429 results on '"Magg A"'
Search Results
2. Next-generation phenotyping integrated in a national framework for patients with ultrarare disorders improves genetic diagnostics and yields new molecular findings
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Schmidt, Axel, Danyel, Magdalena, Grundmann, Kathrin, Brunet, Theresa, Klinkhammer, Hannah, Hsieh, Tzung-Chien, Engels, Hartmut, Peters, Sophia, Knaus, Alexej, Moosa, Shahida, Averdunk, Luisa, Boschann, Felix, Sczakiel, Henrike Lisa, Schwartzmann, Sarina, Mensah, Martin Atta, Pantel, Jean Tori, Holtgrewe, Manuel, Bösch, Annemarie, Weiß, Claudia, Weinhold, Natalie, Suter, Aude-Annick, Stoltenburg, Corinna, Neugebauer, Julia, Kallinich, Tillmann, Kaindl, Angela M., Holzhauer, Susanne, Bührer, Christoph, Bufler, Philip, Kornak, Uwe, Ott, Claus-Eric, Schülke, Markus, Nguyen, Hoa Huu Phuc, Hoffjan, Sabine, Grasemann, Corinna, Rothoeft, Tobias, Brinkmann, Folke, Matar, Nora, Sivalingam, Sugirthan, Perne, Claudia, Mangold, Elisabeth, Kreiss, Martina, Cremer, Kirsten, Betz, Regina C., Mücke, Martin, Grigull, Lorenz, Klockgether, Thomas, Spier, Isabel, Heimbach, André, Bender, Tim, Brand, Fabian, Stieber, Christiane, Morawiec, Alexandra Marzena, Karakostas, Pantelis, Schäfer, Valentin S., Bernsen, Sarah, Weydt, Patrick, Castro-Gomez, Sergio, Aziz, Ahmad, Grobe-Einsler, Marcus, Kimmich, Okka, Kobeleva, Xenia, Önder, Demet, Lesmann, Hellen, Kumar, Sheetal, Tacik, Pawel, Basin, Meghna Ahuja, Incardona, Pietro, Lee-Kirsch, Min Ae, Berner, Reinhard, Schuetz, Catharina, Körholz, Julia, Kretschmer, Tanita, Di Donato, Nataliya, Schröck, Evelin, Heinen, André, Reuner, Ulrike, Hanßke, Amalia-Mihaela, Kaiser, Frank J., Manka, Eva, Munteanu, Martin, Kuechler, Alma, Cordula, Kiewert, Hirtz, Raphael, Schlapakow, Elena, Schlein, Christian, Lisfeld, Jasmin, Kubisch, Christian, Herget, Theresia, Hempel, Maja, Weiler-Normann, Christina, Ullrich, Kurt, Schramm, Christoph, Rudolph, Cornelia, Rillig, Franziska, Groffmann, Maximilian, Muntau, Ania, Tibelius, Alexandra, Schwaibold, Eva M. C., Schaaf, Christian P., Zawada, Michal, Kaufmann, Lilian, Hinderhofer, Katrin, Okun, Pamela M., Kotzaeridou, Urania, Hoffmann, Georg F., Choukair, Daniela, Bettendorf, Markus, Spielmann, Malte, Ripke, Annekatrin, Pauly, Martje, Münchau, Alexander, Lohmann, Katja, Hüning, Irina, Hanker, Britta, Bäumer, Tobias, Herzog, Rebecca, Hellenbroich, Yorck, Westphal, Dominik S., Strom, Tim, Kovacs, Reka, Riedhammer, Korbinian M., Mayerhanser, Katharina, Graf, Elisabeth, Brugger, Melanie, Hoefele, Julia, Oexle, Konrad, Mirza-Schreiber, Nazanin, Berutti, Riccardo, Schatz, Ulrich, Krenn, Martin, Makowski, Christine, Weigand, Heike, Schröder, Sebastian, Rohlfs, Meino, Vill, Katharina, Hauck, Fabian, Borggraefe, Ingo, Müller-Felber, Wolfgang, Kurth, Ingo, Elbracht, Miriam, Knopp, Cordula, Begemann, Matthias, Kraft, Florian, Lemke, Johannes R., Hentschel, Julia, Platzer, Konrad, Strehlow, Vincent, Abou Jamra, Rami, Kehrer, Martin, Demidov, German, Beck-Wödl, Stefanie, Graessner, Holm, Sturm, Marc, Zeltner, Lena, Schöls, Ludger J., Magg, Janine, Bevot, Andrea, Kehrer, Christiane, Kaiser, Nadja, Turro, Ernest, Horn, Denise, Grüters-Kieslich, Annette, Klein, Christoph, Mundlos, Stefan, Nöthen, Markus, Riess, Olaf, Meitinger, Thomas, Krude, Heiko, Krawitz, Peter M., Haack, Tobias, Ehmke, Nadja, and Wagner, Matias
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- 2024
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3. Causal State Distillation for Explainable Reinforcement Learning
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Lu, Wenhao, Zhao, Xufeng, Fryen, Thilo, Lee, Jae Hee, Li, Mengdi, Magg, Sven, and Wermter, Stefan
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Computer Science - Machine Learning ,Computer Science - Artificial Intelligence ,Statistics - Methodology - Abstract
Reinforcement learning (RL) is a powerful technique for training intelligent agents, but understanding why these agents make specific decisions can be quite challenging. This lack of transparency in RL models has been a long-standing problem, making it difficult for users to grasp the reasons behind an agent's behaviour. Various approaches have been explored to address this problem, with one promising avenue being reward decomposition (RD). RD is appealing as it sidesteps some of the concerns associated with other methods that attempt to rationalize an agent's behaviour in a post-hoc manner. RD works by exposing various facets of the rewards that contribute to the agent's objectives during training. However, RD alone has limitations as it primarily offers insights based on sub-rewards and does not delve into the intricate cause-and-effect relationships that occur within an RL agent's neural model. In this paper, we present an extension of RD that goes beyond sub-rewards to provide more informative explanations. Our approach is centred on a causal learning framework that leverages information-theoretic measures for explanation objectives that encourage three crucial properties of causal factors: causal sufficiency, sparseness, and orthogonality. These properties help us distill the cause-and-effect relationships between the agent's states and actions or rewards, allowing for a deeper understanding of its decision-making processes. Our framework is designed to generate local explanations and can be applied to a wide range of RL tasks with multiple reward channels. Through a series of experiments, we demonstrate that our approach offers more meaningful and insightful explanations for the agent's action selections., Comment: https://lukaswill.github.io/; Accepted as oral by CLeaR 2024
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- 2023
4. A Closer Look at Reward Decomposition for High-Level Robotic Explanations
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Lu, Wenhao, Zhao, Xufeng, Magg, Sven, Gromniak, Martin, Li, Mengdi, and Wermter, Stefan
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Computer Science - Machine Learning ,Computer Science - Artificial Intelligence ,Computer Science - Robotics - Abstract
Explaining the behaviour of intelligent agents learned by reinforcement learning (RL) to humans is challenging yet crucial due to their incomprehensible proprioceptive states, variational intermediate goals, and resultant unpredictability. Moreover, one-step explanations for RL agents can be ambiguous as they fail to account for the agent's future behaviour at each transition, adding to the complexity of explaining robot actions. By leveraging abstracted actions that map to task-specific primitives, we avoid explanations on the movement level. To further improve the transparency and explainability of robotic systems, we propose an explainable Q-Map learning framework that combines reward decomposition (RD) with abstracted action spaces, allowing for non-ambiguous and high-level explanations based on object properties in the task. We demonstrate the effectiveness of our framework through quantitative and qualitative analysis of two robotic scenarios, showcasing visual and textual explanations, from output artefacts of RD explanations, that are easy for humans to comprehend. Additionally, we demonstrate the versatility of integrating these artefacts with large language models (LLMs) for reasoning and interactive querying., Comment: https://lukaswill.github.io
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- 2023
5. Neural Field Conditioning Strategies for 2D Semantic Segmentation
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Gromniak, Martin, Magg, Sven, and Wermter, Stefan
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Computer Science - Computer Vision and Pattern Recognition ,Computer Science - Machine Learning ,Electrical Engineering and Systems Science - Image and Video Processing - Abstract
Neural fields are neural networks which map coordinates to a desired signal. When a neural field should jointly model multiple signals, and not memorize only one, it needs to be conditioned on a latent code which describes the signal at hand. Despite being an important aspect, there has been little research on conditioning strategies for neural fields. In this work, we explore the use of neural fields as decoders for 2D semantic segmentation. For this task, we compare three conditioning methods, simple concatenation of the latent code, Feature Wise Linear Modulation (FiLM), and Cross-Attention, in conjunction with latent codes which either describe the full image or only a local region of the image. Our results show a considerable difference in performance between the examined conditioning strategies. Furthermore, we show that conditioning via Cross-Attention achieves the best results and is competitive with a CNN-based decoder for semantic segmentation., Comment: 13 pages, 4 figures, submitted to ICANN 2023
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- 2023
6. Population III X-ray Binaries and their Impact on the Early Universe
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Sartorio, Nina S., Fialkov, A., Hartwig, T., Mirouh, G. M., Izzard, R. G., Magg, M., Klessen, R. S., Glover, S. C. O., Chen, L., Tarumi, Y., and Hendriks, D. D.
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Astrophysics - High Energy Astrophysical Phenomena ,Astrophysics - Cosmology and Nongalactic Astrophysics - Abstract
The first population of X-ray binaries (XRBs) is expected to affect the thermal and ionization states of the gas in the early Universe. Although these X-ray sources are predicted to have important implications for high-redshift observable signals, such as the hydrogen 21-cm signal from cosmic dawn and the cosmic X-ray background, their properties are poorly explored, leaving theoretical models largely uninformed. In this paper we model a population of X-ray binaries arising from zero metallicity stars. We explore how their properties depend on the adopted initial mass function (IMF) of primordial stars, finding a strong effect on their number and X-ray production efficiency. We also present scaling relations between XRBs and their X-ray emission with the local star formation rate, which can be used in sub-grid models in numerical simulations to improve the X-ray feedback prescriptions. Specifically, we find that the uniformity and strength of the X-ray feedback in the intergalactic medium is strongly dependant on the IMF. Bottom-heavy IMFs result in a smoother distribution of XRBs, but have a luminosity orders of magnitude lower than more top-heavy IMFs. Top-heavy IMFs lead to more spatially uneven, albeit strong, X-ray emission. An intermediate IMF has a strong X-ray feedback while sustaining an even emission across the intergalactic medium. These differences in X-ray feedback could be probed in the future with measurements of the cosmic dawn 21-cm line of neutral hydrogen, which offers us a new way of constraining population III IMF., Comment: Accepted for publication in MNRAS, 17 pages, 9 figures
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- 2023
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7. KLK7 expression in human tumors: a tissue microarray study on 13,447 tumors
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Simon Kind, Carolina Palacios Castillo, Ria Schlichter, Natalia Gorbokon, Maximilian Lennartz, Lisa S. Hornsteiner, Sebastian Dwertmann Rico, Viktor Reiswich, Florian Viehweger, Martina Kluth, Claudia Hube-Magg, Christian Bernreuther, Franziska Büscheck, Till S. Clauditz, Christoph Fraune, Andrea Hinsch, Till Krech, Patrick Lebok, Stefan Steurer, Eike Burandt, Sarah Minner, Andreas H. Marx, Ronald Simon, Waldemar Wilczak, Guido Sauter, Anne Menz, and Frank Jacobsen
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KLK7 ,Tissue microarray ,Immunohistochemistry ,Neoplastic human tissues ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Kallikrein-related peptidase 7 (KLK7) is a chymotrypsin-like serine protease which is essential for the desquamation of corneocytes and thus plays a pivotal role in maintaining skin homeostasis. In cancer, KLK7 overexpression was suggested to represent a route for metastasis through cleavage of cell junction and extracellular matrix proteins of cancer cells. Methods To comprehensively determine KLK7 protein expression in normal and neoplastic tissues, a tissue microarray containing 13,447 samples from 147 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. Results KLK7 positivity was found in 64 of 147 tumor categories, including 17 tumor categories with at least one strongly positive case. The highest rate of KLK7 positivity was found in squamous cell carcinomas from various sites of origin (positive in 18.1%-63.8%), ovarian and endometrium cancers (4.8%-56.2%), salivary gland tumors (4.8%-13.7%), bilio-pancreatic adenocarcinomas (20.0%-40.4%), and adenocarcinomas of the upper gastrointestinal tract (3.3%-12.5%). KLK7 positivity was linked to nodal metastasis (p = 0.0005), blood vessel infiltration (p = 0.0037), and lymph vessel infiltration (p
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- 2024
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8. Metal Mixing in the R-Process Enhanced Ultra-Faint Dwarf Galaxy Reticulum II
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Ji, Alexander P., Simon, Joshua D., Roederer, Ian U., Magg, Ekaterina, Frebel, Anna, Johnson, Christian I., Klessen, Ralf S., Magg, Mattis, Cescutti, Gabriele, Mateo, Mario, Bergemann, Maria, and Bailey III, John I.
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Astrophysics - Astrophysics of Galaxies - Abstract
The ultra-faint dwarf galaxy Reticulum~II was enriched by a single rare and prolific r-process event. The r-process content of Reticulum~II thus provides a unique opportunity to study metal mixing in a relic first galaxy. Using multi-object high-resolution spectroscopy with VLT/GIRAFFE and Magellan/M2FS, we identify 32 clear spectroscopic member stars and measure abundances of Mg, Ca, Fe, and Ba where possible. We find $72^{+10}_{-12}$% of the stars are r-process-enhanced, with a mean $\left\langle\mbox{[Ba/H]}\right\rangle=-1.68~\pm~0.07$ and unresolved intrinsic dispersion $\sigma_{\rm [Ba/H]} < 0.20$. The homogeneous r-process abundances imply that Ret~II's metals are well-mixed by the time the r-enhanced stars form, which simulations have shown requires at least 100 Myr of metal mixing in between bursts of star formation to homogenize. This is the first direct evidence of bursty star formation in an ultra-faint dwarf galaxy. The homogeneous dilution prefers a prompt and high-yield r-process site, such as collapsar disk winds or prompt neutron star mergers. We also find evidence from [Ba/H] and [Mg/Ca] that the r-enhanced stars in Ret~II formed in the absence of substantial pristine gas accretion, perhaps indicating that ${\approx}70$% of Ret~II stars formed after reionization., Comment: 37 pages, 12 figures, 10 tables, accepted to AJ
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- 2022
9. Causal State Distillation for Explainable Reinforcement Learning.
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Wenhao Lu, Xufeng Zhao, Thilo Fryen, Jae Hee Lee 0001, Mengdi Li, Sven Magg, and Stefan Wermter
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- 2024
10. A-SLOTH: Ancient Stars and Local Observables by Tracing Halos
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Magg, Mattis, Hartwig, Tilman, Chen, Li-Hsin, and Tarumi, Yuta
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Astrophysics - Instrumentation and Methods for Astrophysics ,Astrophysics - Cosmology and Nongalactic Astrophysics ,Astrophysics - Astrophysics of Galaxies - Abstract
Galaxies are thought to reside inside of large gravitationally bound structures of dark matter, so-called haloes. While the smallest of these haloes host no or only a few stars, the biggest host entire clusters of galaxies. Over cosmic history, haloes often collided and merged, forming bigger and bigger structures. Merger trees, i.e., catalogues of haloes evolving and connections between them as they grow and merge, have become a vital tool in describing and understanding the history of cosmological objects such as our Galaxy. Semi-analytical models, built on top of such merger trees, are a common approach for theoretical studies in cosmology. The semi-analytical nature of such models is especially beneficial when the dynamic range in spatial and time scales that need to be considered becomes too large for numerical simulations. Ancient Stars and Local Observables by Tracing Halos (A-SLOTH) is such a semi-analytical model and it is designed to simulate star formation in the early Universe in a fast and accessible way. It uses merger trees, either from numerical simulations or generated by statistical algorithms to describe the history of galaxies. The processes of baryonic physics, in particular gas cooling, star formation and stellar feedback are described with approximations and statistical models. The range of applications for this model is extensive and we, therefore, make it available to the scientific community., Comment: Published in JOSS. Git repo is available at https://gitlab.com/thartwig/asloth
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- 2022
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11. Non-LTE Radiative Transfer with Turbospectrum
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Gerber, Jeffrey M., Magg, Ekaterina, Plez, Bertrand, Bergemann, Maria, Heiter, Ulrike, Olander, Terese, and Hoppe, Richard
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Astrophysics - Solar and Stellar Astrophysics ,Astrophysics - Earth and Planetary Astrophysics ,Astrophysics - Astrophysics of Galaxies ,Astrophysics - Instrumentation and Methods for Astrophysics - Abstract
Physically realistic models of stellar spectra are needed in a variety of astronomical studies, from the analysis of fundamental stellar parameters, to studies of exoplanets and stellar populations in galaxies. Here we present a new version of the widely-used radiative transfer code Turbospectrum, which we update with the capacity to perform spectrum synthesis for lines of multiple chemical elements in Non-Local Thermodynamic Equilibrium (NLTE). We use the code in the analysis of metallicites and abundances of the Gaia FGK benchmark stars, using one-dimensional MARCS atmospheric models and the averages of 3D radiation-hydrodynamics simulations of stellar surface convection. We show that the new more physically realistic models offer a better description of the observed data and make the program and the associated microphysics data publicly available, including grids of NLTE departure coefficients for H, O, Na, Mg, Si, Ca, Ti, Mn, Fe, Co, Ni, Sr, and Ba.
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- 2022
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12. Public Release of A-SLOTH: Ancient Stars and Local Observables by Tracing Halos
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Hartwig, Tilman, Magg, Mattis, Chen, Li-Hsin, Tarumi, Yuta, Bromm, Volker, Glover, Simon C. O., Ji, Alexander P., Klessen, Ralf S., Latif, Muhammad A., Volonteri, Marta, and Yoshida, Naoki
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Astrophysics - Astrophysics of Galaxies ,Astrophysics - Cosmology and Nongalactic Astrophysics - Abstract
The semi-analytical model A-SLOTH (Ancient Stars and Local Observables by Tracing Halos) is the first public code that connects the formation of the first stars and galaxies to observables. After several successful projects with this model, we publish the source code and describe the public version in this paper. The model is based on dark matter merger trees that can either be generated based on Extended Press-Schechter theory or that can be imported from dark matter simulations. On top of these merger trees, A-SLOTH applies analytical recipes for baryonic physics to model the formation of both metal-free and metal-poor stars and the transition between them with unprecedented precision and fidelity. A-SLOTH samples individual stars and includes radiative, chemical, and mechanical feedback. It is calibrated based on six observables, such as the optical depth to Thomson scattering, the stellar mass of the Milky Way and its satellite galaxies, the number of extremely-metal poor stars, and the cosmic star formation rate density at high redshift. A-SLOTH has versatile applications with moderate computational requirements. It can be used to constrain the properties of the first stars and high-z galaxies based on local observables, predicts properties of the oldest and most metal-poor stars in the Milky Way, can serve as a subgrid model for larger cosmological simulations, and predicts next-generation observables of the early Universe, such as supernova rates or gravitational wave events., Comment: Published in ApJ, 35 pages, video summary can be watched at https://www.youtube.com/watch?v=M_JRT2AsOqg and git repository is available at https://gitlab.com/thartwig/asloth
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- 2022
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13. Observational constraints on the origin of the elements. IV: The standard composition of the Sun
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Magg, Ekaterina, Bergemann, Maria, Serenelli, Aldo, Bautista, Manuel, Plez, Bertrand, Heiter, Ulrike, Gerber, Jeffrey M., Ludwig, Hans-Günter, Basu, Sarbani, Ferguson, Jason W., Gallego, Helena Carvajal, Gamrath, Sébastien, Palmeri, Patrick, and Quinet, Pascal
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Astrophysics - Solar and Stellar Astrophysics - Abstract
The chemical composition of the Sun is requested in the context of various studies in astrophysics, among them in the calculation of the standard solar models (SSMs), which describe the evolution of the Sun from the pre-main-sequence to its present age. In this work, we provide a critical re-analysis of the solar chemical abundances and corresponding SSMs. For the photospheric values, we employ new high-quality solar observational data collected with the IAG facility, state-of-the art non-equilibrium modelling, new oscillator strengths, and different atmospheric models, including the MARCS model, but also averages based on Stagger and CO5BOLD 3D radiation-hydrodynamics simulations of stellar convection. We perform new calculations of oscillator strengths for transitions in O I and N I. For O I - the critical element for the interior models - calculations are carried out using several independent methods. We find unprecedented agreement between the new estimates of transition probabilities, thus supporting our revised solar oxygen abundance. We also provide new estimates of the noble gas Ne abundance. We investigate our results in comparison with the previous estimates. We discuss the consistency of our photospheric measurements with meteoritic values taking into account systematic and correlated errors. Finally, we provide revised chemical abundances, leading to a new value of the solar photospheric present-day metallicity $Z/X = 0.0225$, and employ them in the calculations of the SSM. We find that the puzzling mismatch between the helioseismic constraints on the solar interior structure and the model is resolved with the new chemical composition., Comment: accepted for publication in A&A
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- 2022
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14. Impact of the Primordial Stellar Initial Mass Function on the 21-cm Signal
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Gessey-Jones, T., Sartorio, N. S., Fialkov, A., Mirouh, G. M., Magg, M., Izzard, R. G., Acedo, E. de Lera, Handley, W. J., and Barkana, R.
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Astrophysics - Cosmology and Nongalactic Astrophysics ,Astrophysics - Astrophysics of Galaxies ,Astrophysics - Solar and Stellar Astrophysics - Abstract
Properties of the first generation of stars (Pop III), such as their initial mass function (IMF), are poorly constrained by observations and have yet to converge between simulations. The cosmological 21-cm signal of neutral hydrogen is predicted to be sensitive to Lyman-band photons produced by these stars, thus providing a unique way to probe the first stellar population. In this paper, we investigate the impacts of the Pop III IMF on the cosmic dawn 21-cm signal via the Wouthuysen-Field effect, Lyman-Werner feedback, Ly-alpha heating, and CMB heating. We calculate the emission spectra of star-forming halos for different IMFs by integrating over individual metal-free stellar spectra, computed from a set of stellar evolution histories and stellar atmospheres, and taking into account variability of the spectra with stellar age. Through this study, we therefore relax two common assumptions: that the zero-age main sequence emission rate of a Pop III star is representative of its lifetime mean emission rate, and that Pop III emission can be treated as instantaneous. Exploring a bottom-heavy, a top-heavy, and intermediate IMFs, we show that variations in the 21-cm signal are driven by stars lighter than 20 solar masses. For the explored models we find maximum relative differences of 59% in the cosmic dawn global 21-cm signal, and 131% between power spectra. Although this impact is modest, precise modelling of the first stars and their evolution is necessary for accurate prediction and interpretation of the 21-cm signal., Comment: 20 pages, 16 figures. Accepted for publication in MNRAS, updated to accepted version
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- 2022
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15. Tracing stars in Milky Way satellites with A-SLOTH
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Chen, Li-Hsin, Magg, Mattis, Hartwig, Tilman, Glover, Simon C. O., Ji, Alexander P., and Klessen, Ralf S.
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Astrophysics - Astrophysics of Galaxies - Abstract
We study the stellar mass-to-halo mass relation at $z=0$ in 30 Milky Way-like systems down to the ultra-faint ($M_* < 10^5 M_\odot$) regime using the semi-analytic model A-SLOTH. A new model allows us to follow star formation and the stochastic stellar feedback from individually sampled Pop II stars. Our fiducial model produces consistent results with the stellar mass-to-halo mass relation derived from abundance matching and the observed cumulative stellar mass function above the observational completeness. We find a plateau in the stellar mass-to-halo mass relation in the ultra-faint regime. The stellar mass of this plateau tells us how many stars formed before supernovae occur and regulate further star formation, which is determined by the Pop~II star formation efficiency. We also find that the number of luminous satellites increases rapidly as $M_*$ decreases until $M_* \approx 10^4 M_\odot$. Finally, we find that the relative streaming velocity between baryons and dark matter at high redshift is important in determining the number of ultra-faint dwarf galaxies at $z=0$. The new model in A-SLOTH provides a framework to study the stellar properties and the formation history of metal-poor stars in Milky Way and its satellites., Comment: 18 pages, 11 figures, 3 tables
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- 2022
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16. Prostein expression in human tumors: a tissue microarray study on 19,202 tumors from 152 different Tumor entities
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Florian Viehweger, Carola Böcker, Sören Weidemann, Morton Freytag, Anne Menz, Franziska Büscheck, Andreas M. Luebke, Devita Putri, Martina Kluth, Claudia Hube-Magg, Andrea Hinsch, Maximilian Lennartz, Florian Lutz, Viktor Reiswich, Doris Höflmayer, Christoph Fraune, Katharina Möller, Christian Bernreuther, Patrick Lebok, Guido Sauter, Stefan Steurer, David Dum, Andreas H. Marx, Ronald Simon, Till Krech, Till S. Clauditz, Frank Jacobsen, Natalia Gorbokon, Eike Burandt, Sarah Minner, and Simon Kind
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Prostein ,Tissue microarray ,Immunohistochemistry ,Human cancers ,Pathology ,RB1-214 - Abstract
Abstract Background Prostein (P501S), also termed solute carrier family 45 member 3 (SLC45A3) is an androgen regulated protein which is preferentially expressed in prostate epithelial cells. Because of its frequent expression in prostate cancer, prostein was suggested a diagnostic prostate cancer marker. Methods In order to comprehensively assess the diagnostic utility of prostein immunohistochemistry, a tissue microarray containing 19,202 samples from 152 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. Results Prostein immunostaining was typically cytoplasmic, granular and perinuclear. Prostein positivity was seen in 96.7% of 419 prostate cancers including 78.3% with strong staining. In 16,709 extra-prostatic tumors, prostein positivity was observed in 7.2% of all cases but only 0.3% had a strong staining. Overall, 50 different extra-prostatic tumor categories were prostein positive, 12 of which included at least one strongly positive case. Extra-prostatic tumors with highest rates of prostein positivity included different subtypes of salivary gland tumors (7.6-44.4%), neuroendocrine neoplasms (15.8-44.4%), adenocarcinomas of the gastrointestinal tract (7.3-14.8%), biliopancreatic adenocarcinomas (3.6-38.7%), hepatocellular carcinomas (8.1%), and adenocarcinomas of other organs (up to 21%). Conclusions Our data provide a comprehensive overview on prostein expression in human cancers. Prostein is a highly sensitive prostate cancer marker occurring in > 96% of prostate cancers. Because prostein can also be expressed in various other tumor entities, classifying of a tumor mass as a prostate cancer should not be based on prostein positivity alone.
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- 2024
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17. Hierarchical goals contextualize local reward decomposition explanations
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Rietz, Finn, Magg, Sven, Heintz, Fredrik, Stoyanov, Todor, Wermter, Stefan, and Stork, Johannes A.
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- 2023
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18. The chemical composition of globular clusters in the Local Group
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Larsen, S. S., Eitner, P., Magg, E., Bergemann, M., Moltzer, C. A. S., Brodie, J. P., Romanowsky, A. J., and Strader, J.
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Astrophysics - Astrophysics of Galaxies ,Astrophysics - Solar and Stellar Astrophysics - Abstract
We present detailed abundance measurements for 45 globular clusters (GCs) in galaxies in (and, in one case, beyond) the Local Group. The measurements are based on new high-resolution integrated-light spectra of GCs in NGC 185, NGC 205, M31, M33, and NGC 2403, combined with reanalysis of previous observations of GCs in the Fornax dSph, WLM, NGC 147, NGC 6822, and the Milky Way. The GCs cover the range -2.8 < [Fe/H] < -0.1 and we determined abundances for Fe, Na, Mg, Si, Ca, Sc, Ti, Cr, Mn, Ni, Cu, Zn, Zr, Ba, and Eu. Corrections for non local thermodynamic equilibrium effects are included for Na, Mg, Ca, Ti, Mn, Fe, Ni, and Ba. For several of the galaxies, our measurements provide the first quantitative constraints on the detailed composition of their metal-poor stellar populations. Overall, the GCs in different galaxies exhibit remarkably uniform abundance patterns of the alpha-, iron-peak, and neutron-capture elements, with a dispersion of less than 0.1 dex in [alpha/Fe] for the full sample. There is a hint that GCs in dwarf galaxies are slightly less alpha-enhanced (by about 0.04 dex on average) than those in larger galaxies. One GC in M33 (HM33-B) resembles the most metal-rich GCs in the Fornax dSph (Fornax 4) and NGC 6822 (SC7) by having alpha-element abundances closer to scaled-solar values, possibly hinting at an accretion origin. We find that the alpha-element abundances strongly correlate with those of Na, Sc, Ni, and Zn. Several GCs with [Fe/H]<-1.5 are deficient in Mg compared to other alpha-elements. We find no GCs with strongly enhanced r-process abundances as reported for metal-poor stars in some ultra-faint dwarfs and the Magellanic Clouds. The similarity of the abundance patterns for metal-poor GCs in different environments points to similar early enrichment histories and only allow for minor variations in the initial mass function., Comment: 34 pages + 6 appendices. Accepted for publication in Astronomy & Astrophysics
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- 2021
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19. TRPS1 is a Highly Sensitive Marker for Breast Cancer: A Tissue Microarray Study Evaluating More Than 19,000 Tumors From 152 Different Tumor Entities
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Lennartz, Maximilian, Löhr, Neele, Höflmayer, Doris, Dwertmann Rico, Sebastian, von Bargen, Clara, Kind, Simon, Reiswich, Viktor, Viehweger, Florian, Lutz, Florian, Bertram, Veit, Fraune, Christoph, Gorbokon, Natalia, Weidemann, Sören, Blessin, Niclas C., Hube-Magg, Claudia, Menz, Anne, Schlichter, Ria, Krech, Till, Hinsch, Andrea, Burandt, Eike, Sauter, Guido, Simon, Ronald, Kluth, Martina, Marx, Andreas H., Lebok, Patrick, Dum, David, Minner, Sarah, Jacobsen, Frank, Clauditz, Till S., Bernreuther, Christian, and Steurer, Stefan
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- 2024
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20. Effect of the cosmological transition to metal-enriched star-formation on the hydrogen 21-cm signal
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Magg, Mattis, Reis, Itamar, Fialkov, Anastasia, Barkana, Rennan, Klessen, Ralf S., Glover, Simon C. O., Chen, Li-Hsin, Hartwig, Tilman, and Schauer, Anna T. P.
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Astrophysics - Cosmology and Nongalactic Astrophysics ,Astrophysics - Astrophysics of Galaxies - Abstract
Mapping Cosmic Dawn with 21-cm tomography offers an exciting new window into the era of primordial star formation. However, self-consistent implementation of both the process of star formation and the related 21-cm signal is challenging, due to the multi-scale nature of the problem. In this study, we develop a flexible semi-analytical model to follow the formation of the first stars and the process of gradual transition from primordial to metal-enriched star formation. For this transition we use different in scenarios with varying time-delays (or recovery times) between the first supernovae and the formation of the second generation of stars. We use recovery times between 10 and 100\,Myr and find that these delays have a strong impact on the redshift at which the transition to metal-enriched star formation occurs. We then explore the effect of this transition on the 21-cm signal and find that the recovery time has a distinctive imprint in the signal. Together with an improved understanding of how this time-delay relates to the properties of Population~III stars, future 21-cm observations can give independent constraints on the earliest epoch of star formation., Comment: 17 pages, 11 Figures, submitted to MNRAS, comments very welcome
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- 2021
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21. Metal Mixing in Minihalos: The Descendants of Pair-Instability Supernovae
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Magg, Mattis, Schauer, Anna T. P., Klessen, Ralf S., Glover, Simon C. O., Tress, Robin G., and Jaura, Ondrej
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Astrophysics - Astrophysics of Galaxies ,Astrophysics - Cosmology and Nongalactic Astrophysics - Abstract
The lack of observations of abundance patterns originating in pair-instability supernovae has been a long-standing problem in relation to the first stars. This class of supernovae is expected to have an abundance pattern with a strong odd-even effect, making it substantially different from present-day supernovae. In this study, we use a cosmological radiation hydrodynamics simulation to model such supernovae and the subsequent formation of the second generation of stars. We incorporate streaming velocities for the first time. There are 14 star-forming minihalos in our $1\,\mathrm{Mpc}\,h^{-1}$ box, leading to 14 supernovae occurring before redshift $z=19.5$, where we start reducing the complexity of the simulation. Following the explosions, extremely metal-poor stars form in 10 halos via internal and external enrichment, which makes it the most common outcome. Only one halo does not recollapse during the simulations. This result is at tension with the current (lack of) observations of metal-poor stars with pair instability supernova abundance patterns, suggesting that these very massive stars might be rare even in the early Universe. The results from this simulation also give us insights into what drives different modes of recollapse and what determines the mixing behavior of metals after very energetic supernovae., Comment: 21 pages, 17 figures, accepted for publication in ApJ
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- 2021
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22. Correction to: A Novel Biallelic LCK Variant Resulting in Profound T-Cell Immune Deficiency and Review of the Literature
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Lanz, Anna-Lisa, Erdem, Serife, Ozcan, Alper, Ceylaner, Gulay, Cansever, Murat, Ceylaner, Serdar, Conca, Raffaele, Magg, Thomas, Acuto, Oreste, Latour, Sylvain, Klein, Christoph, Patiroglu, Turkan, Unal, Ekrem, Eken, Ahmet, and Hauck, Fabian
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- 2024
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23. A Novel Biallelic LCK Variant Resulting in Profound T-Cell Immune Deficiency and Review of the Literature
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Lanz, Anna-Lisa, Erdem, Serife, Ozcan, Alper, Ceylaner, Gulay, Cansever, Murat, Ceylaner, Serdar, Conca, Raffaele, Magg, Thomas, Acuto, Oreste, Latour, Sylvain, Klein, Christoph, Patiroglu, Turkan, Unal, Ekrem, Eken, Ahmet, and Hauck, Fabian
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- 2024
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24. Multimodal video retrieval with CLIP: a user study
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Alpay, Tayfun, Magg, Sven, Broze, Philipp, and Speck, Daniel
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- 2023
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25. Cadherin-16 (CDH16) immunohistochemistry: a useful diagnostic tool for renal cell carcinoma and papillary carcinomas of the thyroid
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Lennartz, Maximilian, Csomós, Henrietta, Chirico, Viktoria, Weidemann, Sören, Gorbokon, Natalia, Menz, Anne, Büscheck, Franziska, Hube-Magg, Claudia, Höflmayer, Doris, Bernreuther, Christian, Blessin, Niclas C., Lebok, Patrick, Sauter, Guido, Steurer, Stefan, Burandt, Eike, Dum, David, Krech, Till, Simon, Ronald, Minner, Sarah, Jacobsen, Frank, Clauditz, Till S., Luebke, Andreas M., Siraj, Abdul Khalid, Al-Dayel, Fouad, Al-Kuraya, Khawla S., and Hinsch, Andrea
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- 2023
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26. Turnover of PPP1R15A mRNA encoding GADD34 controls responsiveness and adaptation to cellular stress
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Vera Magg, Alessandro Manetto, Katja Kopp, Chia Ching Wu, Mohsen Naghizadeh, Doris Lindner, Lucy Eke, Julia Welsch, Stefan M. Kallenberger, Johanna Schott, Volker Haucke, Nicolas Locker, Georg Stoecklin, and Alessia Ruggieri
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CP: Cell biology ,CP: Molecular biology ,Biology (General) ,QH301-705.5 - Abstract
Summary: The integrated stress response (ISR) is a key cellular signaling pathway activated by environmental alterations that represses protein synthesis to restore homeostasis. To prevent sustained damage, the ISR is counteracted by the upregulation of growth arrest and DNA damage-inducible 34 (GADD34), a stress-induced regulatory subunit of protein phosphatase 1 that mediates translation reactivation and stress recovery. Here, we uncover a novel ISR regulatory mechanism that post-transcriptionally controls the stability of PPP1R15A mRNA encoding GADD34. We establish that the 3′ untranslated region of PPP1R15A mRNA contains an active AU-rich element (ARE) recognized by proteins of the ZFP36 family, promoting its rapid decay under normal conditions and stabilization for efficient expression of GADD34 in response to stress. We identify the tight temporal control of PPP1R15A mRNA turnover as a component of the transient ISR memory, which sets the threshold for cellular responsiveness and mediates adaptation to repeated stress conditions.
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- 2024
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27. Cadherin-16 (CDH16) immunohistochemistry: a useful diagnostic tool for renal cell carcinoma and papillary carcinomas of the thyroid
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Maximilian Lennartz, Henrietta Csomós, Viktoria Chirico, Sören Weidemann, Natalia Gorbokon, Anne Menz, Franziska Büscheck, Claudia Hube-Magg, Doris Höflmayer, Christian Bernreuther, Niclas C. Blessin, Patrick Lebok, Guido Sauter, Stefan Steurer, Eike Burandt, David Dum, Till Krech, Ronald Simon, Sarah Minner, Frank Jacobsen, Till S. Clauditz, Andreas M. Luebke, Abdul Khalid Siraj, Fouad Al-Dayel, Khawla S. Al-Kuraya, and Andrea Hinsch
- Subjects
Medicine ,Science - Abstract
Abstract Cadherin-16 (CDH16) plays a role in the embryonal development in kidney and thyroid. Downregulation of CDH16 RNA was found in papillary carcinomas of the thyroid. To determine the expression of CDH16 in tumors and to assess the diagnostic utility a tissue microarray containing 15,584 samples from 152 different tumor types as well as 608 samples of 76 different normal tissue types was analyzed. A membranous CDH16 immunostaining was predominantly seen in thyroid, kidney, cauda epididymis, and mesonephric remnants. In the thyroid, CDH16 staining was seen in 100% of normal samples, 86% of follicular adenomas, 60% of follicular carcinomas, but only 7% of papillary carcinomas (p
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- 2023
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28. Turnover of PPP1R15A mRNA encoding GADD34 controls responsiveness and adaptation to cellular stress
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Magg, Vera, Manetto, Alessandro, Kopp, Katja, Wu, Chia Ching, Naghizadeh, Mohsen, Lindner, Doris, Eke, Lucy, Welsch, Julia, Kallenberger, Stefan M., Schott, Johanna, Haucke, Volker, Locker, Nicolas, Stoecklin, Georg, and Ruggieri, Alessia
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- 2024
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29. Cadherin-17 (CDH17) expression in human cancer: A tissue microarray study on 18,131 tumors
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Jacobsen, Frank, Pushpadevan, Ramesh, Viehweger, Florian, Freytag, Morton, Schlichter, Ria, Gorbokon, Natalia, Büscheck, Franziska, Luebke, Andreas M., Putri, Devita, Kluth, Martina, Hube-Magg, Claudia, Hinsch, Andrea, Höflmayer, Doris, Fraune, Christoph, Bernreuther, Christian, Lebok, Patrick, Sauter, Guido, Minner, Sarah, Steurer, Stefan, Simon, Ronald, Burandt, Eike, Dum, David, Lutz, Florian, Marx, Andreas H., Krech, Till, and Clauditz, Till S.
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- 2024
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30. Comparison of INSM1 immunostaining with established neuroendocrine markers synaptophysin and chromogranin A in over 14,000 neuroendocrine and non-neuroendocrine tumors
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Möller, Katharina, Uhlig, Ria, Gorbokon, Natalia, Dum, David, Menz, Anne, Büscheck, Franziska, Luebke, Andreas M., Hube-Magg, Claudia, Hinsch, Andrea, Höflmayer, Doris, Fraune, Christoph, Lebok, Patrick, Weidemann, Sören, Lennartz, Maximilian, Jacobsen, Frank, Clauditz, Till S., Steurer, Stefan, Burandt, Eike, Krech, Rainer, Krech, Till, Marx, Andreas H., Sauter, Guido, Simon, Ronald, Bernreuther, Christian, and Minner, Sarah
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- 2024
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31. Stimulator of Interferon Genes Protein (STING) Expression in Cancer Cells: A Tissue Microarray Study Evaluating More than 18,000 Tumors from 139 Different Tumor Entities
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Anne Menz, Julia Zerneke, Florian Viehweger, Seyma Büyücek, David Dum, Ria Schlichter, Andrea Hinsch, Ahmed Abdulwahab Bawahab, Christoph Fraune, Christian Bernreuther, Martina Kluth, Claudia Hube-Magg, Katharina Möller, Florian Lutz, Viktor Reiswich, Andreas M. Luebke, Patrick Lebok, Sören A. Weidemann, Guido Sauter, Maximilian Lennartz, Frank Jacobsen, Till S. Clauditz, Andreas H. Marx, Ronald Simon, Stefan Steurer, Eike Burandt, Natalia Gorbokon, Sarah Minner, and Till Krech
- Subjects
STING ,immunohistochemistry ,tissue microarray ,human carcinoma ,PD-L1 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Stimulator of interferon genes protein (STING) activates the immune response in inflammatory cells. STING expression in cancer cells is less well characterized, but STING agonists are currently being evaluated as anticancer drugs. A tissue microarray containing 18,001 samples from 139 different tumor types was analyzed for STING by immunohistochemistry. STING-positive tumor cells were found in 130 (93.5%) of 139 tumor entities. The highest STING positivity rates occurred in squamous cell carcinomas (up to 96%); malignant mesothelioma (88.5%–95.7%); adenocarcinoma of the pancreas (94.9%), lung (90.3%), cervix (90.0%), colorectum (75.2%), and gallbladder (68.8%); and serous high-grade ovarian cancer (86.0%). High STING expression was linked to adverse phenotypes in breast cancer, clear cell renal cell carcinoma, colorectal adenocarcinoma, hepatocellular carcinoma, and papillary carcinoma of the thyroid (p < 0.05). In pTa urothelial carcinomas, STING expression was associated with low-grade carcinoma (p = 0.0002). Across all tumors, STING expression paralleled PD-L1 positivity of tumor and inflammatory cells (p < 0.0001 each) but was unrelated to the density of CD8+ lymphocytes. STING expression is variable across tumor types and may be related to aggressive tumor phenotype and PD-L1 positivity. The lack of relationship with tumor-infiltrating CD8+ lymphocytes argues against a significant IFN production by STING positive tumor cells.
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- 2024
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32. Epithelial Cell Adhesion Molecule (EpCAM) Expression in Human Tumors: A Comparison with Pan-Cytokeratin and TROP2 in 14,832 Tumors
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Anne Menz, Nora Lony, Maximilian Lennartz, Sebastian Dwertmann Rico, Ria Schlichter, Simon Kind, Viktor Reiswich, Florian Viehweger, David Dum, Andreas M. Luebke, Martina Kluth, Natalia Gorbokon, Claudia Hube-Magg, Christian Bernreuther, Ronald Simon, Till S. Clauditz, Guido Sauter, Andrea Hinsch, Frank Jacobsen, Andreas H. Marx, Stefan Steurer, Sarah Minner, Eike Burandt, Till Krech, Patrick Lebok, and Sören Weidemann
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EpCAM ,TROP2 ,CKpan ,tissue microarray ,immunohistochemistry ,Medicine (General) ,R5-920 - Abstract
EpCAM is expressed in many epithelial tumors and is used for the distinction of malignant mesotheliomas from adenocarcinomas and as a surrogate pan-epithelial marker. A tissue microarray containing 14,832 samples from 120 different tumor categories was analyzed by immunohistochemistry. EpCAM staining was compared with TROP2 and CKpan. EpCAM staining was detectable in 99 tumor categories. Among 78 epithelial tumor types, the EpCAM positivity rate was ≥90% in 60 categories—including adenocarcinomas, neuroendocrine neoplasms, and germ cell tumors. EpCAM staining was the lowest in hepatocellular carcinomas, adrenocortical tumors, renal cell neoplasms, and in poorly differentiated carcinomas. A comparison of EpCAM and CKpan staining identified a high concordance but EpCAM was higher in testicular seminomas and neuroendocrine neoplasms and CKpan in hepatocellular carcinomas, mesotheliomas, and poorly differentiated non-neuroendocrine tumors. A comparison of EpCAM and TROP2 revealed a higher rate of TROP2 positivity in squamous cell carcinomas and lower rates in many gastrointestinal adenocarcinomas, testicular germ cell tumors, neuroendocrine neoplasms, and renal cell tumors. These data confirm EpCAM as a surrogate epithelial marker for adenocarcinomas and its diagnostic utility for the distinction of malignant mesotheliomas. In comparison to CKpan and TROP2 antibodies, EpCAM staining is particularly common in seminomas and in neuroendocrine neoplasms.
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- 2024
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33. A Closer Look at Reward Decomposition for High-Level Robotic Explanations.
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Wenhao Lu, Xufeng Zhao, Sven Magg, Martin Gromniak, Mengdi Li, and Stefan Wermter
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- 2023
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34. SATB2 Expression in Human Tumors: A Tissue Microarray Study on More Than 15 000 Tumors
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Dum, David, Kromm, Daniela, Lennartz, Maximilian, De Wispelaere, Noemi, Buscheck, Franziska, Luebke, Andreas M., Burandt, Eike, Menz, Anne, Kluth, Martina, Hube-Magg, Claudia, Hinsch, Andrea, Hoflmayer, Doris, Weidemann, Soren, Fraune, Christoph, Moller, Katharina, Lebok, Patrick, Sauter, Guido, Simon, Ronald, Uhlig, Ria, Wilczak, Waldemar, Minner, Sarah, Krech, Rainer, Bernreuther, Christian, Marx, Andreas, Steurer, Stefan, Jacobsen, Frank, Clauditz, Till, and Krech, Till
- Subjects
Binding proteins -- Health aspects ,Gene expression -- Health aspects ,Kidney cancer -- Genetic aspects -- Care and treatment ,Prognosis -- Genetic aspects ,Colorectal cancer -- Genetic aspects -- Care and treatment ,Health - Abstract
Context.--Special AT-rich sequence-binding protein 2 (SATB2) induces local chromatin loops to facilitate transcription. SATB2 immunostaining is commonly used as a marker for colorectal adenocarcinoma and osteosarcoma. Objective.--To extend our knowledge on the diagnostic value of SATB2 analysis in a comprehensive set of human tumors. Design.--Tissue microarrays with 15 012 samples from 120 tumor types and 608 samples of 76 different normal tissues were analyzed. Results.--SATB2 positivity was found in 89 of 120 different tumor types (74%), including 59 of 120 (49%) with at least 1 moderately positive tumor and 38 of 120 tumor types (32%) with at least 1 strongly positive tumor. Expression was frequent in adenomas (44/42-47/44; 94%9-6% positive), adenocarcinomas (1747 of 2023; 86%), and various subtypes of neuroendocrine neoplasms (3/7-12/12; 43%-100%) of the colorectum and appendix, Merkel cell carcinoma (25 of 34, 74%), osteosarcomas (15 of 25; 60%), and papillary renal cell carcinoma (RCC) (121 of 235; 52%). Associations to clinicopathologic tumor features were assessed in colorectal and kidney cancers. In colorectal cancer, weak SATB2 expression was linked to high pT (P < .001), nodal metastasis (P < .001), right-sided tumor location (P < .001), microsatellite instability (P < .001), and BRAF mutations (P = .02). In papillary RCC, low SATB2 expression was associated with high pT (P = .02), distant metastasis (P = .04), and reduced tumor-specific survival (P = .04). In clear cell RCC, low SATB2 expression was linked to high pT (P < .001), high Union for International Cancer Control stage (P < .001), high Thoenes grade (P = .02), and reduced recurrence-free survival (P = .02). Conclusions.--Strong SATB2 expression argues for a colorectal origin within adenocarcinomas and neuroendocrine neoplasms. Weak SATB2 expression reflects progression and poor prognosis in colorectal and kidney cancer. doi: 10.5858/arpa.2021-0317-OA, Special AT-rich sequence-binding protein 2 (SATB2) is an 82.5-kDa protein encoded by the SATB2 gene on 2q33. The protein is very highly conserved during evolution with only 3 of 733 [...]
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- 2023
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35. FABP1 expression in human tumors: a tissue microarray study on 17,071 tumors
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Dum, David, Ocokoljic, Ana, Lennartz, Maximilian, Hube-Magg, Claudia, Reiswich, Viktor, Höflmayer, Doris, Jacobsen, Frank, Bernreuther, Christian, Lebok, Patrick, Sauter, Guido, Luebke, Andreas M., Burandt, Eike, Marx, Andreas H., Simon, Ronald, Clauditz, Till S., Minner, Sarah, Menz, Anne, Büscheck, Franziska, Gorbokon, Natalia, Steurer, Stefan, Blessin, Niclas C., and Krech, Till
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- 2022
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36. Hierarchical goals contextualize local reward decomposition explanations.
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Finn Rietz, Sven Magg, Fredrik Heintz, Todor Stoyanov, Stefan Wermter, and Johannes A. Stork
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- 2023
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37. Frequency of Androgen Receptor Positivity in Tumors: A Study Evaluating More Than 18,000 Tumors
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Florian Viehweger, Jennifer Hoop, Lisa-Marie Tinger, Christian Bernreuther, Franziska Büscheck, Till S. Clauditz, Andrea Hinsch, Frank Jacobsen, Andreas M. Luebke, Stefan Steurer, Claudia Hube-Magg, Martina Kluth, Andreas H. Marx, Till Krech, Patrick Lebok, Christoph Fraune, Eike Burandt, Guido Sauter, Ronald Simon, and Sarah Minner
- Subjects
androgen receptor ,immunohistochemistry ,cancer ,tissue microarray ,prognosis ,Biology (General) ,QH301-705.5 - Abstract
Androgen receptor (AR) is a transcription factor expressed in various normal tissues and is a therapeutic target for prostate and possibly other cancers. A TMA containing 18,234 samples from 141 different tumor types/subtypes and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. AR positivity was found in 116 tumor types including 66 tumor types (46.8%) with ≥1 strongly positive tumor. Moderate/strong AR positivity was detected in testicular sex cord-stromal tumors (93.3–100%) and neoplasms of the prostate (79.3–98.7%), breast (25.0–75.5%), other gynecological tumors (0.9–100%), kidney (5.0–44.1%), and urinary bladder (5.4–24.2%). Low AR staining was associated with advanced tumor stage (pTa versus pT2-4; p < 0.0001) in urothelial carcinoma; advanced pT (p < 0.0001), high tumor grade (p < 0.0001), nodal metastasis (p < 0.0001), and reduced survival (p = 0.0024) in invasive breast carcinoma; high pT (p < 0.0001) and grade (p < 0.0001) in clear cell renal cell carcinoma (RCC); and high pT (p = 0.0055) as well as high grade (p < 0.05) in papillary RCC. AR staining was unrelated to histopathological/clinical features in 157 endometrial carcinomas and in 221 ovarian carcinomas. Our data suggest a limited role of AR immunohistochemistry for tumor distinction and a prognostic role in breast and clear cell RCC and highlight tumor entities that might benefit from AR-targeted therapy.
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- 2024
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38. CD10 Expression Correlates with Earlier Tumour Stages and Left-Sided Tumour Location in Colorectal Cancer but Has No Prognostic Impact in a European Cohort
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Julia-Kristin Grass, Katharina Grupp, Martina Kluth, Claudia Hube-Magg, Ronald Simon, Marius Kemper, Jakob R. Izbicki, Guido Sauter, and Nathaniel Melling
- Subjects
CD10 ,tissue microarray ,immunohistochemistry ,colorectal cancer ,overall survival ,metalloprotease ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The role of CD10 expression in colorectal cancer has been controversially discussed in the literature. Some data suggest a predictive capacity for lymph node and liver metastases, thus influencing overall survival (OS) and disease-free survival (DFS). This study aims to analyse the relationship between CD10 expression and overall survival (OS) in a European cohort. To determine the association of CD10 expression with tumour phenotype, molecular features, and prognosis, a tissue microarray of 1469 colorectal carcinomas was analysed using immunohistochemistry and was compared with matched clinicopathologic data. CD10 expression correlated with earlier tumour stages (p = 0.017) and left-sided colon cancer (p < 0.001). However, no correlation was found between CD10 expression and lymph node involvement (p = 0.711), tumour grading (p = 0.397), or overall survival (p = 0.562). Even in the subgroup analysis of tumour or nodal stage, CD10 did not affect overall survival, although it was significantly associated with p53 and nuclear β-catenin expression (p = 0.013 and p < 0.001, respectively). CD10 expression correlates with earlier tumour stages, colon cancer location, and indicators of aggressive CRC subtypes. However, we can exclude CD10 as a relevant independent prognosticator for CRC.
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- 2024
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39. Enhanced SARS-CoV-2 entry via UPR-dependent AMPK-related kinase NUAK2
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Prasad, Vibhu, Cerikan, Berati, Stahl, Yannick, Kopp, Katja, Magg, Vera, Acosta-Rivero, Nelson, Kim, Heeyoung, Klein, Katja, Funaya, Charlotta, Haselmann, Uta, Cortese, Mirko, Heigwer, Florian, Bageritz, Josephine, Bitto, David, Jargalsaikhan, Saruul, Neufeldt, Christopher, Pahmeier, Felix, Boutros, Michael, Yamauchi, Yohei, Ruggieri, Alessia, and Bartenschlager, Ralf
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- 2023
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40. Procurement and Functional Specification of HVDC Systems
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Magg, Thomas, primary
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- 2023
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41. Visual Analytics to Assess Deep Learning Models for Cross-Modal Brain Tumor Segmentation.
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Caroline Magg and Renata Georgia Raidou
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- 2022
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42. Diagnostic and prognostic role of pancreatic secretory granule membrane major glycoprotein 2 (GP2) immunohistochemistry: A TMA study on 27,681 tumors
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Uhlig, Ria, Günther, Karin, Bröker, Nina, Gorbokon, Natalia, Lennartz, Maximilian, Dwertmann Rico, Sebastian, Reiswich, Viktor, Viehweger, Florian, Büscheck, Franziska, Kluth, Martina, Hube-Magg, Claudia, Hinsch, Andrea, Fraune, Christoph, Bernreuther, Christian, Lebok, Patrick, Sauter, Guido, Izbicki, Jakob R., Steurer, Stefan, Burandt, Eike, Marx, Andreas H., Krech, Till, Simon, Ronald, Minner, Sarah, Clauditz, Till S., and Jacobsen, Frank
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- 2022
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43. Cytokeratin 10 (CK10) expression in cancer: A tissue microarray study on 11,021 tumors
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Uhlig, Ria, Abboud, Moussa, Gorbokon, Natalia, Lennartz, Maximilian, Dwertmann Rico, Sebastian, Kind, Simon, Reiswich, Viktor, Viehweger, Florian, Kluth, Martina, Hube-Magg, Claudia, Bernreuther, Christian, Büscheck, Franziska, Clauditz, Till S., Fraune, Christoph, Hinsch, Andrea, Jacobsen, Frank, Krech, Till, Lebok, Patrick, Steurer, Stefan, Burandt, Eike, Minner, Sarah, Marx, Andreas, Simon, Ronald, Sauter, Guido, and Menz, Anne
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- 2022
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44. Synaptophysin and chromogranin A expression analysis in human tumors
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Uhlig, Ria, Dum, David, Gorbokon, Natalia, Menz, Anne, Büscheck, Franziska, Luebke, Andreas M., Hube-Magg, Claudia, Hinsch, Andrea, Höflmayer, Doris, Fraune, Christoph, Möller, Katharina, Bernreuther, Christian, Lebok, Patrick, Weidemann, Sören, Lennartz, Maximilian, Jacobsen, Frank, Clauditz, Till S., Sauter, Guido, Wilczak, Waldemar, Steurer, Stefan, Burandt, Eike, Krech, Rainer, Krech, Till, Marx, Andreas H., Simon, Ronald, and Minner, Sarah
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- 2022
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45. Genomics Driving Diagnosis and Treatment of Inborn Errors of Immunity With Cancer Predisposition
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Barmettler, Sara, Sharapova, Svetlana O., Milota, Tomas, Greif, Philipp A., Magg, Thomas, and Hauck, Fabian
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- 2022
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46. Cytokeratin 7 and cytokeratin 20 expression in cancer: A tissue microarray study on 15,424 cancers
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Dum, David, Menz, Anne, Völkel, Cosima, De Wispelaere, Noémi, Hinsch, Andrea, Gorbokon, Natalia, Lennartz, Maximilian, Luebke, Andreas M., Hube-Magg, Claudia, Kluth, Martina, Fraune, Christoph, Möller, Katharina, Bernreuther, Christian, Lebok, Patrick, Clauditz, Till S., Jacobsen, Frank, Sauter, Guido, Uhlig, Ria, Wilczak, Waldemar, Steurer, Stefan, Minner, Sarah, Marx, Andreas H., Simon, Ronald, Burandt, Eike, and Krech, Till
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- 2022
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47. Cytokeratin 5 and cytokeratin 6 expressions are unconnected in normal and cancerous tissues and have separate diagnostic implications
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Völkel, Cosima, De Wispelaere, Noémi, Weidemann, Sören, Gorbokon, Natalia, Lennartz, Maximilian, Luebke, Andreas M., Hube-Magg, Claudia, Kluth, Martina, Fraune, Christoph, Möller, Katharina, Bernreuther, Christian, Lebok, Patrick, Clauditz, Till S., Jacobsen, Frank, Sauter, Guido, Uhlig, Ria, Wilczak, Waldemar, Steurer, Stefan, Minner, Sarah, Krech, Rainer H., Dum, David, Krech, Till, Marx, Andreas H., Simon, Ronald, Burandt, Eike, and Menz, Anne
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- 2022
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48. Valosin-containing protein-regulated endoplasmic reticulum stress causes NOD2-dependent inflammatory responses
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Ghalandary, Maryam, Li, Yue, Fröhlich, Thomas, Magg, Thomas, Liu, Yanshan, Rohlfs, Meino, Hollizeck, Sebastian, Conca, Raffaele, Schwerd, Tobias, Uhlig, Holm H., Bufler, Philip, Koletzko, Sibylle, Muise, Aleixo M., Snapper, Scott B., Hauck, Fabian, Klein, Christoph, and Kotlarz, Daniel
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- 2022
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49. Neural Field Conditioning Strategies for 2D Semantic Segmentation.
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Martin Gromniak, Sven Magg, and Stefan Wermter
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- 2023
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50. Valosin-containing protein-regulated endoplasmic reticulum stress causes NOD2-dependent inflammatory responses
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Maryam Ghalandary, Yue Li, Thomas Fröhlich, Thomas Magg, Yanshan Liu, Meino Rohlfs, Sebastian Hollizeck, Raffaele Conca, Tobias Schwerd, Holm H. Uhlig, Philip Bufler, Sibylle Koletzko, Aleixo M. Muise, Scott B. Snapper, Fabian Hauck, Christoph Klein, and Daniel Kotlarz
- Subjects
Medicine ,Science - Abstract
Abstract NOD2 polymorphisms may affect sensing of the bacterial muramyl dipeptide (MDP) and trigger perturbed inflammatory responses. Genetic screening of a patient with immunodeficiency and enteropathy revealed a rare homozygous missense mutation in the first CARD domain of NOD2 (ENST00000300589; c.160G > A, p.E54K). Biochemical assays confirmed impaired NOD2-dependent signaling and proinflammatory cytokine production in patient’s cells and heterologous cellular models with overexpression of the NOD2 mutant. Immunoprecipitation-coupled mass spectrometry unveiled the ATPase valosin-containing protein (VCP) as novel interaction partner of wildtype NOD2, while the binding to the NOD2 variant p.E54K was abrogated. Knockdown of VCP in coloncarcinoma cells led to impaired NF-κB activity and IL8 expression upon MDP stimulation. In contrast, tunicamycin-induced ER stress resulted in increased IL8, CXCL1, and CXCL2 production in cells with knockdown of VCP, while enhanced expression of these proinflammatory molecules was abolished upon knockout of NOD2. Taken together, these data suggest that VCP-mediated inflammatory responses upon ER stress are NOD2-dependent.
- Published
- 2022
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