TY - JOUR A1 - Peters, Simon A1 - Kaiser, Lena A1 - Fink, Julian A1 - Schumacher, Fabian A1 - Perschin, Veronika A1 - Schlegel, Jan A1 - Sauer, Markus A1 - Stigloher, Christian A1 - Kleuser, Burkhard A1 - Seibel, Juergen A1 - Schubert-Unkmeir, Alexandra T1 - Click-correlative light and electron microscopy (click-AT-CLEM) for imaging and tracking azido-functionalized sphingolipids in bacteria JF - Scientific Reports N2 - Sphingolipids, including ceramides, are a diverse group of structurally related lipids composed of a sphingoid base backbone coupled to a fatty acid side chain and modified terminal hydroxyl group. Recently, it has been shown that sphingolipids show antimicrobial activity against a broad range of pathogenic microorganisms. The antimicrobial mechanism, however, remains so far elusive. Here, we introduce 'click-AT-CLEM', a labeling technique for correlated light and electron microscopy (CLEM) based on the super-resolution array tomography (srAT) approach and bio-orthogonal click chemistry for imaging of azido-tagged sphingolipids to directly visualize their interaction with the model Gram-negative bacterium Neisseria meningitidis at subcellular level. We observed ultrastructural damage of bacteria and disruption of the bacterial outer membrane induced by two azido-modified sphingolipids by scanning electron microscopy and transmission electron microscopy. Click-AT-CLEM imaging and mass spectrometry clearly revealed efficient incorporation of azido-tagged sphingolipids into the outer membrane of Gram-negative bacteria as underlying cause of their antimicrobial activity. KW - antimicrobials KW - biological techniques KW - imaging KW - microbiology KW - microbiology techniques KW - microscopy Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259147 VL - 11 IS - 1 ER - TY - JOUR A1 - Scheer, Monika A1 - Vokuhl, Christian A1 - Blank, Bernd A1 - Hallmen, Erika A1 - von Kalle, Thekla A1 - Münter, Marc A1 - Wessalowski, Rüdiger A1 - Hartwig, Maite A1 - Sparber-Sauer, Monika A1 - Schlegel, Paul-Gerhardt A1 - Kramm, Christof M. A1 - Kontny, Udo A1 - Spriewald, Bernd A1 - Kegel, Thomas A1 - Bauer, Sebastian A1 - Kazanowska, Bernarda A1 - Niggli, Felix A1 - Ladenstein, Ruth A1 - Ljungman, Gustaf A1 - Jahnukainen, Kirsi A1 - Fuchs, Jörg A1 - Bielack, Stefan S. A1 - Klingebiel, Thomas A1 - Koscielniak, Ewa T1 - Desmoplastic small round cell tumors: Multimodality treatment and new risk factors JF - Cancer Medicine N2 - Background To evaluate optimal therapy and potential risk factors. Methods Data of DSRCT patients <40 years treated in prospective CWS trials 1997-2015 were analyzed. Results Median age of 60 patients was 14.5 years. Male:female ratio was 4:1. Tumors were abdominal/retroperitoneal in 56/60 (93%). 6/60 (10%) presented with a localized mass, 16/60 (27%) regionally disseminated nodes, and 38/60 (63%) with extraperitoneal metastases. At diagnosis, 23/60 (38%) patients had effusions, 4/60 (7%) a thrombosis, and 37/54 (69%) elevated CRP. 40/60 (67%) patients underwent tumor resection, 21/60 (35%) macroscopically complete. 37/60 (62%) received chemotherapy according to CEVAIE (ifosfamide, vincristine, actinomycin D, carboplatin, epirubicin, etoposide), 15/60 (25%) VAIA (ifosfamide, vincristine, adriamycin, actinomycin D) and, 5/60 (8%) P6 (cyclophosphamide, doxorubicin, vincristine, ifosfamide, etoposide). Nine received high-dose chemotherapy, 6 received regional hyperthermia, and 20 received radiotherapy. Among 25 patients achieving complete remission, 18 (72%) received metronomic therapies. Three-year event-free (EFS) and overall survival (OS) were 11% (±8 confidence interval [CI] 95%) and 30% (±12 CI 95%), respectively, for all patients and 26.7% (±18.0 CI 95%) and 56.9% (±20.4 CI 95%) for 25 patients achieving remission. Extra-abdominal site, localized disease, no effusion or ascites only, absence of thrombosis, normal CRP, complete tumor resection, and chemotherapy with VAIA correlated with EFS in univariate analysis. In multivariate analysis, significant factors were no thrombosis and chemotherapy with VAIA. In patients achieving complete remission, metronomic therapy with cyclophosphamide/vinblastine correlated with prolonged time to relapse. Conclusion Pleural effusions, venous thrombosis, and CRP elevation were identified as potential risk factors. The VAIA scheme showed best outcome. Maintenance therapy should be investigated further. KW - C-reactive protein KW - desmoplastic small round cell tumor KW - maintenance therapy KW - soft tissue sarcoma KW - Trousseau's syndrome Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228444 VL - 8 IS - 2 ER - TY - THES A1 - Sauer, Christian T1 - Development, Simulation and Evaluation of Mobile Wireless Networks in Industrial Applications T1 - Entwicklung, Simulation und Bewertung von Mobilen Kabellosen Netzwerken in Industriellen Anwendungen N2 - Manyindustrialautomationsolutionsusewirelesscommunicationandrelyontheavail- ability and quality of the wireless channel. At the same time the wireless medium is highly congested and guaranteeing the availability of wireless channels is becoming increasingly difficult. In this work we show, that ad-hoc networking solutions can be used to provide new communication channels and improve the performance of mobile automation systems. These ad-hoc networking solutions describe different communi- cation strategies, but avoid relying on network infrastructure by utilizing the Peer-to- Peer (P2P) channel between communicating entities. This work is a step towards the effective implementation of low-range communication technologies(e.g. VisibleLightCommunication(VLC), radarcommunication, mmWave communication) to the industrial application. Implementing infrastructure networks with these technologies is unrealistic, since the low communication range would neces- sitate a high number of Access Points (APs) to yield full coverage. However, ad-hoc networks do not require any network infrastructure. In this work different ad-hoc net- working solutions for the industrial use case are presented and tools and models for their examination are proposed. The main use case investigated in this work are Automated Guided Vehicles (AGVs) for industrial applications. These mobile devices drive throughout the factory trans- porting crates, goods or tools or assisting workers. In most implementations they must exchange data with a Central Control Unit (CCU) and between one another. Predicting if a certain communication technology is suitable for an application is very challenging since the applications and the resulting requirements are very heterogeneous. The proposed models and simulation tools enable the simulation of the complex inter- action of mobile robotic clients and a wireless communication network. The goal is to predict the characteristics of a networked AGV fleet. Theproposedtoolswereusedtoimplement, testandexaminedifferentad-hocnetwork- ing solutions for industrial applications using AGVs. These communication solutions handle time-critical and delay-tolerant communication. Additionally a control method for the AGVs is proposed, which optimizes the communication and in turn increases the transport performance of the AGV fleet. Therefore, this work provides not only tools for the further research of industrial ad-hoc system, but also first implementations of ad-hoc systems which address many of the most pressing issues in industrial applica- tions. N2 - Viele industrielle Automatisierungslösungen verwenden drahtlose Kommunikations- systeme und sind daher auf die Verfügbarkeit und Qualität des drahtlosen Kanals an- gewiesen. Gleichzeitig ist das drahtlose Medium stark belastet und die Gewährleis- tung der Verfügbarkeit der drahtlosen Kanäle wird zunehmends herrausfordernder. In dieser Arbeit wird gezeigt, dass Ad-hoc-Netzwerklösungen genutzt werden können, um neue Kommunikationskanäle bereitzustellen und die Leistung von mobilen Au- tomatisierungssystemen zu verbessern. Diese Ad-hoc-Netzwerklösungen können un- terschiedliche Kommunikationsstrategien bezeichnen. In all diesen Strategien wird der Peer-to-Peer (P2P)-Kanal zwischen zwei kommunizierenden Systemen verwendet statt Netzwerk-Infrastruktur. Diese Arbeit ist ein Schritt hin zur effektiven Implementierung von Kommunikations- technologien mit geringer Reichweite (z.B. Visible Light Communication (VLC), Radar- kommunikation, mmWave-Kommunikation) in der industriellen Anwendung. Die Im- plementierung von Infrastrukturnetzen mit diesen Technologien ist unrealistisch, da die geringe Kommunikationsreichweite eine hohe Anzahl von Access Points (APs) er- fordern würde um eine flächendeckende Bereitstellung von Kommunikationskanälen zu gewährleisten. Ad-hoc-Netzwerke hingegen benötigen keine Netzwerkinfrastruk- tur. In dieser Arbeit werden verschiedene Ad-hoc-Netzwerklösungen für den industri- ellenAnwendungsfallvorgestelltundWerkzeugeundModellefürderenUntersuchung vorgeschlagen. Der Hauptanwendungsfall, der in dieser Arbeit untersucht wird, sind Fahrerlose Trans- portSysteme (FTS) (fortführend als Automated Guided Vehicles (AGVs)) für industri- elle Anwendungen. Diese FTS fahren durch die Produktionsanlage um Kisten, Waren oder Werkzeuge zu transportieren oder um Mitarbeitern zu assistieren. In den meisten Implementierungen müssen sie Daten mit einer Central Control Unit (CCU) und unter- einander austauschen. Die Vorhersage, ob eine bestimmte Kommunikationstechnologie für eine Anwendung geeignet ist, ist sehr anspruchsvoll, da sowohl Anwendungen als auch Anforderungen sehr heterogen sind. Die präsentierten Modelle und Simulationswerkzeuge ermöglichen die Simulation der komplexen Interaktion von mobilen Robotern und drahtlosen Kommunikationsnetz- werken. Das Ziel ist die Vorhersage der Eigenschaften einer vernetzten FTS-Flotte. Mit den vorgestellten Werkzeugen wurden verschiedene Ad-hoc-Netzwerklösungen für industrielle Anwendungen mit FTS implementiert, getestet und untersucht. Die- se Kommunikationssysteme übertragen zeitkritische und verzögerungstolerante Nach- richten. Zusätzlich wird eine Steuerungsmethode für die FTS vorgeschlagen, die die KommunikationoptimiertunddamiteinhergehenddieTransportleistungderFTS-Flotte erhöht. Dieses Werk führt also nicht nur neue Werkzeuge ein um die Entwicklung in- dustrieller Ad-hoc Systeme zu ermöglichen, sondern schlägt auch einige Systeme für die kritischsten Kommunikationsprobleme industrieller Anwendungen vor. KW - Industrie KW - Routing KW - Funknetz KW - Autonomer Roboter KW - Drahtloses vermaschtes Netzwerk KW - Industrie-Roboter KW - Kabellose Netzwerke KW - Simulation Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-299238 ER -