TY - JOUR A1 - de Blois, Eric A1 - de Zanger, Rory M. S. A1 - Paulßen, Elisabeth A1 - Sze Chan, Ho A1 - Breeman, Wouter A. P. T1 - Semi-automated system for concentrating 68Ga-eluate to obtain high molar and volume concentration of 68Ga-Radiopharmaca for preclinical applications JF - Nuclear Medicine and Biology N2 - 68Ga-radiopharmaceuticals are common in the field of Nuclear Medicine to visualize receptor-mediated processes. In contrast to straightforward labeling procedures for clinical applications, preclinical in vitro and in vivo applications are hampered for reasons like e.g. volume restriction, activity concentration, molar activity and osmolality. Therefore, we developed a semiautomatic system specifically to overcome these problems. A difficulty appeared unexpectedly, as intrinsic trace metals derived from eluate (Zn, Fe and Cu) are concentrated as well in amounts that influence radiochemical yield and thus lower molar activity. Y1 - 2018 U6 - https://doi.org/10.1016/j.nucmedbio.2018.06.006 VL - 64-65 SP - 16 EP - 21 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Eckert, Alexander A1 - Abbasi, Mozhdeh A1 - Mang, Thomas A1 - Saalwächter, Kay A1 - Walther, Andreas T1 - Structure, Mechanical Properties, and Dynamics of Polyethylenoxide/Nanoclay Nacre-Mimetic Nanocomposites JF - Macromolecules N2 - Nacre-mimetic nanocomposites based on high fractions of synthetic high-aspect-ratio nanoclays in combination with polymers are continuously pushing boundaries for advanced material properties, such as high barrier against oxygen, extraordinary mechanical behavior, fire shielding, and glass-like transparency. Additionally, they provide interesting model systems to study polymers under nanoconfinement due to the well-defined layered nanocomposite arrangement. Although the general behavior in terms of forming such layered nanocomposite materials using evaporative self-assembly and controlling the nanoclay gallery spacing by the nanoclay/polymer ratio is understood, some combinations of polymer matrices and nanoclay reinforcement do not comply with the established models. Here, we demonstrate a thorough characterization and analysis of such an unusual polymer/nanoclay pair that falls outside of the general behavior. Poly(ethylene oxide) (PEO) and sodium fluorohectorite form nacre-mimetic, lamellar nanocomposites that are completely transparent and show high mechanical stiffness and high gas barrier, but there is only limited expansion of the nanoclay gallery spacing when adding increasing amounts of polymer. This behavior is maintained for molecular weights of PEO varied over four orders of magnitude and can be traced back to depletion forces. By careful investigation via X-ray diffraction and proton low-resolution solid-state NMR, we are able to quantify the amount of mobile and immobilized polymer species in between the nanoclay galleries and around proposed tactoid stacks embedded in a PEO matrix. We further elucidate the unusual confined polymer dynamics, indicating a relevant role of specific surface interactions. Y1 - 2020 U6 - https://doi.org/10.1021/acs.macromol.9b01931 SN - 1520-5835 VL - 53 IS - 5 SP - 1716 EP - 1725 PB - ACS Publications CY - Washington, DC ER - TY - JOUR A1 - Jildeh, Zaid B. A1 - Wagner, Patrick H. A1 - Schöning, Michael Josef T1 - Sterilization of Objects, Products, and Packaging Surfaces and Their Characterization in Different Fields of Industry: The Status in 2020 JF - physica status solidi (a) applications and materials science N2 - The treatment method to deactivate viable microorganisms from objects or products is termed sterilization. There are multiple forms of sterilization, each intended to be applied for a specific target, which depends on—but not limited to—the thermal, physical, and chemical stability of that target. Herein, an overview on the currently used sterilization processes in the global market is provided. Different sterilization techniques are grouped under a category that describes the method of treatment: radiation (gamma, electron beam, X-ray, and ultraviolet), thermal (dry and moist heat), and chemical (ethylene oxide, ozone, chlorine dioxide, and hydrogen peroxide). For each sterilization process, the typical process parameters as defined by regulations and the mode of antimicrobial activity are summarized. Finally, the recommended microorganisms that are used as biological indicators to validate sterilization processes in accordance with the rules that are established by various regulatory agencies are summarized. KW - bioburdens KW - sterility tests KW - sterilization efficacy KW - sterilization methods KW - validation methods Y1 - 2021 U6 - https://doi.org/10.1002/pssa.202000732 SN - 1862-6319 N1 - Corresponding author: Michael J. Schöning VL - 218 IS - 13 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Wert, Stefan A1 - Iken, Heiko A1 - Schöning, Michael Josef A1 - Matysik, Frank-Michael T1 - Development of a temperature‐pulse enhanced electrochemical glucose biosensor and characterization of its stability via scanning electrochemical microscopy JF - Electroanalysis N2 - Glucose oxidase (GOx) is an enzyme frequently used in glucose biosensors. As increased temperatures can enhance the performance of electrochemical sensors, we investigated the impact of temperature pulses on GOx that was drop-coated on flattened Pt microwires. The wires were heated by an alternating current. The sensitivity towards glucose and the temperature stability of GOx was investigated by amperometry. An up to 22-fold increase of sensitivity was observed. Spatially resolved enzyme activity changes were investigated via scanning electrochemical microscopy. The application of short (<100 ms) heat pulses was associated with less thermal inactivation of the immobilized GOx than long-term heating. Y1 - 2021 U6 - https://doi.org/10.1002/elan.202100089 SN - 1521-4109 IS - Early View PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Fiedler, Thomas M. A1 - Orzada, Stephan A1 - Flöser, Martina A1 - Rietsch, Stefan H. G. A1 - Schmidt, Simon A1 - Stelter, Jonathan K. A1 - Wittrich, Marco A1 - Quick, Harald H. A1 - Bitz, Andreas A1 - Ladd, Mark E. T1 - Performance and safety assessment of an integrated transmit array for body imaging at 7 T under consideration of specificabsorption rate, tissue temperature, and thermal dose JF - NMR in Biomedicine N2 - In this study, the performance of an integrated body-imaging array for 7 T with 32 radiofrequency (RF) channels under consideration of local specific absorption rate (SAR), tissue temperature, and thermal dose limits was evaluated and the imaging performance was compared with a clinical 3 T body coil. Thirty-two transmit elements were placed in three rings between the bore liner and RF shield of the gradient coil. Slice-selective RF pulse optimizations for B1 shimming and spokes were performed for differently oriented slices in the body under consideration of realistic constraints for power and local SAR. To improve the B1+ homogeneity, safety assessments based on temperature and thermal dose were performed to possibly allow for higher input power for the pulse optimization than permissible with SAR limits. The results showed that using two spokes, the 7 T array outperformed the 3 T birdcage in all the considered regions of interest. However, a significantly higher SAR or lower duty cycle at 7 T is necessary in some cases to achieve similar B1+ homogeneity as at 3 T. The homogeneity in up to 50 cm-long coronal slices can particularly benefit from the high RF shim performance provided by the 32 RF channels. The thermal dose approach increases the allowable input power and the corresponding local SAR, in one example up to 100 W/kg, without limiting the exposure time necessary for an MR examination. In conclusion, the integrated antenna array at 7 T enables a clinical workflow for body imaging and comparable imaging performance to a conventional 3 T clinical body coil. KW - body imaging at 7 T MRI KW - thermal dose KW - tissue temperature KW - transmit antenna arrays Y1 - 2022 U6 - https://doi.org/10.1002/nbm.4656 SN - 0952-3480 (Print) SN - 1099-1492 (Online) VL - 35 IS - 5 SP - 1 EP - 17 PB - Wiley ER - TY - JOUR A1 - Haeger, Gerrit A1 - Grankin, Alina A1 - Wagner, Michaela T1 - Construction of an Aspergillus oryzae triple amylase deletion mutant as a chassis to evaluate industrially relevant amylases using multiplex CRISPR/Cas9 editing technology JF - Applied Research N2 - Aspergillus oryzae is an industrially relevant organism for the secretory production of heterologous enzymes, especially amylases. The activities of potential heterologous amylases, however, cannot be quantified directly from the supernatant due to the high background activity of native α-amylase. This activity is caused by the gene products of amyA, amyB, and amyC. In this study, an in vitro CRISPR/Cas9 system was established in A. oryzae to delete these genes simultaneously. First, pyrG of A. oryzae NSAR1 was mutated by exploiting NHEJ to generate a counter-selection marker. Next, all amylase genes were deleted simultaneously by co-transforming a repair template carrying pyrG of Aspergillus nidulans and flanking sequences of amylase gene loci. The rate of obtained triple knock-outs was 47%. We showed that triple knockouts do not retain any amylase activity in the supernatant. The established in vitro CRISPR/Cas9 system was used to achieve sequence-specific knock-in of target genes. The system was intended to incorporate a single copy of the gene of interest into the desired host for the development of screening methods. Therefore, an integration cassette for the heterologous Fpi amylase was designed to specifically target the amyB locus. The site-specific integration rate of the plasmid was 78%, with exceptional additional integrations. Integration frequency was assessed via qPCR and directly correlated with heterologous amylase activity. Hence, we could compare the efficiency between two different signal peptides. In summary, we present a strategy to exploit CRISPR/Cas9 for gene mutation, multiplex knock-out, and the targeted knock-in of an expression cassette in A. oryzae. Our system provides straightforward strain engineering and paves the way for development of fungal screening systems. KW - aspergillus KW - CRISPR/Cas9 KW - filamentous fungi KW - genome engineering Y1 - 2023 U6 - https://doi.org/10.1002/appl.202200106 SN - 2702-4288 IS - Early View SP - 1 EP - 15 PB - Wiley-VCH ER - TY - JOUR A1 - Kempt, Hendrik A1 - Freyer, Nils A1 - Nagel, Saskia K. T1 - Justice and the normative standards of explainability in healthcare JF - Philosophy & Technology N2 - Providing healthcare services frequently involves cognitively demanding tasks, including diagnoses and analyses as well as complex decisions about treatments and therapy. From a global perspective, ethically significant inequalities exist between regions where the expert knowledge required for these tasks is scarce or abundant. One possible strategy to diminish such inequalities and increase healthcare opportunities in expert-scarce settings is to provide healthcare solutions involving digital technologies that do not necessarily require the presence of a human expert, e.g., in the form of artificial intelligent decision-support systems (AI-DSS). Such algorithmic decision-making, however, is mostly developed in resource- and expert-abundant settings to support healthcare experts in their work. As a practical consequence, the normative standards and requirements for such algorithmic decision-making in healthcare require the technology to be at least as explainable as the decisions made by the experts themselves. The goal of providing healthcare in settings where resources and expertise are scarce might come with a normative pull to lower the normative standards of using digital technologies in order to provide at least some healthcare in the first place. We scrutinize this tendency to lower standards in particular settings from a normative perspective, distinguish between different types of absolute and relative, local and global standards of explainability, and conclude by defending an ambitious and practicable standard of local relative explainability. KW - Clinical decision support systems KW - Justice KW - Medical AI KW - Explainability KW - Normative standards Y1 - 2022 U6 - https://doi.org/10.1007/s13347-022-00598-0 VL - 35 IS - Article number: 100 SP - 1 EP - 19 PB - Springer Nature CY - Berlin ER - TY - JOUR A1 - Özsoylu, Dua A1 - Aliazizi, Fereshteh A1 - Wagner, Patrick A1 - Schöning, Michael Josef T1 - Template bacteria-free fabrication of surface imprinted polymer-based biosensor for E. coli detection using photolithographic mimics: Hacking bacterial adhesion JF - Biosensors and Bioelectronics N2 - As one class of molecular imprinted polymers (MIPs), surface imprinted polymer (SIP)-based biosensors show great potential in direct whole-bacteria detection. Micro-contact imprinting, that involves stamping the template bacteria immobilized on a substrate into a pre-polymerized polymer matrix, is the most straightforward and prominent method to obtain SIP-based biosensors. However, the major drawbacks of the method arise from the requirement for fresh template bacteria and often non-reproducible bacteria distribution on the stamp substrate. Herein, we developed a positive master stamp containing photolithographic mimics of the template bacteria (E. coli) enabling reproducible fabrication of biomimetic SIP-based biosensors without the need for the “real” bacteria cells. By using atomic force and scanning electron microscopy imaging techniques, respectively, the E. coli-capturing ability of the SIP samples was tested, and compared with non-imprinted polymer (NIP)-based samples and control SIP samples, in which the cavity geometry does not match with E. coli cells. It was revealed that the presence of the biomimetic E. coli imprints with a specifically designed geometry increases the sensor E. coli-capturing ability by an “imprinting factor” of about 3. These findings show the importance of geometry-guided physical recognition in bacterial detection using SIP-based biosensors. In addition, this imprinting strategy was employed to interdigitated electrodes and QCM (quartz crystal microbalance) chips. E. coli detection performance of the sensors was demonstrated with electrochemical impedance spectroscopy (EIS) and QCM measurements with dissipation monitoring technique (QCM-D). KW - Surface imprinted polymer KW - E. coli detection KW - Photolithographic mimics KW - Master stamp KW - Quartz crystal microbalance Y1 - 2024 U6 - https://doi.org/10.1016/j.bios.2024.116491 SN - 1873-4235 (eISSN) SN - 0956-5663 N1 - Corresponding author: Michael J. Schöning VL - 261 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Werkhausen, Amelie A1 - Willwacher, Steffen A1 - Albracht, Kirsten T1 - Medial gastrocnemius muscle fascicles shorten throughout stance during sprint acceleration JF - Scandinavian Journal of Medicine & Science in Sports N2 - The compliant nature of distal limb muscle-tendon units is traditionally considered suboptimal in explosive movements when positive joint work is required. However, during accelerative running, ankle joint net mechanical work is positive. Therefore, this study aims to investigate how plantar flexor muscle-tendon behavior is modulated during fast accelerations. Eleven female sprinters performed maximum sprint accelerations from starting blocks, while gastrocnemius muscle fascicle lengths were estimated using ultrasonography. We combined motion analysis and ground reaction force measurements to assess lower limb joint kinematics and kinetics, and to estimate gastrocnemius muscle-tendon unit length during the first two acceleration steps. Outcome variables were resampled to the stance phase and averaged across three to five trials. Relevant scalars were extracted and analyzed using one-sample and two-sample t-tests, and vector trajectories were compared using statistical parametric mapping. We found that an uncoupling of muscle fascicle behavior from muscle-tendon unit behavior is effectively used to produce net positive mechanical work at the joint during maximum sprint acceleration. Muscle fascicles shortened throughout the first and second steps, while shortening occurred earlier during the first step, where negative joint work was lower compared with the second step. Elastic strain energy may be stored during dorsiflexion after touchdown since fascicles did not lengthen at the same time to dissipate energy. Thus, net positive work generation is accommodated by the reuse of elastic strain energy along with positive gastrocnemius fascicle work. Our results show a mechanism of how muscles with high in-series compliance can contribute to net positive joint work. KW - locomotion KW - muscle mechanics KW - running KW - sprint start KW - ultrasonography Y1 - 2021 U6 - https://doi.org/10.1111/sms.13956 SN - 0905-7188 (Druckausgabe) SN - 1600-0838 (Onlineausgabe) VL - 31 IS - 7 SP - 1471 EP - 1480 PB - Wiley-Blackwell CY - Oxford ER - TY - JOUR A1 - Kuchler, Timon A1 - Günthner, Roman A1 - Ribeiro, Andrea A1 - Hausinger, Renate A1 - Streese, Lukas A1 - Wöhnl, Anna A1 - Kesseler, Veronika A1 - Negele, Johanna A1 - Assali, Tarek A1 - Carbajo-Lozoya, Javier A1 - Lech, Maciej A1 - Adorjan, Kristina A1 - Stubbe, Hans Christian A1 - Hanssen, Henner A1 - Kotliar, Konstantin A1 - Haller, Berhard A1 - Heemann, Uwe A1 - Schmaderer, Christoph T1 - Persistent endothelial dysfunction in post-COVID-19 syndrome and its associations with symptom severity and chronic inflammation N2 - Background Post-COVID-19 syndrome (PCS) is a lingering disease with ongoing symptoms such as fatigue and cognitive impairment resulting in a high impact on the daily life of patients. Understanding the pathophysiology of PCS is a public health priority, as it still poses a diagnostic and treatment challenge for physicians. Methods In this prospective observational cohort study, we analyzed the retinal microcirculation using Retinal Vessel Analysis (RVA) in a cohort of patients with PCS and compared it to an age- and gender-matched healthy cohort (n = 41, matched out of n = 204). Measurements and main results PCS patients exhibit persistent endothelial dysfunction (ED), as indicated by significantly lower venular flicker-induced dilation (vFID; 3.42% ± 1.77% vs. 4.64% ± 2.59%; p = 0.02), narrower central retinal artery equivalent (CRAE; 178.1 [167.5–190.2] vs. 189.1 [179.4–197.2], p = 0.01) and lower arteriolar-venular ratio (AVR; (0.84 [0.8–0.9] vs. 0.88 [0.8–0.9], p = 0.007). When combining AVR and vFID, predicted scores reached good ability to discriminate groups (area under the curve: 0.75). Higher PCS severity scores correlated with lower AVR (R = − 0.37 p = 0.017). The association of microvascular changes with PCS severity were amplified in PCS patients exhibiting higher levels of inflammatory parameters. Conclusion Our results demonstrate that prolonged endothelial dysfunction is a hallmark of PCS, and impairments of the microcirculation seem to explain ongoing symptoms in patients. As potential therapies for PCS emerge, RVA parameters may become relevant as clinical biomarkers for diagnosis and therapy management. KW - Endothelial dysfunction KW - Long COVID KW - Post-COVID-19 syndrome KW - retinal microvasculature Y1 - 2023 U6 - https://doi.org/10.1007/s10456-023-09885-6 N1 - Corresponding author: Christoph Schmaderer VL - 26 SP - 547 EP - 563 PB - Springer Nature CY - Dordrecht ER -