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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.
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.
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.
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.
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).
In the Laser Powder Bed Fusion (LPBF) process, parts are built out of metal powder material by exposure of a laser beam. During handling operations of the powder material, several influencing factors can affect the properties of the powder material and therefore directly influence the processability during manufacturing. Contamination by moisture due to handling operations is one of the most critical aspects of powder quality. In order to investigate the influences of powder humidity on LPBF processing, four materials (AlSi10Mg, Ti6Al4V, 316L and IN718) are chosen for this study. The powder material is artificially humidified, subsequently characterized, manufactured into cubic samples in a miniaturized process chamber and analyzed for their relative density. The results indicate that the processability and reproducibility of parts made of AlSi10Mg and Ti6Al4V are susceptible to humidity, while IN718 and 316L are barely influenced.
Additive Manufacturing (AM) of metallic workpieces faces a continuously rising technological relevance and market size. Producing complex or highly strained unique workpieces is a significant field of application, making AM highly relevant for tool components. Its successful economic application requires systematic workpiece based decisions and optimizations. Considering geometric and technological requirements as well as the necessary post-processing makes deciding effortful and requires in-depth knowledge. As design is usually adjusted to established manufacturing, associated technological and strategic potentials are often neglected. To embed AM in a future proof industrial environment, software-based self-learning tools are necessary. Integrated into production planning, they enable companies to unlock the potentials of AM efficiently. This paper presents an appropriate methodology for the analysis of process-specific AM-eligibility and optimization potential, added up by concrete optimization proposals. For an integrated workpiece characterization, proven methods are enlarged by tooling-specific figures.
The first stage of the approach specifies the model’s initialization. A learning set of tooling components is described using the developed key figure system. Based on this, a set of applicable rules for workpiece-specific result determination is generated through clustering and expert evaluation. Within the following application stage, strategic orientation is quantified and workpieces of interest are described using the developed key figures. Subsequently, the retrieved information is used for automatically generating specific recommendations relying on the generated ruleset of stage one. Finally, actual experiences regarding the recommendations are gathered within stage three. Statistic learning transfers those to the generated ruleset leading to a continuously deepening knowledge base. This process enables a steady improvement in output quality.
Gamification applications are on the rise in the manufacturing sector to customize working scenarios, offer user-specific feedback, and provide personalized learning offerings. Commonly, different sensors are integrated into work environments to track workers’ actions. Game elements are selected according to the work task and users’ preferences. However, implementing gamified workplaces remains challenging as different data sources must be established, evaluated, and connected. Developers often require information from several areas of the companies to offer meaningful gamification strategies for their employees. Moreover, work environments and the associated support systems are usually not flexible enough to adapt to personal needs. Digital twins are one primary possibility to create a uniform data approach that can provide semantic information to gamification applications. Frequently, several digital twins have to interact with each other to provide information about the workplace, the manufacturing process, and the knowledge of the employees. This research aims to create an overview of existing digital twin approaches for digital support systems and presents a concept to use digital twins for gamified support and training systems. The concept is based upon the Reference Architecture Industry 4.0 (RAMI 4.0) and includes information about the whole life cycle of the assets. It is applied to an existing gamified training system and evaluated in the Industry 4.0 model factory by an example of a handle mounting.
Virtual Reality (VR) offers novel possibilities for remote training regardless of the availability of the actual equipment, the presence of specialists, and the training locations. Research shows that training environments that adapt to users' preferences and performance can promote more effective learning. However, the observed results can hardly be traced back to specific adaptive measures but the whole new training approach. This study analyzes the effects of a combined point and leveling VR-based gamification system on assembly training targeting specific training outcomes and users' motivations. The Gamified-VR-Group with 26 subjects received the gamified training, and the Non-Gamified-VR-Group with 27 subjects received the alternative without gamified elements. Both groups conducted their VR training at least three times before assembling the actual structure. The study found that a level system that gradually increases the difficulty and error probability in VR can significantly lower real-world error rates, self-corrections, and support usages. According to our study, a high error occurrence at the highest training level reduced the Gamified-VR-Group's feeling of competence compared to the Non-Gamified-VR-Group, but at the same time also led to lower error probabilities in real-life. It is concluded that a level system with a variable task difficulty should be combined with carefully balanced positive and negative feedback messages. This way, better learning results, and an improved self-evaluation can be achieved while not causing significant impacts on the participants' feeling of competence.
Searching optimal interplanetary trajectories for low-thrust spacecraft is usually a difficult and time-consuming task that involves much experience and expert knowledge in astrodynamics and optimal control theory. This is because the convergence behavior of traditional local optimizers, which are based on numerical optimal control methods, depends on an adequate initial guess, which is often hard to find, especially for very-low-thrust trajectories that necessitate many revolutions around the sun. The obtained solutions are typically close to the initial guess that is rarely close to the (unknown) global optimum. Within this paper, trajectory optimization problems are attacked from the perspective of artificial intelligence and machine learning. Inspired by natural archetypes, a smart global method for low-thrust trajectory optimization is proposed that fuses artificial neural networks and evolutionary algorithms into so-called evolutionary neurocontrollers. This novel method runs without an initial guess and does not require the attendance of an expert in astrodynamics and optimal control theory. This paper details how evolutionary neurocontrol works and how it could be implemented. The performance of the method is assessed for three different interplanetary missions with a thrust to mass ratio <0.15mN/kg (solar sail and nuclear electric).
Unsteady shallow meandering flows in rectangular reservoirs: a modal analysis of URANS modelling
(2022)
Shallow flows are common in natural and human-made environments. Even for simple rectangular shallow reservoirs, recent laboratory experiments show that the developing flow fields are particularly complex, involving large-scale turbulent structures. For specific combinations of reservoir size and hydraulic conditions, a meandering jet can be observed. While some aspects of this pseudo-2D flow pattern can be reproduced using a 2D numerical model, new 3D simulations, based on the unsteady Reynolds-Averaged Navier-Stokes equations, show consistent advantages as presented herein. A Proper Orthogonal Decomposition was used to characterize the four most energetic modes of the meandering jet at the free surface level, allowing comparison against experimental data and 2D (depth-averaged) numerical results. Three different isotropic eddy viscosity models (RNG k-ε, k-ε, k-ω) were tested. The 3D models accurately predicted the frequency of the modes, whereas the amplitudes of the modes and associated energy were damped for the friction-dominant cases and augmented for non-frictional ones. The performance of the three turbulence models remained essentially similar, with slightly better predictions by RNG k-ε model in the case with the highest Reynolds number. Finally, the Q-criterion was used to identify vortices and study their dynamics, assisting on the identification of the differences between: i) the three-dimensional phenomenon (here reproduced), ii) its two-dimensional footprint in the free surface (experimental observations) and iii) the depth-averaged case (represented by 2D models).
Solar thermal concentrated power is an emerging technology that provides clean electricity for the growing energy market. To the solar thermal concentrated power plant systems belong the parabolic trough, the Fresnel collector, the solar dish, and the central receiver system.
For high-concentration solar collector systems, optical and thermal analysis is essential. There exist a number of measurement techniques and systems for the optical and thermal characterization of the efficiency of solar thermal concentrated systems.
For each system, structure, components, and specific characteristics types are described. The chapter presents additionally an outline for the calculation of system performance and operation and maintenance topics. One main focus is set to the models of components and their construction details as well as different types on the market. In the later part of this article, different criteria for the choice of technology are analyzed in detail.
Concentrating solar power
(2022)
The focus of this chapter is the production of power and the use of the heat produced from concentrated solar thermal power (CSP) systems.
The chapter starts with the general theoretical principles of concentrating systems including the description of the concentration ratio, the energy and mass balance. The power conversion systems is the main part where solar-only operation and the increase in operational hours.
Solar-only operation include the use of steam turbines, gas turbines, organic Rankine cycles and solar dishes. The operational hours can be increased with hybridization and with storage.
Another important topic is the cogeneration where solar cooling, desalination and of heat usage is described.
Many examples of commercial CSP power plants as well as research facilities from the past as well as current installed and in operation are described in detail.
The chapter closes with economic and environmental aspects and with the future potential of the development of CSP around the world.
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.
Adapting augmented reality systems to the users’ needs using gamification and error solving methods
(2021)
Animations of virtual items in AR support systems are typically predefined and lack interactions with dynamic physical environments. AR applications rarely consider users’ preferences and do not provide customized spontaneous support under unknown situations. This research focuses on developing adaptive, error-tolerant AR systems based on directed acyclic graphs and error resolving strategies. Using this approach, users will have more freedom of choice during AR supported work, which leads to more efficient workflows. Error correction methods based on CAD models and predefined process data create individual support possibilities. The framework is implemented in the Industry 4.0 model factory at FH Aachen.
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.