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1. Magnetic-field induced band-structure change in CeBiPt

Author

Kozlova, N., Hagel, J., Doerr, M., Wosnitza, J., Eckert, D., Mueller, K. -H., Schultz, L., Opahle, I., Elgazzar, S., Richter, Manuel, Goll, G., Zwicknagl, G., Yoshino, T., and Takabatake, T.

Subjects
Condensed Matter - Strongly Correlated Electrons
Abstract

We report on a field-induced change of the electronic band structure of CeBiPt as evidenced by electrical-transport measurements in pulsed magnetic fields. Above ~25 T, the charge-carrier concentration increases nearly 30% with a concomitant disappearance of the Shubnikov-de Haas signal. These features are intimately related to the Ce 4f electrons since for the non-4f compound LaBiPt the Fermi surface remains unaffected. Electronic band-structure calculations point to a 4f-polarization-induced change of the Fermi-surface topology., Comment: 4 pages, 4 figures

Published
2005
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2. Spin-zero anomaly in the magnetic quantum oscillations of a two-dimensional metal

Author

Wosnitza, J., Gvozdikov, V. M., Hagel, J., Meeson, P. J., Schlueter, J. A., Winter, R. W., and Gard, G. L.

Subjects
Condensed Matter - Strongly Correlated Electrons, Condensed Matter - Other Condensed Matter
Abstract

We report on an anomalous behavior of the spin-splitting zeros in the de Haas-van Alphen (dHvA) signal of a quasi-two-dimensional organic superconductor. The zeros as well as the angular dependence of the amplitude of the second harmonic deviate remarkably from the standard Lifshitz-Kosevich (LK) prediction. In contrast, the angular dependence of the fundamental dHvA amplitude as well as the spin-splitting zeros of the Shubnikov-de Haas signal follow the LK theory. We can explain this behavior by small chemical-potential oscillations and find a very good agreement between theory and experiment. A detailed wave-shape analysis of the dHvA signal corroborates the existence of an oscillating chemical potential.

Published
2004
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3. Irreversible Magnetization Deep in the Vortex-Liquid State of a 2D Superconductor at High Magnetic Fields

Author

Maniv, T., Zhuravlev, V., Wosnitza, J., and Hagel, J.

Subjects
Condensed Matter - Superconductivity
Abstract

The remarkable phenomenon of weak magnetization hysteresis loops, observed recently deep in the vortex-liquid state of a nearly two-dimensional (2D) superconductor at low temperatures, is shown to reflect the existence of an unusual vortex-liquid state, consisting of collectively pinned crystallites of easily sliding vortex chains., Comment: 5 pages, 4 figures

Published
2004
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4. Coherent vs incoherent interlayer transport in layered metals

Author

Wosnitza, J., Hagel, J., Qualls, J. S., Brooks, J. S., Balthes, E., Schweitzer, D., Schlueter, J. A., Geiser, U., Mohtasham, J., Winter, R. W., and Gard, G. L.

Subjects
Condensed Matter - Strongly Correlated Electrons, Condensed Matter - Superconductivity
Abstract

The magnetic-field, temperature, and angular dependence of the interlayer magnetoresistance of two different quasi-two-dimensional (2D) organic superconductors is reported. For $\kappa$-(BEDT-TTF)$_2$I$_3$ we find a well-resolved peak in the angle-dependent magnetoresistance at $\Theta = 90^\circ$ (field parallel to the layers). This clear-cut proof for the coherent nature of the interlayer transport is absent for $\beta$''-(BEDT-TTF)$_2$SF$_5$CH$_2$CF$_2$SO$_3$. This and the non-metallic behavior of the magnetoresistance suggest an incoherent quasiparticle motion for the latter 2D metal., Comment: 4 pages, 4 figures. Phys. Rev. B, in press

Published
2002
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5. Superconducting energy gap distribution of MgB$_2$ investigated by point-contact spectroscopy

Author

Laube, F., Goll, G., Hagel, J., Löhneysen, H. v., Ernst, D., and Wolf, T.

Subjects
Condensed Matter - Superconductivity
Abstract

We performed point-contact spectroscopy on the binary superconductor MgB$_2$. The differential conductance shows gap-related structures which vary in width and position from contact to contact. The distribution of energy gaps shows a distinct accumulation around 1.7 and 7 meV which is associated with the occurrence of a small and a large energy gap in MgB$_2$. While with increasing $T$ the structure in $dI/dV$ associated with the small gap is present up to $T_C$, in magnetic field it is suppressed well below $B_{c2}$., Comment: 4 pages, 6 figures

Published
2001
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6. Field-induced metal-insulator transition in a two-dimensional organic superconductor

Author

Wosnitza, J., Wanka, S., Hagel, J., Loehneysen, H. v., Qualls, J. S., Brooks, J. S., Balthes, E., Schlueter, J. A., Geiser, U., Mohtasham, J., Winter, R. W., and Gard, G. L.

Subjects
Condensed Matter - Superconductivity
Abstract

The quasi-two-dimensional organic superconductor beta-(BEDT-TTF)_2SF_5CH_2CF_2SO_3 (T_c approx 4.4 K)shows very strong Shubnikov-de Haas (SdH) oscillations which are superimposed on a highly anomalous steady background magnetoresistance, R_b. Comparison with de Haas- van Alphen oscillations allow a reliable estimate of R_b which is crucial for the correct extraction of the SdH signal. At low temperatures and high magnetic fields insulating behavior evolves. The magnetoresistance data violate Kohler's rule, i.e., cannot be described within the framework of semiclassical transport theory, but converge onto a universal curve appropriate for dynamical scaling at a metal-insulator transition., Comment: 4 pages, 4 figures, Phys. Rev. Lett., in press

Published
2000
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7. Anomalous temperature dependence of magnetic quantum oscillations in CeBiPt

Author

Goll, G., Hagel, J., Loehneysen, H. v., Pietrus, T., Wanka, S., Wosnitza, J., Yoshino, T., and Takabatake, T.

Subjects
Condensed Matter - Strongly Correlated Electrons
Abstract

Shubnikov--de Haas (SdH) and Hall-effect measurements of CeBiPt and LaBiPt reveal the presence of simple and very small Fermi surfaces with hole-like charge carriers for both semimetals. In the magnetic material, CeBiPt, we observe a strong temperature dependence of the SdH frequency. This highly unusual effect might be connected with an internal exchange field within the material and a strongly spin-dependent scattering of the charge carriers., Comment: 4 pages, 4 figures

Published
2000

8. kappa-(BEDT-TTF)_2Cu[N(CN)_2]Br: a Fully Gapped Strong-Coupling Superconductor

Author

Elsinger, H., Wosnitza, J., Wanka, S., Hagel, J., Schweitzer, D., and Strunz, W.

Subjects
Condensed Matter - Superconductivity
Abstract

High-resolution specific-heat measurements of the organic superconductor kappa-(BEDT-TTF)_2Cu[N(CN)_2]Br in the superconducting (B = 0) and normal (B = 14 T) state show a clearly resolvable anomaly at Tc = 11.5 K and an electronic contribution, Ces, which can be reasonably well described by strong-coupling BCS theory. Most importantly, Ces vanishes exponentially in the superconducting state which gives evidence for a fully gapped order parameter., Comment: 4 pages, 4 figures

Published
1999
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9. Safety and efficacy of once-daily risdiplam in type 2 and non-ambulant type 3 spinal muscular atrophy (SUNFISH part 2): a phase 3, double-blind, randomised, placebo-controlled trial

Author

Mercuri, Eugenio Maria, Deconinck, N., Mazzone, Elena Stacy, Nascimento, A., Oskoui, M., Saito, K., Vuillerot, C., Baranello, Giovanni, Boespflug-Tanguy, O., Goemans, N., Kirschner, J., Kostera-Pruszczyk, A., Servais, L., Gerber, M., Gorni, K., Khwaja, O., Kletzl, H., Scalco, R. S., Staunton, H., Yeung, W. Y., Martin, Craig, Fontoura, P., Day, J. W., Volpe, J. J., Posner, J., Kellner, U., Quinlivan, R., Fuerst-Recktenwald, S., Marquet, A., Mulhardt, N., Trundell, D., Daron, A., Delstanche, S., Romain, B., Dal Farra, F., Schneider, O., Balikova, I., Delbeke, P., Joniau, I., Tahon, V., Wittevrongel, S., De Vos, E., Casteels, I., De Waele, L., Cassiman, C., Prove, L., Kinoo, D., Vancampenhout, L., Van Den Hauwe, M., Van Impe, A., Prufer de Queiroz Campos Araujo, A., Chacon Pereira, A., Nardes, F., Haefeli, L., Rossetto, J., Almeida Pereira, J., Ferreira Rebel, M., Campbell, C., Sharan, S., Mcdonald, W., Scholtes, C., Mah, J., Sframeli, M., Chiu, A., Hagel, J., Beneish, R., Pham, C., Toffoli, D., Arpin, S., Turgeon Desilets, S., Wang, Y., Hu, C., Huang, J., Qian, C., Shen, L., Xiao, Y., Zhou, Z., Li, H., Wang, S., Xiong, H., Chang, X., Dong, H., Liu, Y., Sang, T., Wei, C., Wen, J., Cao, Y., Lv, X., Zhao, J., Li, W., Qin, L., Barisic, N., Galiot Delic, M., Ivkic, P. K., Vukojevic, N., Kern, I., Najdanovic, B., Skugor, M., Gidaro, T., Seferian, A., De Lucia, Sara Sofia, Barreau, E., Mnafek, N., Momtchilova, M. M., Peche, H., Valherie, C., Grange, A., Lilien, C., Milascevic, D., Tachibana, S., Ravelli, C., Cardas, R., Vanden Brande, L., Davion, J. -B., Coopman, S., Bouacha, I., Debruyne, P., Defoort, S., Derlyn, G., Leroy, F., Danjoux, L., Guilbaud, J., Desguerre, I., Barnerias, C., Semeraro, M., Bremond-Gignac, D., Bruere, L., Rateaux, M., Deladriere, E., Germa, V., Pereon, Y., Magot, A., Mercie, S., Billaud, F., Le Goff, L., Letellier, G., Portefaix, A., Fontaine, S., De-Montferrand, C., Le-Goff, L., Saidi, M., Bouzid, N., Barriere, A., Tinat, M., Dreesbach, M., Lagreze, W., Michaelis, B., Molnar, F., Seger, D., Vogt, S., Bertini, Enrico Silvio, D'Amico, Adele, Petroni, S., Bonetti, A. M., Carlesi, A., Mizzoni, I., Bruno, C., Priolo, E., Rao, G., Morando, S., Tacchetti, P., Zuffi, A., Comi, G. P., Brusa, R., Corti, Serafino, Daniele, V., Govoni, A., Magri, F., Minorini, V., Osnaghi, S. G., Abbati, F., Fassini, F., Foa, M., Lopopolo, A., Meneri, M., Zoppas, F., Parente, V., Masson, R., Bianchi Marzoli, Stefania, Santarsiero, Rocco Domenico, Garcia Sierra, M., Tremolada, G., Arnoldi, M. T., Vigano, M., Zanin, Renata, Amorelli, Giulia Maria, Barresi, C., D'Amico, Guglielmo, Orazi, Lorenzo, Coratti, Giorgia, Haginoya, K., Kato, A., Morishita, Y., Kira, R., Akiyama, K., Goto, M., Mori, Y., Okamoto, M., Tsutsui, S., Takatsuji, Y., Tanaka, A., Komaki, H., Suzuki, I., Takeuchi, M., Todoroki, D., Watanabe, S., Omori, M., Matsubayashi, T., Inakazu, E., Nagura, H., Suzuki, A., Osaka, H., Ohashi, M., Ishikawa, N., Harada, Y., Fudeyasu, K., Hirata, K., Michiue, K., Ueda, K., Yashiro, S., Seki, M., Sano, N., Uemura, A., Fukuyama, K., Matsumoto, Y., Miyazaki, H., Shibata, M., Kobayashi, K., Nakamura, Y., Takeshima, Y., Kuma, M., Fraczek, A., Jedrzejowska, M., Lusakowska, A., Czeszyk-Piotrowicz, A., Hautz, W., Rakusiewicz, K., Burlewicz, M., Gierlak-Wojcicka, Z., Kepa, M., Sikorski, A., Sobieraj, M., Mazurkiewicz-Beldzinska, M., Lemska, A., Modrzejewska, S., Koberda, M., Stodolska-Koberda, U., Waskowska, A., Kolendo, J., Sobierajska-Rek, A., Steinborn, B., Dalz, M., Grabowska, J., Hajduk, W., Janasiewicz-Karachitos, J., Klimas, M., Stopa, M., Gajewska, E., Pusz, B., Vlodavets, D., Melnik, E., Leppenen, N., Yupatova, N., Monakhova, A., Papina, Y., Shidlovsckaia, O., Milic Rasic, V., Brankovic, V., Kosac, A., Djokic, O., Jaksic, V., Pepic, A., Martinovic, J., Munell Casadesus, F., Tizzano, E., Martin Begue, N., Wolley Dod, C., Subira, O., Planas Pascual, B., Toro Tamargo, E., Madruga Garrido, M., Medina Romero, J. D., Salinas, M. P., Nascimento Osorio, A., Diaz Cortes, A., Jimenez Ganan, E., Suh, S. D., Medina Cantillo, J., Moya, O., Padros, N., Roca Urraca, S., Gonzalez Valdivia, H., Pascual Pascual, S., de Manuel, S., Noval Martin, S., Burnham, P., Espinosa Garcia, S., Martinez Moreno, M., Topaloglu, H., Oncel, I., Eroglu Ertugrul, N., Konuskan, B., Eldem, B., Kadayifcilar, S., Alemdaroglu, I., Ayse Karaduman, A., Tunca Yilmaz, O., Bilgin, N., Sari, S., Chiriboga, C., Kane, S., Lee, J., Rome-Martin, D., Beres, S., Duong, T., Gee, R., Dunaway Young, S., Mercuri E. (ORCID:0000-0002-9851-5365), Mazzone E. S., Baranello G., Martin C., De Lucia S., Bertini E., D'Amico A., Corti S., Bianchi Marzoli S., Santarsiero D., Zanin R., Amorelli G. M., D'Amico G., Orazi L., Coratti G. (ORCID:0000-0001-6666-5628), Mercuri, Eugenio Maria, Deconinck, N., Mazzone, Elena Stacy, Nascimento, A., Oskoui, M., Saito, K., Vuillerot, C., Baranello, Giovanni, Boespflug-Tanguy, O., Goemans, N., Kirschner, J., Kostera-Pruszczyk, A., Servais, L., Gerber, M., Gorni, K., Khwaja, O., Kletzl, H., Scalco, R. S., Staunton, H., Yeung, W. Y., Martin, Craig, Fontoura, P., Day, J. W., Volpe, J. J., Posner, J., Kellner, U., Quinlivan, R., Fuerst-Recktenwald, S., Marquet, A., Mulhardt, N., Trundell, D., Daron, A., Delstanche, S., Romain, B., Dal Farra, F., Schneider, O., Balikova, I., Delbeke, P., Joniau, I., Tahon, V., Wittevrongel, S., De Vos, E., Casteels, I., De Waele, L., Cassiman, C., Prove, L., Kinoo, D., Vancampenhout, L., Van Den Hauwe, M., Van Impe, A., Prufer de Queiroz Campos Araujo, A., Chacon Pereira, A., Nardes, F., Haefeli, L., Rossetto, J., Almeida Pereira, J., Ferreira Rebel, M., Campbell, C., Sharan, S., Mcdonald, W., Scholtes, C., Mah, J., Sframeli, M., Chiu, A., Hagel, J., Beneish, R., Pham, C., Toffoli, D., Arpin, S., Turgeon Desilets, S., Wang, Y., Hu, C., Huang, J., Qian, C., Shen, L., Xiao, Y., Zhou, Z., Li, H., Wang, S., Xiong, H., Chang, X., Dong, H., Liu, Y., Sang, T., Wei, C., Wen, J., Cao, Y., Lv, X., Zhao, J., Li, W., Qin, L., Barisic, N., Galiot Delic, M., Ivkic, P. K., Vukojevic, N., Kern, I., Najdanovic, B., Skugor, M., Gidaro, T., Seferian, A., De Lucia, Sara Sofia, Barreau, E., Mnafek, N., Momtchilova, M. M., Peche, H., Valherie, C., Grange, A., Lilien, C., Milascevic, D., Tachibana, S., Ravelli, C., Cardas, R., Vanden Brande, L., Davion, J. -B., Coopman, S., Bouacha, I., Debruyne, P., Defoort, S., Derlyn, G., Leroy, F., Danjoux, L., Guilbaud, J., Desguerre, I., Barnerias, C., Semeraro, M., Bremond-Gignac, D., Bruere, L., Rateaux, M., Deladriere, E., Germa, V., Pereon, Y., Magot, A., Mercie, S., Billaud, F., Le Goff, L., Letellier, G., Portefaix, A., Fontaine, S., De-Montferrand, C., Le-Goff, L., Saidi, M., Bouzid, N., Barriere, A., Tinat, M., Dreesbach, M., Lagreze, W., Michaelis, B., Molnar, F., Seger, D., Vogt, S., Bertini, Enrico Silvio, D'Amico, Adele, Petroni, S., Bonetti, A. M., Carlesi, A., Mizzoni, I., Bruno, C., Priolo, E., Rao, G., Morando, S., Tacchetti, P., Zuffi, A., Comi, G. P., Brusa, R., Corti, Serafino, Daniele, V., Govoni, A., Magri, F., Minorini, V., Osnaghi, S. G., Abbati, F., Fassini, F., Foa, M., Lopopolo, A., Meneri, M., Zoppas, F., Parente, V., Masson, R., Bianchi Marzoli, Stefania, Santarsiero, Rocco Domenico, Garcia Sierra, M., Tremolada, G., Arnoldi, M. T., Vigano, M., Zanin, Renata, Amorelli, Giulia Maria, Barresi, C., D'Amico, Guglielmo, Orazi, Lorenzo, Coratti, Giorgia, Haginoya, K., Kato, A., Morishita, Y., Kira, R., Akiyama, K., Goto, M., Mori, Y., Okamoto, M., Tsutsui, S., Takatsuji, Y., Tanaka, A., Komaki, H., Suzuki, I., Takeuchi, M., Todoroki, D., Watanabe, S., Omori, M., Matsubayashi, T., Inakazu, E., Nagura, H., Suzuki, A., Osaka, H., Ohashi, M., Ishikawa, N., Harada, Y., Fudeyasu, K., Hirata, K., Michiue, K., Ueda, K., Yashiro, S., Seki, M., Sano, N., Uemura, A., Fukuyama, K., Matsumoto, Y., Miyazaki, H., Shibata, M., Kobayashi, K., Nakamura, Y., Takeshima, Y., Kuma, M., Fraczek, A., Jedrzejowska, M., Lusakowska, A., Czeszyk-Piotrowicz, A., Hautz, W., Rakusiewicz, K., Burlewicz, M., Gierlak-Wojcicka, Z., Kepa, M., Sikorski, A., Sobieraj, M., Mazurkiewicz-Beldzinska, M., Lemska, A., Modrzejewska, S., Koberda, M., Stodolska-Koberda, U., Waskowska, A., Kolendo, J., Sobierajska-Rek, A., Steinborn, B., Dalz, M., Grabowska, J., Hajduk, W., Janasiewicz-Karachitos, J., Klimas, M., Stopa, M., Gajewska, E., Pusz, B., Vlodavets, D., Melnik, E., Leppenen, N., Yupatova, N., Monakhova, A., Papina, Y., Shidlovsckaia, O., Milic Rasic, V., Brankovic, V., Kosac, A., Djokic, O., Jaksic, V., Pepic, A., Martinovic, J., Munell Casadesus, F., Tizzano, E., Martin Begue, N., Wolley Dod, C., Subira, O., Planas Pascual, B., Toro Tamargo, E., Madruga Garrido, M., Medina Romero, J. D., Salinas, M. P., Nascimento Osorio, A., Diaz Cortes, A., Jimenez Ganan, E., Suh, S. D., Medina Cantillo, J., Moya, O., Padros, N., Roca Urraca, S., Gonzalez Valdivia, H., Pascual Pascual, S., de Manuel, S., Noval Martin, S., Burnham, P., Espinosa Garcia, S., Martinez Moreno, M., Topaloglu, H., Oncel, I., Eroglu Ertugrul, N., Konuskan, B., Eldem, B., Kadayifcilar, S., Alemdaroglu, I., Ayse Karaduman, A., Tunca Yilmaz, O., Bilgin, N., Sari, S., Chiriboga, C., Kane, S., Lee, J., Rome-Martin, D., Beres, S., Duong, T., Gee, R., Dunaway Young, S., Mercuri E. (ORCID:0000-0002-9851-5365), Mazzone E. S., Baranello G., Martin C., De Lucia S., Bertini E., D'Amico A., Corti S., Bianchi Marzoli S., Santarsiero D., Zanin R., Amorelli G. M., D'Amico G., Orazi L., and Coratti G. (ORCID:0000-0001-6666-5628)

Abstract

Background: Risdiplam is an oral small molecule approved for the treatment of patients with spinal muscular atrophy, with approval for use in patients with type 2 and type 3 spinal muscular atrophy granted on the basis of unpublished data. The drug modifies pre-mRNA splicing of the SMN2 gene to increase production of functional SMN. We aimed to investigate the safety and efficacy of risdiplam in patients with type 2 or non-ambulant type 3 spinal muscular atrophy. Methods: In this phase 3, randomised, double-blind, placebo-controlled study, patients aged 2–25 years with confirmed 5q autosomal recessive type 2 or type 3 spinal muscular atrophy were recruited from 42 hospitals in 14 countries across Europe, North America, South America, and Asia. Participants were eligible if they were non-ambulant, could sit independently, and had a score of at least 2 in entry item A of the Revised Upper Limb Module. Patients were stratified by age and randomly assigned (2:1) to receive either daily oral risdiplam, at a dose of 5·00 mg (for individuals weighing ≥20 kg) or 0·25 mg/kg (for individuals weighing <20 kg), or daily oral placebo (matched to risdiplam in colour and taste). Randomisation was conducted by permutated block randomisation with a computerised system run by an external party. Patients, investigators, and all individuals in direct contact with patients were masked to treatment assignment. The primary endpoint was the change from baseline in the 32-item Motor Function Measure total score at month 12. All individuals who were randomly assigned to risdiplam or placebo, and who did not meet the prespecified missing item criteria for exclusion, were included in the primary efficacy analysis. Individuals who received at least one dose of risdiplam or placebo were included in the safety analysis. SUNFISH is registered with ClinicalTrials.gov, NCT02908685. Recruitment is closed; the study is ongoing. Findings: Between Oct 9, 2017, and Sept 4, 2018, 180 patients were rand

Published
2022

15. TCR and inflammatory signals tune human MAIT cells to exert specific tissue repair and effector functions

Author

Leng, T, Delowar Akther, H, Hackstein, C-P, Powell, K, King, T, Friedrich, M, Christoforidou, Z, McCuaig, S, Neyazi, M, Arancibia-Carcamo, C, Hagel, J, Powrie, F, Oxford IBD Investigators, Peres, R, Millar, V, Ebner, D, Lamichhane, R, Ussher, J, Hinks, T, Marchi, E, Willberg, C, and Klenerman, P

Abstract

MAIT cells are an unconventional T cell population that can be activated through both TCR-dependent and TCR-independent mechanisms. Here, we examined the impact of combinations of TCR-dependent and TCR-independent signals in human CD8+ MAIT cells. TCR-independent activation of these MAIT cells from blood and gut was maximized by extending the panel of cytokines to include TNF-superfamily member TL1A. RNA-seq experiments revealed that TCR-dependent and TCR-independent signals drive MAIT cells to exert overlapping and specific effector functions, affecting both host defense and tissue homeostasis. Although TCR triggering alone is insufficient to drive sustained activation, TCR-triggered MAIT cells showed specific enrichment of tissue-repair functions at the gene and protein levels and in in vitro assays. Altogether, these data indicate the blend of TCR-dependent and TCR-independent signaling to CD8+ MAIT cells may play a role in controlling the balance between healthy and pathological processes of tissue inflammation and repair.

Published
2019

23. An oncolytic virus expressing a T-cell engager simultaneously targets cancer and immunosuppressive stromal cells

Author

Freedman, J, Duffy, M, Lei-Rossmann, J, Muntzer, A, Scott, E, Hagel, J, Campo, L, Bryant, R, Verrill, C, Lambert, A, Miller, P, Champion, B, Seymour, L, and Fisher, K

Subjects
Immunosuppression Therapy, Inflammation, CD3 Complex, Biopsy, T-Lymphocytes, Fibroblasts, Lymphocyte Activation, Combined Modality Therapy, Coculture Techniques, Adenoviridae, Oncolytic Viruses, HEK293 Cells, Neoplasms, Leukocytes, Mononuclear, Cytokines, Humans
Abstract

Effective immunotherapy of stromal-rich tumors requires simultaneous targeting of cancer cells and immunosuppressive elements of the microenvironment. Here, we modified the oncolytic group B adenovirus enadenotucirev to express a stroma-targeted bispecific T-cell engager (BiTE). This BiTE bound fibroblast activation protein on cancer-associated fibroblasts (CAF) and CD3ε on T cells, leading to potent T-cell activation and fibroblast death. Treatment of fresh clinical biopsies, including malignant ascites and solid prostate cancer tissue, with FAP-BiTE–encoding virus induced activation of tumor-infiltrating PD1+ T cells to kill CAFs. In ascites, this led to depletion of CAF-associated immunosuppressive factors, upregulation of proinflammatory cytokines, and increased gene expression of markers of antigen presentation, T-cell function, and trafficking. M2-like ascites macrophages exhibited a proinflammatory repolarization, indicating spectrum-wide alteration of the tumor microenvironment. With this approach, we have actively killed both cancer cells and tumor fibroblasts, reversing CAF-mediated immunosuppression and yielding a potent single-agent therapeutic that is ready for clinical assessment.

Published
2019
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26. Human MAIT cells show metabolic quiescence with rapid glucose-dependent upregulation of granzyme B upon stimulation

Author

Zinser, ME, Highton, AJ, Kurioka, A, Kronsteiner, B, Hagel, J, Leng, T, Marchi, E, Phetsouphanh, C, Willberg, CB, Dunachie, SJ, and Klenerman, P

Subjects
Glucose, mucosal immunology, Short Communication, T cells, Humans, MAIT cells, Lymphocyte Activation, metabolism, Granzymes, Mucosal-Associated Invariant T Cells, Up-Regulation
Abstract

Mucosal-associated invariant T (MAIT) cells are a well-characterized innate-like T cell population abundant in the human liver, peripheral tissues and blood. MAIT cells serve in the first line of defense against infections, through engagement of their T cell receptor, which recognizes microbial metabolites presented on MR1, and through cytokine-mediated triggering. Typically, they show a quiescent memory phenotype but can undergo rapid up-regulation of effector functions including cytolysis upon stimulation. T cells profoundly change their cellular metabolism during their maturation and activation. We sought to determine how MAIT cell metabolism may facilitate both the long-term memory phase in tissue and the transition to rapid effector function. Here, we show, by flow cytometric metabolism assays and extracellular flux analysis that, despite an effector-memory profile, human MAIT cells are metabolically quiescent in a resting state comparable to naïve and central memory T cells. Upon stimulation, they rapidly increase uptake of glucose and show a concomitant upregulation of the effector molecules notably granzyme B, which is impaired by inhibition of glycolysis with 2-deoxyglucose. These findings suggest that MAIT cells share some metabolic characteristics of both resting and effector T cell subsets, with a rapid transition upon triggering. Metabolic programming of this cell type may be of interest in understanding and modulating their function in infectious diseases and cancer. This article is protected by copyright. All rights reserved.

Published
2017

31. Postersession IV : Gastroenterologie

Author

Kurtz, W., Classen, M., Schmidt, H., Riddell, R. H., Walther, B., Riemann, J. F., Raedsch, R., Stiehl, A., Sieg, A., Walker, S., Kommerell, B., Gregor, M., Hartmann, K., Riecken, E. O., Dammann, H. G., Walter, Th. A., Müller, P., Simon, B., Fölsch, U. R., Wichmann, G.-Ch., v. Kleist, E., Körber, R., Dillon, M., Clowdus, B., Creutzfeldt, W., Singer, M. V., Calden, H., Eysselein, V. E., Leffmann, C., Goebell, H., Müller-Lissner, St. A., Störkel, S., Dienes, H. P., Schneider, H.-M., Loos, M., Emde, C., Göring, M., Liehr, R.-M., Kruis, W., Azpiroz, F., Phillips, S. F., Stöcker, W., Ulrich, S., Normann, D., Stöcker, K., Jantschek, G., Otte, M., Seyfarth, K., Bührer, Ch., Winkler, R., Raedler, A., Malchow, H., Hoffmann, R., Daiss, W., Jenss, H., Dölle, W., Purrmann, J., Bertrams, J., Rietzler, M., Wolf, E., Miller, B., Strohmeÿer, G., Göke, B., Schwartz, P., Rahlf, G., Goerg, K. J., Wanitschke, R., Breiling, K., Franke, M., Rabast, U., Kemkes-Matthes, B., Abermann, C., Matthes, K. J., Schulzke, J.-D., Fromm, M., Menge, H., Löffler, A., Dienst, C., Thon, H. J., Wüstenberg, E., Corman, G., von Kachel, G., Ruppin, H., Hagel, J., Barina, W., Meinhardt, M., Domschke, W., Sandforth, F., Gutschmidt, S., Karbach, U., Rummel, W., Seitz, H. K., Feurle, G., Huefner, M., Lichtwald, K., Schmidt-Gayk, H., Janisch, H. D., Beuth, A., von Kleist, D., Bauer, F. E., Hampel, K. E., Blasberg, M., Wienbeck, M., Körner, M., Erckenbrecht, J. F., Berges, W., Miehlke, Klaus, editor, and Bergmann, J. F.

Published
1984
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32. Gastroenterologie

Author

Berges, W., Baumgärtner, U., Baum, J., Ulrich, B., Wienbeck, M., Sauerbruch, T., Weinzierl, M., Köpcke, W., Paumgartner, G., Singer, M. V., Eysselein, V., Goebell, H., Hanrath, R.-D., Müller, J. E., Fritsch, W.-P., Rohner, H. G., Blömer, A., Echterhoff, H.-M., Gugler, R., Kachel, G., Ruppin, H., Hagel, J., Goertzen, W., Domschke, W., Müller, P., Seitz, K. S., Simon, B., Dammann, H. G., Schepp, W., Ruoff, H.-J., Maśliński, S., Miederer, S. E., Sommer, H., Grün, M., Koop, H., Arnold, R., Staritz, M., Ewe, K., Meyer zum Büschenfelde, K.-H., Niederau, C., Erckenbrecht, J., Scholten, T., Sonnenberg, A., Stock, K. P., Riemann, J. F., Müller, M. K., Demol, P., Fladrich, G., Pederson, R., Herr Raptis, S., Malfertheiner, P., Walliser, A., Maier, W., Ditschuneit, H., Cichy, W., Lankisch, P. G., Creutzfeldt, W., Räth, U., Johnson, P. J., Greenway, B. A., Corbishley, T. P., Williams, R., Hildebrandt, R., Häger, V., Erckenbrecht, J. F., Schneider, M. U., Domschke, S., Lembcke, B., Göke, B., Kalek, H. D., Stellaard, F., Kruis, W., Lösler, A., Schürnbrand, P., Caspary, W. F., Emrich, D., Hagemann, H., Müller, I., Karaus, M., Reimann, H.-J., Ultsch, B., Schmidt, U., Bader, M., Langer, C., Wendt, P., Köttgen, E., Volk, B., Kluge, F., Gerok, W., West, T. B., Peerenboom, H., Keck, E., Kohlsdorfer, W., Krüskemper, H. L., Otte, M., Normann, D., Bellinger, H., Friedrich, H. J., Jantschek, G., Studt, J., Waller, D., Wood, W. G., Auer, I. O., Röder, A., Wensinck, F., van de Merwe, J. P., Schmiedt, H., Förster, S., Karbach, U., Dehos, H., Feurle, G. E., Keller, O., Herzog, P., Ebener, B., Fischer, J., Brod, J., Holtermüller, K. H., Mannes, G. A., Wiebecke, B., Thieme, C., Winter, H.-J., Cicmir, I., Berger, H., Gries, F. A., and Schlegel, Bernhard, editor

Published
1983
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37. Simultaneous Sb doping and formation of self-aligned TiSi2 by codeposition of Ti and Sb.

Author

Li, X.-H., Gong, S. F., Hentzell, H. T. G., Hagel, J., and Robertsson, A.

Subjects
ANTIMONY, SEMICONDUCTOR doping, TITANIUM compounds, ANNEALING of metals
Abstract

Deals with a study which examined the simultaneous antimony doping and formation of self-aligned titanium silicide. Analysis of the structure of the films after annealing; Microstructures of titanium silicides and antimony behavior during silicide formation; Formation of shallow junctions in silicon substrate.

Published
1991

38. Gastrale Mikroblutung und Acetylsalicylsäure: Prophylaxe durch Prostaglandin E2

Author

Goertzen W, G Kachel, Wolfram Domschke, Ruppin H, and Hagel J

Subjects
medicine.medical_specialty, business.industry, Internal medicine, Healthy volunteers, medicine, General Medicine, Prostaglandin E2, business, Gastroenterology, medicine.drug
Abstract

The possible prophylactic effect of prostaglandin E2 (PGE2) pretreatment against gastric microbleedings caused by acetylsalicylic acid was investigated in six healthy volunteers. Gastric microbleeding rate was determined by the gastric tube technique of Fisher and Hunt, at first without any medication. The test was repeated after a two-day intake of acetylsalicylic acid (four times 0.5 g/d) and after two days of the same dose, 15 minutes after the administration of PGE2 (four times 0.5 mg/d). Between the two treatment periods, their sequence randomized, there was a treatment-free pause of at least eight days. Basic gastric microbleeding rate was 0.42 +/- 0.10 ml/d (means +/- Smeans). After administration of acetylsalicylic acid this rose highly significantly elevenfold (4.59 +/- 1.64 ml/d). Prophylactic administration of PGE2 prevented this rise (0.24; 0.04-2.55 ml/d) (median; 10th-90th percentile). There were no side effects to the administration of PGE2.

Published
2008
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43. Pressure dependence of the electronic properties of the quasi-two-dimensional organic superconductor beta'-(ET)2SF5CH2CF2SO3

Author

Hagel, J., Ignatchik, O., Wosnitza, J., Pfleiderer, C., Schlueter, J. A., Davis, H., Winter, R., and Gard, G. L.

Abstract

We report on pressure-dependent superconducting and transport properties of the quasi-two-dimensional organic superconductor b"-(ET)2SF5CH2CF2SO3. With increasing pressure both the superconducting transition temperature, Tc, as well as the effective mass, mc, decrease monotonously. By assuming a direct relationship between mc and the superconducting coupling parameter λ, the pressure dependence of Tc can be well described by the modified McMillan equation. For all pressures in the metallic state the resistance follows q = q0 + AT2 at low temperatures. The coefficient A, however, is found to be not proportional to m2c as expected for a purely electronic origin of the T2 behavior.

Published
2007

44. Postersession IV

Author

Kurtz, W., primary, Classen, M., additional, Schmidt, H., additional, Riddell, R. H., additional, Walther, B., additional, Riemann, J. F., additional, Raedsch, R., additional, Stiehl, A., additional, Sieg, A., additional, Walker, S., additional, Kommerell, B., additional, Gregor, M., additional, Hartmann, K., additional, Riecken, E. O., additional, Dammann, H. G., additional, Walter, Th. A., additional, Müller, P., additional, Simon, B., additional, Fölsch, U. R., additional, Wichmann, G.-Ch., additional, v. Kleist, E., additional, Körber, R., additional, Dillon, M., additional, Clowdus, B., additional, Creutzfeldt, W., additional, Singer, M. V., additional, Calden, H., additional, Eysselein, V. E., additional, Leffmann, C., additional, Goebell, H., additional, Müller-Lissner, St. A., additional, Störkel, S., additional, Dienes, H. P., additional, Schneider, H.-M., additional, Loos, M., additional, Emde, C., additional, Göring, M., additional, Liehr, R.-M., additional, Kruis, W., additional, Azpiroz, F., additional, Phillips, S. F., additional, Stöcker, W., additional, Ulrich, S., additional, Normann, D., additional, Stöcker, K., additional, Jantschek, G., additional, Otte, M., additional, Seyfarth, K., additional, Bührer, Ch., additional, Winkler, R., additional, Raedler, A., additional, Malchow, H., additional, Hoffmann, R., additional, Daiss, W., additional, Jenss, H., additional, Dölle, W., additional, Purrmann, J., additional, Bertrams, J., additional, Rietzler, M., additional, Wolf, E., additional, Miller, B., additional, Strohmeÿer, G., additional, Göke, B., additional, Schwartz, P., additional, Rahlf, G., additional, Goerg, K. J., additional, Wanitschke, R., additional, Breiling, K., additional, Franke, M., additional, Rabast, U., additional, Kemkes-Matthes, B., additional, Abermann, C., additional, Matthes, K. J., additional, Schulzke, J.-D., additional, Fromm, M., additional, Menge, H., additional, Löffler, A., additional, Dienst, C., additional, Thon, H. J., additional, Wüstenberg, E., additional, Corman, G., additional, von Kachel, G., additional, Ruppin, H., additional, Hagel, J., additional, Barina, W., additional, Meinhardt, M., additional, Domschke, W., additional, Sandforth, F., additional, Gutschmidt, S., additional, Karbach, U., additional, Rummel, W., additional, Seitz, H. K., additional, Feurle, G., additional, Huefner, M., additional, Lichtwald, K., additional, Schmidt-Gayk, H., additional, Janisch, H. D., additional, Beuth, A., additional, von Kleist, D., additional, Bauer, F. E., additional, Hampel, K. E., additional, Blasberg, M., additional, Wienbeck, M., additional, Körner, M., additional, Erckenbrecht, J. F., additional, and Berges, W., additional

Published
1984
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45. Fermi Surface of the Half Heusler Compounds Ce1−xLaxBiPt

Author

Bianchi, A. D., Wosnitza, J., Kozlova, N., Eckert, D., Schultz, L., Opahle, I., Elgazzar, S., Richter, M., Doerr, M., Hagel, J., Goll, G., Löhneysen, H., Zwicknagel, G., Yoshino, T., and Takabatake, T.

Subjects
Condensed Matter::Strongly Correlated Electrons, Condensed Matter::Mesoscopic Systems and Quantum Hall Effect
Abstract

We report on the Fermi surface in the correlated half-Heusler compound Ce1-xLaxBiPt. In CeBiPt we find a field-induced change of the electronic band structure as discovered by electrical-transport measurements in pulsed magnetic fields. For magnetic fields above ca 25 T, the charge-carrier concentration determined from Hall-effect measurements increases nearly 30%, whereas the Shubnikov-de Haas (SdH) signal disappears at the same field. In the non-4f compound LaBiPt the Fermi surface remains unaffected, suggesting that these features are intimately related to the Ce 4F electrons. Electronic band-structure calculations point to a 4f-polarization-induced change of the Fermi-surfache topology. In order to test this hypothesis, we have measured the (SdH) signal in a Ce0.95La0.05BiPt sample with a low La concentration.

Published
2006

46. Pressure dependence of the electronic properties of the quasi-two-dimensional organic superconductor β' - (BEDT-TTF)2SF5CH2CF2SO3

Author

Ignatchik, O., Hagel, J., Wosnitza, J., Pfleiderer, C., Schlueter, J. A., Mohtasham, J., and Gard, G. L.

Subjects
Condensed Matter::Superconductivity, Condensed Matter::Strongly Correlated Electrons
Abstract

We report on the pressure-dependent superconducting and transport properties of the quasi-two-dimensional organic superconductor beta"-(BEDT-TTF)2SF5CH2CF2SO3, where BEDT-TTF stands for bisethylenedithio-tetrathiafulvalene (or ET for short). With increasing pressure the superconducting transition temperature, Tc, decreases monotonously. Superconducting traces can be observed up to 11.7 kbar; at higher pressures an insulating state appears. By use of Shubnikov-de Haas (SdH) and angular-dependent magnetoresistance oscillations the Fermi-surface topology as well as the effective masses were determined. Close to the insulating state a new SdH frequency can be resolved. The effective mass, mc, of the main orbit decreases approximately linear with pressure. By assuming a direct relationship between mc and the superconducting coupling parameter lambda, the pressure dependence of Tc can be well explained by the modi-fied McMillan equation. For all pressures in the metallic state the resistance can be described by R = R0 + AT2 at low temperatures. The coefficient A, however, is found to be not proportional to m2c as expected for a purely electronic origin of the T2 behavior.

Published
2006

47. β′′-(ET)2SF5CH2CF2SO3 – a Layered 2D Metal with Vanishing Interlayer Coupling

Author

Wosnitza, J., Hagel, J., Ignatchik, O., Bergk, B., Gvozdikov, V. M., Schlueter, J. A., Winter, R. W., and Gard, G. L.

Subjects
Condensed Matter::Superconductivity
Abstract

We report on electrical transport and magnetization measurements of the quasi-two-dimensional layered superconductor β′′-(ET)2SF5CH2CF2SO3. The absence of a resistive peak when a strong magnetic field is aligned along the conducting planes reflects the fact that the material is one of the most anisotropic ET-based metals with possible incoherent interlayer transport. Consequences of this feature may be the enhanced amplitude of magnetic quantum oscillations in the superconducting state and an unusual angulardependent metal-insulator transition.

Published
2006

48. Magnetic quantum oscillations in the normal state of YNi2B2C

Author

Ignatchik, O., Coffey, T., Hagel, J., Jäckel, M., Jobiliong, E., Souptel, D., Behr, G., and Wosnitza, J.

Subjects
Electronic structure, Superconductivity, de Haas–van Alphen effect, Rare earth–transition metal alloys
Abstract

We present de Haas–van Alphen (dHvA) measurements of different YNi2B2C single crystals in magnetic fields up to 32 T. At high magnetic fields three different dHvA frequencies could be detected. The lowest frequency, Fα; could be well resolved down to lower fields just above the upper critical field. An unexpectedly sudden vanishing of the dHvA signal in the mixed state has been observed

Published
2005

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