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2. Reference Network and Localization Architecture for Smart Manufacturing based on 5G

Author

Ludwig, Stephan, Aschenbrenner, Doris, Scharle, Marvin, Klessig, Henrik, Karrenbauer, Michael, Wu, Huanzhuo, Taghouti, Maroua, Lozano, Pedro, Schotten, Hans D., and Fitzek, Frank H. P.

Subjects
Computer Science - Networking and Internet Architecture
Abstract

5G promises to shift Industry 4.0 to the next level by allowing flexible production. However, many communication standards are used throughout a production site, which will stay so in the foreseeable future. Furthermore, localization of assets will be equally valuable in order to get to a higher level of automation. This paper proposes a reference architecture for a convergent localization and communication network for smart manufacturing that combines 5G with other existing technologies and focuses on high-mix low-volume application, in particular at small and medium-sized enterprises. The architecture is derived from a set of functional requirements, and we describe different views on this architecture to show how the requirements can be fulfilled. It connects private and public mobile networks with local networking technologies to achieve a flexible setup addressing many industrial use cases., Comment: 10 pages; submitted to 6th International Conference on System-Integrated Intelligence. Intelligent, flexible and connected systems in products and production, 7-9 September Genova, Italy

Published
2022

4. Impaired humoral immunity to BQ.1.1 in convalescent and vaccinated patients

Author

Dewald, Felix, Pirkl, Martin, Paluschinski, Martha, Kühn, Joachim, Elsner, Carina, Schulte, Bianca, Knüfer, Jacqueline, Ahmadov, Elvin, Schlotz, Maike, Oral, Göksu, Bernhard, Michael, Michael, Mark, Luxenburger, Maura, Andrée, Marcel, Hennies, Marc Tim, Hafezi, Wali, Müller, Marlin Maybrit, Kümpers, Philipp, Risse, Joachim, Kill, Clemens, Manegold, Randi Katrin, von Frantzki, Ute, Richter, Enrico, Emmert, Dorian, Monzon-Posadas, Werner O., Gräff, Ingo, Kogej, Monika, Büning, Antonia, Baum, Maximilian, Teipel, Finn, Mochtarzadeh, Babak, Wolff, Martin, Gruell, Henning, Di Cristanziano, Veronica, Burst, Volker, Streeck, Hendrik, Dittmer, Ulf, Ludwig, Stephan, Timm, Jörg, and Klein, Florian

Published
2023
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6. Reference Network and Localization Architecture for Smart Manufacturing Based on 5G

Author

Ludwig, Stephan, Aschenbrenner, Doris, Scharle, Marvin, Klessig, Henrik, Karrenbauer, Michael, Wu, Huanzhuo, Taghouti, Maroua, Lozano, Pedro, Schotten, Hans D., Fitzek, Frank H. P., Kacprzyk, Janusz, Series Editor, Gomide, Fernando, Advisory Editor, Kaynak, Okyay, Advisory Editor, Liu, Derong, Advisory Editor, Pedrycz, Witold, Advisory Editor, Polycarpou, Marios M., Advisory Editor, Rudas, Imre J., Advisory Editor, Wang, Jun, Advisory Editor, Valle, Maurizio, editor, Lehmhus, Dirk, editor, Gianoglio, Christian, editor, Ragusa, Edoardo, editor, Seminara, Lucia, editor, Bosse, Stefan, editor, Ibrahim, Ali, editor, and Thoben, Klaus-Dieter, editor

Published
2023
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9. Differential interferon-α subtype induced immune signatures are associated with suppression of SARS-CoV-2 infection

Author

Schuhenn, Jonas, Meister, Toni Luise, Todt, Daniel, Bracht, Thilo, Schork, Karin, Billaud, Jean-Noel, Elsner, Carina, Heinen, Natalie, Karakoese, Zehra, Haid, Sibylle, Kumar, Sriram, Brunotte, Linda, Eisenacher, Martin, Di, Yunyun, Lew, Jocelyne, Falzarano, Darryl, Chen, Jieliang, Yuan, Zhenghong, Pietschmann, Thomas, Wiegmann, Bettina, Uebner, Hendrik, Taube, Christian, Le-Trilling, Vu Thuy Khanh, Trilling, Mirko, Krawczyk, Adalbert, Ludwig, Stephan, Sitek, Barbara, Steinmann, Eike, Dittmer, Ulf, Lavender, Kerry J., Sutter, Kathrin, and Pfaender, Stephanie

Published
2022

14. Inhibition of p38 signaling curtails the SARS-CoV-2 induced inflammatory response but retains the IFN-dependent antiviral defense of the lung epithelial barrier

Author

Faist, Aileen, Schloer, Sebastian, Mecate-Zambrano, Angeles, Janowski, Josua, Schreiber, André, Boergeling, Yvonne, Conrad, Beate C.G., Kumar, Sriram, Toebben, Leonie, Schughart, Klaus, Baumgardt, Morris, Kessler, Mirjana, Hoenzke, Katja, Hocke, Andreas, Trautmann, Marcel, Hartmann, Wolfgang, Kato, Hiroki, Rescher, Ursula, Christersson, Anmari, Kuehn, Joachim, Mellmann, Alexander, Wolff, Thorsten, Kuempers, Philip, Rovas, Alexandros, Wiewrodt, Rainer, Wiebe, Karsten, Barth, Peter, Ludwig, Stephan, and Brunotte, Linda

Published
2023
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15. A 5G Architecture for The Factory of the Future

Author

Ludwig, Stephan, Karrenbauer, Michael, Fellan, Amina, Schotten, Hans D., Buhr, Henning, Seetaraman, Savita, Niebert, Norbert, Bernardy, Anne, Seelmann, Vasco, Stich, Volker, Hoell, Andreas, Stimming, Christian, Wu, Huanzhuo, Wunderlich, Simon, Taghouti, Maroua, Fitzek, Frank, Pallasch, Christoph, Hoffmann, Nicolai, Herfs, Werner, Eberhardt, Elena, and Schildknecht, Thomas

Subjects
Computer Science - Networking and Internet Architecture
Abstract

Factory automation and production are currently undergoing massive changes, and 5G is considered being a key enabler. In this paper, we state uses cases for using 5G in the factory of the future, which are motivated by actual needs of the industry partners of the "5Gang" consortium. Based on these use cases and the ones by 3GPP, a 5G system architecture for the factory of the future is proposed. It is set in relation to existing architectural frameworks., Comment: 8 pages, 7 figures Accepted for publication at 2018 IEEE 23rd International Conference on Emerging Technologies and Factory Automation (ETFA), Torino, Italy

Published
2018

16. Towards a Flexible Architecture for Industrial Networking

Author

Karrenbauer, Michael, Fellan, Amina, Schotten, Hans D., Buhr, Henning, Seetaraman, Savita, Niebert, Norbert, Ludwig, Stephan, Bernardy, Anne, Seelmann, Vasco, Stich, Volker, Hoell, Andreas, Stimming, Christian, Wu, Huanzhuo, Wunderlich, Simon, Taghouti, Maroua, Fitzek, Frank, Pallasch, Christoph, Hoffmann, Nicolai, Herfs, Werner, Eberhardt, Elena, and Schildknecht, Thomas

Subjects
Computer Science - Networking and Internet Architecture
Abstract

The digitalization of manufacturing processes is expected to lead to a growing interconnection of production sites, as well as machines, tools and work pieces. In the course of this development, new use-cases arise which have challenging requirements from a communication technology point of view. In this paper we propose a communication network architecture for Industry 4.0 applications, which combines new 5G and non-cellular wireless network technologies with existing (wired) fieldbus technologies on the shop floor. This architecture includes the possibility to use private and public mobile networks together with local networking technologies to achieve a flexible setup that addresses many different industrial use cases. It is embedded into the Industrial Internet Reference Architecture and the RAMI4.0 reference architecture. The paper shows how the advancements introduced around the new 5G mobile technology can fulfill a wide range of industry requirements and thus enable new Industry 4.0 applications. Since 5G standardization is still ongoing, the proposed architecture is in a first step mainly focusing on new advanced features in the core network, but will be developed further later., Comment: 8 pages, 4 figures, to appear in Proceedings of 23th VDE/ITG Conference on Mobile Communication (23. VDE/ITG Fachtagung Mobilkommunikation), Osnabr\"uck, May 2018

Published
2018

22. Decontamination of disposable respirators for reuse in a pandemic employing in-situ-generated peracetic acid

Author

Boeing, Christian, Sandten, Christian, Hrincius, Eike R., Anhlan, Darisuren, Dworog, Andreas, Hanning, Stephanie, Kuennemann, Thilo, Niehues, Christopher, Schupp, Thomas, Stec, Edyta, Thume, Julius, Triphaus, Daniel, Wilkens, Markus, Uphoff, Holger, Zuendorf, Josef, Jacobshagen, Anja, Kreyenschmidt, Martin, Ludwig, Stephan, Mertins, Hans-Christoph, and Mellmann, Alexander

Published
2022
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24. MCMV-based vaccine vectors expressing full-length viral proteins provide long-term humoral immune protection upon a single-shot vaccination

Author

Kim, Yeonsu, Zheng, Xiaoyan, Eschke, Kathrin, Chaudhry, M. Zeeshan, Bertoglio, Federico, Tomić, Adriana, Krmpotić, Astrid, Hoffmann, Markus, Bar-On, Yotam, Boehme, Julia, Bruder, Dunja, Ebensen, Thomas, Brunotte, Linda, Ludwig, Stephan, Messerle, Martin, Guzman, Carlos, Mandelboim, Ofer, Hust, Michael, Pöhlmann, Stefan, Jonjić, Stipan, and Čičin-Šain, Luka

Published
2022
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28. Camostat mesylate inhibits SARS-CoV-2 activation by TMPRSS2-related proteases and its metabolite GBPA exerts antiviral activity

Author

Hoffmann, Markus, Hofmann-Winkler, Heike, Smith, Joan C., Krüger, Nadine, Arora, Prerna, Sørensen, Lambert K., Søgaard, Ole S., Hasselstrøm, Jørgen Bo, Winkler, Michael, Hempel, Tim, Raich, Lluís, Olsson, Simon, Danov, Olga, Jonigk, Danny, Yamazoe, Takashi, Yamatsuta, Katsura, Mizuno, Hirotaka, Ludwig, Stephan, Noé, Frank, Kjolby, Mads, Braun, Armin, Sheltzer, Jason M., and Pöhlmann, Stefan

Published
2021
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29. Relevance of angiotensin-(1-7) and its receptor Mas in pneumonia caused by influenza virus and post-influenza pneumococcal infection

Author

Melo, Eliza M., Del Sarto, Juliana, Vago, Juliana P., Tavares, Luciana P., Rago, Flávia, Gonçalves, Ana Paula F., Machado, Marina G., Aranda-Pardos, Irene, Valiate, Bruno V.S., Cassali, Geovanni D., Pinho, Vanessa, Sousa, Lirlândia P., A-Gonzalez, Noelia, Campagnole-Santos, Maria José, Bader, Michael, Santos, Robson A.S., Machado, Alexandre V., Ludwig, Stephan, and Teixeira, Mauro M.

Published
2021
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30. Characterisation of the antibody-mediated selective pressure driving intra-host evolution of SARS-CoV-2 in prolonged infection.

Author

Schoefbaenker, Michael, Günther, Theresa, Lorentzen, Eva Ulla, Romberg, Marie-Luise, Hennies, Marc Tim, Neddermeyer, Rieke, Müller, Marlin Maybrit, Mellmann, Alexander, Bojarzyn, Chiara Robin, Lenz, Georg, Stelljes, Matthias, Hrincius, Eike Roman, Vollenberg, Richard, Ludwig, Stephan, Tepasse, Phil-Robin, and Kühn, Joachim Ewald

Subjects
HUMORAL immunity, ANTIBODY formation, IMMUNE response, SARS-CoV-2, SARS-CoV-2 Omicron variant, B cells, IMMUNOGLOBULIN M
Abstract

Neutralising antibodies against the SARS-CoV-2 spike (S) protein are major determinants of protective immunity, though insufficient antibody responses may cause the emergence of escape mutants. We studied the humoral immune response causing intra-host evolution in a B-cell depleted, haemato-oncologic patient experiencing clinically severe, prolonged SARS-CoV-2 infection with a virus of lineage B.1.177.81. Following bamlanivimab treatment at an early stage of infection, the patient developed a bamlanivimab-resistant mutation, S:S494P. After five weeks of apparent genetic stability, the emergence of additional substitutions and deletions within the N-terminal domain (NTD) and the receptor binding domain (RBD) of S was observed. Notably, the composition and frequency of escape mutations changed in a short period with an unprecedented dynamic. The triple mutant S:Delta141-4 E484K S494P became dominant until virus elimination. Routine serology revealed no evidence of an antibody response in the patient. A detailed analysis of the variant-specific immune response by pseudotyped virus neutralisation test, surrogate virus neutralisation test, and immunoglobulin-capture enzyme immunoassay showed that the onset of an IgM-dominated antibody response coincided with the appearance of escape mutations. The formation of neutralising antibodies against S:Delta141-4 E484K S494P correlated with virus elimination. One year later, the patient experienced clinically mild re-infection with Omicron BA.1.18, which was treated with sotrovimab and resulted in an increase in Omicron-reactive antibodies. In conclusion, the onset of an IgM-dominated endogenous immune response in an immunocompromised patient coincided with the appearance of additional mutations in the NTD and RBD of S in a bamlanivimab-resistant virus. Although virus elimination was ultimately achieved, this humoral immune response escaped detection by routine diagnosis and created a situation temporarily favouring the rapid emergence of various antibody escape mutants with known epidemiological relevance. Author summary: In the immunocompromised host, prolonged infection and insufficient antibody responses favour the emergence of highly mutated SARS-CoV-2 variants. To better understand the selective pressure exerted by antiviral antibodies, we characterised the variant-specific humoral immune response and resulting intra-host evolution of SARS-CoV-2 in a B-lymphocyte-depleted patient experiencing severe infection. Treatment with a monoclonal antibody early in infection led to the selection and outgrowth of resistant virus. As their B-cell function recovered, the patient mounted an IgM-dominated antiviral antibody response, the onset of which closely correlated with the appearance of additional escape mutations within the spike protein. The strength and breadth of this antibody response gradually increased, resulting in the selection of a variant carrying several escape mutations within spike. The formation of neutralising antibodies against this variant resulted in virus elimination. Our study provides new insights into the selection process of viral escape mutants in immunocompromised patients. The resuming humoral immunity against SARS-CoV-2 can be dominated by IgM. This immune response is poorly detectable with routine diagnostic procedures yet may trigger and drive substantial viral intra-host evolution. Determination of antiviral antibody responses and correlating them with intra-host evolution may provide a better picture of the adaptability of currently circulating SARS-CoV-2 variants. [ABSTRACT FROM AUTHOR]

Published
2024
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31. The anti-inflammatory and tolerogenic potential of small spleen peptides.

Author

Wixler, Viktor, Zaytsev, Igor Z., Boergeling, Yvonne, and Ludwig, Stephan

Subjects
IMMUNOLOGICAL tolerance, REGULATORY T cells, EXPERIMENTAL arthritis, IMMUNE system, DENDRITIC cells, ADENOSINES
Abstract

Maintaining peripheral immune tolerance and preventing harmful autoimmune reactions is a fundamental task of the immune system. However, these essential functions are significantly compromised during autoimmune disorders, creating a major challenge in treating these conditions. In this context, we provide an overview of research on small spleen polypeptides (SSPs) that naturally regulate peripheral immune tolerance. Alongside outlining the observed effects of SSPs, we summarize here the findings on the cellular and molecular mechanisms that underlie their regulatory impact. Specifically, SSPs have demonstrated remarkable effectiveness in halting the progression of developing or established autoimmune disorders like psoriasis or arthritis in animal models. They primarily target dendritic cells (DCs), swiftly prompting the production of extracellular ATP, which is then degraded and sensed by adenosine receptors. This process triggers the mTOR signaling cascade, similar to powerful immune triggers, but instead of a rapid and intense reaction, it leads to a moderate yet significant activation of the mTOR signaling cascade. This induces a tolerogenic state in dendritic cells, ultimately leading to the generation of Foxp3+ immunosuppressor Treg cells. In addition, SSPs may indirectly attenuate the autoimmune response by reducing extracellular ATP synthesis in non-immune cells, such as endothelial cells, when exposed to elevated levels of proinflammatory cytokines. SSPs thus have the potential to contribute to the restoration of peripheral immune tolerance and may offer valuable therapeutic benefits in treating autoimmune diseases. [ABSTRACT FROM AUTHOR]

Published
2024
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39. Roadmap on chaos-inspired imaging technologies (CI2-Tech)

Author

Rosen, Joseph, de Aguiar, Hilton B., Anand, Vijayakumar, Baek, YoonSeok, Gigan, Sylvain, Horisaki, Ryoichi, Hugonnet, Hervé, Juodkazis, Saulius, Lee, KyeoReh, Liang, Haowen, Liu, Yikun, Ludwig, Stephan, Osten, Wolfgang, Park, YongKeun, Pedrini, Giancarlo, Sarkar, Tushar, Schindler, Johannes, Singh, Alok Kumar, Singh, Rakesh Kumar, Situ, Guohai, Takeda, Mitsuo, Xie, Xiangsheng, Yang, Wanqin, and Zhou, Jianying

Published
2022
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42. SARS-CoV-2 neutralizing human recombinant antibodies selected from pre-pandemic healthy donors binding at RBD-ACE2 interface

Author

Bertoglio, Federico, Meier, Doris, Langreder, Nora, Steinke, Stephan, Rand, Ulfert, Simonelli, Luca, Heine, Philip Alexander, Ballmann, Rico, Schneider, Kai-Thomas, Roth, Kristian Daniel Ralph, Ruschig, Maximilian, Riese, Peggy, Eschke, Kathrin, Kim, Yeonsu, Schäckermann, Dorina, Pedotti, Mattia, Kuhn, Philipp, Zock-Emmenthal, Susanne, Wöhrle, Johannes, Kilb, Normann, Herz, Tobias, Becker, Marlies, Grasshoff, Martina, Wenzel, Esther Veronika, Russo, Giulio, Kröger, Andrea, Brunotte, Linda, Ludwig, Stephan, Fühner, Viola, Krämer, Stefan Daniel, Dübel, Stefan, Varani, Luca, Roth, Günter, Čičin-Šain, Luka, Schubert, Maren, and Hust, Michael

Published
2021
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44. Cannabigerol and Cannabicyclol Block SARS-CoV-2 Cell Fusion.

Author

Classen, Nica, Pitakbut, Thanet, Schöfbänker, Michael, Kühn, Joachim, Hrincius, Eike R., Ludwig, Stephan, Hensel, Andreas, and Kayser, Oliver

Subjects
IN vitro studies, MICROBIAL virulence, ANTIVIRAL agents, PLANT extracts, CELL lines, EXPERIMENTAL design, CELL culture, IMMUNOHISTOCHEMISTRY, CORONAVIRUS spike protein, ONE-way analysis of variance, MOLECULAR structure, CELL survival, CANNABINOIDS, COVID-19, PHARMACODYNAMICS
Abstract

The search for new active substances against SARS-CoV-2 is still a central challenge after the COVID-19 pandemic. Antiviral agents to complement vaccination are an important pillar in the clinical situation. Selected cannabinoids such as cannabigerol, cannabicyclol, cannabichromene, and cannabicitran from Cannabis sativa and synthetic homologues of cannabigerol and cannabicyclol were evaluated for effects on the cell viability of Vero cells (CC50 of cannabigerol and cannabicyclol 40 resp. 38 µM) and reduced virus entry of vesicular stomatitis pseudotyped viruses with surface-expressed SARS-CoV-2 spike protein at 20 µM. In addition to a reduction of pseudotyped virus entry, a titer reduction assay on Vero cells after preincubation of Wuhan SARS-CoV-2 significantly confirmed antiviral activity. Investigations on the molecular targets addressed by cannabigerol and cannabicyclol indicated that both compounds are inhibitors of SARS-CoV-2 spike protein-mediated membrane fusion, as could be shown by a virus-free reporter fusion inhibition assay (EC50 for cannabigerol 5.5 µM and for cannabicyclol 10.8 µM) and by monitoring syncytia formation in Vero reporter cells. Selectivity indices were calculated as 7.4 for cannabigerol and 3.5 for cannabicyclol. Systematic semisynthetic alterations of cannabigerol and cannabicyclol indicated that the side chains of both compounds do not contribute to the observed anti-membrane fusion activity. [ABSTRACT FROM AUTHOR]

Published
2024
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45. Variant-specific humoral immune response to SARS-CoV-2 escape mutants arising in clinically severe, prolonged infection

Author

Günther, Theresa, primary, Schöfbänker, Michael, additional, Lorentzen, Eva Ulla, additional, Romberg, Marie-Luise, additional, Hennies, Marc Tim, additional, Neddermeyer, Rieke, additional, Müller, Marlin Maybrit, additional, Mellmann, Alexander, additional, Lenz, Georg, additional, Stelljes, Matthias, additional, Hrincius, Eike Roman, additional, Vollenberg, Richard, additional, Ludwig, Stephan, additional, Tepasse, Phil-Robin, additional, and Kühn, Joachim Ewald, additional

Published
2024
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46. Surrogate Virus Neutralisation Test Based on Nanoluciferase-Tagged Antigens to Quantify Inhibitory Antibodies against SARS-CoV-2 and Characterise Omicron-Specific Reactivity in a Vaccination Cohort

Author

Schoefbaenker, Michael, primary, Neddermeyer, Rieke, additional, Guenther, Theresa, additional, Mueller, Marlin M., additional, Romberg, Marie-Luise, additional, Classen, Nica, additional, Hennies, Marc T., additional, Hrincius, Eike R., additional, Ludwig, Stephan, additional, Kuehn, Joachim E., additional, and Lorentzen, Eva U., additional

Published
2023
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50. PAR1 contributes to influenza A virus pathogenicity in mice

Author

Khoufache, Khaled, Berri, Fatma, Nacken, Wolfgang, Vogel, Annette B, Delenne, Marie, Camerer, Eric, Coughlin, Shaun R, Carmeliet, Peter, Lina, Bruno, Rimmelzwaan, Guus F, Planz, Oliver, Ludwig, Stephan, and Riteau, Béatrice

Subjects
Pneumonia & Influenza, Biodefense, Prevention, Influenza, Infectious Diseases, Emerging Infectious Diseases, Vaccine Related, 2.1 Biological and endogenous factors, Aetiology, Infection, Animals, Dogs, Humans, Influenza A Virus, H1N1 Subtype, Influenza A Virus, H5N1 Subtype, Influenza, Human, Mice, Mice, Knockout, NIH 3T3 Cells, Oligopeptides, Orthomyxoviridae Infections, Plasminogen, Receptor, PAR-1, Medical and Health Sciences, Immunology
Abstract

Influenza causes substantial morbidity and mortality, and highly pathogenic and drug-resistant strains are likely to emerge in the future. Protease-activated receptor 1 (PAR1) is a thrombin-activated receptor that contributes to inflammatory responses at mucosal surfaces. The role of PAR1 in pathogenesis of virus infections is unknown. Here, we demonstrate that PAR1 contributed to the deleterious inflammatory response after influenza virus infection in mice. Activating PAR1 by administering the agonist TFLLR-NH2 decreased survival and increased lung inflammation after influenza infection. Importantly, both administration of a PAR1 antagonist and PAR1 deficiency protected mice from infection with influenza A viruses (IAVs). Treatment with the PAR1 agonist did not alter survival of mice deficient in plasminogen (PLG), which suggests that PLG permits and/or interacts with a PAR1 function in this model. PAR1 antagonists are in human trials for other indications. Our findings suggest that PAR1 antagonism might be explored as a treatment for influenza, including that caused by highly pathogenic H5N1 and oseltamivir-resistant H1N1 viruses.

Published
2013

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