@article{HerssensCowburnAlbrachtetal.2022, author = {Herssens, Nolan and Cowburn, James and Albracht, Kirsten and Braunstein, Bjoern and Cazzola, Dario and Colyer, Steffi and Minetti, Alberto E. and Pavei, Gaspare and Rittweger, J{\"o}rn and Weber, Tobias and Green, David A.}, title = {Movement in low gravity environments (MoLo) programme - the MoLo-L.O.O.P. study protocol}, series = {PLOS ONE / Public Library of Science}, volume = {17}, journal = {PLOS ONE / Public Library of Science}, number = {11}, editor = {Cattaneo, Luigi}, publisher = {Plos}, address = {San Francisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0278051}, pages = {e0278051}, year = {2022}, abstract = {Exposure to prolonged periods in microgravity is associated with deconditioning of the musculoskeletal system due to chronic changes in mechanical stimulation. Given astronauts will operate on the Lunar surface for extended periods of time, it is critical to quantify both external (e.g., ground reaction forces) and internal (e.g., joint reaction forces) loads of relevant movements performed during Lunar missions. Such knowledge is key to predict musculoskeletal deconditioning and determine appropriate exercise countermeasures associated with extended exposure to hypogravity.}, language = {en} } @article{CollPeralesSchulteTiggesRondinoneetal.2022, author = {Coll-Perales, Baldomero and Schulte-Tigges, Joschua and Rondinone, Michele and Gozalvez, Javier and Reke, Michael and Matheis, Dominik and Walter, Thomas}, title = {Prototyping and evaluation of infrastructure-assisted transition of control for cooperative automated vehicles}, series = {IEEE Transactions on Intelligent Transportation Systems}, volume = {23}, journal = {IEEE Transactions on Intelligent Transportation Systems}, number = {7}, publisher = {IEEE}, issn = {1524-9050 (Print)}, doi = {10.1109/TITS.2021.3061085}, pages = {6720 -- 6736}, year = {2022}, abstract = {Automated driving is now possible in diverse road and traffic conditions. However, there are still situations that automated vehicles cannot handle safely and efficiently. In this case, a Transition of Control (ToC) is necessary so that the driver takes control of the driving. Executing a ToC requires the driver to get full situation awareness of the driving environment. If the driver fails to get back the control in a limited time, a Minimum Risk Maneuver (MRM) is executed to bring the vehicle into a safe state (e.g., decelerating to full stop). The execution of ToCs requires some time and can cause traffic disruption and safety risks that increase if several vehicles execute ToCs/MRMs at similar times and in the same area. This study proposes to use novel C-ITS traffic management measures where the infrastructure exploits V2X communications to assist Connected and Automated Vehicles (CAVs) in the execution of ToCs. The infrastructure can suggest a spatial distribution of ToCs, and inform vehicles of the locations where they could execute a safe stop in case of MRM. This paper reports the first field operational tests that validate the feasibility and quantify the benefits of the proposed infrastructure-assisted ToC and MRM management. The paper also presents the CAV and roadside infrastructure prototypes implemented and used in the trials. The conducted field trials demonstrate that infrastructure-assisted traffic management solutions can reduce safety risks and traffic disruptions.}, language = {en} } @article{KemptFreyerNagel2022, author = {Kempt, Hendrik and Freyer, Nils and Nagel, Saskia K.}, title = {Justice and the normative standards of explainability in healthcare}, series = {Philosophy \& Technology}, volume = {35}, journal = {Philosophy \& Technology}, number = {Article number: 100}, publisher = {Springer Nature}, address = {Berlin}, doi = {10.1007/s13347-022-00598-0}, pages = {1 -- 19}, year = {2022}, abstract = {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.}, language = {en} } @article{QuittmannAbelAlbrachtetal.2022, author = {Quittmann, Oliver J. and Abel, Thomas and Albracht, Kirsten and Str{\"u}der, Heiko K.}, title = {Biomechanics of all-out handcycling exercise: kinetics, kinematics and muscular activity of a 15-s sprint test in able-bodied participants}, series = {Sports Biomechanics}, volume = {21}, journal = {Sports Biomechanics}, number = {10}, publisher = {Taylor \& Francis}, address = {London}, issn = {1752-6116 (Onlineausgabe)}, doi = {10.1080/14763141.2020.1745266}, pages = {1200 -- 1223}, year = {2022}, abstract = {This study aims to quantify the kinematics, kinetics and muscular activity of all-out handcycling exercise and examine their alterations during the course of a 15-s sprint test. Twelve able-bodied competitive triathletes performed a 15-s all-out sprint test in a recumbent racing handcycle that was attached to an ergometer. During the sprint test, tangential crank kinetics, 3D joint kinematics and muscular activity of 10 muscles of the upper extremity and trunk were examined using a power metre, motion capturing and surface electromyography (sEMG), respectively. Parameters were compared between revolution one (R1), revolution two (R2), the average of revolution 3 to 13 (R3) and the average of the remaining revolutions (R4). Shoulder abduction and internal-rotation increased, whereas maximal shoulder retroversion decreased during the sprint. Except for the wrist angles, angular velocity increased for every joint of the upper extremity. Several muscles demonstrated an increase in muscular activation, an earlier onset of muscular activation in crank cycle and an increased range of activation. During the course of a 15-s all-out sprint test in handcycling, the shoulder muscles and the muscles associated to the push phase demonstrate indications for short-duration fatigue. These findings are helpful to prevent injuries and improve performance in all-out handcycling.}, language = {en} } @article{AngermannGuenthnerHanssenetal.2022, author = {Angermann, Susanne and G{\"u}nthner, Roman and Hanssen, Henner and Lorenz, Georg and Braunisch, Matthias C. and Steubl, Dominik and Matschkal, Julia and Kemmner, Stephan and Hausinger, Renate and Block, Zenonas and Haller, Bernhard and Heemann, Uwe and Kotliar, Konstantin and Grimmer, Timo and Schmaderer, Christoph}, title = {Cognitive impairment and microvascular function in end-stage renal disease}, series = {International Journal of Methods in Psychiatric Research (MPR)}, volume = {31}, journal = {International Journal of Methods in Psychiatric Research (MPR)}, number = {2}, publisher = {Wiley}, issn = {1049-8931 (Print)}, doi = {10.1002/mpr.1909}, pages = {1 -- 10}, year = {2022}, abstract = {Objective Hemodialysis patients show an approximately threefold higher prevalence of cognitive impairment compared to the age-matched general population. Impaired microcirculatory function is one of the assumed causes. Dynamic retinal vessel analysis is a quantitative method for measuring neurovascular coupling and microvascular endothelial function. We hypothesize that cognitive impairment is associated with altered microcirculation of retinal vessels. Methods 152 chronic hemodialysis patients underwent cognitive testing using the Montreal Cognitive Assessment. Retinal microcirculation was assessed by Dynamic Retinal Vessel Analysis, which carries out an examination recording retinal vessels' reaction to a flicker light stimulus under standardized conditions. Results In unadjusted as well as in adjusted linear regression analyses a significant association between the visuospatial executive function domain score of the Montreal Cognitive Assessment and the maximum arteriolar dilation as response of retinal arterioles to the flicker light stimulation was obtained. Conclusion This is the first study determining retinal microvascular function as surrogate for cerebral microvascular function and cognition in hemodialysis patients. The relationship between impairment in executive function and reduced arteriolar reaction to flicker light stimulation supports the involvement of cerebral small vessel disease as contributing factor for the development of cognitive impairment in this patient population and might be a target for noninvasive disease monitoring and therapeutic intervention.}, language = {en} } @article{KotliarOrtnerConradietal.2022, author = {Kotliar, Konstantin and Ortner, Marion and Conradi, Anna and Hacker, Patricia and Hauser, Christine and G{\"u}nthner, Roman and Moser, Michaela and Muggenthaler, Claudia and Diehl-Schmid, Janine and Priller, Josef and Schmaderer, Christoph and Grimmer, Timo}, title = {Altered retinal cerebral vessel oscillation frequencies in Alzheimer's disease compatible with impaired amyloid clearance}, series = {Neurobiology of Aging}, volume = {120}, journal = {Neurobiology of Aging}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0197-4580}, doi = {10.1016/j.neurobiolaging.2022.08.012}, pages = {117 -- 127}, year = {2022}, abstract = {Retinal vessels are similar to cerebral vessels in their structure and function. Moderately low oscillation frequencies of around 0.1 Hz have been reported as the driving force for paravascular drainage in gray matter in mice and are known as the frequencies of lymphatic vessels in humans. We aimed to elucidate whether retinal vessel oscillations are altered in Alzheimer's disease (AD) at the stage of dementia or mild cognitive impairment (MCI). Seventeen patients with mild-to-moderate dementia due to AD (ADD); 23 patients with MCI due to AD, and 18 cognitively healthy controls (HC) were examined using Dynamic Retinal Vessel Analyzer. Oscillatory temporal changes of retinal vessel diameters were evaluated using mathematical signal analysis. Especially at moderately low frequencies around 0.1 Hz, arterial oscillations in ADD and MCI significantly prevailed over HC oscillations and correlated with disease severity. The pronounced retinal arterial vasomotion at moderately low frequencies in the ADD and MCI groups would be compatible with the view of a compensatory upregulation of paravascular drainage in AD and strengthen the amyloid clearance hypothesis.}, language = {en} } @article{WerfelGuenthnerHapfelmeieretal.2022, author = {Werfel, Stanislas and G{\"u}nthner, Roman and Hapfelmeier, Alexander and Hanssen, Henner and Kotliar, Konstantin and Heemann, Uwe and Schmaderer, Christoph}, title = {Identification of cardiovascular high-risk groups from dynamic retinal vessel signals using untargeted machine learning}, series = {Cardiovascular Research}, volume = {118}, journal = {Cardiovascular Research}, number = {2}, editor = {Guzik, Tomasz J.}, publisher = {Oxford University Press}, address = {Oxford}, issn = {0008-6363}, doi = {10.1093/cvr/cvab040}, pages = {612 -- 621}, year = {2022}, abstract = {Dynamic retinal vessel analysis (DVA) provides a non-invasive way to assess microvascular function in patients and potentially to improve predictions of individual cardiovascular (CV) risk. The aim of our study was to use untargeted machine learning on DVA in order to improve CV mortality prediction and identify corresponding response alterations.}, language = {en} } @article{UysalCreutzFiratetal.2022, author = {Uysal, Karya and Creutz, Till and Firat, Ipek Seda and Artmann, Gerhard and Teusch, Nicole and Temiz Artmann, Ayseg{\"u}l}, title = {Bio-functionalized ultra-thin, large-area and waterproof silicone membranes for biomechanical cellular loading and compliance experiments}, series = {Polymers}, volume = {14}, journal = {Polymers}, number = {11}, publisher = {MDPI}, address = {Basel}, issn = {2073-4360}, pages = {2213}, year = {2022}, abstract = {Biocompatibility, flexibility and durability make polydimethylsiloxane (PDMS) membranes top candidates in biomedical applications. CellDrum technology uses large area, <10 µm thin membranes as mechanical stress sensors of thin cell layers. For this to be successful, the properties (thickness, temperature, dust, wrinkles, etc.) must be precisely controlled. The following parameters of membrane fabrication by means of the Floating-on-Water (FoW) method were investigated: (1) PDMS volume, (2) ambient temperature, (3) membrane deflection and (4) membrane mechanical compliance. Significant differences were found between all PDMS volumes and thicknesses tested (p < 0.01). They also differed from the calculated values. At room temperatures between 22 and 26 °C, significant differences in average thickness values were found, as well as a continuous decrease in thicknesses within a 4 °C temperature elevation. No correlation was found between the membrane thickness groups (between 3-4 µm) in terms of deflection and compliance. We successfully present a fabrication method for thin bio-functionalized membranes in conjunction with a four-step quality management system. The results highlight the importance of tight regulation of production parameters through quality control. The use of membranes described here could also become the basis for material testing on thin, viscous layers such as polymers, dyes and adhesives, which goes far beyond biological applications.}, language = {en} } @article{HeinEubanksLingametal.2022, author = {Hein, Andreas M. and Eubanks, T. Marshall and Lingam, Manasvi and Hibberd, Adam and Fries, Dan and Schneider, Jean and Kervella, Pierre and Kennedy, Robert and Perakis, Nikolaos and Dachwald, Bernd}, title = {Interstellar now! Missions to explore nearby interstellar objects}, series = {Advances in Space Research}, volume = {69}, journal = {Advances in Space Research}, number = {1}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0273-1177}, doi = {10.1016/j.asr.2021.06.052}, pages = {402 -- 414}, year = {2022}, abstract = {The recently discovered first hyperbolic objects passing through the Solar System, 1I/'Oumuamua and 2I/Borisov, have raised the question about near term missions to Interstellar Objects. In situ spacecraft exploration of these objects will allow the direct determination of both their structure and their chemical and isotopic composition, enabling an entirely new way of studying small bodies from outside our solar system. In this paper, we map various Interstellar Object classes to mission types, demonstrating that missions to a range of Interstellar Object classes are feasible, using existing or near-term technology. We describe flyby, rendezvous and sample return missions to interstellar objects, showing various ways to explore these bodies characterizing their surface, dynamics, structure and composition. Their direct exploration will constrain their formation and history, situating them within the dynamical and chemical evolution of the Galaxy. These mission types also provide the opportunity to explore solar system bodies and perform measurements in the far outer solar system.}, language = {en} } @article{vonHaefenKrautwaldStolleetal.2022, author = {von H{\"a}fen, Hajo and Krautwald, Clemens and Stolle, Jacob and Bung, Daniel Bernhard and Goseberg, Nils}, title = {Overland flow of broken solitary waves over a two-dimensional coastal plane}, series = {Coastal Engineering}, volume = {175}, journal = {Coastal Engineering}, number = {August}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1872-7379}, doi = {10.1016/j.coastaleng.2022.104125}, pages = {14 Seiten}, year = {2022}, abstract = {Landslides, rock falls or related subaerial and subaqueous mass slides can generate devastating impulse waves in adjacent waterbodies. Such waves can occur in lakes and fjords, or due to glacier calving in bays or at steep ocean coastlines. Infrastructure and residential houses along coastlines of those waterbodies are often situated on low elevation terrain, and are potentially at risk from inundation. Impulse waves, running up a uniform slope and generating an overland flow over an initially dry adjacent horizontal plane, represent a frequently found scenario, which needs to be better understood for disaster planning and mitigation. This study presents a novel set of large-scale flume test focusing on solitary waves propagating over a 1:14.5 slope and breaking onto a horizontal section. Examining the characteristics of overland flow, this study gives, for the first time, insight into the fundamental process of overland flow of a broken solitary wave: its shape and celerity, as well as its momentum when wave breaking has taken place beforehand.}, language = {en} } @article{TopcuMadabhushiStaat2022, author = {Top{\c{c}}u, Murat and Madabhushi, Gopal S.P. and Staat, Manfred}, title = {A generalized shear-lag theory for elastic stress transfer between matrix and fibres having a variable radius}, series = {International Journal of Solids and Structures}, volume = {239-240}, journal = {International Journal of Solids and Structures}, number = {Art. No. 111464}, publisher = {Elsevier}, address = {New York, NY}, issn = {0020-7683}, doi = {10.1016/j.ijsolstr.2022.111464}, year = {2022}, abstract = {A generalized shear-lag theory for fibres with variable radius is developed to analyse elastic fibre/matrix stress transfer. The theory accounts for the reinforcement of biological composites, such as soft tissue and bone tissue, as well as for the reinforcement of technical composite materials, such as fibre-reinforced polymers (FRP). The original shear-lag theory proposed by Cox in 1952 is generalized for fibres with variable radius and with symmetric and asymmetric ends. Analytical solutions are derived for the distribution of axial and interfacial shear stress in cylindrical and elliptical fibres, as well as conical and paraboloidal fibres with asymmetric ends. Additionally, the distribution of axial and interfacial shear stress for conical and paraboloidal fibres with symmetric ends are numerically predicted. The results are compared with solutions from axisymmetric finite element models. A parameter study is performed, to investigate the suitability of alternative fibre geometries for use in FRP.}, language = {en} } @article{BhattaraiHorbachStaatetal.2022, author = {Bhattarai, Aroj and Horbach, Andreas and Staat, Manfred and Kowalczyk, Wojciech and Tran, Thanh Ngoc}, title = {Virgin passive colon biomechanics and a literature review of active contraction constitutive models}, series = {Biomechanics}, volume = {2}, journal = {Biomechanics}, number = {2}, publisher = {MDPI}, address = {Basel}, issn = {2673-7078}, doi = {10.3390/biomechanics2020013}, pages = {138 -- 157}, year = {2022}, abstract = {The objective of this paper is to present our findings on the biomechanical aspects of the virgin passive anisotropic hyperelasticity of the porcine colon based on equibiaxial tensile experiments. Firstly, the characterization of the intestine tissues is discussed for a nearly incompressible hyperelastic fiber-reinforced Holzapfel-Gasser-Ogden constitutive model in virgin passive loading conditions. The stability of the evaluated material parameters is checked for the polyconvexity of the adopted strain energy function using positive eigenvalue constraints of the Hessian matrix with MATLAB. The constitutive material description of the intestine with two collagen fibers in the submucosal and muscular layer each has been implemented in the FORTRAN platform of the commercial finite element software LS-DYNA, and two equibiaxial tensile simulations are presented to validate the results with the optical strain images obtained from the experiments. Furthermore, this paper also reviews the existing models of the active smooth muscle cells, but these models have not been computationally studied here. The review part shows that the constitutive models originally developed for the active contraction of skeletal muscle based on Hill's three-element model, Murphy's four-state cross-bridge chemical kinetic model and Huxley's sliding-filament hypothesis, which are mainly used for arteries, are appropriate for numerical contraction numerical analysis of the large intestine.}, language = {en} } @article{MarinkovićButenweg2022, author = {Marinković, Marko and Butenweg, Christoph}, title = {Experimental testing of decoupled masonry infills with steel anchors for out-of-plane support under combined in-plane and out-of-plane seismic loading}, series = {Construction and Building Materials}, volume = {318}, journal = {Construction and Building Materials}, number = {1}, editor = {Ford, Michael C.}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1879-0526}, doi = {10.1016/j.conbuildmat.2021.126041}, year = {2022}, abstract = {Because of simple construction process, high energy efficiency, significant fire resistance and excellent sound isolation, masonry infilled reinforced concrete (RC) frame structures are very popular in most of the countries in the world, as well as in seismic active areas. However, many RC frame structures with masonry infills were seriously damaged during earthquake events, as the traditional infills are generally constructed with direct contact to the RC frame which brings undesirable infill/frame interaction. This interaction leads to the activation of the equivalent diagonal strut in the infill panel, due to the RC frame deformation, and combined with seismically induced loads perpendicular to the infill panel often causes total collapses of the masonry infills and heavy damages to the RC frames. This fact was the motivation for developing different approaches for improving the behaviour of masonry infills, where infill isolation (decoupling) from the frame has been more intensively studied in the last decade. In-plane isolation of the infill wall reduces infill activation, but causes the need for additional measures to restrain out-of-plane movements. This can be provided by installing steel anchors, as proposed by some researchers. Within the framework of European research project INSYSME (Innovative Systems for Earthquake Resistant Masonry Enclosures in Reinforced Concrete Buildings) the system based on a use of elastomers for in-plane decoupling and steel anchors for out-of-plane restrain was tested. This constructive solution was tested and deeply investigated during the experimental campaign where traditional and decoupled masonry infilled RC frames with anchors were subjected to separate and combined in-plane ‬and out-of-plane loading. Based on a detailed evaluation and comparison of the test results, the performance and effectiveness of the developed system are illustrated.}, language = {en} } @article{TranTrinhDaoetal.2022, author = {Tran, Ngoc Trinh and Trinh, Tu Luc and Dao, Ngoc Tien and Giap, Van Tan and Truong, Manh Khuyen and Dinh, Thuy Ha and Staat, Manfred}, title = {FEM shakedown analysis of structures under random strength with chance constrained programming}, series = {Vietnam Journal of Mechanics}, volume = {44}, journal = {Vietnam Journal of Mechanics}, number = {4}, publisher = {Vietnam Academy of Science and Technology (VAST)}, issn = {0866-7136}, doi = {10.15625/0866-7136/17943}, pages = {459 -- 473}, year = {2022}, abstract = {Direct methods, comprising limit and shakedown analysis, are a branch of computational mechanics. They play a significant role in mechanical and civil engineering design. The concept of direct methods aims to determine the ultimate load carrying capacity of structures beyond the elastic range. In practical problems, the direct methods lead to nonlinear convex optimization problems with a large number of variables and constraints. If strength and loading are random quantities, the shakedown analysis can be formulated as stochastic programming problem. In this paper, a method called chance constrained programming is presented, which is an effective method of stochastic programming to solve shakedown analysis problems under random conditions of strength. In this study, the loading is deterministic, and the strength is a normally or lognormally distributed variable.}, language = {en} } @article{HeuermannEmmrichBongartz2022, author = {Heuermann, Holger and Emmrich, Thomas and Bongartz, Simon}, title = {Microwave spark plug to support ignitions with high compression ratios}, series = {IEEE Transactions on Plasma Science}, journal = {IEEE Transactions on Plasma Science}, number = {Early Access}, publisher = {IEEE}, issn = {1939-9375}, doi = {10.1109/TPS.2022.3183690}, pages = {1 -- 6}, year = {2022}, abstract = {Upcoming gasoline engines should run with a larger number of fuels beginning from petrol over methanol up to gas by a wide range of compression ratios and a homogeneous charge. In this article, the microwave (MW) spark plug, based on a high-speed frequency hopping system, is introduced as a solution, which can support a nitrogen compression ratio up to 1:39 in a chamber and more. First, an overview of the high-speed frequency hopping MW ignition and operation system as well as the large number of applications are presented. Both gives an understanding of this new base technology for MW plasma generation. Focus of the theoretical part is the explanation of the internal construction of the spark plug, on the achievable of the high voltage generation as well as the high efficiency to hold the plasma. In detail, the development process starting with circuit simulations and ending with the numerical multiphysics field simulations is described. The concept is evaluated with a reference prototype covering the frequency range between 2.40 and 2.48 GHz and working over a large power range from 20 to 200 W. A larger number of different measurements starting by vector hot-S11 measurements and ending by combined working scenarios out of hot temperature, high pressure and charge motion are winding up the article. The limits for the successful pressure tests were given by the pressure chamber. Pressures ranged from 1 to 39 bar and charge motion up to 25 m/s as well as temperatures from 30◦ to 125◦.}, language = {en} } @article{MonakhovaDiehl2022, author = {Monakhova, Yulia and Diehl, Bernd W.K.}, title = {Multinuclear NMR screening of pharmaceuticals using standardization by 2H integral of a deuterated solvent}, series = {Journal of Pharmaceutical and Biomedical Analysis}, volume = {209}, journal = {Journal of Pharmaceutical and Biomedical Analysis}, number = {Article number: 114530}, publisher = {Elsevier}, isbn = {0731-7085}, doi = {10.1016/j.jpba.2021.114530}, year = {2022}, abstract = {NMR standardization approach that uses the 2H integral of deuterated solvent for quantitative multinuclear analysis of pharmaceuticals is described. As a proof of principle, the existing NMR procedure for the analysis of heparin products according to US Pharmacopeia monograph is extended to the determination of Na+ and Cl- content in this matrix. Quantification is performed based on the ratio of a 23Na (35Cl) NMR integral and 2H NMR signal of deuterated solvent, D2O, acquired using the specific spectrometer hardware. As an alternative, the possibility of 133Cs standardization using the addition of Cs2CO3 stock solution is shown. Validation characteristics (linearity, repeatability, sensitivity) are evaluated. A holistic NMR profiling of heparin products can now also be used for the quantitative determination of inorganic compounds in a single analytical run using a single sample. In general, the new standardization methodology provides an appealing alternative for the NMR screening of inorganic and organic components in pharmaceutical products.}, language = {en} } @article{EngelmannPourshahidiShalabyetal.2022, author = {Engelmann, Ulrich M. and Pourshahidi, Mohammad Ali and Shalaby, Ahmed and Krause, Hans-Joachim}, title = {Probing particle size dependency of frequency mixing magnetic detection with dynamic relaxation simulation}, series = {Journal of Magnetism and Magnetic Materials}, volume = {563}, journal = {Journal of Magnetism and Magnetic Materials}, number = {In progress, Art. No. 169965}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0304-8853}, doi = {10.1016/j.jmmm.2022.169965}, year = {2022}, abstract = {Biomedical applications of magnetic nanoparticles (MNP) fundamentally rely on the particles' magnetic relaxation as a response to an alternating magnetic field. The magnetic relaxation complexly depends on the interplay of MNP magnetic and physical properties with the applied field parameters. It is commonly accepted that particle core size is a major contributor to signal generation in all the above applications, however, most MNP samples comprise broad distribution spanning nm and more. Therefore, precise knowledge of the exact contribution of individual core sizes to signal generation is desired for optimal MNP design generally for each application. Specifically, we present a magnetic relaxation simulation-driven analysis of experimental frequency mixing magnetic detection (FMMD) for biosensing to quantify the contributions of individual core size fractions towards signal generation. Applying our method to two different experimental MNP systems, we found the most dominant contributions from approx. 20 nm sized particles in the two independent MNP systems. Additional comparison between freely suspended and immobilized MNP also reveals insight in the MNP microstructure, allowing to use FMMD for MNP characterization, as well as to further fine-tune its applicability in biosensing.}, language = {en} } @article{PourshahidiEngelmannOffenhaeusseretal.2022, author = {Pourshahidi, Ali Mohammad and Engelmann, Ulrich M. and Offenh{\"a}usser, Andreas and Krause, Hans-Joachim}, title = {Resolving ambiguities in core size determination of magnetic nanoparticles from magnetic frequency mixing data}, series = {Journal of Magnetism and Magnetic Materials}, volume = {563}, journal = {Journal of Magnetism and Magnetic Materials}, number = {In progress, Art. No. 169969}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0304-8853}, doi = {10.1016/j.jmmm.2022.169969}, year = {2022}, abstract = {Frequency mixing magnetic detection (FMMD) has been widely utilized as a measurement technique in magnetic immunoassays. It can also be used for the characterization and distinction (also known as "colourization") of different types of magnetic nanoparticles (MNPs) based on their core sizes. In a previous work, it was shown that the large particles contribute most of the FMMD signal. This leads to ambiguities in core size determination from fitting since the contribution of the small-sized particles is almost undetectable among the strong responses from the large ones. In this work, we report on how this ambiguity can be overcome by modelling the signal intensity using the Langevin model in thermodynamic equilibrium including a lognormal core size distribution fL(dc,d0,σ) fitted to experimentally measured FMMD data of immobilized MNPs. For each given median diameter d0, an ambiguous amount of best-fitting pairs of parameters distribution width σ and number of particles Np with R2 > 0.99 are extracted. By determining the samples' total iron mass, mFe, with inductively coupled plasma optical emission spectrometry (ICP-OES), we are then able to identify the one specific best-fitting pair (σ, Np) one uniquely. With this additional externally measured parameter, we resolved the ambiguity in core size distribution and determined the parameters (d0, σ, Np) directly from FMMD measurements, allowing precise MNPs sample characterization.}, language = {en} } @article{MonakhovaDiehl2022, author = {Monakhova, Yulia and Diehl, Bernd W.K.}, title = {Nuclear magnetic resonance spectroscopy as an elegant tool for a complete quality control of crude heparin material}, series = {Journal of Pharmaceutical and Biomedical Analysis}, volume = {219}, journal = {Journal of Pharmaceutical and Biomedical Analysis}, number = {Article number: 114915}, publisher = {Elsevier}, address = {New York, NY}, issn = {0731-7085}, doi = {10.1016/j.jpba.2022.114915}, year = {2022}, abstract = {Nuclear magnetic resonance (NMR) spectrometric methods for the quantitative analysis of pure heparin in crude heparin is proposed. For quantification, a two-step routine was developed using a USP heparin reference sample for calibration and benzoic acid as an internal standard. The method was successfully validated for its accuracy, reproducibility, and precision. The methodology was used to analyze 20 authentic porcine heparinoid samples having heparin content between 4.25 w/w \% and 64.4 w/w \%. The characterization of crude heparin products was further extended to a simultaneous analysis of these common ions: sodium, calcium, acetate and chloride. A significant, linear dependence was found between anticoagulant activity and assayed heparin content for thirteen heparinoids samples, for which reference data were available. A Diffused-ordered NMR experiment (DOSY) can be used for qualitative analysis of specific glycosaminoglycans (GAGs) in heparinoid matrices and, potentially, for quantitative prediction of molecular weight of GAGs. NMR spectrometry therefore represents a unique analytical method suitable for the simultaneous quantitative control of organic and inorganic composition of crude heparin samples (especially heparin content) as well as an estimation of other physical and quality parameters (molecular weight, animal origin and activity).}, language = {en} } @article{BurgerLindnerRumpfetal.2022, author = {Burger, Ren{\´e} and Lindner, Simon and Rumpf, Jessica and Do, Xuan Tung and Diehl, Bernd W.K. and Rehahn, Matthias and Monakhova, Yulia and Schulze, Margit}, title = {Benchtop versus high field NMR: Comparable performance found for the molecular weight determination of lignin}, series = {Journal of Pharmaceutical and Biomedical Analysis}, volume = {212}, journal = {Journal of Pharmaceutical and Biomedical Analysis}, number = {Article number: 114649}, publisher = {Elsevier}, address = {New York, NY}, isbn = {0731-7085}, doi = {10.1016/j.jpba.2022.114649}, year = {2022}, abstract = {Lignin is a promising renewable biopolymer being investigated worldwide as an environmentally benign substitute of fossil-based aromatic compounds, e.g. for the use as an excipient with antioxidant and antimicrobial properties in drug delivery or even as active compound. For its successful implementation into process streams, a quick, easy, and reliable method is needed for its molecular weight determination. Here we present a method using 1H spectra of benchtop as well as conventional NMR systems in combination with multivariate data analysis, to determine lignin's molecular weight (Mw and Mn) and polydispersity index (PDI). A set of 36 organosolv lignin samples (from Miscanthus x giganteus, Paulownia tomentosa and Silphium perfoliatum) was used for the calibration and cross validation, and 17 samples were used as external validation set. Validation errors between 5.6\% and 12.9\% were achieved for all parameters on all NMR devices (43, 60, 500 and 600 MHz). Surprisingly, no significant difference in the performance of the benchtop and high-field devices was found. This facilitates the application of this method for determining lignin's molecular weight in an industrial environment because of the low maintenance expenditure, small footprint, ruggedness, and low cost of permanent magnet benchtop NMR systems.}, language = {en} }