår i: Episodes. - : International Union of Geological Sciences. - 0705-3797 .- 2586-1298. ; 44:2, s. 151-173
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Tidskriftsartikel (refereegranskat)abstract
- The base of the Priabonian Stage is one of two stage boundaries in the Paleogene that remains to be formalized. The Alano section (NE Italy) was elected by consensus as a suitable candidate for the base of the Priabonian during the Priabonian Working Group meeting held in Alano di Piave in June 2012. Further detailed research on the section is now followed by a formal proposal, which identifies the base of a prominent crystal tuff layer, the Tiziano bed, at meter 63.57 of the Alano section, as a suitable candidate for the Priabonian Stage. The choice of the Tiziano bed is appropriate from the historical point of view and several bio-magnetostratigraphic events are available to approximate this chronostratigraphic boundary and guarantee a high degree of correlatability over wide geographic areas. Events which approximate the base of the Priabonian Stage in the Alano section are the successive extinction of large acarininids and Morozovelloides (planktonic foraminifera), the Base of common and continuous Cribrocentrum erbae and the Top of Chiasmolithus grandis (nannofossils), as well as the Base of Subchron C17n.2n and the Base of Chron C17n (magnetostratigraphy). Cyclostratigraphic analysis of the Bartonian-Priabonian transition of the Alano section as well as radioisotopic data of the Tiziano tuff layer provide an absolute age (37.710 - 37.762 Ma, respectively) of this bed and, consequently, of the base of the Priabonian Stage.
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