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20 results on '"Lugert, S."'

1. Photoproduction of {\omega} Mesons off the Proton

Author

Wilson, A., Crede, V., Anisovich, A. V., Bacelar, J. C. S., Bantes, B., Bartholomy, O., Bayadilov, D., Beck, R., Beloglazov, Y. A., Brinkmann, K. T., Castelijns, R., Dutz, H., Elsner, D., Ewald, R., Frommberger, F., Fuchs, M., Funke, Chr., Gregor, R., Gridnev, A., Gutz, E., Hannappel, J., Hillert, W., Hoffmeister, P., Horn, I., Jaegle, I., Jude, T., Junkersfeld, J., Kalinowsky, H., Kleber, V., Klein, Frank, Klein, Friedrich, Klempt, E., Kotulla, M., Krusche, B., Lang, M., Löhner, H., Lopatin, I. V., Lugert, S., Mertens, T., Messchendorp, J. G., Metag, V., Nanova, M., Nikonov, V. A., Novinski, D., Novotny, R., Ostrick, M., Pant, L. M., van Pee, H., Pfeiffer, M., Roy, A., Sarantsev, A. V., Schmidt, C., Schmieden, H., Shende, S., Sokhoyan, V., Sparks, N., Süle, A., Sumachev, V. V., Szczepanek, T., Thoma, U., Trnka, D., Varma, R., Walther, D., Wendel, Ch., and Wiedner, U.

Subjects
Nuclear Experiment, High Energy Physics - Experiment
Abstract

The differential cross sections and unpolarized spin-density matrix elements for the reaction $\gamma p\to p\omega$ were measured using the CBELSA/TAPS experiment for initial photon energies ranging from the reaction threshold to 2.5 GeV. These observables were measured from the radiative decay of the $\omega$ meson, $\omega\to\pi^0\gamma$. The cross sections cover the full angular range and show the full extent of the $t$-channel forward rise. The overall shape of the angular distributions in the differential cross sections and unpolarized spin-density matrix elements are in fair agreement with previous data. In addition, for the first time, a beam of linearly-polarized tagged photons in the energy range from 1150 MeV to 1650 MeV was used to extract polarized spin-density matrix elements. These data were included in the Bonn-Gatchina partial wave analysis (PWA). The dominant contribution to $\omega$ photoproduction near threshold was found to be the $3/2^+$ partial wave, which is primarily due to the sub-threshold $N(1720)\,3/2^+$ resonance. At higher energies, pomeron-exchange was found to dominate whereas $\pi$-exchange remained small. These $t$-channel contributions as well as further contributions from nucleon resonances were necessary to describe the entire dataset: the $1/2^-$, $3/2^-$, and $5/2^+$ partial waves were also found to contribute significantly., Comment: 8 pages, 5 figures, accepted for publication in Physics Letters B

Published
2015
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2. High statistics study of the reaction $\gamma p\to p\;2\pi^0$

Author

Sokhoyan, V., Gutz, E., Crede, V., van Pee, H., Anisovich, A. V., Bacelar, J. C. S., Bantes, B., Bartholomy, O., Bayadilov, D., Beck, R., Beloglazov, Y. A., Castelijns, R., Dutz, H., Elsner, D., Ewald, R., Frommberger, F., Fuchs, M., Funke, Ch., Gregor, R., Gridnev, A. B., Hillert, W., Hoffmeister, Ph., Horn, I., Jaegle, I., Junkersfeld, J., Kalinowsky, H., Kammer, S., Kleber, V., Klein, Frank, Klein, Friedrich, Klempt, E., Kotulla, M., Krusche, B., Lang, M., Löhner, H., Lopatin, I. V., Lugert, S., Mertens, T., Messchendorp, J. G., Metag, V., Metsch, B., Nanova, M., Nikonov, V. A., Novinsky, D., Novotny, R., Ostrick, M., Pant, L., Pfeiffer, M., Piontek, D., Roy, A., Sarantsev, A. V., Schmidt, Ch., Schmieden, H., Seifen, T., Shende, S., Süle, A., Sumachev, V. V., Szczepanek, T., Thiel, A., Thoma, U., Trnka, D., Varma, R., Walther, D., Wendel, Ch., and Wilson, A.

Subjects
Nuclear Experiment
Abstract

The photoproduction of 2$\pi^0$ mesons off protons was studied with the Crystal Barrel/TAPS experiment at the electron accelerator ELSA in Bonn. The energy of photons produced in a radiator was tagged in the energy range from 600\,MeV to 2.5\,GeV. Differential and total cross sections and $p\pi^0\pi^0$ Dalitz plots are presented. Part of the data was taken with a diamond radiator producing linearly polarized photons, and beam asymmetries were derived. Properties of nucleon and $\Delta$ resonances contributing to the $p\pi^0\pi^0$ final state were determined within the BnGa partial wave analysis. The data presented here allow us to determine branching ratios of nucleon and $\Delta$ resonances for their decays into $p\pi^0\pi^0$ via several intermediate states. Most prominent are decays proceeding via $\Delta(1232)\pi$, $N(1440)1/2^+\pi$, $N(1520)3/2^-\pi$, $N(1680)5/2^+\pi$, but also $pf_0(500)$, $pf_0(980)$, and $pf_2(1270)$ contribute to the reaction., Comment: 28 pages, 17 figures, 7 tables

Published
2015
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3. Cellular effects of paclitaxel-loaded iron oxide nanoparticles on breast cancer using different 2D and 3D cell culture models

Author

Lugert S, Unterweger H, Mühlberger M, Janko C, Draack S, Ludwig F, Eberbeck D, Alexiou C, and Friedrich RP

Subjects
superparamagnetic iron oxide nanoparticles, SPION, 3D cell culture, toxicity, flow cytometry, Magnetic Drug Targeting, Medicine (General), R5-920
Abstract

Stephan Lugert,1,2 Harald Unterweger,1 Marina Mühlberger,1 Christina Janko,1 Sebastian Draack,3 Frank Ludwig,3 Dietmar Eberbeck,4 Christoph Alexiou,1 Ralf P Friedrich1 1Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung-Professorship, Universitätsklinikum Erlangen, Erlangen, Germany; 2Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany; 3Institut für Elektrische Messtechnik und Grundlagen der Elektrotechnik, TU Braunschweig, Braunschweig, Germany; 4Physikalisch-Technische Bundesanstalt Braunschweig und Berlin, Berlin, Germany Background: Magnetic drug targeting (MDT) is an effective alternative for common drug applications, which reduces the systemic drug load and maximizes the effect of, eg, chemotherapeutics at the site of interest. After the conjugation of a magnetic carrier to a chemotherapeutic agent, the intra-arterial injection into a tumor-afferent artery in the presence of an external magnetic field ensures the accumulation of the drug within the tumor tissue.Materials and methods: In this study, we used superparamagnetic iron oxide nanoparticles (SPIONs) coated with lauric acid and human serum albumin as carriers for paclitaxel (SPIONLA-HSA-Ptx). To investigate whether this particle system is suitable for a potential treatment of cancer, we investigated its physicochemical properties by dynamic light scattering, ζ potential measurements, isoelectric point titration, infrared spectroscopy, drug release quantification, and magnetic susceptibility measurements. The cytotoxic effects were evaluated using extensive toxicological methods using flow cytometry, IncuCyte® live-cell imaging, and growth experiments on different human breast cancer cell lines in two- and three-dimensional cell cultures.Conclusion: The data showed that next to their high magnetization capability, SPIONLA-HSA-Ptx have similar cytostatic effects on human breast cancer cells as pure paclitaxel, suggesting their usage for future MDT-based cancer therapy. Keywords: superparamagnetic iron oxide nanoparticles, SPIONs, three-dimensional cell culture, toxicity, flow cytometry, magnetic drug targeting

Published
2018

4. Photoproduction of ω mesons off protons and neutrons

Author

Dietz, F., Metag, V., Anisovich, A. V., Bacelar, J. C. S., Bantes, B., Bartholomy, O., Bayadilov, D. E., Beck, R., Belogazov, Y. A., Castelijns, R., Crede, V., Dutz, H., Elsner, D., Ewald, R., Frommberger, F., Funke, C., Gothe, R., Gregor, R., Gridnev, A. B., Gutz, E., Hillert, W., Höffgren, S., Hoffmeister, P., Horn, I., Jaegle, I., Junkersfeld, J., Kalinowsky, H., Kammer, S., Kleber, V., Klein, Frank, Klein, Friedrich, Klempt, E., Konrad, M., Kotulla, M., Krusche, B., Lang, M., Löhner, H., Lopatin, I. V., Lugert, S., Menze, D., Mertens, T., Messchendorp, J. G., Nikonov, V. A., Nanova, M., Novinski, D. V., Novotny, R., Ostrick, M., Pant, L. M., van Pee, H., Pfeiffer, M., Rostomyan, T., Roy, A., Schadmand, S., Schmidt, C., Schmieden, H., Schoch, B., Shende, S. V., Shklyar, V., Süle, A., Sumachev, V. V., Szczepanek, T., Thoma, U., Trnka, D., Varma, R., Walter, D., Wendel, C., Wilson, A., and The CBELSA/TAPS Collaboration

Published
2015
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5. Erratum to: High-statistics study of the reaction $\gamma p\rightarrow p2\pi^{0}$

Author

Sokhoyan, V., Gutz, E., Crede, V., van Pee, H., Anisovich, A. V., Bacelar, J. C. S., Bantes, B., Bartholomy, O., Bayadilov, D., Beck, R., Beloglazov, Y. A., Castelijns, R., Dutz, H., Elsner, D., Ewald, R., Frommberger, F., Fuchs, M., Funke, Ch., Gregor, R., Gridnev, A. B., Hillert, W., Hoffmeister, Ph., Horn, I., Jaegle, I., Junkersfeld, J., Kalinowsky, H., Kammer, S., Kleber, V., Klein, Frank, Klein, Friedrich, Klempt, E., Kotulla, M., Krusche, B., Lang, M., Löhner, H., Lopatin, I. V., Lugert, S., Mertens, T., Messchendorp, J. G., Metag, V., Metsch, B., Nanova, M., Nikonov, V. A., Novinsky, D., Novotny, R., Ostrick, M., Pant, L., Pfeiffer, M., Piontek, D., Roy, A., Sarantsev, A. V., Schmidt, Ch., Schmieden, H., Seifen, T., Shende, S., Süle, A., Sumachev, V. V., Szczepanek, T., Thiel, A., Thoma, U., Trnka, D., Varma, R., Walther, D., Wendel, Ch., Wilson, A., and The CBELSA/TAPS Collaboration

Published
2015
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6. Quasi-free photoproduction of η -mesons off the deuteron

Author

Jaegle, I., Krusche, B., Anisovich, A., Bacelar, J., Bantes, B., Bartholomy, O., Bayadilov, D., Beck, R., Beloglazov, Y., Castelijns, R., Crede, V., Dieterle, M., Dutz, H., Elsner, D., Ewald, R., Frommberger, F., Funke, C., Gothe, R., Gregor, R., Gridnev, A., Gutz, E., Hillert, W., Höffgen, S., Hoffmeister, P., Horn, I., Junkersfeld, J., Kalinowsky, H., Kammer, S., Keshelashvili, I., Kleber, V., Klein, Frank, Klein, Friedrich, Klempt, E., Konrad, M., Kotulla, M., Lang, M., Löhner, H., Lopatin, I., Lugert, S., Maghrbi, Y., Menze, D., Mertens, T., Messchendorp, J., Metag, V., Nikonov, V., Nanova, M., Novinski, D., Novotny, R., Oberle, M., Ostrick, M., Pant, L., van Pee, H., Pfeiffer, M., Pheron, F., Roy, A., Sarantsev, A., Schadmand, S., Schmidt, C., Schmieden, H., Schoch, B., Shende, S., Sokhoyan, V., Süle, A., Sumachev, V., Szczepanek, T., Thoma, U., Trnka, D., Varma, R., Walther, D., Wendel, C., Werthmüller, D., and Witthauer, L.

Subjects
Nuclear Theory, Nuclear Experiment
Abstract

Precise data for quasi-free photoproduction of η-mesons off the deuteron have been measured at the Bonn ELSA accelerator with the combined Crystal Barrel/TAPS detector for incident photon energies up to 2.5GeV. The η-mesons have been detected in coincidence with recoil protons and neutrons. Possible nuclear effects like Fermi motion and re-scattering can be studied via a comparison of the quasi-free reaction off the bound proton to η-production off the free proton. No significant effects beyond the folding of the free cross-section with the momentum distribution of the bound protons have been found. These Fermi motion effects can be removed by an analysis using the invariant mass of the η-nucleon pairs reconstructed from the final-state four-momenta of the particles. The total cross-section for quasi-free η-photoproduction off the neutron reveals even without correction for Fermi motion a pronounced bump-like structure around 1GeV of incident photon energy, which is not observed for the proton. This structure is even narrower in the invariant-mass spectrum of the η-neutron pairs. Position and width of the peak in the invariant-mass spectrum are W ≈ 1665 MeV and FWHM Γ ≈ 25 MeV. The data are compared to the results of different models

Published
2018

7. Data on Is and Ic in γ→p→pπ0π0 reveal cascade decays of N(1900) via N(1520)π

Author

Sokhoyan, V., Gutz, E., van Pee, H., Anisovich, A.V., Bacelar, J.C.S., Bantes, B., Bartholomy, O., Bayadilov, D., Beck, R., Beloglazov, Y., Castelijns, R., Crede, V., Dutz, H., Elsner, D., Ewald, R., Frommberger, F., Fuchs, M., Funke, Ch., Gregor, R., Gridnev, A., Hillert, W., Hoffmeister, Ph., Horn, I., Jaegle, I., Junkersfeld, J., Kalinowsky, H., Kammer, S., Kleber, V., Klein, Frank, Klein, Friedrich, Klempt, E., Kotulla, M., Krusche, B., Lang, M., Löhner, H., Lopatin, I., Lugert, S., Mertens, T., Messchendorp, J.G., Metag, V., Nanova, M., Nikonov, V.A., Novinski, D., Novotny, R., Ostrick, M., Pant, L., Pfeiffer, M., Piontek, D., Roy, A., Sarantsev, A.V., Schmidt, Ch., Schmieden, H., Shende, S., Süle, A., Sumachev, V.V., Szczepanek, T., Thiel, A., Thoma, U., Trnka, D., Varma, R., Walther, D., Wendel, Ch., and Wilson, A.

Subjects
Nuclear and High Energy Physics
Published
2015
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8. High-statistics study of the reaction gamma p -> p 2 pi(0) (vol 51, pg 95, 2015)

Author

Sokhoyan, V., Gutz, E., Crede, V., van Pee, H., Anisovich, A. V., Bacelar, J. C. S., Bantes, B., Bartholomy, O., Bayadilov, D., Beck, R., Beloglazov, Y. A., Castelijns, R., Dutz, H., Elsner, D., Ewald, R., Frommberger, F., Fuchs, M., Funke, Ch., Gregor, R., Gridnev, A. B., Hillert, W., Hoffmeister, Ph., Horn, I., Jaegle, I., Junkersfeld, J., Kalinowsky, H., Kammer, S., Kleber, V., Klein, Frank, Klein, Friedrich, Klempt, E., Kotulla, M., Krusche, B., Lang, M., Löhner, H., Lopatin, I. V., Lugert, S., Mertens, T., Messchendorp, J. G., Metag, V., Metsch, B., Nanova, M., Nikonov, V. A., Novinsky, D., Novotny, R., Ostrick, M., Pant, L., Pfeiffer, M., Piontek, D., Shende, S., and Research unit Nuclear & Hadron Physics

Published
2015

9. Glypican-2 levels in cerebrospinal fluid predict the status of adult hippocampal neurogenesis

Author

Lugert, S., primary, Kremer, T., additional, Jagasia, R., additional, Herrmann, A., additional, Aigner, S., additional, Giachino, C., additional, Mendez-David, I., additional, Gardier, A. M., additional, Carralot, J. P., additional, Meistermann, H., additional, Augustin, A., additional, Saxe, M. D., additional, Lamerz, J., additional, Duran-Pacheco, G., additional, Ducret, A., additional, Taylor, V., additional, David, D. J., additional, and Czech, C., additional

Published
2017
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10. Three-Body Nature of N* and Delta* Resonances from Sequential Decay Chains

Author

Thiel, A., Sokhoyan, V., Gutz, E., van Pee, H., Anisovich, A. V., Bacelar, J. C. S., Bantes, B., Bartholomy, O., Bayadilov, D., Beck, R., Beloglazov, Yu., Castelijns, R., Crede, V., Dutz, H., Elsner, D., Ewald, R., Frommberger, F., Fuchs, M., Funke, Ch., Gregor, R., Gridnev, A., Hillert, W., Hoffmeister, Ph., Horn, I., Jaegle, I., Junkersfeld, J., Kalinowsky, H., Kammer, S., Kleber, V., Klein, Frank, Klein, Friedrich, Klempt, E., Kotulla, M., Krusche, B., Lang, M., Löhner, Herbert, Lopatin, I., Lugert, S., Mertens, T., Messchendorp, J. G., Metag, V., Metsch, B., Nanova, M., Nikonov, V., Novinski, D., Novotny, R., Ostrick, M., Pant, L., Pfeiffer, M., Shende, S., and Research unit Nuclear & Hadron Physics

Subjects
SPECTRUM, BARYON SPECTROSCOPY, STATES, SYMMETRY, Nuclear Theory, PHOTOPRODUCTION, CHIRAL DYNAMICS, High Energy Physics::Experiment, SPECTROMETER, Nuclear Experiment, QUARK-MODEL, ELSA, RESTORATION
Abstract

The N pi(0)pi(0) decays of positive-parity N* and Delta* resonances at about 2 GeV are studied at ELSA by photoproduction of two neutral pions off protons. The data reveal clear evidence for several intermediate resonances: Delta(1232), N(1520)3/2(-), and N(1680)5/2(+), with spin parities J(P) = 3/2(+), 3/2(-), and 5/2(+). The partial wave analysis (within the Bonn-Gatchina approach) identifies N(1440)1/2(+) and the N(pi pi)s (wave) (abbreviated as N sigma here) as further isobars and assigns the final states to the formation of nucleon and Delta resonances and to nonresonant contributions. We observe the know Delta(1232)pi decays of Delta(1910)1/2(+), Delta(1920)3/2(+), Delta(1905)5/2(+), Delta(1950)7/2(+), and of the corresponding spin-parity series in the nucleon sector, N(1880)1/2(+), N(1900)3/2(+), N(2000)5/2(+), and N(1990)7/2(+). For the nucleon resonances, these decay modes are reported here for the first time. Further new decay modes proceed via N(1440)1/2(pi)(+), N(1520)3/2(pi)(-) , N(1680)5/2(pi)(+), and N sigma. The latter decay modes are observed in the decay of N* resonances and at most weakly in Delta(*) decays. It is argued that these decay modes provide evidence for a 3-quark nature of N* resonances rather than a quark-diquark structure.

Published
2015

11. Photoproduction of �� Mesons off the Proton

Author

Wilson, A., Crede, V., Anisovich, A. V., Bacelar, J. C. S., Bantes, B., Bartholomy, O., Bayadilov, D., Beck, R., Beloglazov, Y. A., Brinkmann, K. T., Castelijns, R., Dutz, H., Elsner, D., Ewald, R., Frommberger, F., Fuchs, M., Funke, Chr., Gregor, R., Gridnev, A., Gutz, E., Hannappel, J., Hillert, W., Hoffmeister, P., Horn, I., Jaegle, I., Jude, T., Junkersfeld, J., Kalinowsky, H., Kleber, V., Klein, Frank, Klein, Friedrich, Klempt, E., Kotulla, M., Krusche, B., Lang, M., L��hner, H., Lopatin, I. V., Lugert, S., Mertens, T., Messchendorp, J. G., Metag, V., Nanova, M., Nikonov, V. A., Novinski, D., Novotny, R., Ostrick, M., Pant, L. M., van Pee, H., Pfeiffer, M., Roy, A., Sarantsev, A. V., Schmidt, C., Schmieden, H., Shende, S., Sokhoyan, V., Sparks, N., S��le, A., Sumachev, V. V., Szczepanek, T., Thoma, U., Trnka, D., Varma, R., Walther, D., Wendel, Ch., and Wiedner, U.

Subjects
High Energy Physics - Experiment (hep-ex), FOS: Physical sciences, Nuclear Experiment (nucl-ex), Nuclear Experiment
Abstract

The differential cross sections and unpolarized spin-density matrix elements for the reaction $��p\to p��$ were measured using the CBELSA/TAPS experiment for initial photon energies ranging from the reaction threshold to 2.5 GeV. These observables were measured from the radiative decay of the $��$ meson, $��\to��^0��$. The cross sections cover the full angular range and show the full extent of the $t$-channel forward rise. The overall shape of the angular distributions in the differential cross sections and unpolarized spin-density matrix elements are in fair agreement with previous data. In addition, for the first time, a beam of linearly-polarized tagged photons in the energy range from 1150 MeV to 1650 MeV was used to extract polarized spin-density matrix elements. These data were included in the Bonn-Gatchina partial wave analysis (PWA). The dominant contribution to $��$ photoproduction near threshold was found to be the $3/2^+$ partial wave, which is primarily due to the sub-threshold $N(1720)\,3/2^+$ resonance. At higher energies, pomeron-exchange was found to dominate whereas $��$-exchange remained small. These $t$-channel contributions as well as further contributions from nucleon resonances were necessary to describe the entire dataset: the $1/2^-$, $3/2^-$, and $5/2^+$ partial waves were also found to contribute significantly., 8 pages, 5 figures, accepted for publication in Physics Letters B

Published
2015
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12. High statistics study of the reaction $��p\to p\;2��^0$

Author

Sokhoyan, V., Gutz, E., Crede, V., van Pee, H., Anisovich, A. V., Bacelar, J. C. S., Bantes, B., Bartholomy, O., Bayadilov, D., Beck, R., Beloglazov, Y. A., Castelijns, R., Dutz, H., Elsner, D., Ewald, R., Frommberger, F., Fuchs, M., Funke, Ch., Gregor, R., Gridnev, A. B., Hillert, W., Hoffmeister, Ph., Horn, I., Jaegle, I., Junkersfeld, J., Kalinowsky, H., Kammer, S., Kleber, V., Klein, Frank, Klein, Friedrich, Klempt, E., Kotulla, M., Krusche, B., Lang, M., L��hner, H., Lopatin, I. V., Lugert, S., Mertens, T., Messchendorp, J. G., Metag, V., Metsch, B., Nanova, M., Nikonov, V. A., Novinsky, D., Novotny, R., Ostrick, M., Pant, L., Pfeiffer, M., Piontek, D., Roy, A., Sarantsev, A. V., Schmidt, Ch., Schmieden, H., Seifen, T., Shende, S., S��le, A., Sumachev, V. V., Szczepanek, T., Thiel, A., Thoma, U., Trnka, D., Varma, R., Walther, D., Wendel, Ch., and Wilson, A.

Subjects
FOS: Physical sciences, Nuclear Experiment (nucl-ex)
Abstract

The photoproduction of 2$��^0$ mesons off protons was studied with the Crystal Barrel/TAPS experiment at the electron accelerator ELSA in Bonn. The energy of photons produced in a radiator was tagged in the energy range from 600\,MeV to 2.5\,GeV. Differential and total cross sections and $p��^0��^0$ Dalitz plots are presented. Part of the data was taken with a diamond radiator producing linearly polarized photons, and beam asymmetries were derived. Properties of nucleon and $��$ resonances contributing to the $p��^0��^0$ final state were determined within the BnGa partial wave analysis. The data presented here allow us to determine branching ratios of nucleon and $��$ resonances for their decays into $p��^0��^0$ via several intermediate states. Most prominent are decays proceeding via $��(1232)��$, $N(1440)1/2^+��$, $N(1520)3/2^-��$, $N(1680)5/2^+��$, but also $pf_0(500)$, $pf_0(980)$, and $pf_2(1270)$ contribute to the reaction., 28 pages, 17 figures, 7 tables

Published
2015
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13. Photoproduction of ω mesons off the proton

Author

Wilson, A., primary, Crede, V., additional, Anisovich, A.V., additional, Bacelar, J.C.S., additional, Bantes, B., additional, Bartholomy, O., additional, Bayadilov, D., additional, Beck, R., additional, Beloglazov, Y.A., additional, Brinkmann, K.T., additional, Castelijns, R., additional, Dutz, H., additional, Elsner, D., additional, Ewald, R., additional, Frommberger, F., additional, Fuchs, M., additional, Funke, Chr., additional, Gregor, R., additional, Gridnev, A., additional, Gutz, E., additional, Hannappel, J., additional, Hillert, W., additional, Hoffmeister, P., additional, Horn, I., additional, Jaegle, I., additional, Jude, T., additional, Junkersfeld, J., additional, Kalinowsky, H., additional, Kleber, V., additional, Klein, Frank, additional, Klein, Friedrich, additional, Klempt, E., additional, Kotulla, M., additional, Krusche, B., additional, Lang, M., additional, Löhner, H., additional, Lopatin, I.V., additional, Lugert, S., additional, Mertens, T., additional, Messchendorp, J.G., additional, Metag, V., additional, Nanova, M., additional, Nikonov, V.A., additional, Novinski, D., additional, Novotny, R., additional, Ostrick, M., additional, Pant, L.M., additional, van Pee, H., additional, Pfeiffer, M., additional, Roy, A., additional, Sarantsev, A.V., additional, Schmidt, C., additional, Schmieden, H., additional, Shende, S., additional, Sokhoyan, V., additional, Sparks, N., additional, Süle, A., additional, Sumachev, V.V., additional, Szczepanek, T., additional, Thoma, U., additional, Trnka, D., additional, Varma, R., additional, Walther, D., additional, Wendel, Ch., additional, and Wiedner, U., additional

Published
2015
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14. Data onIsandIcinγ→p→pπ0π0reveal cascade decays ofN(1900)viaN(1520)π

Author

Sokhoyan, V., primary, Gutz, E., additional, van Pee, H., additional, Anisovich, A.V., additional, Bacelar, J.C.S., additional, Bantes, B., additional, Bartholomy, O., additional, Bayadilov, D., additional, Beck, R., additional, Beloglazov, Y., additional, Castelijns, R., additional, Crede, V., additional, Dutz, H., additional, Elsner, D., additional, Ewald, R., additional, Frommberger, F., additional, Fuchs, M., additional, Funke, Ch., additional, Gregor, R., additional, Gridnev, A., additional, Hillert, W., additional, Hoffmeister, Ph., additional, Horn, I., additional, Jaegle, I., additional, Junkersfeld, J., additional, Kalinowsky, H., additional, Kammer, S., additional, Kleber, V., additional, Klein, Frank, additional, Klein, Friedrich, additional, Klempt, E., additional, Kotulla, M., additional, Krusche, B., additional, Lang, M., additional, Löhner, H., additional, Lopatin, I., additional, Lugert, S., additional, Mertens, T., additional, Messchendorp, J.G., additional, Metag, V., additional, Nanova, M., additional, Nikonov, V.A., additional, Novinski, D., additional, Novotny, R., additional, Ostrick, M., additional, Pant, L., additional, Pfeiffer, M., additional, Piontek, D., additional, Roy, A., additional, Sarantsev, A.V., additional, Schmidt, Ch., additional, Schmieden, H., additional, Shende, S., additional, Süle, A., additional, Sumachev, V.V., additional, Szczepanek, T., additional, Thiel, A., additional, Thoma, U., additional, Trnka, D., additional, Varma, R., additional, Walther, D., additional, Wendel, Ch., additional, and Wilson, A., additional

Published
2015
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15. Brain expression profiles of two SCN1A antisense RNAs in children and adolescents with epilepsy.

Author

Schneider MF, Vogt M, Scheuermann J, Müller V, Fischer-Hentrich AHL, Kremer T, Lugert S, Metzger F, Kudernatsch M, Kluger G, Hartlieb T, Noachtar S, Vollmar C, Kunz M, Tonn JC, Coras R, Blümcke I, Pace C, Heinen F, Klein C, Potschka H, and Borggraefe I

Abstract

Objective: Heterozygous mutations within the voltage-gated sodium channel α subunit ( SCN1A ) are responsible for the majority of cases of Dravet syndrome (DS), a severe developmental and epileptic encephalopathy. Development of novel therapeutic approaches is mandatory in order to directly target the molecular consequences of the genetic defect. The aim of the present study was to investigate whether cis-acting long non-coding RNAs (lncRNAs) of SCN1A are expressed in brain specimens of children and adolescent with epilepsy as these molecules comprise possible targets for precision-based therapy approaches., Methods: We investigated SCN1A mRNA expression and expression of two SCN1A related antisense RNAs in brain tissues in different age groups of pediatric non-Dravet patients who underwent surgery for drug resistant epilepsy. The effect of different antisense oligonucleotides (ASOs) directed against SCN1A specific antisense RNAs on SCN1A expression was tested., Results: The SCN1A related antisense RNAs SCN1A -dsAS (downstream antisense, RefSeq identifier: NR_110598) and SCN1A -usAS (upstream AS, SCN1A -AS, RefSeq identifier: NR_110260) were widely expressed in the brain of pediatric patients. Expression patterns revealed a negative correlation of SCN1A-dsAS and a positive correlation of lncRNA SCN1A -usAS with SCN1A mRNA expression. Transfection of SK-N-AS cells with an ASO targeted against SCN1A -dsAS was associated with a significant enhancement of SCN1A mRNA expression and reduction in SCN1A -dsAS transcripts., Conclusion: These findings support the role of SCN1A -dsAS in the suppression of SCN1A mRNA generation. Considering the haploinsufficiency in genetic SCN1A related DS, SCN1A -dsAS is an interesting target candidate for the development of ASOs (AntagoNATs) based precision medicine therapeutic approaches aiming to enhance SCN1A expression in DS., Competing Interests: Conflict of interest: M.F.S., J.S., V.M., M.V., A.H.L.F., H.P., and I.Bor. received funding from Roche Ltd, Basel, Switzerland. T.K. and S.L. are employee at F. Hoffmann-La Roche Ltd, Basel, Switzerland. F.M. is a former employee of F. Hoffmann-La Roche Ltd, Basel, Switzerland. This does not alter our adherence to policies on sharing data and materials. All other authors state no conflict of interest., (© 2024 the author(s), published by De Gruyter.)

Published
2024
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16. mTORC1 Inhibition Corrects Neurodevelopmental and Synaptic Alterations in a Human Stem Cell Model of Tuberous Sclerosis.

Author

Costa V, Aigner S, Vukcevic M, Sauter E, Behr K, Ebeling M, Dunkley T, Friedlein A, Zoffmann S, Meyer CA, Knoflach F, Lugert S, Patsch C, Fjeldskaar F, Chicha-Gaudimier L, Kiialainen A, Piraino P, Bedoucha M, Graf M, Jessberger S, Ghosh A, Bischofberger J, and Jagasia R

Subjects
Cell Line, Embryonic Stem Cells cytology, Embryonic Stem Cells metabolism, Humans, Mechanistic Target of Rapamycin Complex 1, Multiprotein Complexes metabolism, Neural Stem Cells cytology, Neural Stem Cells physiology, Synapses physiology, Synaptic Transmission, TOR Serine-Threonine Kinases metabolism, Tuberous Sclerosis genetics, Tuberous Sclerosis Complex 2 Protein, Tumor Suppressor Proteins genetics, Multiprotein Complexes antagonists & inhibitors, Neural Stem Cells metabolism, Neurogenesis, Synapses metabolism, TOR Serine-Threonine Kinases antagonists & inhibitors, Tuberous Sclerosis metabolism
Abstract

Hyperfunction of the mTORC1 pathway has been associated with idiopathic and syndromic forms of autism spectrum disorder (ASD), including tuberous sclerosis, caused by loss of either TSC1 or TSC2. It remains largely unknown how developmental processes and biochemical signaling affected by mTORC1 dysregulation contribute to human neuronal dysfunction. Here, we have characterized multiple stages of neurogenesis and synapse formation in human neurons derived from TSC2-deleted pluripotent stem cells. Homozygous TSC2 deletion causes severe developmental abnormalities that recapitulate pathological hallmarks of cortical malformations in patients. Both TSC2(+/-) and TSC2(-/-) neurons display altered synaptic transmission paralleled by molecular changes in pathways associated with autism, suggesting the convergence of pathological mechanisms in ASD. Pharmacological inhibition of mTORC1 corrects developmental abnormalities and synaptic dysfunction during independent developmental stages. Our results uncouple stage-specific roles of mTORC1 in human neuronal development and contribute to a better understanding of the onset of neuronal pathophysiology in tuberous sclerosis., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2016
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17. A Tumor Suppressor Function for Notch Signaling in Forebrain Tumor Subtypes.

Author

Giachino C, Boulay JL, Ivanek R, Alvarado A, Tostado C, Lugert S, Tchorz J, Coban M, Mariani L, Bettler B, Lathia J, Frank S, Pfister S, Kool M, and Taylor V

Subjects
Animals, Basic Helix-Loop-Helix Transcription Factors genetics, Basic Helix-Loop-Helix Transcription Factors metabolism, Brain Neoplasms genetics, Brain Neoplasms mortality, Brain Neoplasms pathology, Cell Proliferation, Databases, Genetic, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Gene Transfer Techniques, Glioma genetics, Glioma mortality, Glioma pathology, Humans, Immunoglobulin J Recombination Signal Sequence-Binding Protein genetics, Immunoglobulin J Recombination Signal Sequence-Binding Protein metabolism, Infusions, Intraventricular, Kaplan-Meier Estimate, Mice, Knockout, Neoplasm Grading, Neoplastic Stem Cells pathology, Neural Stem Cells pathology, Phenotype, Platelet-Derived Growth Factor administration & dosage, Prosencephalon pathology, Proto-Oncogene Proteins c-sis genetics, Proto-Oncogene Proteins c-sis metabolism, Receptor, Notch1 genetics, Receptor, Notch1 metabolism, Receptor, Notch2 genetics, Receptor, Notch2 metabolism, Receptors, Notch genetics, Recombinant Proteins administration & dosage, Repressor Proteins genetics, Repressor Proteins metabolism, Time Factors, Tumor Burden, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 metabolism, Tumor Suppressor Proteins genetics, Brain Neoplasms metabolism, Glioma metabolism, Neoplastic Stem Cells metabolism, Neural Stem Cells metabolism, Prosencephalon metabolism, Receptors, Notch metabolism, Signal Transduction, Tumor Suppressor Proteins metabolism
Abstract

In the brain, Notch signaling maintains normal neural stem cells, but also brain cancer stem cells, indicating an oncogenic role. Here, we identify an unexpected tumor suppressor function for Notch in forebrain tumor subtypes. Genetic inactivation of RBP-Jκ, a key Notch mediator, or Notch1 and Notch2 receptors accelerates PDGF-driven glioma growth in mice. Conversely, genetic activation of the Notch pathway reduces glioma growth and increases survival. In humans, high Notch activity strongly correlates with distinct glioma subtypes, increased patient survival, and lower tumor grade. Additionally, simultaneous inactivation of RBP-Jκ and p53 induces primitive neuroectodermal-like tumors in mice. Hence, Notch signaling cooperates with p53 to restrict cell proliferation and tumor growth in mouse models of human brain tumors., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Published
2015
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18. Characterization of a human pluripotent stem cell-derived model of neuronal development using multiplexed targeted proteomics.

Author

Dunkley T, Costa V, Friedlein A, Lugert S, Aigner S, Ebeling M, Miller MT, Patsch C, Piraino P, Cutler P, and Jagasia R

Subjects
Cell Differentiation, Cell Line, Cluster Analysis, Humans, Models, Biological, Principal Component Analysis, Time Factors, Neurons cytology, Neurons metabolism, Pluripotent Stem Cells cytology, Pluripotent Stem Cells metabolism, Proteomics methods
Abstract

Purpose: Human pluripotent stem cell (hPSC)-derived cellular models have great potential to enable drug discovery and improve translation of preclinical insights to the clinic. We have developed a hPSC-derived neural precursor cell model for studying early events in human brain development. We present protein-level characterization of this model, using a multiplexed SRM approach, to establish reproducibility and physiological relevance; essential prerequisites for utilization of the neuronal development model in phenotypic screening-based drug discovery., Experimental Design: Profiles of 246 proteins across three key stages of in vitro neuron differentiation were analyzed by SRM. Three independently hPSC-derived isogenic neural stem cell (NSC) lines were analyzed across five to nine independent neuronal differentiations., Results: One hundred seventy-five proteins were reliably quantified revealing a time-dependent pattern of protein regulation that reflected protein dynamics during in vivo brain development and that was conserved across replicate differentiations and multiple cell lines., Conclusions and Clinical Relevance: SRM-based protein profiling enabled establishment of the reproducibility and physiological relevance of the hPSC-derived neuronal model. Combined with the successful quantification of proteins relevant to neurodevelopmental diseases, this validates the platform for use as a model to enable neuroscience drug discovery., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Published
2015
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19. Three-body nature of N(*) and Δ(*) resonances from sequential decay chains.

Author

Thiel A, Sokhoyan V, Gutz E, van Pee H, Anisovich AV, Bacelar JC, Bantes B, Bartholomy O, Bayadilov D, Beck R, Beloglazov Y, Castelijns R, Crede V, Dutz H, Elsner D, Ewald R, Frommberger F, Fuchs M, Funke Ch, Gregor R, Gridnev A, Hillert W, Hoffmeister P, Horn I, Jaegle I, Junkersfeld J, Kalinowsky H, Kammer S, Kleber V, Klein F, Klein F, Klempt E, Kotulla M, Krusche B, Lang M, Löhner H, Lopatin I, Lugert S, Mertens T, Messchendorp JG, Metag V, Metsch B, Nanova M, Nikonov V, Novinski D, Novotny R, Ostrick M, Pant L, Pfeiffer M, Piontek D, Roy A, Sarantsev AV, Schmidt Ch, Schmieden H, Shende S, Süle A, Sumachev VV, Szczepanek T, Thoma U, Trnka D, Varma R, Walther D, Wendel Ch, and Wilson A

Abstract

The Nπ^{0}π^{0} decays of positive-parity N^{*} and Δ^{*} resonances at about 2 GeV are studied at ELSA by photoproduction of two neutral pions off protons. The data reveal clear evidence for several intermediate resonances: Δ(1232), N(1520)3/2^{-}, and N(1680)5/2^{+}, with spin parities J^{P}=3/2^{+}, 3/2^{-}, and 5/2^{+}. The partial wave analysis (within the Bonn-Gatchina approach) identifies N(1440)1/2^{+} and the N(ππ)_{S wave} (abbreviated as Nσ here) as further isobars and assigns the final states to the formation of nucleon and Δ resonances and to nonresonant contributions. We observe the known Δ(1232)π decays of Δ(1910)1/2^{+}, Δ(1920)3/2^{+}, Δ(1905)5/2^{+}, Δ(1950)7/2^{+}, and of the corresponding spin-parity series in the nucleon sector, N(1880)1/2^{+}, N(1900)3/2^{+}, N(2000)5/2^{+}, and N(1990)7/2^{+}. For the nucleon resonances, these decay modes are reported here for the first time. Further new decay modes proceed via N(1440)1/2^{+}π, N(1520)3/2^{-}π, N(1680)5/2^{+}π, and Nσ. The latter decay modes are observed in the decay of N^{*} resonances and at most weakly in Δ^{*} decays. It is argued that these decay modes provide evidence for a 3-quark nature of N^{*} resonances rather than a quark-diquark structure.

Published
2015
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20. Role of adult hippocampal neurogenesis in cognition in physiology and disease: pharmacological targets and biomarkers.

Author

Costa V, Lugert S, and Jagasia R

Subjects
Animals, Cognition Disorders drug therapy, Cognition Disorders physiopathology, Cognition Disorders psychology, Drug Design, Gene Expression Regulation, Hippocampus physiopathology, Humans, Mental Disorders genetics, Mental Disorders metabolism, Mental Disorders physiopathology, Mental Disorders psychology, Molecular Targeted Therapy, Signal Transduction drug effects, Biomarkers metabolism, Cognition drug effects, Hippocampus drug effects, Mental Disorders drug therapy, Neurogenesis drug effects, Nootropic Agents therapeutic use
Abstract

Adult hippocampal neurogenesis is a remarkable form of brain structural plasticity by which new functional neurons are generated from adult neural stem cells/precursors. Although the precise role of this process remains elusive, adult hippocampal neurogenesis is important for learning and memory and it is affected in disease conditions associated with cognitive impairment, depression, and anxiety. Immature neurons in the adult brain exhibit an enhanced structural and synaptic plasticity during their maturation representing a unique population of neurons to mediate specific hippocampal function. Compelling preclinical evidence suggests that hippocampal neurogenesis is modulated by a broad range of physiological stimuli which are relevant in cognitive and emotional states. Moreover, multiple pharmacological interventions targeting cognition modulate adult hippocampal neurogenesis. In addition, recent genetic approaches have shown that promoting neurogenesis can positively modulate cognition associated with both physiology and disease. Thus the discovery of signaling pathways that enhance adult neurogenesis may lead to therapeutic strategies for improving memory loss due to aging or disease. This chapter endeavors to review the literature in the field, with particular focus on (1) the role of hippocampal neurogenesis in cognition in physiology and disease; (2) extrinsic and intrinsic signals that modulate hippocampal neurogenesis with a focus on pharmacological targets; and (3) efforts toward novel strategies pharmacologically targeting neurogenesis and identification of biomarkers of human neurogenesis.

Published
2015
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