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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- 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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| 3. |
- Bhadoria, Shikha, 1991, et al.
(författare)
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Energy enhancement of laser-driven ions by radiation reaction and Breit-Wheeler pair production in the ultra-relativistic transparency regime
- 2024
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Ingår i: High Power Laser Science and Engineering. - 2052-3289. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- The impact of radiation reaction and Breit-Wheeler pair production on acceleration of fully ionized Carbon ions driven by an intense linearly-polarized laser pulse has been investigated in the ultrarelativistic transparency regime. Against initial expectations radiation reaction and pair production at ultra-high laser intensities is found to enhance the energy gained by the ions. The electrons lose most of their transverse momentum and the additionally produced pair plasma of Breit-Wheeler electrons and positrons co-stream in the forward direction as opposed to the existing electrons streaming at an angle above zero. We discuss how these observations could be explained by the changes in the phase velocity of the Buneman instability, that is known to aid ion acceleration in the Breakout-Afterburner regime, by tapping the free energy in the relative electron and ion streams. We present evidence that these non-classical effects can further improve the highest Carbon ion energies in this transparency regime.
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| 4. |
- Fickert, Peter, et al.
(författare)
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Characterization of animal models for primary sclerosing cholangitis (PSC).
- 2014
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Ingår i: Journal of hepatology. - : Elsevier BV. - 1600-0641 .- 0168-8278. ; 60:6, s. 1290-1303
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Forskningsöversikt (refereegranskat)abstract
- Primary sclerosing cholangitis (PSC) is a chronic cholangiopathy characterized by biliary fibrosis, development of cholestasis and end stage liver disease, high risk of malignancy, and frequent need for liver transplantation. The poor understanding of its pathogenesis is also reflected in the lack of effective medical treatment. Well-characterized animal models are utterly needed to develop novel pathogenetic concepts and study new treatment strategies. Currently there is no consensus on how to evaluate and characterize potential PSC models, which makes direct comparison of experimental results and effective exchange of study material between research groups difficult. The International Primary Sclerosing Cholangitis Study Group (IPSCSG) has therefore summarized these key issues in a position paper proposing standard requirements for the study of animal models of PSC.
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| 5. |
- Tajima, Toshiki, et al.
(författare)
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Science of Extreme Light Infrastructure
- 2010
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Ingår i: LIGHT AT EXTREME INTENSITIES. - : AIP. - 9780735407718 ; , s. 11-35
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Konferensbidrag (refereegranskat)abstract
- The infrastructure of Extreme Light Infrastructure (ELI) provides an unprecedented opportunity for a broad range of frontier science. Its highest ever intensity of lasers, as well as high fluence, high power, and/or ultrafast optical characteristics carve out new territories of discovery, ranging from attosecond science to photonuclear science, laser acceleration and associated beams, and high field science (Four Pillars of ELI). Its applications span from medicine, biology, engineering, energy, chemistry, physics, and fundamental understanding of the Universe. The relativistic optics that intense lasers have begun exploring may be extended into a new regime of ultra-relativistic regime, where even protons fly relativistically in the optical fields. ELI provides the highest intensity to date such that photon fields begin to feel even the texture of vacuum. This is a singular appeal of ELI with its relatively modest infrastructure (compared to the contemporary largest scientific infrastructures), yet provides an exceptional avenue along which the 21(st) Century science and society need to answer the toughest questions. The intensity frontier simultaneously brings in the energy horizon (TeV and PeV) as well as temporal frontier (attoseconds and zeptoseconds). It also turns over optics of atoms and molecules into that of nuclei with the ability to produce monoenergetic collimated gamma-ray photons. As such, the ELI concept acutely demands an effort to encompass and integrate its Four Pillars.
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| 6. |
- Yordanov, Deyan T., et al.
(författare)
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Structural trends in atomic nuclei from laser spectroscopy of tin
- 2020
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Ingår i: Communications Physics. - : Springer Nature. - 2399-3650. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Tin is the chemical element with the largest number of stable isotopes. Its complete proton shell, comparable with the closed electron shells in the chemically inert noble gases, is not a mere precursor to extended stability; since the protons carry the nuclear charge, their spatial arrangement also drives the nuclear electromagnetism. We report high-precision measurements of the electromagnetic moments and isomeric differences in charge radii between the lowest 1/2(+), 3/2(+), and 11/2(-) states in Sn117-131, obtained by collinear laser spectroscopy. Supported by state-of-the-art atomic-structure calculations, the data accurately show a considerable attenuation of the quadrupole moments in the closed-shell tin isotopes relative to those of cadmium, with two protons less. Linear and quadratic mass-dependent trends are observed. While microscopic density functional theory explains the global behaviour of the measured quantities, interpretation of the local patterns demands higher-fidelity modelling. Measurements of the hyperfine structure of chemical elements isotopes provide unique insight into the atomic nucleus in a nuclear model-independent way. The authors present collinear laser spectroscopy data obtained at the CERN ISOLDE and measure hyperfine splitting along a long chain of odd-mass tin isotopes.
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