122 results on '"Friedrichs, J."'
Search Results
2. System Performance of Wing and Propellers in a Periodic Distributed Propulsion Experiment
- Author
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Lindner, T.K., primary, Oldeweme, J., additional, Scholz, P., additional, and Friedrichs, J., additional
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- 2024
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3. Layout and yaw optimisation of an offshore wind farm through analytical modelling
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Sukhman, D, primary, Lück, S, additional, Göing, J, additional, Bartl, J, additional, Hansen, T, additional, Stenfelt, G, additional, and Friedrichs, J, additional
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- 2023
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4. Polyacrylamide Bead Sensors for in vivo Quantification of Cell-Scale Stress in Zebrafish Development
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Träber, N., Uhlmann, K., Girardo, S., Kesavan, G., Wagner, K., Friedrichs, J., Goswami, R., Bai, K., Brand, M., Werner, C., Balzani, D., and Guck, J.
- Published
- 2019
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5. Comparison of sensitivities to geometrical properties of front and aft high pressure compressor stages
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Reitz, G., Kellersmann, A., Schlange, S., and Friedrichs, J.
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- 2018
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6. Systematic Review and Meta-analysis of Surgery for Hilar Cholangiocarcinoma with Arterial Resection
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Rebelo, A., primary, Friedrichs, J., additional, Grilli, M., additional, Wahbeh, N., additional, Partsakhashvili, J., additional, Klose, J., additional, Ukkat, J., additional, Ronellenfitsch, U., additional, and Kleeff, J., additional
- Published
- 2023
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7. Development and Evaluation of Strategies for Parallel Operation of Fuel Cell Stacks
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Nicolay, S., Fritsche, L., Lück, S., Friedrichs, J., and Doering, R.
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fuel cell ,aircraft propulsion ,electric flight ,DGLR ,hydrogen ,control design ,DLRK ,modeling - Abstract
This paper describes the modeling of a fuel cell system, a model-based development of corresponding automation strategies, and an experimental evaluation of the model and automation on a scaled system test rig. The developed system model includes the fuel cell stack and associated peripheral components such as air blowers and valves. The focus of the modeling is laid on transient effects and, in particular, the influences of stack temperature, partial pressures and humidities of the reaction gases on the voltage characteristics of the stacks. The automation strategy developed in the subsequent step includes control of hydrogen pressure, air ratio and coolant temperature using PI controllers. The automation strategy also includes a superordinate state machine for controlling and monitoring the entire system. The automation strategy is evaluated experimentally on two stacks which are electrically interconnected in parallel. The challenge of an unequal current distribution between fuel cell stacks due to different stack performances is also addressed. In order to be able to react to larger load changes and to failure cases, the switching on and off of an entire stack during operation is also investigated and evaluated for the parallel interconnection.
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- 2023
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8. Experimental investigation and design of a shape-variable compressor cascade
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Krone, J. H., Huxdorf, O., Riemenschneider, J., Monner, H. P., Schur, F., Friedrichs, J., and Wiedemann, M.
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- 2017
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9. Bürgernahes flugzeug: testing technology for the high power propeller of a wind tunnel model
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Bauer, M., Wulff, D., and Friedrichs, J.
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- 2016
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10. Interventionen zur Reduktion der Inzidenz postoperativer Infektionen im Operationsgebiet nach kolorektalen Resektionen: Systematische Übersichtsarbeit mit Multikomponenten-Netzwerk-Meta-Analyse (INTRISSI) - Studienprotokoll
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Friedrichs, J, Vey, J, Zimmermann, S, Hardt, J, Kleeff, J, Klose, J, Michalski, C, Kieser, M, Pilz, M, Ronellenfitsch, U, Friedrichs, J, Vey, J, Zimmermann, S, Hardt, J, Kleeff, J, Klose, J, Michalski, C, Kieser, M, Pilz, M, and Ronellenfitsch, U
- Published
- 2022
11. The preliminary design of a scaled Composite UHBR Fan for a wind tunnel test campaign
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Paletta, N., Flüh, J., Lindemann, J., Seume, J., Goessling, J., Friedrichs, J., Eggers, T., Russo, S., Natale, N., Vlachos, D., Mazarakos, D., Baltopoulos, A., Vavouliotis, A., Paletta, N., Flüh, J., Lindemann, J., Seume, J., Goessling, J., Friedrichs, J., Eggers, T., Russo, S., Natale, N., Vlachos, D., Mazarakos, D., Baltopoulos, A., and Vavouliotis, A.
- Abstract
The ambition of the CA3ViAR project is to design an open test case fan that experiences instability mechanisms, which are representative for ultra-high bypass ratio (UHBR) fans of civil aircrafts, and to perform a comprehensive experimental investigation to measure aerodynamic, aeroelastic and aeroacoustic performance in a wide range of operational conditions. Experimental tests will be performed in the Propulsion-Test-Facility (PTF) of the Institute of Jet Propulsion and Turbomachinery (IFAS) of Technische Universität Braunschweig, Germany. The final objective of the project is to provide an open test case for the entire research community, with geometries, numerical and experimental results to establish a new reference for composite UHBR fan design. This will support the development of new methods and tools for the development of safer, lighter and more efficient composite fans for greener UHBR engines. In this work the preliminary design of the low transonic fan (LTF) to be used as test article, whose main requirement is to be operated in a safe and controlled way in conditions of aerodynamic and/or aeroelastic instability during wind tunnel operations, is presented. More in particular, consolidated aerodynamic design, strategy adopted to drive the structural design, flutter analysis taking into account acoustic reflection at the intake, dynamic and stress analyses, as well as aeroacoustic measurement optimization are presented and discussed. The preliminary mechanical design of composite blades and the rotor hub, together with the rotor instrumentation and related studies to embed sensors in the composite blades, are also part of this article, and complemented by manufacturing trials and demonstration tests give the full picture of all the project activities up to the preliminary design review.
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- 2022
12. Aerodynamic Analysis of a scaled UHBR Fan
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Natale, N., primary, Egger, T., additional, Friedrichs, J., additional, and Russo, S., additional
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- 2022
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13. The preliminary design of a scaled Composite UHBR Fan for a wind tunnel test campaign
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Paletta, N., primary, Flüh, J., additional, Lindemann, J., additional, Seume, J., additional, Goessling, J., additional, Friedrichs, J., additional, Eggers, T., additional, Russo, S., additional, Natale, N., additional, Vlachos, D., additional, Mazarakos, D., additional, Baltopoulos, A., additional, and Vavouliotis, A., additional
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- 2022
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14. Investigation and analysis of deterioration in high pressure compressors due to operation
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Marx, J., Städing, J., Reitz, G., and Friedrichs, J.
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- 2014
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15. Experiment Design for a Distributed Propulsion Configuration at High Lift
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Oldeweme, J., Lindner, T., Scholz, P., and Friedrichs, J.
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Distributed Propulsion ,DGLR ,DLRK ,High-lift ,Wind tunnel model - Abstract
The complexity of propeller wing interactions in a distributed propulsion (DP) configuration requires high quality wind tunnel data to fully exploit the benefit of such a configuration. Benefits of DP are most pronounced in high lift, high thrust configurations, which sets the focus for the proposed experiment. The designed wind tunnel model features a two element wing with three co-rotating propulsion units on a separate carrier that can be readily traversed and pitched relative to the wing. This enables a thorough investigation of propeller position from 0 x/D 1 and -0.25 z/D 0.25, excluding nacelle effects. Experiments are conducted up to Re = 2.9 * 10^6 based on wing chord. The 2D wing spans 2.4 m in the closed test section of the Propulsion Test Facility, TU Braunschweig. It features an adjustable fowler flap. To avoid data contamination from side wall effects, the model is split in three sections, each representing a periodic section from an infinite DP wing. While the outboard sections provide the quasi periodic conditions but suffer from side wall effects, the centre section is instrumented. This includes angle resolved thrust and torque measurements of the drive train, internal 6K force measurement on the profile section and pressure sensitive paint on the suction side. Multiple sets of propellers with two different diameters are installed, following different design strategies. A homogeneous induced axial velocity design and a MIL propeller are compared regarding propeller wing interaction. The constant speed propellers are pitched to deliver thrust in the range of 0.07 cT 0.3 at two different advance ratios. The propellers are designed to have a constant Matip for all operation points and a scaled D/c, J and cT . With the proposed instrumentation plan a full set of integral parameters for drive train and wing can be measured, while keeping the configuration highly modular. Time resolved pressure measurement and time-averaged PSP allow an in depth analysis of three dimensional pressure distribution and instationary effects on the wing.
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- 2022
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16. Die Luftversorgung von PEM-Brennstoffzellen in großen Flughöhen
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Wittmann, T., Hertwig, T., Lück, S., Zenyuk, I., and Friedrichs, J.
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Befeuchtung ,Verdichter ,DGLR ,Luftversorgung ,DLRK ,Brennstoffzelle ,Wasserhaushalt ,Kondensation ,Turbine - Abstract
Das Luftmanagementsystem eines Brennstoffzellenflugzeugs versorgt die Brennstoffzelle mit verdichteter, befeuchteter und erwärmter Umgebungsluft. Die Wahl der optimalen Betriebsparameter und der besten Systemarchitektur ist insbesondere in großen Flughöhen eine komplexe Optimierungsaufgabe. Diese Arbeit untersucht auf Grundlage eines analytischen Modells den Entwurfsraum eines solchen Luftmanagementsystems. Als wichtigste Freiheitsgrade konnten die Wahl des Verdichtungsverhältnisses, der Sauerstoffstöchiometrie und der Befeuchtung stromauf der Brennstoffzelle identifiziert werden. Die wesentlichen Limitierungen des Entwurfsraums sind die Wasserbilanzen von Brennstoffzelle und System, sowie die maximal mögliche Befeuchtung. Für zwei Anwendungsfälle wurden optimale Betriebsparameter und Systemarchitekturen bestimmt. Es wurde gezeigt, dass Turbinen von grundlegender Bedeutung für den Wasserhaushalt und die Effizienz des Systems sind. Außerdem ist in den meisten Fällen eine Verdampfungskühlung der verdichteten Luft ausreichend. Ein Wärmetauscher wird nicht benötigt.
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- 2022
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17. P34 - Topic: AS04-MDS Biology and Pathogenesis/AS04i-Microenvironment and stem cell niche: ABERRANT SMAD2/3 SIGNALING IN MDS BONE MARROW STROMA CONTRIBUTES TO ALTERED ECM PROTEIN DEPOSITION AND CAN BE RESCUED BY LUSPATERCEPT
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Wobus, M., Magno, V., Mies, A., Winter, S., Bains, A., Wu, L. Behrens, Cross, M., Friedrichs, J., Werner, C., Bornhäuser, M., and Platzbecker, U.
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- 2021
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18. Topic: AS04-MDS Biology and Pathogenesis/AS04i-Microenvironment and stem cell niche
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Wobus, M., primary, Magno, V., additional, Mies, A., additional, Winter, S., additional, Bains, A., additional, Wu, L. Behrens, additional, Cross, M., additional, Friedrichs, J., additional, Werner, C., additional, Bornhäuser, M., additional, and Platzbecker, U., additional
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- 2021
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19. Die Rolle der Pflegenden in der pharmazeutischen Versorgung in Deutschland
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Klatt, T, Friedrichs, J, Baltes, M, Langer, G, and Meyer, G
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ddc: 610 ,610 Medical sciences ,Medicine - Abstract
Hintergrund/Fragestellung: Pflegende in anderen europäischen Ländern übernehmen deutlich erweiterte Aufgaben in der pharmazeutischen Versorgung, zum Beispiel die Verschreibung vorab festgelegter Medikamente. Im Rahmen der europäischen Studie DeMoPhaC in 14 Ländern[zum vollständigen Text gelangen Sie über die oben angegebene URL], Who cares? – EbM und Transformation im Gesundheitswesen; 22. Jahrestagung des Deutschen Netzwerks Evidenzbasierte Medizin
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- 2021
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20. Consequences of pharmacophagous uptake from plants and conspecifics in a sawfly elucidated using chemical and molecular techniques
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Friedrichs J, Sarah Catherine Paul, Lisa Johanna Tewes, Alice B. Dennis, and Mueller C
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Sawfly ,Metabolic pathway ,biology ,Detoxification ,Turnip sawfly ,Niche ,Metabolic phenotype ,Zoology ,Athalia rosae ,biology.organism_classification ,Ajuga - Abstract
Pharmacophagy involves the sequestration of specialised plant metabolites for non-nutritive purposes and commonly occurs in insects. Here we investigate pharmacophagy in the turnip sawfly, Athalia rosae, where adults not only collect specialised metabolites (clerodanoids) from a plant (Ajuga reptans), but also from the exterior of conspecifics via fighting. Using behavioural assays, chemical analytics, and RNAseq we show that when individuals nibble on conspecifics that have already acquired clerodanoids from A. reptans leaves, this nibbling results in the transfer of compounds between individuals. Furthermore, unlike other pharmacophagous insects, the acquisition of clerodanoids by A. rosae from the leaves of A. reptans does not induce the upregulation of known detoxification or sequestration genes and pathways. In contrast, pharmacophagous nibbling on conspecifics results in the upregulation of metabolic pathways associated with elevated metabolic rates and increased energy consumption. It therefore seems that individuals attack conspecifics to acquire clerodanoids despite the apparent metabolic costs of this form of pharmacophagy compared to clerodanoid uptake from a plant. Changes in the metabolic phenotype of A.rosae individuals consequently has profound consequences for social interactions with possible ramifications for their social niche.Summary statementThe turnip sawfly (Athalia rosae) gains potentially beneficial compounds from the leaf surface of non-food plants (e.g. Ajuga reptans), but can also steal these compounds from conspecifics via aggressive nibbling.
- Published
- 2021
21. Multidisziplinäre Prähabilitation zur Verbesserung postoperativer Outcomes gebrechlicher onkologischer Patienten, welche sich einer neoadjuvanten Therapie unterziehen: randomisiert-kontrollierte Pilotstudie
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Friedrichs, J, Kleeff, J, Michl, P, Klose, J, Vordermark, D, Schmidt, H, Röder, C, Regenspurger, K, Jahn, P, Medenwald, D, Ronellenfitsch, U, Friedrichs, J, Kleeff, J, Michl, P, Klose, J, Vordermark, D, Schmidt, H, Röder, C, Regenspurger, K, Jahn, P, Medenwald, D, and Ronellenfitsch, U
- Published
- 2021
22. Soft and flexible poly(ethylene glycol) nanotubes for local drug delivery† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c8nr00603b
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Newland, B., Taplan, C., Pette, D., Friedrichs, J., Steinhart, M., Wang, W., Voit, B., Seib, F. P., and Werner, C.
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Nanotubes ,Polymers ,Breast Neoplasms ,3T3 Cells ,Neoplasms, Experimental ,Polyethylene Glycols ,Chemistry ,Drug Liberation ,Mice ,Drug Delivery Systems ,Doxorubicin ,Cell Line, Tumor ,Animals ,Humans - Abstract
Soft/flexible PEG-based polymer nanotubes released doxorubicin over a sustained period and reduced tumor growth in a metastatic breast cancer model., Nanotubes are emerging as promising materials for healthcare applications but the selection of clinically relevant starting materials for their synthesis remains largely unexplored. Here we present, for the first time, the synthesis of poly(ethylene glycol) (PEG) based nanotubes via the photopolymerization of poly(ethylene glycol) diacrylate and other diacrylate derivatives within the pores of anodized aluminum oxide templates. Template-assisted synthesis allowed the manufacture of a diverse set of polymeric nanotubes with tunable physical characteristics including diameter (∼200–400 nm) and stiffness (405–902 kPa). PEG nanotubes were subjected to cytotoxicty assessment in cell lines and primary stem cells and showed excellent cytocompatability (IC50 > 120 μg ml–1). Nanotubes were readily drug loaded but released the majority of the drug over 5 days. Direct administration of drug loaded nanotubes to human orthotopic breast tumors substantially reduced tumor growth and metastasis and outperformed i.v. administration at the equivalent dose. Overall, this nanotube templating platform is emerging as a facile route for the manufacture of poly(ethylene glycol) nanotubes.
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- 2018
23. Explaining China's popularity in the Middle East and Africa
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Friedrichs, J
- Abstract
China enjoys considerable popularity in the Middle East and Africa, not only among elites but also at street level. This article draws on international relations theories to explain this general pattern, as well as intra- and interregional variation. Every approach has something to contribute, but international political economy more so than realism. Constructivist theories are particularly useful in explaining China’s popularity in the Middle East and Africa.
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- 2019
24. Layer-by-Layer assembly of heparin and peptide-polyethylene glycol conjugates to form hybrid nanothin films of biomatrices
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Thomas, A. K., Wieduwild, R., Zimmermann, R., Lin, W., Friedrichs, J., Bickle, M., Fahmy, K., Werner, C., Zhang, Y., Thomas, A. K., Wieduwild, R., Zimmermann, R., Lin, W., Friedrichs, J., Bickle, M., Fahmy, K., Werner, C., and Zhang, Y.
- Abstract
We investigated the utility of a heparin/peptide-polyethylene glycol conjugate system to build Layer-by-Layer (LbL) structures, to assemble tailored multilayer-biomatrices for cell culture. The LbL assembly balances the advantages of polyelectrolyte systems and protein-based systems. Human umbilical vein endothelial cells showed distinct responses to: the film thickness and structure; the presence, density and spatial arrangement of a cell adhesion ligand within the nanothin film; and the pretreatment of the film with morphogens. The LbL technique presents a versatile tool for modifying cell culture substrates with defined and diverse biochemical and structural features, for investigating cell-material interactions.
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- 2018
25. Polyacrylamide Bead Sensors for in vivo Quantification of Cell-Scale Stress in Zebrafish Development
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Träber, N., primary, Uhlmann, K., additional, Girardo, S., additional, Kesavan, G., additional, Wagner, K., additional, Friedrichs, J., additional, Goswami, R., additional, Bai, K., additional, Brand, M., additional, Werner, C., additional, Balzani, D., additional, and Guck, J., additional
- Published
- 2018
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26. Over the Edge: Industrial Civilization and the Twin Challenges of Climate Change and Energy Scarcity
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Friedrichs, J
- Published
- 2016
27. Causal mechanisms and process patterns in international relations: Thinking within and without the box
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Friedrichs, J
- Abstract
This article makes the case for process patterns as an alternative to causal mechanisms. Causal mechanisms are explanatory tools to unpack the “black boxes” separating the input and output of models. Unlike causal mechanisms, process patterns do not require such a black box. They refer to recurrent sequences of interaction observed across any number of empirical domains. Scholars can apply them across disciplines when similar processes occur in different domains. The article provides examples from International Relations where scholars have sometimes studied process patterns in all but name.
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- 2016
28. Aerodynamic investigation of S-duct intake for high power turboprop installed on a channel wing
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Atalayer, Ç., primary, Friedrichs, J., additional, and Wulff, D., additional
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- 2017
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29. Experimental investigation and design of a shape-variable compressor cascade
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Krone, J. H., primary, Huxdorf, O., additional, Riemenschneider, J., additional, Monner, H. P., additional, Schur, F., additional, Friedrichs, J., additional, and Wiedemann, M., additional
- Published
- 2016
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30. Brush Seal Frictional Heat Generation: Test Rig Design and Validation Under Steam Environment
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Raben, M., primary, Friedrichs, J., additional, and Flegler, J., additional
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- 2016
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31. Preliminary Investigations for a Pressure Balanced Back Plate at Low Inclined Brush Seals
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Schwarz, H., primary and Friedrichs, J., additional
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- 2015
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32. Brush Seals Used in Steam Environments: Chronological Wear Development and the Impact of Different Seal Designs
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Raben, M., primary, Friedrichs, J., additional, Flegler, J., additional, and Helmis, T., additional
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- 2015
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33. In Extremis: Exploring gender, faith, and identity in the experiences of young South Asian British Muslim women who have joined or considered joining violent or non-violent extremist Islamist organisations
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Washington, K, Jaschok, M, Gentry, C, Bano, M, and Friedrichs, J
- Abstract
This thesis explores the role of gender, faith, and identity in the experiences of second-and third-generation South Asian British Muslim women who have joined or considered joining a violent or non-violent Islamist extremist organisation. It explores how growing up as a South Asian British Muslim woman in the UK has shaped the individual experiences of those who have joined or considered joining the so-called Islamic State of Iraq and Syria (ISIS) or Hizb ut-Tahrir (HT). Embedded in a feminist research framework, I draw on ethnographic fieldwork and interviews conducted between 2017-2018 to centre the voices of the women in the academic research that focuses on their lives. Conceptually I draw on a Bourdieusan framework alongside a rich history of theoretical research on women who participate in conservative religious movements and political violence to examine the ways in which their agency and experiences are embedded in the different social fields and normative frameworks which they navigate between. Focusing on the multiple choices they make, I explore the ways their embodied capacity to critically engage is shaped by the different social contexts and norms they inhabit, experience, resist, subvert, and perform daily. Consequently, I advocate for the introduction of ‘relationality’ to the study of ‘radicalisation’ to understand the mutually constituted relationship that unites agents and structures to tackle the overwhelming nomothetic nature of ‘radicalisation’ research. The accounts of the women who participated in this research raise some very worrying questions about the way Muslim minorities are treated in the UK. With this in mind, the title of this thesis: “In Extremis” is intended as a subversive reference to what the word “extreme” conjures in social consciousness. By definition, it refers to being in an extremely difficult situation and is crafted to draw attention to the difficult situations and challenges faced by all women in this thesis.
- Published
- 2022
34. State building and state-society relations in Libya (1911-1969): An examination of associations, trade unions and religious actors
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El Taraboulsi, SN, Armbrust, W, and Friedrichs, J
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Social history ,Social sciences and history - Abstract
This thesis is an examination of state-society relations in Libya during the period preceding the rise of Gaddafi in 1969. It addresses the roots of Libya’s recurring state failure by examining the role played by Libyan social actors in state building during the period between 1911 and 1969. Three key periods in Libya’s history are addressed: the colonial period under the Italians (1911–1943), then the years under the British Military Administration (1943–1951) and then the period as an independent monarchy (1951– 1969). Three social actors are explored: associations or jamʿiyyat, trade unions, and religious groups. Based on Migdal (2004) and Saouli (2012), I approach state formation as a process, not as a finished outcome, and the state as a social field wherein social actors engage with one another as well as with state structures rather than a fixed entity. This approach allows a deeper understanding of the temporal dimensions of Libya’s experience with state building as well as the different processes at play through which states are formed and (un)formed. The thesis makes three key arguments. First, contrary to the majority of Western scholarship on Libya which ascribes Libya’s “statelessness” to a failure to adopt modern state formation following independence, I argue that this linear view oversimplifies a much more complex local power dynamic among social actors, and between social actors and the state (colonial and postcolonial) that manifested itself in modes of cooperation and contestation that shaped Libya’s experience with state building. This view of “statelessness” also suggests that divisions in Libya’s social fabric are endemic which is not the case. Through a social history of the period in question, the thesis shows that while contestation among social actors before and after independence had been stronger than centralizing forces, this should be explained in context and in history. Second, I argue that 8 within non-Western societies where a normative notion of the modern nation-state was imposed but was adopted by local actors and adapted to social, cultural and historical realities that are local, it is within the civic space that society was empowered to shape the state in both constructive and (de)constructive ways, and that there is a pattern to how this shaping happens that is embedded within the history of those societies. Third, the thesis demonstrates that Libya’s civic space has played a twofold role in state formation. On the one hand, it has actively contributed to the strengthening of resistance forces against colonialism, the development of state institutions and the domestication of state power as experienced in the Kingdom of Libya (1951 – 1969). On the other hand, because of societal differences, many of which resulted from aggressive colonialism, a short history of institutionalization and the entrenchment of fragmentation and regional differences, Libya’s civic space manifested processes of localism or bonding and coalescing that occurred within groups which compromised the development of a Libyan state as in the case of the Tripolitanian Republic (1918 – 1922). The thesis demonstrates that state building can be compromised by contested state-society relations and that a state in the making would need to incorporate various forms of its civic space within its bureaucracies and overall model of government to ensure its local legitimacy and geopolitical unity. Using a sociohistorical approach which includes primary data from archives in London, Rome and Tunis, as well as 80 semi-structured interviews, this research makes a contribution to a social history of twentieth-century Libya by exploring its civic space and its engagement with governing structures, colonial and independent.
- Published
- 2020
35. Parallel states, public services, and the competition for legitimacy in Kosovo
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Madison, I, Gledhill, J, and Friedrichs, J
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Politics and government ,Southeast Europe - Abstract
Recent work has illustrated how ‘non-state actors’ can be active and effective governance providers, often at the expense of a state. This has expanded our understanding of the supply side of non-state governance. However, there remains little work on the demand side. How do the people navigate between these different providers? Why do they choose the services of one over another? I argue that the answer rests on two factors: the level of group solidarity individuals are subject to and the unique characteristics of the services they are receiving. Groups are an important part of our social lives, but the extent to which we depend on them varies. I argue that external threats increase group solidarity, which then constrains how individual members decide between providers. Second, public services have different characteristics that influence how people relate to them. Education is collectively delivered and tied to a national identity; decisions depend on social norms. Healthcare is individual and immediate; decisions are rooted in trust. Justice varies between discreet civil cases where people can ‘shop’ between authorities to gain the ‘best’ outcome, and criminal cases, which can comprise highly visible, collective events with significant social pressure. Understanding how the factors of group solidarity and service characteristics intersect is key to understanding the demand-side of non-state governance. Drawing on extensive fieldwork, this thesis examines these factors across two periods of competitive governance pluralism in Kosovo. During the first period, from 1989 to 1999, an Albanian ‘parallel state’ formed in opposition to Serbia and provided education, healthcare, and access to justice in ‘parallel’ to the services of Serbia. Following the 1999 war and the beginning of the UN administration, parallel authorities were then established in Kosovo’s remaining Serb-majority enclaves. Again, education, justice, and healthcare were provided in parallel to the formal Kosovar state.
- Published
- 2020
36. Microgels With Electrostatically Controlled Molecular Affinity to Direct Morphogenesis.
- Author
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Kühn S, Magno V, Zimmermann R, Limasale YDP, Atallah P, Stoppa A, Männel MJ, Thiele J, Friedrichs J, Freudenberg U, and Werner C
- Abstract
Concentration gradients of soluble signaling molecules-morphogens-determine the cellular organization in tissue development. Morphogen-releasing microgels have shown potential to recapitulate this principle in engineered tissue constructs, however, with limited control over the molecular cues in space and time. Inspired by the functionality of sulfated glycosaminoglycans (sGAGs) in morphogen signaling in vivo, a library of sGAG-based microgels is developed and designated as µGel Units to Instruct Development (µGUIDEs). Adjustment of the microgel's sGAG sulfation patterns and concentration enabled the programming of electrostatic affinities that control the release of morphogens. Based on computational analyses of molecular transport processes, µGUIDEs provided unprecedented precision in the spatiotemporal modulation of vascular endothelial growth factor (VEGF) gradients in a microgel-in-gel vasculogenesis model and kidney organoid cultures. The versatile approach offers new options for creating morphogen signaling centers to advance the understanding of tissue and organ development., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)
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- 2024
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37. Drowning in emails: investigating email classes and work stressors as antecedents of high email load and implications for well-being.
- Author
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Kern M, Ohly S, Ďuranová L, and Friedrichs J
- Abstract
Introduction: High email load has been associated with impaired well-being because emails impose specific demands, disturb the workflow, and thereby overtax individuals' action regulation toward prioritized goals. However, the causes and well-being-related consequences of email load are not yet well understood, as previous studies have neglected the interaction type and function of emails as well as co-occurring stressors as antecedents of high email load and have relied predominantly on cross-sectional designs., Methods: In two studies, we aimed to clarify the nature of email load through the lens of action regulation theory. The first study, a two-wave investigation with a fortnightly interval, examined the lagged relationships among email load, work stressors, strain, and affective well-being. The sample included 444 individuals across various occupations and organizations, with 196 of them working from home or remotely at least part of the time. In the second cross-sectional study, we surveyed 257 individuals using a convenience sampling approach, 108 of whom worked from home or remotely at least partially. This study focused on evaluating how different email classes-distinguished by email interaction type (received vs. processed) and email function (communication vs. task)-serve as predictors of high email load., Results: In Study 1, we found a positive lagged effect of high email load on strain, even when controlling for the co-occurring stressors time pressure and work interruptions. In addition, lagged effects of email load on time pressure and interruptions were identified, while no evidence was found for the reverse direction. The results of Study 2 suggest that only the number of communication-related emails received, but not the number of task-related emails received, or the number of all emails processed contribute to high email load., Conclusion: Findings suggest that email load can be considered a unique stressor and that different classes of email need to be distinguished to understand its nature. Clarifying the sources of email load can help develop effective strategies to address it., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kern, Ohly, Ďuranová and Friedrichs.)
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- 2024
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38. Preoperative Chemoradiotherapy vs Chemotherapy for Adenocarcinoma of the Esophagogastric Junction: A Network Meta-Analysis.
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Ronellenfitsch U, Friedrichs J, Barbier E, Bass GA, Burmeister B, Cunningham D, Eyck BM, Grilli M, Hofheinz RD, Kieser M, Kleeff J, Klevebro F, Langley R, Lordick F, Lutz M, Mauer M, Michalski CW, Michl P, Nankivell M, Nilsson M, Seide S, Shah MA, Shi Q, Stahl M, Urba S, van Lanschot J, Vordermark D, Walsh TN, Ychou M, Proctor T, and Vey JA
- Subjects
- Humans, Male, Preoperative Care methods, Middle Aged, Female, Aged, Disease-Free Survival, Adenocarcinoma therapy, Adenocarcinoma mortality, Esophagogastric Junction pathology, Esophageal Neoplasms therapy, Esophageal Neoplasms mortality, Network Meta-Analysis, Chemoradiotherapy methods, Stomach Neoplasms therapy, Stomach Neoplasms mortality, Stomach Neoplasms drug therapy
- Abstract
Importance: The prognosis of patients with adenocarcinoma of the esophagus and esophagogastric junction (AEG) is poor. From current evidence, it remains unclear to what extent preoperative chemoradiotherapy (CRT) or preoperative and/or perioperative chemotherapy achieve better outcomes than surgery alone., Objective: To assess the association of preoperative CRT and preoperative and/or perioperative chemotherapy in patients with AEG with overall survival and other outcomes., Data Sources: Literature search in PubMed, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, and International Clinical Trials Registry Platform was performed from inception to April 21, 2023., Study Selection: Two blinded reviewers screened for randomized clinical trials comparing preoperative CRT plus surgery with preoperative and/or perioperative chemotherapy plus surgery, 1 intervention with surgery alone, or all 3 treatments. Only data from participants with AEG were included from trials that encompassed mixed histology or gastric cancer. Among 2768 initially identified studies, 17 (0.6%) met the selection criteria., Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed for extracting data and assessing data quality by 2 independent extractors. A bayesian network meta-analysis was conducted using the 2-stage approach., Main Outcomes and Measures: Overall and disease-free survival, postoperative morbidity, and mortality., Results: The analyses included 2549 patients (2206 [86.5%] male; mean [SD] age, 61.0 [9.4] years) from 17 trials (conducted from 1989-2016). Both preoperative CRT plus surgery (hazard ratio [HR], 0.75 [95% credible interval (CrI), 0.62-0.90]; 3-year difference, 105 deaths per 1000 patients) and preoperative and/or perioperative chemotherapy plus surgery (HR, 0.78 [95% CrI, 0.64-0.91]; 3-year difference, 90 deaths per 1000 patients) showed longer overall survival than surgery alone. Comparing the 2 modalities yielded similar overall survival (HR, 1.04 [95% CrI], 0.83-1.28]; 3-year difference, 15 deaths per 1000 patients fewer for CRT). Similarly, disease-free survival was longer for both modalities compared with surgery alone. Postoperative morbidity was more frequent after CRT plus surgery (odds ratio [OR], 2.94 [95% CrI, 1.01-8.59]) than surgery alone. Postoperative mortality was not significantly more frequent after CRT plus surgery than surgery alone (OR, 2.50 [95% CrI, 0.66-10.56]) or after chemotherapy plus surgery than CRT plus surgery (OR, 0.44 [95% CrI, 0.08-2.00])., Conclusions and Relevance: In this meta-analysis of patients with AEG, both preoperative CRT and preoperative and/or perioperative chemotherapy were associated with longer survival without relevant differences between the 2 modalities. Thus, either of the 2 treatments may be recommended to patients.
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- 2024
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39. Precision Culture Scaling to Establish High-Throughput Vasculogenesis Models.
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Dennison NR, Fusenig M, Grönnert L, Maitz MF, Ramirez Martinez MA, Wobus M, Freudenberg U, Bornhäuser M, Friedrichs J, Westenskow PD, and Werner C
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- Humans, Hydrogels chemistry, Coculture Techniques methods, High-Throughput Screening Assays methods, Mesenchymal Stem Cells cytology, Mesenchymal Stem Cells metabolism, Pericytes cytology, Pericytes metabolism, Pericytes drug effects, Cell Culture Techniques methods, Cell Culture Techniques instrumentation, Endothelial Cells cytology, Endothelial Cells metabolism, Human Umbilical Vein Endothelial Cells metabolism, Neovascularization, Physiologic drug effects
- Abstract
Hydrogel-based 3D cell cultures can recapitulate (patho)physiological phenomena ex vivo. However, due to their complex multifactorial regulation, adapting these tissue and disease models for high-throughput screening workflows remains challenging. In this study, a new precision culture scaling (PCS-X) methodology combines statistical techniques (design of experiment and multiple linear regression) with automated, parallelized experiments and analyses to customize hydrogel-based vasculogenesis cultures using human umbilical vein endothelial cells and retinal microvascular endothelial cells. Variations of cell density, growth factor supplementation, and media composition are systematically explored to induce vasculogenesis in endothelial mono- and cocultures with mesenchymal stromal cells or retinal microvascular pericytes in 384-well plate formats. The developed cultures are shown to respond to vasculogenesis inhibitors in a compound- and dose-dependent manner, demonstrating the scope and power of PCS-X in creating parallelized tissue and disease models for drug discovery and individualized therapies., (© 2024 The Authors. Advanced Healthcare Materials published by Wiley‐VCH GmbH.)
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- 2024
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40. Multivisceral Oncological Resections Involving the Pancreas: Protocol for a Systematic Review and Meta-Analysis.
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Neuhaus M, Friedrichs J, Grilli M, Ukkat J, Klose J, Ronellenfitsch U, Kleeff J, and Rebelo A
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- Humans, Postoperative Complications epidemiology, Systematic Reviews as Topic, Pancreatic Neoplasms surgery, Pancreatic Neoplasms pathology, Pancreatic Neoplasms mortality, Meta-Analysis as Topic, Pancreatectomy methods, Pancreatectomy adverse effects
- Abstract
Background: With the continuous advancement of cancer treatments, a comprehensive analysis of the impact of multivisceral oncological pancreatic resections on morbidity, mortality, and long-term survival is currently lacking., Objective: This manuscript presents the protocol for a systematic review and meta-analysis designed to summarize the existing evidence concerning the outcomes of multivisceral oncological pancreatic resections across diverse tumor entities., Methods: We will conduct a systematic search of the PubMed or MEDLINE, Embase, Cochrane Library, CINAHL, and ClinicalTrials.gov databases in strict accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The predefined outcomes encompass postoperative mortality, postoperative morbidity, overall and disease-free survival (1- to 5-year survival rates), the proportion of macroscopically complete (R0) resections (according to the Royal College of Pathologists definition), duration of hospital stay (in days), reoperation rate (%), postoperative complications (covering all complications according to the Clavien-Dindo classification), as well as pancreatic fistula, postpancreatectomy hemorrhage, and delayed gastric emptying (all according to the definitions of the International Study Group of Pancreas Surgery)., Results: Systematic database searches will begin in July 2024. The completion of the meta-analysis is anticipated by December 2024. Before completion, the literature search will be checked for new publications that must be considered in the context of the work., Conclusions: The forthcoming findings will provide an up-to-date overview of the feasibility, safety, and oncological efficacy of multivisceral pancreatic resections across diverse tumor entities. This data will serve as a valuable resource for health care professionals and patients to make well-informed clinical decisions., Trial Registration: PROSPERO CRD42023437858; https://tinyurl.com/bde5xmfw., International Registered Report Identifier (irrid): PRR1-10.2196/54089., (©Melina Neuhaus, Juliane Friedrichs, Maurizio Grilli, Jörg Ukkat, Johannes Klose, Ulrich Ronellenfitsch, Jörg Kleeff, Artur Rebelo. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 11.06.2024.)
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- 2024
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41. Gregarines impact consumption and development but not glucosinolate metabolism in the mustard leaf beetle.
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Barber A, Friedrichs J, and Müller C
- Abstract
Gregarines are usually classified as parasites, but recent studies suggest that they should be viewed on a parasitism-mutualism spectrum and may even be seen as part of the gut microbiota of host insects. As such, they may also impact the consumption of their hosts and/or be involved in the digestion or detoxification of the host's diet. To study such effects of a gregarine species on those traits in its host, the mustard leaf beetle ( Phaedon cochleariae ) was used. This beetle species feeds on Brassicaceae plants that contain glucosinolates, which form toxic compounds when hydrolyzed by myrosinases. We cleaned host eggs from gametocysts and spores and reinfected half of the larvae with gregarines, to obtain gregarine-free (G-) and gregarine-infected (G+) larvae. Growth and food consumption parameters of these larvae were assessed by rearing individuals on watercress ( Nasturtium officinale , Brassicaceae). A potential involvement of gregarines in the glucosinolate metabolism of P. cochleariae larvae was investigated by offering G- and G+ larvae leaf discs of watercress (containing mainly the benzenic 2-phenylethyl glucosinolate and myrosinases) or pea ( Pisum sativum , Fabaceae, lacking glucosinolates and myrosinases) treated with the aliphatic 4-pentenyl glucosinolate or the indole 1-methoxy-3-indolylmethyl glucosinolate. Larval and fecal samples were analyzed via UHPLC-QTOF-MS/MS to search for breakdown metabolites. Larval development, body mass, growth rate and efficiency to convert food into body mass were negatively affected by gregarine infection while the pupal mass remained unaffected. The breakdown metabolites of benzenic and aliphatic glucosinolates were conjugated with aspartic acid, while those of the indole glucosinolate were conjugated with glutamic acid. Gregarine infection did not alter the larvae's ability to metabolize glucosinolates and was independent of plant myrosinases. In summary, some negative effects of gregarines on host performance could be shown, indicating parasitism. Future studies may further disentangle this gregarine-host relationship and investigate the microbiome potentially involved in the glucosinolate metabolism., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Barber, Friedrichs and Müller.)
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- 2024
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42. Approaches for the treatment of perforated peptic ulcers: a network meta-analysis of randomised controlled trials - study protocol.
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Wadewitz E, Friedrichs J, Grilli M, Vey J, Zimmermann S, Kleeff J, Ronellenfitsch U, Klose J, and Rebelo A
- Abstract
Introduction: Perforated peptic ulcers are a life-threatening complication associated with high morbidity and mortality. Several treatment approaches are available. The aim of this network meta-analysis (NMA) is to compare surgical and alternative approaches for the treatment of perforated peptic ulcers regarding mortality and other patient-relevant outcomes., Methods and Analysis: A systematic literature search of PubMed/MEDLINE, Cochrane Library, Embase, CINAHL, ClinicalTrials.gov trial registry and ICTRP will be conducted with predefined search terms.To address the question of the most effective treatment approach, an NMA will be performed for each of the outcomes mentioned above. A closed network of interventions is expected. The standardised mean difference with its 95% CI will be used as the effect measure for the continuous outcomes, and the ORs with 95% CI will be calculated for the binary outcomes., Ethics and Dissemination: In accordance with the nature of the data used in this meta-analysis, which involves aggregate information from previously published studies ethical approval is deemed unnecessary. Results will be disseminated directly to decision-makers (eg, surgeons, gastroenterologists) through publication in peer-reviewed journals and presentation at conferences., Prospero Registration Number: CRD42023482932., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2024
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43. Discovery of a structural class of antibiotics with explainable deep learning.
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Wong F, Zheng EJ, Valeri JA, Donghia NM, Anahtar MN, Omori S, Li A, Cubillos-Ruiz A, Krishnan A, Jin W, Manson AL, Friedrichs J, Helbig R, Hajian B, Fiejtek DK, Wagner FF, Soutter HH, Earl AM, Stokes JM, Renner LD, and Collins JJ
- Subjects
- Animals, Humans, Mice, Methicillin-Resistant Staphylococcus aureus drug effects, Microbial Sensitivity Tests, Staphylococcal Infections drug therapy, Staphylococcal Infections microbiology, Staphylococcus aureus drug effects, Neural Networks, Computer, Algorithms, Vancomycin-Resistant Enterococci drug effects, Disease Models, Animal, Skin drug effects, Skin microbiology, Anti-Bacterial Agents chemistry, Anti-Bacterial Agents classification, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents toxicity, Deep Learning, Drug Discovery methods, Drug Discovery trends
- Abstract
The discovery of novel structural classes of antibiotics is urgently needed to address the ongoing antibiotic resistance crisis
1-9 . Deep learning approaches have aided in exploring chemical spaces1,10-15 ; these typically use black box models and do not provide chemical insights. Here we reasoned that the chemical substructures associated with antibiotic activity learned by neural network models can be identified and used to predict structural classes of antibiotics. We tested this hypothesis by developing an explainable, substructure-based approach for the efficient, deep learning-guided exploration of chemical spaces. We determined the antibiotic activities and human cell cytotoxicity profiles of 39,312 compounds and applied ensembles of graph neural networks to predict antibiotic activity and cytotoxicity for 12,076,365 compounds. Using explainable graph algorithms, we identified substructure-based rationales for compounds with high predicted antibiotic activity and low predicted cytotoxicity. We empirically tested 283 compounds and found that compounds exhibiting antibiotic activity against Staphylococcus aureus were enriched in putative structural classes arising from rationales. Of these structural classes of compounds, one is selective against methicillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococci, evades substantial resistance, and reduces bacterial titres in mouse models of MRSA skin and systemic thigh infection. Our approach enables the deep learning-guided discovery of structural classes of antibiotics and demonstrates that machine learning models in drug discovery can be explainable, providing insights into the chemical substructures that underlie selective antibiotic activity., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2024
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44. Experimental study and simulations of hydrogen cooling effectiveness for aviation PEM fuel cells.
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Kösters TL, von Schweinitz AG, Heere M, Friedrichs J, and Gao X
- Abstract
Proton exchange membrane fuel cells (PEMFCs) are seen as one possible future means of driving the change towards a zero-emission society. In a civil aircraft, fuel cell systems can have multiple potential benefits, such as reduced noise, lowered emissions and higher fuel economy compared to jet aircraft. For controlling the fuel cell temperature, thermal management systems are required which can be optimized for aircraft applications regarding their weight and reliability. In this work, a simplified and light-weight thermal management system relying on hydrogen cooling is presented and analysed. To investigate the feasibility, a test rig and a three-dimensional, singular channel model in ANSYS Fluent were designed. Fuel cell temperature could be maintained within the set threshold in the model and the test rig, thus showing that controlling the fuel cell temperature via the hydrogen reactant flow is a viable alternative thermal management system. Results from the model indicate that both the hydrogen mass flow and hydrogen inlet temperature should be used to control the fuel cell temperature. Furthermore, operating the fuel cell at medium to low current densities is favourable for hydrogen cooling. Future studies will explore alternate flow field designs to facilitate thermal management system relying on hydrogen., (© 2024. The Author(s).)
- Published
- 2023
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45. Entropic repulsion of cholesterol-containing layers counteracts bioadhesion.
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Friedrichs J, Helbig R, Hilsenbeck J, Pandey PR, Sommer JU, Renner LD, Pompe T, and Werner C
- Subjects
- Adsorption, Wettability, Bacterial Adhesion, Proteins chemistry, Entropy, Cholesterol chemistry
- Abstract
Control of adhesion is a striking feature of living matter that is of particular interest regarding technological translation
1-3 . We discovered that entropic repulsion caused by interfacial orientational fluctuations of cholesterol layers restricts protein adsorption and bacterial adhesion. Moreover, we found that intrinsically adhesive wax ester layers become similarly antibioadhesive when containing small quantities (under 10 wt%) of cholesterol. Wetting, adsorption and adhesion experiments, as well as atomistic simulations, showed that repulsive characteristics depend on the specific molecular structure of cholesterol that encodes a finely balanced fluctuating reorientation at the interface of unconstrained supramolecular assemblies: layers of cholesterol analogues differing only in minute molecular variations showed markedly different interfacial mobility and no antiadhesive effects. Also, orientationally fixed cholesterol layers did not resist bioadhesion. Our insights provide a conceptually new physicochemical perspective on biointerfaces and may guide future material design in regulation of adhesion., (© 2023. The Author(s).)- Published
- 2023
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46. [The role of nurses in pharmaceutical care in Germany: A qualitative analysis].
- Author
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Klatt T, Baltes M, Friedrichs J, and Langer G
- Subjects
- Humans, Germany, Europe, Qualitative Research, Nurse's Role, Pharmaceutical Services
- Abstract
Background: In 13 European countries, laws have been passed that allow nurses to prescribe medicines, but mostly within a limited framework and with a doctor involved. Germany is not among these countries. Only the prescription of medical aids has already been included into the development of extended nursing competencies. We investigated the views of the health care professions involved (doctors, pharmacists and nurses) regarding the role of nurses in pharmaceutical care., Method: We conducted 22 semi-structured interviews with 23 members of the three professional groups involved in the European research project DeMoPhaC. These data collected in Germany were analysed using qualitative content analysis. Five main categories were developed., Results: Pharmaceutical care by nurses can be described within the following main categories: 1. Knowledge and competences, 2. Patient care, 3. Communication, 4. Multi-professional team and 5. System. The communication between the professional groups involved and with patients and caregivers is of particular importance. Interaction in the multi-professional team is just as crucial. Pharmaceutical care takes place within the health system which sets the framework and often boundaries as well. The current and ideally conceived roles of nurses are seen differently in the respondents' respective contexts. Between the professional groups there is both agreement and dissent on the topics addressed. However, the development of nursing roles requires collaborative and transparent processes in teams and organisations. Particularly in the hospital setting, the participants saw a great need for change in order to achieve cooperation at eye level., Discussion: The results show that nurses play their role in the complex field of pharmaceutical care under very heterogeneous circumstances. The empowerment of nurses, which was called for by some participants, cannot be achieved from within the professional group alone. Cooperation from all the players involved is needed. The development of nursing roles in the medication process with simultaneous expansion of qualifications and competences can contribute to making the nursing role more attractive. Clear role models promote the transparency of processes for all involved. If all players know what they can expect of nurses, tasks can be redistributed in the multiprofessional team., Conclusion: The above-mentioned diversity of perspectives can be a resource for development and individual solutions. However, it can also be interpreted negatively as a sign of uncertainty and less standardised ways of working. In view of the data evaluated here, the prescription of medicines by non-medical professionals remains a distant goal for developments in the German health care system. First of all, structures and processes are required that permanently guarantee safe pharmaceutical care with equal participation of all relevant stakeholders., (Copyright © 2022. Published by Elsevier GmbH.)
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- 2023
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47. Systematic review and meta-analysis of surgery for hilar cholangiocarcinoma with arterial resection.
- Author
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Rebelo A, Friedrichs J, Grilli M, Wahbeh N, Partsakhashvili J, Ukkat J, Klose J, Ronellenfitsch U, and Kleeff J
- Subjects
- Humans, Retrospective Studies, Treatment Outcome, Hepatectomy, Hepatic Artery surgery, Bile Ducts, Intrahepatic surgery, Klatskin Tumor surgery, Klatskin Tumor pathology, Bile Duct Neoplasms pathology, Cholangiocarcinoma
- Abstract
Background: With the advances in multimodality treatment, an analysis of the outcome of arterial resections (AR) in surgery of cholangiocarcinoma is lacking. The aim of this meta-analysis was to summarize the currently available evidence onof AR for the treatment of cholangiocarcinoma., Methods: A systematic literature search was carried out according to PRISMA guidelines., Results: 10 retrospective cohort studies published from 2007 to 2020 with 2530 patients (408 AR group and 2122 control group) were identified. Higher in-hospital mortality rates (6.8% vs 3.3%, OR 2.65, 95% CI [1.27; 5.32], p = 0.009), higher morbidity rates (Clavien-Dindo classification ≥3 ) (52% vs 47%, OR 1.44, 95% CI [1.02; 1.75], p = 0.04) and lower 1-year, 3-year and 5-year survival rates (54% vs 69%, OR 0.55, 95% CI [0.34; 0.91 p = 0.02), (34% vs 38%, OR 0.74, 95% CI [0.55; 0.98, p = 0.03), (18% vs 29%, OR 0.54, 95% CI [0.39; 0.75, p = 0.0002) were observed in the AR group when compared to the control group., Conclusion: Evidence from non-randomized studies shows a higher morbidity and mortality and shorter long-term survival in patients undergoing AR. However, the results are prone to selection bias, and only randomized trials comparing AR and palliative treatments AR might reveal a possible benefit of AR., Systematic Review Registration: PROSPERO ID 223396., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2022
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48. Bone marrow mesenchymal stromal cell-derived extracellular matrix displays altered glycosaminoglycan structure and impaired functionality in Myelodysplastic Syndromes.
- Author
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Bains AK, Behrens Wu L, Rivière J, Rother S, Magno V, Friedrichs J, Werner C, Bornhäuser M, Götze KS, Cross M, Platzbecker U, and Wobus M
- Abstract
Myelodysplastic syndromes (MDS) comprise a heterogeneous group of hematologic malignancies characterized by clonal hematopoiesis, one or more cytopenias such as anemia, neutropenia, or thrombocytopenia, abnormal cellular maturation, and a high risk of progression to acute myeloid leukemia. The bone marrow microenvironment (BMME) in general and mesenchymal stromal cells (MSCs) in particular contribute to both the initiation and progression of MDS. However, little is known about the role of MSC-derived extracellular matrix (ECM) in this context. Therefore, we performed a comparative analysis of in vitro deposited MSC-derived ECM of different MDS subtypes and healthy controls. Atomic force microscopy analyses demonstrated that MDS ECM was significantly thicker and more compliant than those from healthy MSCs. Scanning electron microscopy showed a dense meshwork of fibrillar bundles connected by numerous smaller structures that span the distance between fibers in MDS ECM. Glycosaminoglycan (GAG) structures were detectable at high abundance in MDS ECM as white, sponge-like arrays on top of the fibrillar network. Quantification by Blyscan assay confirmed these observations, with higher concentrations of sulfated GAGs in MDS ECM. Fluorescent lectin staining with wheat germ agglutinin and peanut agglutinin demonstrated increased deposition of N -acetyl-glucosamine GAGs (hyaluronan (HA) and heparan sulfate) in low risk (LR) MDS ECM. Differential expression of N -acetyl-galactosamine GAGs (chondroitin sulfate, dermatan sulfate) was observed between LR- and high risk (HR)-MDS. Moreover, increased amounts of HA in the matrix of MSCs from LR-MDS patients were found to correlate with enhanced HA synthase 1 mRNA expression in these cells. Stimulation of mononuclear cells from healthy donors with low molecular weight HA resulted in an increased expression of various pro-inflammatory cytokines suggesting a contribution of the ECM to the inflammatory BMME typical of LR-MDS. CD34
+ hematopoietic stem and progenitor cells (HSPCs) displayed an impaired differentiation potential after cultivation on MDS ECM and modified morphology accompanied by decreased integrin expression which mediate cell-matrix interaction. In summary, we provide evidence for structural alterations of the MSC-derived ECM in both LR- and HR-MDS. GAGs may play an important role in this remodeling processes during the malignant transformation which leads to the observed disturbance in the support of normal hematopoiesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bains, Behrens Wu, Rivière, Rother, Magno, Friedrichs, Werner, Bornhäuser, Götze, Cross, Platzbecker and Wobus.)- Published
- 2022
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49. Unique metabolism of different glucosinolates in larvae and adults of a leaf beetle specialised on Brassicaceae.
- Author
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Friedrichs J, Schweiger R, and Müller C
- Subjects
- Animals, Aspartic Acid metabolism, Glucosinolates metabolism, Isothiocyanates metabolism, Larva metabolism, Nitriles metabolism, Tandem Mass Spectrometry, Brassicaceae metabolism, Coleoptera metabolism, Nasturtium
- Abstract
Brassicaceae plants contain glucosinolates, which are hydrolysed by myrosinases to toxic products such as isothiocyanates and nitriles, acting as defences. Herbivores have evolved various detoxification strategies, which are reviewed here. Larvae of Phaedon cochleariae (Coleoptera: Chrysomelidae) metabolise hydrolysis products of benzenic glucosinolates by conjugation with aspartic acid. In this study, we investigated whether P. cochleariae uses the same metabolic pathway for structurally different glucosinolates, whether the metabolism differs between adults and larvae and which hydrolysis products are formed as intermediates. Feeding experiments were performed with leaves of watercress (Nasturtium officinale, Brassicaceae) and pea (Pisum sativum, non-Brassicaceae), to which glucosinolates with structurally different side chains (benzenic, indole or aliphatic) or their hydrolysis products were applied. Samples were analysed by UHPLC-QTOF-MS/MS or TD-GC-MS. The same aspartic acid conjugates as previously identified in larvae were also detected as major metabolites of benzenic glucosinolates in adults. Indol-3-ylmethyl glucosinolate was mainly metabolised to N-(1H-indol-3-ylcarbonyl) glutamic acid in adults and larvae, while the metabolism of 2-propenyl glucosinolate remains unclear. The metabolism may thus proceed primarily via isothiocyanates rather than via nitriles, while the hydrolysis occurs independently of plant myrosinases. A detoxification by conjugation with these amino acids is not yet known from other Brassicaceae-feeders., (© 2022. The Author(s).)
- Published
- 2022
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50. Lymph Node Yield in Gastrointestinal Cancer Surgery With or Without Prior Neoadjuvant Therapy: Protocol for a Systematic Review and Meta-analysis.
- Author
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Ronellenfitsch U, Mathis N, Friedrichs J, and Kleeff J
- Abstract
Background: Lymph node yield is the number of lymph nodes retrieved during oncological resection and histopathologically identified in the resection specimen. It is an important surrogate parameter for assessing the oncological radicality of the resection of gastrointestinal carcinomas, as well as a prognostic factor in these diseases. It remains unclear if and to what extent neoadjuvant chemotherapy, radiotherapy, or chemoradiotherapy, which have become established treatments for carcinoma of the esophagus, stomach, and rectum and are increasingly used in pancreatic carcinoma, affect the lymph node yield., Objective: This systematic review with meta-analysis is conducted with the aim of summarizing the available evidence regarding the lymph node yield, an oncological surrogate marker, in patients with gastrointestinal carcinomas undergoing surgery after neoadjuvant therapy compared to those undergoing surgery without neoadjuvant therapy., Methods: Randomized and nonrandomized studies comparing oncological resection of esophageal, stomach, pancreatic, and rectal carcinoma with and without prior neoadjuvant therapy are eligible for inclusion regardless of study design. Publications will be identified with a defined search strategy in 2 electronic databases: PubMed and Cochrane Library. The primary endpoint of the analysis is the number of lymph nodes identified in the resected specimen. Secondary endpoints include the number of harvested metastatic lymph nodes, operation time, postoperative complications, pathological TNM staging, and overall and recurrence-free survival time. Using suitable statistical methods, the endpoints between patients with and without neoadjuvant therapy, as well as in defined subgroups (neoadjuvant chemotherapy, radiotherapy, or chemoradiotherapy; and patients with esophageal, gastric, pancreatic, or rectal cancer), will be compared., Results: The literature search and data collection started in October 2021. Results are expected to be published in mid-2022., Conclusions: This meta-analysis will provide the most up-to-date and complete summary of the evidence on an association between neoadjuvant therapy and lymph node yield in gastrointestinal cancer surgery. The underlying hypothesis is that neoadjuvant therapy decreases the number and size of lymph nodes through lymphocyte depletion and radiation-induced fibrosis, thus leading to a lower possible lymph node yield. The findings of the meta-analysis will show if this hypothesis is supported by evidence., Trial Registration: PROSPERO CRD218459; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021218459., International Registered Report Identifier (irrid): DERR1-10.2196/35243., (©Ulrich Ronellenfitsch, Nika Mathis, Juliane Friedrichs, Jörg Kleeff. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 28.04.2022.)
- Published
- 2022
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