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292 results on '"Sadik, Ahmed'

1. Modeling and Simulation of a Multi Robot System Architecture

Author

Sadik, Ahmed R., Goerick, Christian, and Muehlig, Manuel

Subjects
Computer Science - Artificial Intelligence, Computer Science - Robotics, Computer Science - Software Engineering
Abstract

A Multi Robot System (MRS) is the infrastructure of an intelligent cyberphysical system, where the robots understand the need of the human, and hence cooperate together to fulfill this need. Modeling an MRS is a crucial aspect of designing the proper system architecture, because this model can be used to simulate and measure the performance of the proposed architecture. However, an MRS solution architecture modeling is a very difficult problem, as it contains many dependent behaviors that dynamically change due to the current status of the overall system. In this paper, we introduce a general purpose MRS case study, where the humans initiate requests that are achieved by the available robots. These requests require different plans that use the current capabilities of the available robots. After proposing an architecture that defines the solution components, three steps are followed. First is modeling these components via Business Process Model and Notation (BPMN) language. BPMN provides a graphical notation to precisely represent the behaviors of every component, which is an essential need to model the solution. Second is to simulate these components behaviors and interaction in form of software agents. Java Agent DEvelopment (JADE) middleware has been used to develop and simulate the proposed model. JADE is based on a reactive agent approach, therefore it can dynamically represent the interaction among the solution components. Finally is to analyze the performance of the solution by defining a number of quantitative measurements, which can be obtained while simulating the system model in JADE middleware, therefore the solution can be analyzed and compared to another architecture.

Published
2024

2. LLM as a code generator in Agile Model Driven Development

Author

Sadik, Ahmed R., Brulin, Sebastian, Olhofer, Markus, Ceravola, Antonello, and Joublin, Frank

Subjects
Computer Science - Artificial Intelligence, Computer Science - Emerging Technologies, Computer Science - Robotics, Computer Science - Software Engineering
Abstract

Leveraging Large Language Models (LLM) like GPT4 in the auto generation of code represents a significant advancement, yet it is not without its challenges. The ambiguity inherent in natural language descriptions of software poses substantial obstacles to generating deployable, structured artifacts. This research champions Model Driven Development (MDD) as a viable strategy to overcome these challenges, proposing an Agile Model Driven Development (AMDD) approach that employs GPT4 as a code generator. This approach enhances the flexibility and scalability of the code auto generation process and offers agility that allows seamless adaptation to changes in models or deployment environments. We illustrate this by modeling a multi agent Unmanned Vehicle Fleet (UVF) system using the Unified Modeling Language (UML), significantly reducing model ambiguity by integrating the Object Constraint Language (OCL) for code structure meta modeling, and the FIPA ontology language for communication semantics meta modeling. Applying GPT4 auto generation capabilities yields Java and Python code that is compatible with the JADE and PADE frameworks, respectively. Our thorough evaluation of the auto generated code verifies its alignment with expected behaviors and identifies enhancements in agent interactions. Structurally, we assessed the complexity of code derived from a model constrained solely by OCL meta models, against that influenced by both OCL and FIPA ontology meta models. The results indicate that the ontology constrained meta model produces inherently more complex code, yet its cyclomatic complexity remains within manageable levels, suggesting that additional meta model constraints can be incorporated without exceeding the high risk threshold for complexity.

Published
2024

3. Holon Programming Model -- A Software-Defined Approach for System of Systems

Author

Ashfaq, Muhammad, Sadik, Ahmed R., Mikkonen, Tommi, Waseem, Muhammad, and Makitalo, Niko

Subjects
Computer Science - Artificial Intelligence, Computer Science - Emerging Technologies, Computer Science - Software Engineering
Abstract

As Systems of Systems evolve into increasingly complex networks, harnessing their collective potential becomes paramount. Traditional SoS engineering approaches lack the necessary programmability to develop third party SoS level behaviors. To address this challenge, we propose a software defined approach to enable flexible and adaptive programming of SoS. We introduce the Holon Programming Model, a software-defined framework designed to meet these needs. The Holon Programming Model empowers developers to design and orchestrate complex system behaviors effectively, as illustrated in our disaster management scenario. This research outlines the Holon Programming Model theoretical underpinnings and practical applications, with the aim of driving further exploration and advancement in the field of software defined SoS

Published
2024

4. A self-adaptive system of systems architecture to enable its ad-hoc scalability: Unmanned Vehicle Fleet -- Mission Control Center Case study

Author

Sadik, Ahmed R., Bolder, Bram, and Subasic, Pero

Subjects
Computer Science - Robotics, Computer Science - Artificial Intelligence, Computer Science - Software Engineering, Electrical Engineering and Systems Science - Systems and Control
Abstract

A System of Systems (SoS) comprises Constituent Systems (CSs) that interact to provide unique capabilities beyond any single CS. A key challenge in SoS is ad-hoc scalability, meaning the system size changes during operation by adding or removing CSs. This research focuses on an Unmanned Vehicle Fleet (UVF) as a practical SoS example, addressing uncertainties like mission changes, range extensions, and UV failures. The proposed solution involves a self-adaptive system that dynamically adjusts UVF architecture, allowing the Mission Control Center (MCC) to scale UVF size automatically based on performance criteria or manually by operator decision. A multi-agent environment and rule management engine were implemented to simulate and verify this approach., Comment: 2023 7th International Conference on Intelligent Systems, Metaheuristics & Swarm Intelligence (ISMSI 2023)

Published
2024
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5. Multi-Robot System Architecture design in SysML and BPMN

Author

Sadik, Ahmed R. and Goerick, Christian

Subjects
Computer Science - Artificial Intelligence, Computer Science - Robotics, Computer Science - Software Engineering
Abstract

Multi-Robot System (MRS) is a complex system that contains many different software and hardware components. This main problem addressed in this article is the MRS design complexity. The proposed solution provides a modular modeling and simulation technique that is based on formal system engineering method, therefore the MRS design complexity is decomposed and reduced. Modeling the MRS has been achieved via two formal Architecture Description Languages (ADLs), which are Systems Modeling Language (SysML) and Business Process Model and Notation (BPMN), to design the system blueprints. By using those abstract design ADLs, the implementation of the project becomes technology agnostic. This allows to transfer the design concept from on programming language to another. During the simulation phase, a multi-agent environment is used to simulate the MRS blueprints. The simulation has been implemented in Java Agent Development (JADE) middleware. Therefore, its results can be used to analysis and verify the proposed MRS model in form of performance evaluation matrix.

Published
2024
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6. Enhancing Holonic Architecture with Natural Language Processing for System of Systems

Author

Ashfaq, Muhammad, Sadik, Ahmed R., Mikkonen, Tommi, Waseem, Muhammad, and akitalo, Niko M

Subjects
Electrical Engineering and Systems Science - Systems and Control, Computer Science - Multiagent Systems, Computer Science - Software Engineering
Abstract

The complexity and dynamic nature of System of Systems (SoS) necessitate efficient communication mechanisms to ensure interoperability and collaborative functioning among constituent systems, termed holons. This paper proposes an innovative approach to enhance holon communication within SoS through the integration of Conversational Generative Intelligence (CGI) techniques. Our approach leverages advancements in CGI, specifically Large Language Models (LLMs), to enable holons to understand and act on natural language instructions. This fosters more intuitive human-holon interactions, improving social intelligence and ultimately leading to better coordination among diverse systems. This position paper outlines a conceptual framework for CGI-enhanced holon interaction, discusses the potential impact on SoS adaptability, usability and efficiency, and sets the stage for future exploration and prototype implementation., Comment: Preprint accepted in ICSOFT'24

Published
2024

7. Worker Robot Cooperation and Integration into the Manufacturing Workcell via the Holonic Control Architecture

Author

Sadik, Ahmed R., Urban, Bodo, and Adel, Omar

Subjects
Computer Science - Robotics, Computer Science - Artificial Intelligence, Computer Science - Multiagent Systems, Electrical Engineering and Systems Science - Systems and Control
Abstract

Worker-Robot Cooperation is a new industrial trend, which aims to sum the advantages of both the human and the industrial robot to afford a new intelligent manufacturing techniques. The cooperative manufacturing between the worker and the robot contains other elements such as the product parts and the manufacturing tools. All these production elements must cooperate in one manufacturing workcell to fulfill the production requirements. The manufacturing control system is the mean to connect all these cooperative elements together in one body. This manufacturing control system is distributed and autonomous due to the nature of the cooperative workcell. Accordingly, this article proposes the holonic control architecture as the manufacturing concept of the cooperative workcell. Furthermore, the article focuses on the feasibility of this manufacturing concept, by applying it over a case study that involves the cooperation between a dual-arm robot and a worker. During this case study, the worker uses a variety of hand gestures to cooperate with the robot to achieve the highest production flexibility

Published
2024

8. Ontology in Holonic Cooperative Manufacturing: A Solution to Share and Exchange the Knowledge

Author

Sadik, Ahmed R. and Urban, Bodo

Subjects
Computer Science - Artificial Intelligence
Abstract

Cooperative manufacturing is a new trend in industry, which depends on the existence of a collaborative robot. A collaborative robot is usually a light-weight robot which is capable of operating safely with a human co-worker in a shared work environment. During this cooperation, a vast amount of information is exchanged between the collaborative robot and the worker. This information constructs the cooperative manufacturing knowledge, which describes the production components and environment. In this research, we propose a holonic control solution, which uses the ontology concept to represent the cooperative manufacturing knowledge. The holonic control solution is implemented as an autonomous multi-agent system that exchanges the manufacturing knowledge based on an ontology model. Ultimately, the research illustrates and implements the proposed solution over a cooperative assembly scenario, which involves two workers and one collaborative robot, whom cooperate together to assemble a customized product.

Published
2024

9. Coding by Design: GPT-4 empowers Agile Model Driven Development

Author

Sadik, Ahmed R., Brulin, Sebastian, and Olhofer, Markus

Subjects
Computer Science - Software Engineering, Computer Science - Artificial Intelligence, Computer Science - Formal Languages and Automata Theory, Computer Science - Multiagent Systems, Computer Science - Programming Languages
Abstract

Generating code from a natural language using Large Language Models (LLMs) such as ChatGPT, seems groundbreaking. Yet, with more extensive use, it's evident that this approach has its own limitations. The inherent ambiguity of natural language presents challenges for complex software designs. Accordingly, our research offers an Agile Model-Driven Development (MDD) approach that enhances code auto-generation using OpenAI's GPT-4. Our work emphasizes "Agility" as a significant contribution to the current MDD method, particularly when the model undergoes changes or needs deployment in a different programming language. Thus, we present a case-study showcasing a multi-agent simulation system of an Unmanned Vehicle Fleet. In the first and second layer of our approach, we constructed a textual representation of the case-study using Unified Model Language (UML) diagrams. In the next layer, we introduced two sets of constraints that minimize model ambiguity. Object Constraints Language (OCL) is applied to fine-tune the code constructions details, while FIPA ontology is used to shape communication semantics and protocols. Ultimately, leveraging GPT-4, our last layer auto-generates code in both Java and Python. The Java code is deployed within the JADE framework, while the Python code is deployed in PADE framework. Concluding our research, we engaged in a comprehensive evaluation of the generated code. From a behavioural standpoint, the auto-generated code aligned perfectly with the expected UML sequence diagram. Structurally, we compared the complexity of code derived from UML diagrams constrained solely by OCL to that influenced by both OCL and FIPA-ontology. Results indicate that ontology-constrained model produce inherently more intricate code, but it remains manageable and low-risk for further testing and maintenance.

Published
2023

10. Analysis of ChatGPT on Source Code

Author

Sadik, Ahmed R., Ceravola, Antonello, Joublin, Frank, and Patra, Jibesh

Subjects
Computer Science - Software Engineering, Computer Science - Artificial Intelligence, Computer Science - Programming Languages
Abstract

This paper explores the use of Large Language Models (LLMs) and in particular ChatGPT in programming, source code analysis, and code generation. LLMs and ChatGPT are built using machine learning and artificial intelligence techniques, and they offer several benefits to developers and programmers. While these models can save time and provide highly accurate results, they are not yet advanced enough to replace human programmers entirely. The paper investigates the potential applications of LLMs and ChatGPT in various areas, such as code creation, code documentation, bug detection, refactoring, and more. The paper also suggests that the usage of LLMs and ChatGPT is expected to increase in the future as they offer unparalleled benefits to the programming community., Comment: 40 pages, examples provided for each experiment. arXiv admin note: text overlap with arXiv:2107.03374 by other authors

Published
2023

13. SWAHILI ARCHITECTURE: A HERITAGE OF THE EAST COAST OF AFRICA

Author

Noura Ahmed Sadik, Hassan Siraj, Khalid El Harrouni, and Abderrazak Es-Sdiqui

Subjects
east african coast, kenya, swahili architecture, heritage, culture, Architectural engineering. Structural engineering of buildings, TH845-895
Abstract

Swahili architecture, which developed along the Swahili Coast in East Africa, represents a remarkable amalgamation of African, Arab, and South Asian influences. The region's cultural exchanges gave birth to the distinctive Swahili Culture while thriving trade cities like Mombasa, Mogadishu, and Zanzibar attracted merchants from India, Persia, and China. This cultural convergence also played a pivotal role in the emergence of the Swahili language, which became the widely spoken language across East Africa and the official language of Kenya and Tanzania. However, the impact of Swahili culture extends beyond language; it is also evident in the architectural heritage of the entire Swahili coast. This architectural style holds immense cultural significance and is cherished as a valuable urban asset. Certain sites, including Lamu in Kenya, Kilwa, and Stone Town in Zanzibar, have been granted UNESCO World Heritage status. The enduring allure of Swahili architecture continues to inspire contemporary building designs, celebrating and preserving the rich history and adaptability of Swahili culture to its environment.

Published
2023
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14. Effect of adequacy of empirical antibiotic therapy for hospital-acquired bloodstream infections on intensive care unit patient prognosis: a causal inference approach using data from the Eurobact2 study

Author

Tabah, Alexis, Lipman, Jeffrey, Pollock, Hamish, Ben Margetts, Udy, Andrew, Young, Meredith, Bhadange, Neeraj, Tyler, Steven, Ledtischke, Anne, Finnis, Mackenzie, Dwivedi, Jyotsna, Saxena, Manoj, Biradar, Vishwanath, Soar, Natalie, Sarode, Vineet, Brewster, David, Regli, Adrian, Weeda, Elizabeth, Ahmed, Samiul, Fourie, Cheryl, Laupland, Kevin, Ramanan, Mahesh, Walsham, James, Meyer, Jason, Litton, Edward, Maria Palermo, Anna, Yap, Timothy, Eroglu, Ege, George Attokaran, Antony, Jaramillo, C'havala, Nafees, Khalid Mk, Nafees, Khalid Mahmood Khan, Aqilah Haji Abd Rashid, Nurhikmahtul, Adi Muhamad Ibnu Walid, Haji, Mon, Tomas, Dhakshina Moorthi, P., Sudhirchandra, Shah, Sridharan, Dhadappa Damodar, Haibo, Qiu, Xie, Jianfeng, Jianfeng, Xie, Wei-Hua, Lu, Zhen, Wang, Qian, Chuanyun, Luo, Jili, Chen, Xiaomei, Wang, Hao, Zhao, Peng, Zhao, Juan, Wusi, Qiu, Mingmin, Chen, Xu, Lei, Yin, Chengfen, Wang, Ruilan, Wang, Jinfeng, Yin, Yongjie, Zhang, Min, Ye, Jilu, Hu, Chungfang, Zhou, Suming, Huang, Min, Yan, Jing, Wang, Yan, Qin, Bingyu, Ye, Ling, Weifeng, Xie, Peije, Li, Geng, Nan, Ling, Lowell, Hayashi, Yoshiro, Karumai, Toshiyuki, Yamasaki, Masaki, Hashimoto, Satoru, Hosokawa, Koji, Makino, Jun, Matsuyoshi, Takeo, Kuriyama, Akira, Shigemitsu, Hidenobu, Mishima, Yuka, Nagashima, Michio, Yoshida, Hideki, Fujitani, Shigeki, Omori, Koichiro, Rinka, Hiroshi, Saito, Hiroki, Atobe, Kaori, Kato, Hideaki, Takaki, Shunsuke, Sulaiman, Helmi, Shahnaz Hasan, M., Fadhil Hadi Jamaluddin, Muhamad, Pheng, Lee See, Visvalingam, Sheshendrasurian, Thing Liew, Mun, Ling Danny Wong, Siong, Khang Fong, Kean, Bt Abdul Rahman, Hamizah, Md Noor, Zuraini, Lee, Kok Tong, Hamid Azman, Abd., Zulfakar Mazlan, Mohd, Ali, Saedah, Hernandez, Aaron Mark, Abello, Anton, Jeon, Kyeongman, Lee, Sang-Min, Park, Sunghoon, Park, Seung Yong, Yoon Lim, Sung, Kwa, Andrea Lay Hoon, Yuan Goh, Qing, Ng, Shin Yi, An Lie, Sui, Junyang Goh, Ken, Yunkai Li, Andrew, Ong, Caroline Yu Ming, Yan Lim, Jia, Lishan Quah, Jessica, Ng, Kangqi, Xiang Long Ng, Louis, Yeh, Tony Yu-Chang, Chang Yeh, Yu, Chou, Nai-Kuan, Cia, Cong-Tat, Hu, Ting-Yu, Kuo, Li-Kuo, Ku, Shih-Chi, Wongsurakiat, Phunsup, Apichatbutr, Yutthana, Chiewroongroj, Supattra, Alsisi, Adel, Nadeem, Rashid, El Houfi, Ashraf, Elhadidy, Amr, Barsoum, Mina, Osman, Nermin, Mostafa, Tarek, Elbahnasawy, Mohamed, Saber, Ahmed, Aldhalia, Amer, Elmandouh, Omar, Elsayed, Ahmed, Elbadawy, Merihan A., Awad, Ahmed K., Hemead, Hanan M., Zand, Farid, Ouhadian, Maryam, Hamid Borsi, Seyed, Mehraban, Zahra, Kashipazha, Davood, Ahmadi, Fatemeh, Savaie, Mohsen, Soltani, Farhad, Rashidi, Mahboobeh, Baghbanian, Reza, Javaherforoosh, Fatemeh, Amiri, Fereshteh, Kiani, Arash, Amin Zargar, Mohammad, Mahmoodpoor, Ata, Aalinezhad, Fatemeh, Dabiri, Gholamreza, Sabetian, Golnar, Sarshad, Hakimeh, Masjedi, Mansoor, Tajvidi, Ramin, Nasirodin (S.M.N.) Tabatabaei, Dr Seyed Mohammad, Ahmed, Abdullah Khudhur, Singer, Pierre, Kagan, Ilya, Rigler, Merav, Belman, Daniel, Levin, Phillip, Harara, Belal, Diab, Adei, Abillama, Fayez, Abilama, Fayez, Ibrahim, Rebecca, Fares, Aya, Elhadi, Muhammed, Buimsaedah, Ahmad, Gamra, Marwa, Aqeelah, Ahmed, Ali Mohammed Ali, Almajdoub, Gaber Sadik Homaidan, Ahmed, Almiqlash, Bushray, Bilkhayr, Hala, Bouhuwaish, Ahmad, Sa Taher, Ahmed, Abdulwahed, Eman, Abousnina, Fathi A., Khaled Hdada, Aisha, Jobran, Rania, Ben Hasan, Hayat, Shaban Ben Hasan, Rabab, Khalid Abidi, Serghini, Issam, Seddiki, Rachid, Boukatta, Brahim, Kanjaa, Nabil, Mouhssine, Doumiri, Ahmed Wajdi, Maazouzi, Dendane, Tarek, Ali Zeggwagh, Amine, Housni, Brahim, Younes, Oujidi, Hachimi, Abdelhamid, Ghannam, A., Belkhadir, Z., Abu Jayyab, Mustafa, Aithssain, Ali, Lance, Marcus, Nissar, Shaikh, Sallam, Hend, Elrabi, Omar, Almekhlafi, Ghaleb A., Awad, Maher, Aljabbary, Ahmed, Karam Chaaban, Mohammad, Abu-Sayf, Natalia, Al-Jadaan, Mohammad, Bakr, Lubna, Mounir Bouaziz, Bouaziz, Mounir, Turki, Olfa, Sellami, Walid, Vidal, Gabriela, Centeno, Pablo, Morvillo, Natalia, Oscar Acevedo, José, Mabel Lopez, Patricia, Fernández, Rubén, Segura, Matías, Aparicio, Marta, Alonzo, Irene, Nuccetelli, Yanina, Montefiore, Pablo, Arias, Mario, Felipe Reyes, Luis, Ñamendys-Silva, Silvio A., Romero-Gonzalez, Juan P., Hermosillo, Mariana, Alejandro Castillo, Roberto, Nicolás Pantoja Leal, Jesús, Garcia Aguilar, Candy, Ocotlan Gonzalez Herrera, Mara, Vladimir Espinoza Villafuerte, Missael, Lomeli-Teran, Manuel, Dominguez-Cherit, Jose G., Davalos-Alvarez, Adrian, Sánchez-Hurtado, Luis, Tejeda-Huezo, Brigitte, Perez-Nieto, Orlando R., Deloya Tomas, Ernesto, De Bus, Liesbet, De Waele, Jan, Francois, Guy, Hollevoet, Isabelle, Denys, Wouter, Bourgeois, Marc, Vanderhaeghen, Sofie F.M., Mesland, Jean-Baptiste, Henin, Pierre, Haentjens, Lionel, Biston, Patrick, Noel, Cindérella, Layos, Nathalie, Misset, Benoît, De Schryver, Nicolas, Serck, Nicolas, Wittebole, Xavier, De Waele, Elisabeth, Opdenacker, Godelive, Kovacevic, Pedja, Zlojutro, Biljana, Ina, Filipovic-Grcic, Custovic, Aida, Filipovic-Grcic, Ina, Radonic, Radovan, Vujaklija Brajkovic, Ana, Persec, Jasminka, Sakan, Sanja, Nikolic, Mario, Lasic, Hrvoje, Leone, Marc, Timsit, Jean-François, Ruppe, Etienne, Ruckly, Stephane, Montravers, Philippe, Arbelot, Charlotte, Patrier, Juliette, Zappela, N., Montravers, P., Dulac, Thierry, Castanera, Jérémy, Auchabie, Johann, Le Meur, Anthony, Marchalot, A., Beuzelin, M., Massri, Alexandre, Guesdon, Charlotte, Escudier, Etienne, Mateu, Philippe, Rosman, Jérémy, Leroy, Olivier, Alfandari, Serge, Nica, Alexandru, Souweine, Bertrand, Coupez, Elisabeth, Duburcq, Thibault, Kipnis, Eric, Bortolotti, Perrine, Le Souhaitier, Mathieu, Mira, Jean-Paul, Garcon, Pierre, Duprey, Matthieu, Thyrault, Martial, Paulet, Rémi, Philippart, François, Tran, Marc, Bruel, Cédric, Weiss, Emmanuel, Janny, Sylvie, Foucrier, Arnaud, Perrigault, Pierre-François, Djanikian, Flora, Barbier, François, Gainnier, Marc, Bourenne, Jérémy, Louis, Guillaume, Smonig, Roland, Argaud, Laurent, Baudry, Thomas, Mekonted Dessap, Armand, Razazi, Keyvan, Kalfon, Pierre, Badre, Gaëtan, Larcher, Romaric, Lefrant, Jean-Yves, Roger, Claire, Sarton, Benjamine, Silva, Stein, Demeret, Sophie, Le Guennec, Loïc, Siami, Shidasp, Aparicio, Christelle, Voiriot, Guillaume, Fartoukh, Muriel, Dahyot-Fizelier, Claire, Imzi, Nadia, Klouche, Kada, Bracht, Hendrik, Hoheisen, Sandra, Bloos, Frank, Thomas-Rueddel, Daniel, Petros, Sirak, Pasieka, Bastian, Dubler, Simon, Schmidt, Karsten, Gottschalk, Antje, Wempe, Carola, Lepper, Philippe, Metz, Carlos, Viderman, Dmitriy, Umbetzhanov, Yerlan, Mugazov, Miras, Bazhykayeva, Yelena, Kaligozhin, Zhannur, Babashev, Baurzhan, Merenkov, Yevgeniy, Temirov, Talgat, Arvaniti, Kostoula, Smyrniotis, Dimitrios, Psallida, Vasiliki, Fildisis, Georgios, Soulountsi, Vasiliki, Kaimakamis, Evangelos, Iasonidou, Cristina, Papoti, Sofia, Renta, Foteini, Vasileiou, Maria, Romanou, Vasiliki, Koutsoukou, Vasiliki, Kristina Matei, Mariana, Moldovan, Leora, Karaiskos, Ilias, Paskalis, Harry, Marmanidou, Kyriaki, Papanikolaou, M., Kampolis, C., Oikonomou, Marina, Kogkopoulos, Evangelos, Nikolaou, Charikleia, Sakkalis, Anastasios, Chatzis, Marinos, Georgopoulou, Maria, Efthymiou, Anna, Chantziara, Vasiliki, Sakagianni, Aikaterini, Athanasa (Athanassa), Zoi (Zoe), Papageorgiou, Eirini, Ali, Fadi, Dimopoulos, Georges, Panagiota Almiroudi, Mariota, Malliotakis, Polychronis, Marouli, Diamantina, Theodorou, Vasiliki, Retselas, Ioannis, Kouroulas, Vasilios, Papathanakos, Georgios, Bassetti, Matteo, Giacobbe, Daniele, Montrucchio, Giorgia, Sales, Gabriele, De Pascale, Gennaro, Maria Montini, Luca, Carelli, Simone, Vargas, Joel, Di Gravio, Valentina, Roberto Giacobbe, Daniele, Gratarola, Angelo, Porcile, Elisa, Mirabella, Michele, Daroui, Ivan, Lodi, Giovanni, Zuccaro, Francesco, Grazia Schlevenin, Maria, Pelosi, Paolo, Battaglini, Denise, Cortegiani, Andrea, Ippolito, Mariachiara, Bellina, Davide, Di Guardo, Andrea, Pelagalli, Lorella, Covotta, Marco, Rocco, Monica, Fiorelli, Silvia, Cotoia, Antonella, Chiara Rizzo, Anna, Adam Mikstacki, Mikstacki, Adam, Tamowicz, Barbara, Kaptur Komorowska, Irmina, Szczesniak, Anna, Bojko, Jozef, Kotkowska, Anna, Walczak-Wieteska, Paulina, Wasowska, Dominika, Nowakowski, Tomasz, Broda, Hanna, Mariusz Peichota, Assoc, Pietraszek-Grzywaczewska, Iwona, Martin-Loeches, Ignacio, Bisanti, Alessandra, Paiva, José Artur, Póvoa, Pedro, Cartoze, Nuno, Pereira, Tiago, Guimarães, Nádia, Alves, Madalena, Josefina Pinheiro Marques, Ana, Rios Pinto, Ana, Krystopchuk, Andriy, Teresa, Ana, Manuel Pereira de Figueiredo, António, Botelho, Isabel, Duarte, Tiago, Costa, Vasco, Pedro Cunha, Rui, Molinos, Elena, Tito da Costa, Ledo, Sara, Queiró, Joana, Pascoalinho, Dulce, Nunes, Cristina, Pedro Moura, José, Pereira, Énio, Carvalho Mendes, António, Valeanu, Liana, Bubenek-Turconi, Serban, Marina Grintescu, Ioana, Cobilinschi, Cristian, Carmen Filipescu, Daniela, Elena Predoi, Cornelia, Tomescu, Dana, Popescu, Mihai, Marcu, Alexandra, Grigoras, Ioana, Lungu, Olguta, Gritsan, Alexey, Anderzhanova, Anastasia, Meleshkina, Yulia, Magomedov, Marat, Zubareva, Nadezhda, Tribulev, Maksim, Gaigolnik, Denis, Eremenko, Aleksandr, Vistovskaya, Natala, Chukina, Maria, Belskiy, Vladislav, Furman, Mikhail, Ferrer Rocca, Ricard, Martinez, Maria, Casares, Vanessa, Mellado Artigas, Ricard, Vera, Paula, Flores, Matias, Amador Amerigo, Joaquin, Gracia Arnillas, Maria Pilar, Munoz Bermudez, Rosana, Armestar, Fernando, Catalan, Beatriz, Roig, Regina, Raguer, Laura, Dolores Quesada, María, Diaz Santos, Emilio, Gomà, Gemma, Ubeda, Alejandro, Salgado, Maria, Forcelledo Espina, Lorena, Garcia Prieto, Emilio, Asensio, Mj, Rodriguez, M., Maseda, Dr Emilio, Suarez De La Rica, Alejandro, Ignacio Ayestaran, J., Novo, Mariana, Blasco-Navalpotro, Miguel Angel, Orejas Gallego, Alberto, Sjovall, Fredrik, Sjövall, Fredrik, Spahic, Dzana, Johan Svensson, Carl, Haney, Michael, Edin, Alicia, Åkerlund, Joyce, De Geer, Lina, Prazak, Josef, Buetti, Niccolò, Jakob, Stephan, Pagani, Jl, Abed-Maillard, S., Akova, Murat, Aslan, Abdullah Tarık, Aslan, Abdullah Tarik, Timuroglu, Arif, Kocagoz, Sesin, Kusoglu, Hulya, Mehtap, Selcuk, Ceyhun, Solakoğlu, Altintas, Dr. Neriman Defne, Talan, Leyla, Kayaaslan, Bircan, Kaya Kalem, Ayşe, Kurt, Dr. Ibrahim, Telli, Murat, Ozturk, Barcin, Erol, Çiğdem, Dindar Demiray, Emine Kubra, Çolak, Sait, Akbas, Türkay, Dr. Kursat Gundogan, Sari, Ali, Agalar, Canan, Çolak, Onur, Baykam, Nurcan (N), Akdogan, Ozlem (O), Yilmaz, Mesut, Tunay, Burcu, Cakmak, Rumeysa, Saltoglu, Nese, Karaali, Ridvan, Iftihar Koksal, Firdevs Aksoy, Eroglu, Ahmet, Tolga Saracoglu, Kemal, Bilir, Yeliz, Guzeldag, Seda, Ersoz, Gulden, Evik, Guliz, Sungurtekin, Hulya, Ozgen, Cansu, Erdoğan, Cem, Gürbüz, Yunus, Altin, Nilgün, Bayindir, Yasar, Ersoy, Yasemin, Goksu, Senay, Akyol, Ahmet, Dr, Kartal, Batirel, Ayse, Cagan Aktas, Sabahat, Morris, Andrew Conway, Conway Morris, Andrew, Routledge, Matthew, Ercole, Ari, Antcliffe, David, Rojo, Roceld, Tizard, Kate, Faulkner, Maria, Cowton, Amanda, Kent, Melanie, Raj, Ashok, Zormpa, Artemis, Tinaslanidis, George, Khade, Reena, Torlinski, Tomasz, Mulhi, Randeep, Goyal, Shraddha, Bajaj, Manan, Soltan, Marina, Yonan, Aimee, Dolan, Rachael, Johnson, Aimee, Macfie, Caroline, Lennard, James, Templeton, Maie, Sousa Arias, Sonia, Franke, Uwe, Hugill, Keith, Angell, Hollie, Benjamin J Parcell, Cobb, Katherine, Cole, Stephen, Smith, Tim, Graham, Clive, Cerman, Jaroslav, Keegan, Allison, Ritzema, Jenny, Sanderson, Amanda, Roshdy, Ashraf, Szakmany, Tamas, Baumer, Tom, Longbottom, Rebecca, Hall, Daniel, Tatham, Kate, Loftus, S., Husain, A., Black, E., Jhanji, S., Rao Baikady, R., Mcguigan, Peter, Mckee, Rachel, Kannan, Santhana, Antrolikar, Supriya, Marsden, Nicholas, Della Torre, Valentina, Banach, Dorota, Zaki, Ahmed, Jackson, Matthew, Chikungwa, Moses, Attwood, Ben, Patel, Jamie, Rebecca E Tilley, Humphreys, Sally K., Jean Renaud, Paul, Sokhan, Anton, Burma, Yaroslava, Sligl, Wendy, Baig, Nadia, McCoshen, Lorena, Kutsogiannis, Demetrios J., Thompson, Patricia, Hewer, Tayne, Rabbani, Raihan, Huq, Shihan Mahmud Redwanul, Hasan, Rajib, Motiul Islam, Mohammad, Gurjar, Mohan, Baronia, Arvind, Kothari, Nikhil, Sharma, Ankur, Karmakar, Saurabh, Sharma, Priya, Nimbolkar, Janardan, Samdani, Pratit, Vaidyanathan, R., Ahmedi Rubina, Noor, Jain, Nikhilesh, Pahuja, Madhumati, Singh, Ritu, Shekhar, Saurav, Syed, Nabeel Muzaffar, Ozair, Ahmad, Sarwar Siddiqui, Suhail, Bose, Payel, Datta, Avijatri, Rathod, Darshana, Patel, Mayur, MK, Renuka, Sailaja, K Baby, Dsilva, Carol, Chandran, Jagadish, Ghosh, Pralay, Mukherjee, Sudipta, Sheshala, Kaladhar, Chandra Misra, Krushna, Adekola, Oyebola O., Yusuf Yakubu, Saidu, Mgbosoro Ugwu, Euphemia, Olatosi, John (O), Desalu, Ibironke, Asiyanbi, Gabriel, Oladimeji, Motunrayo, Idowu, Olusola, Adeola, Fowotade, Mer, Mervyn, Mc Cree, Melanie, El Sanousi, Dr. Bashir, Adil Ali Karar, Ali, Saidahmed, Elfayadh, Hamid, Hytham K.S., Loiodice, Ambre, Bailly, Sébastien, Ruckly, Stéphane, and Staiquly, Quentin

Published
2024
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19. Spatial probabilistic mapping of metabolite ensembles in mass spectrometry imaging

Author

Denis Abu Sammour, James L. Cairns, Tobias Boskamp, Christian Marsching, Tobias Kessler, Carina Ramallo Guevara, Verena Panitz, Ahmed Sadik, Jonas Cordes, Stefan Schmidt, Shad A. Mohammed, Miriam F. Rittel, Mirco Friedrich, Michael Platten, Ivo Wolf, Andreas von Deimling, Christiane A. Opitz, Wolfgang Wick, and Carsten Hopf

Subjects
Science
Abstract

Spatial visualization of metabolites in tissues via mass spectrometry imaging can be prone to user perception bias. Here, the authors report the computational framework moleculaR that introduces probabilistic data-dependent molecular mapping of nonrandom spatial patterns of metabolite signals.

Published
2023
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20. Targeting the aryl hydrocarbon receptor (AhR) with BAY 2416964: a selective small molecule inhibitor for cancer immunotherapy

Author

Rienk Offringa, Ralf Lesche, Iris Oezen, Michael Platten, Daniel Baumann, Christiane A Opitz, Ahmed Sadik, Catherine Olesch, Frederik Cichon, Norbert Schmees, Ulrike Roehn, Florian Prinz, Detlef Stoeckigt, Katharina Sahm, Nirmeen Elmadany, Christina Kober, Julian Roewe, Lars Roese, Benjamin Bader, Mátyás Gorjánácz, Helge Gottfried Roider, Gabriele Leder, Horst Irlbacher, Julien Lefranc, Mine Oezcan-Wahlbrink, Ankita Sati Batra, Rafael Carretero, Hilmar Weinmann, Ingo V Hartung, Bertolt Kreft, and Ilona Gutcher

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background The metabolism of tryptophan to kynurenines (KYN) by indoleamine-2,3-dioxygenase or tryptophan-2,3-dioxygenase is a key pathway of constitutive and adaptive tumor immune resistance. The immunosuppressive effects of KYN in the tumor microenvironment are predominantly mediated by the aryl hydrocarbon receptor (AhR), a cytosolic transcription factor that broadly suppresses immune cell function. Inhibition of AhR thus offers an antitumor therapy opportunity via restoration of immune system functions.Methods The expression of AhR was evaluated in tissue microarrays of head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC) and colorectal cancer (CRC). A structure class of inhibitors that block AhR activation by exogenous and endogenous ligands was identified, and further optimized, using a cellular screening cascade. The antagonistic properties of the selected AhR inhibitor candidate BAY 2416964 were determined using transactivation assays. Nuclear translocation, target engagement and the effect of BAY 2416964 on agonist-induced AhR activation were assessed in human and mouse cancer cells. The immunostimulatory properties on gene and cytokine expression were examined in human immune cell subsets. The in vivo efficacy of BAY 2416964 was tested in the syngeneic ovalbumin-expressing B16F10 melanoma model in mice. Coculture of human H1299 NSCLC cells, primary peripheral blood mononuclear cells and fibroblasts mimicking the human stromal-tumor microenvironment was used to assess the effects of AhR inhibition on human immune cells. Furthermore, tumor spheroids cocultured with tumor antigen-specific MART-1 T cells were used to study the antigen-specific cytotoxic T cell responses. The data were analyzed statistically using linear models.Results AhR expression was observed in tumor cells and tumor-infiltrating immune cells in HNSCC, NSCLC and CRC. BAY 2416964 potently and selectively inhibited AhR activation induced by either exogenous or endogenous AhR ligands. In vitro, BAY 2416964 restored immune cell function in human and mouse cells, and furthermore enhanced antigen-specific cytotoxic T cell responses and killing of tumor spheroids. In vivo, oral application with BAY 2416964 was well tolerated, induced a proinflammatory tumor microenvironment, and demonstrated antitumor efficacy in a syngeneic cancer model in mice.Conclusions These findings identify AhR inhibition as a novel therapeutic approach to overcome immune resistance in various types of cancers.

Published
2023
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21. Functional screening identifies aryl hydrocarbon receptor as suppressor of lung cancer metastasis.

Author

Nothdurft, Silke, Thumser-Henner, Clotilde, Breitenbücher, Frank, Okimoto, Ross A, Dorsch, Madeleine, Opitz, Christiane A, Sadik, Ahmed, Esser, Charlotte, Hölzel, Michael, Asthana, Saurabh, Forster, Jan, Beisser, Daniela, Kalmbach, Sophie, Grüner, Barbara M, Bivona, Trever G, Schramm, Alexander, and Schuler, Martin

Subjects
Biochemistry and Cell Biology, Genetics, Oncology and Carcinogenesis
Abstract

Lung cancer mortality largely results from metastasis. Despite curative surgery many patients with early-stage non-small cell lung cancer ultimately succumb to metastatic relapse. Current risk reduction strategies based on cytotoxic chemotherapy and radiation have only modest activity. Against this background, we functionally screened for novel metastasis modulators using a barcoded shRNA library and an orthotopic lung cancer model. We identified aryl hydrocarbon receptor (AHR), a sensor of xenobiotic chemicals and transcription factor, as suppressor of lung cancer metastasis. Knockdown of endogenous AHR induces epithelial-mesenchymal transition signatures, increases invasiveness of lung cancer cells in vitro and metastasis formation in vivo. Low intratumoral AHR expression associates with inferior outcome of patients with resected lung adenocarcinomas. Mechanistically, AHR triggers ATF4 signaling and represses matrix metalloproteinase activity, both counteracting metastatic programs. These findings link the xenobiotic defense system with control of lung cancer progression. AHR-regulated pathways are promising targets for innovative anti-metastatic strategies.

Published
2020

22. Whole pulmonary assessment 1 year after paediatric acute respiratory distress syndrome: prospective multicentre study

Author

Véronique Nève, Ahmed Sadik, Laurent Petyt, Stéphane Dauger, Ahmed Kheniche, André Denjean, Pierre-Louis Léger, François Chalard, Michèle Boulé, Etienne Javouhey, Philippe Reix, Isabelle Canterino, Valérie Deken, Régis Matran, Stéphane Leteurtre, and Francis Leclerc

Subjects
ARDS, Child, Long-term outcomes, Computed tomography, Pulmonary function, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background Long-term pulmonary sequelae, including 1-year thoracic computed tomography (CT) sequelae of paediatric acute respiratory distress syndrome (ARDS) remain unknown. The purpose of the study was to determine pulmonary abnormalities in child survivors of pulmonary (p-ARDS) and extra-pulmonary ARDS (ep-ARDS) 1 year after paediatric intensive care unit discharge (PICUD). Methods Prospective multicentre study in four paediatric academic centres between 2005 and 2014. Patients with ARDS were assessed 1 year after PICUD with respiratory symptom questionnaire, thoracic CT and pulmonary function tests (PFT). Results 39 patients (31 p-ARDS) aged 1.1–16.2 years were assessed. Respiratory symptoms at rest or exercise and/or respiratory maintenance treatment were reported in 23 (74%) of children with p-ARDS but in 1 (13%) of those with ep-ARDS. Thoracic CT abnormalities were observed in 18 (60%) of children with p-ARDS and 4 (50%) of those with ep-ARDS. Diffuse and more important CT abnormalities, such as ground glass opacities or mosaic perfusion patterns, were observed in 5 (13%) of children, all with p-ARDS. PFT abnormalities were observed in 30 (86%) of patients: lung hyperinflation and/or obstructive pattern in 12 (34%) children, restrictive abnormalities in 6 (50%), mild decrease in diffusing capacity in 2 (38%) and 6-min walking distance decrease in 11 (73%). Important PFT abnormalities were observed in 7 (20%) children, all with p-ARDS. Increasing driving pressure (max plateau pressure—max positive end-expiratory pressure) was correlated with increasing CT-scan abnormalities and increasing functional residual capacity (more hyperinflation) (p

Published
2022
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24. Changes in Astigmatism and Visual Acuity after Pterygium Excision in the Ashanti Region of Ghana

Author

Kwadwo Amoah, Seth Yaw Lartey, Abdul-Kabir Mohammed, Abdul-Sadik Ahmed, Ernest Nkansah Kyei, and Kwesi Amissah Nyan Arthur

Subjects
pterygium, astigmatism, visual outcomes, visual acuity, Surgery, RD1-811
Abstract

Background: Pterygium is a conjunctival subepithelial fibrovascular growth commonly occurring in the inter-palpebral conjunctiva nasally or temporally. It tends to grow over the cornea, leading to visual impairment due to various factors, including astigmatism. Methods: This was a prospective, multi-centered, hospital-based, interventional study carried out within 12 months in three eye centers in the Ashanti region of Ghana. One hundred eyes of 100 adults (≥18 years) with primary pterygia were recruited. Operated eyes had measurements of uncorrected visual acuity (UVA), aided visual acuity (AVA), and keratometry readings (K-readings) before pterygium excision with conjunctival autograft (CAG), 2 weeks after surgery, and 6 weeks after surgery. Results: The mean age of patients was 47.1±11.5 years. The mean pre-operative astigmatism was 5.0±5.9 D. The mean astigmatism values at 2 and 6 weeks post-operatively were 1.7±1.5 and 1.3±1.0 D, respectively. Eighty-nine eyes had AVA ≥6/12 (0.11 mean logMAR) before surgery, whereas 97 eyes had AVA ≥6/12 (0.02 mean logMAR) 6 weeks after surgery, and the increase was statistically significant. Conclusion: Pterygia excision with CAG leads to an approximately fourfold reduction in mean pterygium-induced astigmatism by 6 weeks after surgery.

Published
2022
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27. Ontology in Holonic Cooperative Manufacturing: A Solution to Share and Exchange the Knowledge

Author

Sadik, Ahmed R., Urban, Bodo, Barbosa, Simone Diniz Junqueira, Editorial Board Member, Filipe, Joaquim, Editorial Board Member, Ghosh, Ashish, Editorial Board Member, Kotenko, Igor, Editorial Board Member, Washio, Takashi, Editorial Board Member, Yuan, Junsong, Editorial Board Member, Zhou, Lizhu, Editorial Board Member, Fred, Ana, editor, Aveiro, David, editor, Dietz, Jan L. G., editor, Liu, Kecheng, editor, Bernardino, Jorge, editor, and Salgado, Ana, editor

Published
2019
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30. Methylome analyses of three glioblastoma cohorts reveal chemotherapy sensitivity markers within DDR genes

Author

Tobias Kessler, Anne Berberich, Ahmed Sadik, Felix Sahm, Thierry Gorlia, Christoph Meisner, Dirk C. Hoffmann, Antje Wick, Philipp Kickingereder, Petra Rübmann, Martin Bendszus, Christiane Opitz, Michael Weller, Martin van denBent, Roger Stupp, Frank Winkler, Alba Brandes, Andreas vonDeimling, Michael Platten, and Wolfgang Wick

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Gliomas evade current therapies through primary and acquired resistance and the effect of temozolomide is mainly restricted to methylguanin‐O6-methyltransferase promoter (MGMT) promoter hypermethylated tumors. Further resistance markers are largely unknown and would help for better stratification. Methods Clinical data and methylation profiles from the NOA‐08 (104, elderly glioblastoma) and the EORTC 26101 (297, glioblastoma) studies and 398 patients with glioblastoma from the Heidelberg Neuro‐Oncology center have been analyzed focused on the predictive effect of DNA damage response (DDR) gene methylation. Candidate genes were validated in vitro. Results Twenty‐eight glioblastoma 5'‐cytosine‐phosphat‐guanine‐3' (CpGs) from 17 DDR genes negatively correlated with expression and were used together with telomerase reverse transcriptase (TERT) promoter mutations in further analysis. CpG methylation of DDR genes shows highest association with the mesenchymal (MES) and receptor tyrosine kinase (RTK) II glioblastoma subgroup. MES tumors have lower tumor purity compared to RTK I and II subgroup tumors. CpG hypomethylation of DDR genes TP73 and PRPF19 correlated with worse patient survival in particular in MGMT promoter unmethylated tumors. TERT promoter mutation is most frequent in RTK I and II subtypes and associated with worse survival. Primary glioma cells show methylation patterns that resemble RTK I and II glioblastoma and long term established glioma cell lines do not match with glioblastoma subtypes. Silencing of selected resistance genes PRPF19 and TERT increase sensitivity to temozolomide in vitro. Conclusion Hypomethylation of DDR genes and TERT promoter mutations is associated with worse tumor prognosis, dependent on the methylation cluster and MGMT promoter methylation status in IDH wild‐type glioblastoma.

Published
2020
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31. Chicken eggs, childhood stunting and environmental hygiene: an ethnographic study from the Campylobacter genomics and environmental enteric dysfunction (CAGED) project in Ethiopia

Author

Kevin Louis Bardosh, Jeylan Wolyie Hussein, Elias Ahmed Sadik, Jemal Yousuf Hassen, Mengistu Ketema, Abdulmuen Mohammed Ibrahim, Sarah Lindley McKune, and Arie Hendrik Havelaar

Subjects
Poultry, Childhood stunting, Environmental hygiene, Campylobacter, One health, Ethiopia, Environmental sciences, GE1-350, Public aspects of medicine, RA1-1270
Abstract

Abstract Background Childhood stunting and malnutrition condemn millions of people globally to a life of disadvantage and cognitive and physical impairment. Though increasing egg consumption is often seen as an important solution for low and middle income countries (including Ethiopia), emerging evidence suggests that greater exposure to poultry feces may also inhibit child growth due to the effects of enteric bacteria, especially Campylobacter, on gut health. Methods In this rapid ethnographic study, we explored village poultry production, child dietary practices, and environmental hygiene conditions as they relate to Campylobacter risk and intervention in 16 villages in Haramaya Woreda, Eastern Ethiopia. Results In the study area, we found that women assumed primary responsibility to care for both chickens and children: in feeding, housing, and healthcare. Most chickens were free-range local indigenous breeds, and flock sizes were small and unstable due to epidemics, seasonal trends, reproductive patterns, and lack of food. Generally, eggs were seen as “too luxurious” to be eaten, and were predominantly sold at local markets for scarce cash, despite high malnutrition rates. Local narratives of extreme poverty, social dietary norms, parental fatalism, and lack of “dietary consciousness” (as it was called) were invoked to explain this. We found that homesteads were highly contaminated with human and animal feces. Although community members viewed chicken feces and poultry gastrointestinal contents as particularly noxious in comparison to other animals because of their feeding behaviour, they did not relate them to any particular disease. Shared human-animal housing and childcare practices place children at high risk of exposure to enteric bacteria from animal manure, despite daily routines designed to manage the domestic landscape. Conclusions Addressing childhood stunting and malnutrition through egg production in rural landscapes like Haramaya must navigate three distinct health and care regimes: for children, chickens, and home environments. Interventions should be based on a holistic approach to social and economic empowerment, one that considers both women and men and integrates nutrition, health, and community change as its overarching goal.

Published
2020
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32. Heterogeneity of response to immune checkpoint blockade in hypermutated experimental gliomas

Author

Katrin Aslan, Verena Turco, Jens Blobner, Jana K. Sonner, Anna Rita Liuzzi, Nicolás Gonzalo Núñez, Donatella De Feo, Philipp Kickingereder, Manuel Fischer, Ed Green, Ahmed Sadik, Mirco Friedrich, Khwab Sanghvi, Michael Kilian, Frederik Cichon, Lara Wolf, Kristine Jähne, Anna von Landenberg, Lukas Bunse, Felix Sahm, Daniel Schrimpf, Jochen Meyer, Allen Alexander, Gianluca Brugnara, Ralph Röth, Kira Pfleiderer, Beate Niesler, Andreas von Deimling, Christiane Opitz, Michael O. Breckwoldt, Sabine Heiland, Martin Bendszus, Wolfgang Wick, Burkhard Becher, and Michael Platten

Subjects
Science
Abstract

Modeling patient-individual resistance to immunotherapy is challenging. Here, the authors use a syngeneic experimental hypermutated orthotopic glioma model to define radiological and biological features that can predict or explain the mechanistic differences between responders and non-responders to immunotherapy.

Published
2020
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34. Building integration of solar energy systems in Türkiye and world.

Author

Khail (Ahmed Sadık), Ahmad Aboul and Polattaş, Zeynel

Subjects
SOLAR energy, GLOBALIZATION, INDUSTRIAL revolution, RENEWABLE energy sources, FOSSIL fuels
Abstract

Energy is one of the most important issues from the industrial revolution and in the globalizing world. Energy is also a big problem for the Republic of Türkiye, which has made a serious industrial breakthrough in the last 20 years. Because Türkiye, which does not have rich fossil fuels like the Middle Eastern States or Russia, is a foreign-dependent country for its energy needs. It is known that fossil fuels will be depleted in the near future and waste materials generated as a result of energy production pose great threats to the world ecosystem. Therefore, in recent years, developed and developing countries have been developing investment projects for alternative energy sources instead of fossil energy sources. The most efficient and harmless of alternative energy sources is Solar Energy. It should be noted that the use of solar energy, which is so efficient for our world and more attractive than other alternative energy sources in terms of the energy size it produces, requires a certain technical knowledge. Because Türkiye is geographically located in the middle belt and due to its special location, the number of sunny days is much higher than in other countries. In this article, the reality of solar energy in Türkiye and its potential, the solar energy systems used and how they are integrated into buildings, and the advantages and disadvantages of these integrated systems is reviewed. In addition, some examples from some countries of the world will be discussed. Furthermore, projects of integrated solar energy application systems in buildings in Türkiye are reviewed, in addition to some suggestions and recommendations in this field. [ABSTRACT FROM AUTHOR]

Published
2024
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38. Targeting the aryl hydrocarbon receptor (AhR) with BAY 2416964: a selective small molecule inhibitor for cancer immunotherapy

Author

Kober, Christina, primary, Roewe, Julian, additional, Schmees, Norbert, additional, Roese, Lars, additional, Roehn, Ulrike, additional, Bader, Benjamin, additional, Stoeckigt, Detlef, additional, Prinz, Florian, additional, Gorjánácz, Mátyás, additional, Roider, Helge Gottfried, additional, Olesch, Catherine, additional, Leder, Gabriele, additional, Irlbacher, Horst, additional, Lesche, Ralf, additional, Lefranc, Julien, additional, Oezcan-Wahlbrink, Mine, additional, Batra, Ankita Sati, additional, Elmadany, Nirmeen, additional, Carretero, Rafael, additional, Sahm, Katharina, additional, Oezen, Iris, additional, Cichon, Frederik, additional, Baumann, Daniel, additional, Sadik, Ahmed, additional, Opitz, Christiane A, additional, Weinmann, Hilmar, additional, Hartung, Ingo V, additional, Kreft, Bertolt, additional, Offringa, Rienk, additional, Platten, Michael, additional, and Gutcher, Ilona, additional

Published
2023
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39. Identification of astrocyte-driven pseudolineages reveals clinical stratification and therapeutic targets in Glioblastoma

Author

Foerster, Leo Carl, primary, Kaya, Oguzhan, additional, Wust, Valentin, additional, Bekavac, Milica, additional, Ziegler, Kevin Chris, additional, Akcay, Vuslat, additional, Stinchcombe, Nina, additional, Gesteira Perez, Noelia, additional, Ma, Xiujian, additional, Sadik, Ahmed, additional, Le, Phuong Uyen, additional, Petrecca, Kevin, additional, Opitz, Christiane, additional, Liu, Haikun, additional, Wirtz, Christian Rainer, additional, Anders, Simon, additional, Goncalves, Angela, additional, and Martin-Villalba, Ana, additional

Published
2023
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44. Incidence of paediatric pneumococcal meningitis and emergence of new serotypes: a time-series analysis of a 16-year French national survey

Author

Adam, Marie Noelle, Agha-Mir, Ilhem, Akitani, Sylvia, Amara, Marlène, Arlet, Guillaume, Asensio, Valérie, Autret, Fanny, Baleine, Julien, Barnaud, Guilaine, Barrans, Alain, Barsotti, Katia, Basmaci, Romain, Bednarek, Nathalie, Belgaid, Abdelmalek, Benoist, Grégoire, Bertrou, Anne, Biessy, Hélène, Biran, Valérie, Blanc, Véronique, Blondel, Elodie, Bolot, Pascal, Bosi, Claude, Boyer, Sophie, Brouard, Jacques, Cartier-Riviere, Bernadette, Cascarigny, Françoise, Cattoen, Christian, Chace, Anne, Chalumeau, Martin, Chamouilli, Jean Marc, Chaplain, Chantal, Charachon, Sylvie, Charbonneau, Anne, Cheron, Mireille, Chevallier, Bertrand, Chomienne, Francis, Courouble, Gery, Danekova, Nevena, Dao-Dubremetz, Anne, Daoud, Patrick, Dauger, Stéphane, De Champs, Christophe, De Luca, Danièle, De Briel, André, Decobert, Marion, Desbois, Delphine, Despert, Véronique, Dessein, Rodrigue, Dessioux, Emmanuelle, Dieckmann, Katherine, Dommergues, Marie Aliette, Dorangeon, Elodie, Doucet-Populaire, Florence, Dubos, François, Dubourg, Grégory, Dufour, Marie Josée, Duval, Véronique, Eitenschenck, Laurence, Epaud, Ralph, Evreux, Françoise, Eyer, Didier, Eyssette-Gayraud, Stéphanie, Fabbro, Chrystèle, Faye, Albert, Ferroni, Agnes, Fos, Marie Pierre, Gallet, Serge, Garandeau, Caroline, Garrec, Hélène, Gaschignard, Jean, Gaudelus, Joel, Geniez, Laurent, Girard, Florent, Glastre, Catherine, Glatz, Isabelle, Goudeau, Alain, Gougeon Jollivet, Anne, Goumy, Pierre, Gouraud, François, Goux, Alain, Grando, Anna, Grimprel, Emmanuel, Guilluy, Olivier, Guyon, Gael, Guyot, Caroline, Haas, Hervé, Haegy-Doehring, Isabelle, Halna, Muriel, Hamdad, Farida, Haouisee, Severine, Herve, Christian, Heyman Guenais, Rachel, Hochart, Anne Cécile, Honore Bouakline, Stéphanie, Hubert, Nathalie, Jan, Didier, Javouhey, Etienne, Jeannot, Emmanuel, Jehan, Josette, Juvin, Marie Emmanuelle, Kalach, Nicolas, Khalfi, Ali, Labrune, Philippe, Lafendi, Leila, Lahrach, Hakim, Laisney, Norbert, Landragin, Danielle, Lapeyre, Fabrice, Laugel, Vincent, Launay, Elise, Lavigne, Jean Philippe, Le Bideau, Marc, Ledru, Sylvie, Lehours, Philippe, Lejri, Nejib, Lemenand, Olivier, Lorrot, Mathie, Lureau, Pierre, M'Bamba, Célestin, Macchi, Valérie, Madhi, Fouad, Marcou, Valérie, Marin, Mariane, Martha, Sandrine Anne, Martinot, Alain, Mezgueldi, Ellia, Micaelo, Maité, Milcent, Karen, Minette Brunel, Delphine, Moissenet, Didier, Moquet, Olivier, Morisot, Cyril, Moulene, Eric, Nicola, Nawal, Oulepsir, Abdelaziz, Pantalone, Leatitia, Patoz, Pierre, Pellegrino, Beatrice, Penel-Capelle, Delphine, Pierre, Marie Hélène, Pinquier, Didier, Pitsch, Aurélia, Plassart, Claire, Porcheret, Huong, Prere, Marie Françoise, Raymond, Josette, Rey, Agnes, Richardin, Florence, Roussellier, Patricia, Roux, Anne Laure, Roybet, Danielle, Sadik, Ahmed, Sarlangue, Jean, Saumureau, Simone, Savoy, Isabelle, Schneider, Jean Marc, Sebag, Olivier, Sivadon-Tardy, Valérie, Soustelle, Nicolas, Texier, Anthony, Thouvenin, Maxime, Toubiana, Julie, Tronc, Fréderic, Twizeyimana, Eterne, Vachee, Anne, Vernet-Garnier, Véronqiue, Vervel, Christine, Violette, Jérémie, Wallet, Fréderic, Warin, Laure, Yangui, Mohamed Amine, Ythier, Hubert, Zimmermann, Brigitte, Ouldali, Naim, Levy, Corinne, Varon, Emmanuelle, Bonacorsi, Stéphane, Béchet, Stéphane, Cohen, Robert, and Angoulvant, François

Published
2018
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45. Hypoxia Routes Tryptophan Homeostasis Towards Increased Tryptamine Production

Author

Soumya R. Mohapatra, Ahmed Sadik, Suraj Sharma, Gernot Poschet, Hagen M. Gegner, Tobias V. Lanz, Philippe Lucarelli, Ursula Klingmüller, Michael Platten, Ines Heiland, and Christiane A. Opitz

Subjects
liver, hypoxia, tryptophan, TDO2, regulation, AHR activity, Immunologic diseases. Allergy, RC581-607
Abstract

The liver is the central hub for processing and maintaining homeostatic levels of dietary nutrients especially essential amino acids such as tryptophan (Trp). Trp is required not only to sustain protein synthesis but also as a precursor for the production of NAD, neurotransmitters and immunosuppressive metabolites. In light of these roles of Trp and its metabolic products, maintaining homeostatic levels of Trp is essential for health and well-being. The liver regulates global Trp supply by the immunosuppressive enzyme tryptophan-2,3-dioxygenase (TDO2), which degrades Trp down the kynurenine pathway (KP). In the current study, we show that isolated primary hepatocytes when exposed to hypoxic environments, extensively rewire their Trp metabolism by reducing constitutive Tdo2 expression and differentially regulating other Trp pathway enzymes and transporters. Mathematical modelling of Trp metabolism in liver cells under hypoxia predicted decreased flux through the KP while metabolic flux through the tryptamine branch significantly increased. In line, the model also revealed an increased accumulation of tryptamines under hypoxia, at the expense of kynurenines. Metabolic measurements in hypoxic hepatocytes confirmed the predicted reduction in KP metabolites as well as accumulation of tryptamine. Tdo2 expression in cultured primary hepatocytes was reduced upon hypoxia inducible factor (HIF) stabilisation by dimethyloxalylglycine (DMOG), demonstrating that HIFs are involved in the hypoxic downregulation of hepatic Tdo2. DMOG abrogated hepatic luciferase signals in Tdo2 reporter mice, indicating that HIF stability also recapitulates hypoxic rewiring of Trp metabolism in vivo. Also in WT mice HIF stabilization drove homeostatic Trp metabolism away from the KP towards enhanced tryptamine production, leading to enhanced levels of tryptamine in liver, serum and brain. As tryptamines are the most potent hallucinogens known, the observed upregulation of tryptamine in response to hypoxic exposure of hepatocytes may be involved in the generation of hallucinations occurring at high altitude. KP metabolites are known to activate the aryl hydrocarbon receptor (AHR). The AHR-activating properties of tryptamines may explain why immunosuppressive AHR activity is maintained under hypoxia despite downregulation of the KP. In summary our results identify hypoxia as an important factor controlling Trp metabolism in the liver with possible implications for immunosuppressive AHR activation and mental disturbances.

Published
2021
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46. Hypoxia Inducible Factor 1α Inhibits the Expression of Immunosuppressive Tryptophan-2,3-Dioxygenase in Glioblastoma

Author

Soumya R. Mohapatra, Ahmed Sadik, Lars-Oliver Tykocinski, Jørn Dietze, Gernot Poschet, Ines Heiland, and Christiane A. Opitz

Subjects
hypoxia, HIF1α, tryptophan, TDO2, immunosuppression, Immunologic diseases. Allergy, RC581-607
Abstract

Abnormal circulation in solid tumors results in hypoxia, which modulates both tumor intrinsic malignant properties as well as anti-tumor immune responses. Given the importance of hypoxia in glioblastoma (GBM) biology and particularly in shaping anti-tumor immunity, we analyzed which immunomodulatory genes are differentially regulated in response to hypoxia in GBM cells. Gene expression analyses identified the immunosuppressive enzyme tryptophan-2,3-dioxygenase (TDO2) as the second most downregulated gene in GBM cells cultured under hypoxic conditions. TDO2 catalyses the oxidation of tryptophan to N-formyl kynurenine, which is the first and rate-limiting step of Trp degradation along the kynurenine pathway (KP). In multiple GBM cell lines hypoxia reduced TDO2 expression both at mRNA and protein levels. The downregulation of TDO2 through hypoxia was reversible as re-oxygenation rescued TDO2 expression. Computational modeling of tryptophan metabolism predicted reduced flux through the KP and lower intracellular concentrations of kynurenine and its downstream metabolite 3-hydroxyanthranilic acid under hypoxia. Metabolic measurements confirmed the predicted changes, thus demonstrating the ability of the mathematical model to infer intracellular tryptophan metabolite concentrations. Moreover, we identified hypoxia inducible factor 1α (HIF1α) to regulate TDO2 expression under hypoxic conditions, as the HIF1α-stabilizing agents dimethyloxalylglycine (DMOG) and cobalt chloride reduced TDO2 expression. Knockdown of HIF1α restored the expression of TDO2 upon cobalt chloride treatment, confirming that HIF1α controls TDO2 expression. To investigate the immunoregulatory effects of this novel mechanism of TDO2 regulation, we co-cultured isolated T cells with TDO2-expressing GBM cells under normoxic and hypoxic conditions. Under normoxia TDO2-expressing GBM cells suppressed T cell proliferation, while hypoxia restored the proliferation of the T cells, likely due to the reduction in kynurenine levels produced by the GBM cells. Taken together, our data suggest that the regulation of TDO2 expression by HIF1α may be involved in modulating anti-tumor immunity in GBM.

Published
2019
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