@phdthesis{Schilling2020, author = {Schilling, Klaus Jussi}, title = {Liquid chromatographic analysis of weakly- and non-chromophore compounds focusing on Charged Aerosol Detection}, doi = {10.25972/OPUS-20211}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202114}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2020}, abstract = {Liquid chromatography has become the gold standard for modern quality control and purity analytics since its establishment in the 1930s. However, some analytical questions remain very challenging even today. Several molecules and impurities do not possess a suitable chromophore for the application of UV detection or cannot be retained well on regular RP columns. Possible solutions are found in derivatization procedures, but they are time consuming and can be prone to errors. In order to detect non chromophore molecules underivatized, the concept of aerosol based universal detection was established with the introduction of the evaporative light scattering detector (ELSD) in the 1970s and the charged aerosol detector (CAD) followed in 2002. These two challenging fields - polar and non chromophore molecules - are tackled in this thesis. An overview of applications of the CAD in the literature and a comparison to its aerosol based competitors and MS is presented, emphasizing on its high sensitivity and robustness. Parameters and techniques to overcome the drawbacks of CAD, such as the use of gradient compensation or adjusted evaporation temperatures are discussed. A consideration of aspects and drawbacks of data transformation such as the integrated power function value (PFV) in the GMP environment is performed. A method for the fatty acid analysis in polysorbate 80 that was developed on HPLC CAD was transferred to UHPLC CAD. Time and eluent savings of over 75\% and 40\%, respectively, as well as ways to determine the optimal CAD parameters resulted from this investigation. The evaporation temperature was determined as the most crucial setting, which has to be adjusted with care. Optimal signal to noise ratios are found at a compromise between maintaining analyte signal and reducing background noise. The incorporation of semi volatile short chain fatty acids enabled the observation of differences based on volatility of the analyte. E.g. for semi volatiles, an improved linearity by means of adjusting the PFV is achieved at values below 1.0 instead of at elevated PFVs. Using sugars and sugar related antibiotics, a proof-of-concept was given that artificial neural networks can describe correlations between the structure and physicochemical properties of molecules and their response in CAD. Quantitative structure property relationships obtained by design of experiment approaches were able to predict the response of unseen substances and yielded insights on the response generation of the detector, which heavily relies on the formed surface area of the dried particle. Further work can substantiate upon these findings, eventually building a library of diverse eluent compositions, analytes and settings. In order to cope with a chromatographically challenging substances, the application of ion pairing reversed phase chromatography coupled to low wavelength UV detection has been shown as a possible approach for the amino acid L asparagine. A method capable of compendial purity analysis in one single HPLC approach, thus making the utilization of the semi quantitative TLC-ninhydrin analysis obsolete, resulted from this. One cyclic dipeptide impurity (diketoasparagine) that was formerly not assessed, could be identified in several batches and added to the monograph of the Ph.Eur. Studying ibandronate sodium with CAD and ELSD, it was found that randomly occurring spike peaks represent a major flaw of the ELSD when high sample load is present. The research with this non chromophore bisphosphonate drug furthermore shed light on possible drawbacks of mixed mode chromatography methods and ways to overcome these issues. Due to strong adsorption of the analyte onto the column, over ten injections of the highly concentrated test solution were found to be necessary to ensure reproducible peak areas. Preconditioning steps should thus be evaluated for mixed mode approaches during method development and validation. Last, using a ternary mixed mode stationary phase coupled to CAD, a method for the impurity profiling of pamidronate disodium, also applicable to the assessment of phosphate and phosphite in four other bisphosphonate drugs, has been developed. This represents a major advantage over the Ph.Eur. impurity profiling of pamidronate, which requires two different methods, one of which is only a semi quantitative TLC approach.}, subject = {HPLC}, language = {en} } @article{BaierBaierSaipSchillingetal.2016, author = {Baier, Pablo A. and Baier-Saip, J{\"u}rgen A. and Schilling, Klaus and Oliveira, Jauvane C.}, title = {Simulator for Minimally Invasive Vascular Interventions: Hardware and Software}, series = {Presence}, volume = {25}, journal = {Presence}, number = {2}, issn = {1531-3263}, doi = {10.1162/PRES_a_00250}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-140580}, pages = {108-128}, year = {2016}, abstract = {In the present work, a simulation system is proposed that can be used as an educational tool by physicians in training basic skills of minimally invasive vascular interventions. In order to accomplish this objective, initially the physical model of the wire proposed by Konings has been improved. As a result, a simpler and more stable method was obtained to calculate the equilibrium configuration of the wire. In addition, a geometrical method is developed to perform relaxations. It is particularly useful when the wire is hindered in the physical method because of the boundary conditions. Then a recipe is given to merge the physical and the geometrical methods, resulting in efficient relaxations. Moreover, tests have shown that the shape of the virtual wire agrees with the experiment. The proposed algorithm allows real-time executions, and furthermore, the hardware to assemble the simulator has a low cost.}, language = {en} } @article{LauterbachBorrmannHessetal.2015, author = {Lauterbach, Helge A. and Borrmann, Dorit and Heß, Robin and Eck, Daniel and Schilling, Klaus and N{\"u}chter, Andreas}, title = {Evaluation of a Backpack-Mounted 3D Mobile Scanning System}, series = {Remote Sensing}, volume = {7}, journal = {Remote Sensing}, number = {10}, doi = {10.3390/rs71013753}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126247}, pages = {13753-13781}, year = {2015}, abstract = {Recently, several backpack-mounted systems, also known as personal laser scanning systems, have been developed. They consist of laser scanners or cameras that are carried by a human operator to acquire measurements of the environment while walking. These systems were first designed to overcome the challenges of mapping indoor environments with doors and stairs. While the human operator inherently has the ability to open doors and to climb stairs, the flexible movements introduce irregularities of the trajectory to the system. To compete with other mapping systems, the accuracy of these systems has to be evaluated. In this paper, we present an extensive evaluation of our backpack mobile mapping system in indoor environments. It is shown that the system can deal with the normal human walking motion, but has problems with irregular jittering. Moreover, we demonstrate the applicability of the backpack in a suitable urban scenario.}, language = {en} } @article{GuentzelSchillingHanioetal.2020, author = {G{\"u}ntzel, Paul and Schilling, Klaus and Hanio, Simon and Schlauersbach, Jonas and Schollmayer, Curd and Meinel, Lorenz and Holzgrabe, Ulrike}, title = {Bioinspired Ion Pairs Transforming Papaverine into a Protic Ionic Liquid and Salts}, series = {ACS Omega}, volume = {5}, journal = {ACS Omega}, number = {30}, doi = {10.1021/acsomega.0c02630}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230265}, pages = {19202-19209}, year = {2020}, abstract = {Microbial, mammalian, and plant cells produce and contain secondary metabolites, which typically are soluble in water to prevent cell damage by crystallization. The formation of ion pairs, for example, with carboxylic acids or mineral acids, is a natural blueprint to maintain basic metabolites in solution. Here, we aim at showing whether the mostly large carboxylates form soluble protic ionic liquids (PILs) with the basic natural product papaverine resulting in enhanced aqueous solubility. The obtained PILs were characterized by H-1-N-15 HMBC nuclear magnetic resonance (NMR) and in the solid state using X-ray powder diffraction, differential scanning calorimetry, and dissolution measurements. Furthermore, their supramolecular pattern in aqueous solution was studied by means of potentiometric and photometrical solubility, NMR aggregation assay, dynamic light scattering, zeta potential, and viscosity measurements. Thereby, we identified the naturally occurring carboxylic acids, citric acid, malic acid, and tartaric acid, as being appropriate counterions for papaverine and which will facilitate the formation of PILs with their beneficial characteristics, like the improved dissolution rate and enhanced apparent solubility.}, language = {en} } @article{KramerBangertSchilling2020, author = {Kramer, Alexander and Bangert, Philip and Schilling, Klaus}, title = {UWE-4: First Electric Propulsion on a 1U CubeSat — In-Orbit Experiments and Characterization}, series = {Aerospace}, volume = {7}, journal = {Aerospace}, number = {7}, doi = {10.3390/aerospace7070098}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236124}, year = {2020}, abstract = {The electric propulsion system NanoFEEP was integrated and tested in orbit on the UWE-4 satellite, which marks the first successful demonstration of an electric propulsion system on board a 1U CubeSat. In-orbit characterization measurements of the heating process of the propellant and the power consumption of the propulsion system at different thrust levels are presented. Furthermore, an analysis of the thrust vector direction based on its effect on the attitude of the spacecraft is described. The employed heater liquefies the propellant for a duration of 30 min per orbit and consumes 103 ± 4 mW. During this time, the respective thruster can be activated. The propulsion system including one thruster head, its corresponding heater, the neutralizer and the digital components of the power processing unit consume 8.5 ± 0.1 mW ⋅μ A\(^{-1}\) + 184 ± 8.5 mW and scales with the emitter current. The estimated thrust directions of two thruster heads are at angles of 15.7 ± 7.6∘ and 13.2 ± 5.5∘ relative to their mounting direction in the CubeSat structure. In light of the very limited power on a 1U CubeSat, the NanoFEEP propulsion system renders a very viable option. The heater of subsequent NanoFEEP thrusters was already improved, such that the system can be activated during the whole orbit period.}, language = {en} } @article{ScharnaglKempfSchilling2019, author = {Scharnagl, Julian and Kempf, Florian and Schilling, Klaus}, title = {Combining Distributed Consensus with Robust H-infinity-Control for Satellite Formation Flying}, series = {Electronics}, volume = {8}, journal = {Electronics}, number = {319}, doi = {10.3390/electronics8030319}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228431}, pages = {1-27}, year = {2019}, abstract = {Control methods that guarantee stability in the presence of uncertainties are mandatory in space applications. Further, distributed control approaches are beneficial in terms of scalability and to achieve common goals, especially in multi-agent setups like formation control. This paper presents a combination of robust H-infinity control and distributed control using the consensus approach by deriving a distributed consensus-based generalized plant description that can be used in H-infinity synthesis. Special focus was set towards space applications, namely satellite formation flying. The presented results show the applicability of the developed distributed robust control method to a simple, though realistic space scenario, namely a spaceborne distributed telescope. By using this approach, an arbitrary number of satellites/agents can be controlled towards an arbitrary formation geometry. Because of the combination with robust H-infinity control, the presented method satisfies the high stability and robustness demands as found e.g., in space applications.}, language = {en} } @article{KempfScharnaglHeiletal.2022, author = {Kempf, Florian and Scharnagl, Julian and Heil, Stefan and Schilling, Klaus}, title = {Self-organizing control-loop recovery for predictive networked formation control of fractionated spacecraft}, series = {Aerospace}, volume = {9}, journal = {Aerospace}, number = {10}, issn = {2226-4310}, doi = {10.3390/aerospace9100529}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-288041}, year = {2022}, abstract = {Going beyond the current trend of cooperating multiple small satellites we arrive at fractionated satellite architectures. Here the subsystems of all satellites directly self-organize and cooperate among themselves to achieve a common mission goal. Although this leads to a further increase of the advantages of the initial trend it also introduces new challenges, one of which is how to perform closed-loop control of a satellite over a network of subsystems. We present a two-fold approach to deal with the two main disturbances, data losses in the network and failure of the controller, in a networked predictive formation control scenario. To deal with data loss an event based networked model predictive control approach is extended to enable it to adapt to changing network conditions. The controller failure detection and compensation approach is tailored for a possibly large network of heterogeneous cooperating actuator- and controller nodes. The self-organized control task redistribution uses an auction-based methodology. It scales well with the number of nodes and allows to optimize for continuing good control performance despite the controller switch. The stability and smooth control behavior of our approach during a self-organized controller failure compensation while also being subject to data losses was demonstrated on a hardware testbed using as mission a formation control scenario.}, language = {en} } @article{WangLiuXiaoetal.2023, author = {Wang, Xiaoliang and Liu, Xuan and Xiao, Yun and Mao, Yue and Wang, Nan and Wang, Wei and Wu, Shufan and Song, Xiaoyong and Wang, Dengfeng and Zhong, Xingwang and Zhu, Zhu and Schilling, Klaus and Damaren, Christopher}, title = {On-orbit verification of RL-based APC calibrations for micrometre level microwave ranging system}, series = {Mathematics}, volume = {11}, journal = {Mathematics}, number = {4}, issn = {2227-7390}, doi = {10.3390/math11040942}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-303970}, year = {2023}, abstract = {Micrometre level ranging accuracy between satellites on-orbit relies on the high-precision calibration of the antenna phase center (APC), which is accomplished through properly designed calibration maneuvers batch estimation algorithms currently. However, the unmodeled perturbations of the space dynamic and sensor-induced uncertainty complicated the situation in reality; ranging accuracy especially deteriorated outside the antenna main-lobe when maneuvers performed. This paper proposes an on-orbit APC calibration method that uses a reinforcement learning (RL) process, aiming to provide the high accuracy ranging datum for onboard instruments with micrometre level. The RL process used here is an improved Temporal Difference advantage actor critic algorithm (TDAAC), which mainly focuses on two neural networks (NN) for critic and actor function. The output of the TDAAC algorithm will autonomously balance the APC calibration maneuvers amplitude and APC-observed sensitivity with an object of maximal APC estimation accuracy. The RL-based APC calibration method proposed here is fully tested in software and on-ground experiments, with an APC calibration accuracy of less than 2 mrad, and the on-orbit maneuver data from 11-12 April 2022, which achieved 1-1.5 mrad calibration accuracy after RL training. The proposed RL-based APC algorithm may extend to prove mass calibration scenes with actions feedback to attitude determination and control system (ADCS), showing flexibility of spacecraft payload applications in the future.}, language = {en} } @article{SalihogluSrivastavaLiangetal.2023, author = {Salihoglu, Rana and Srivastava, Mugdha and Liang, Chunguang and Schilling, Klaus and Szalay, Aladar and Bencurova, Elena and Dandekar, Thomas}, title = {PRO-Simat: Protein network simulation and design tool}, series = {Computational and Structural Biotechnology Journal}, volume = {21}, journal = {Computational and Structural Biotechnology Journal}, issn = {2001-0370}, doi = {10.1016/j.csbj.2023.04.023}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350034}, pages = {2767-2779}, year = {2023}, abstract = {PRO-Simat is a simulation tool for analysing protein interaction networks, their dynamic change and pathway engineering. It provides GO enrichment, KEGG pathway analyses, and network visualisation from an integrated database of more than 8 million protein-protein interactions across 32 model organisms and the human proteome. We integrated dynamical network simulation using the Jimena framework, which quickly and efficiently simulates Boolean genetic regulatory networks. It enables simulation outputs with in-depth analysis of the type, strength, duration and pathway of the protein interactions on the website. Furthermore, the user can efficiently edit and analyse the effect of network modifications and engineering experiments. In case studies, applications of PRO-Simat are demonstrated: (i) understanding mutually exclusive differentiation pathways in Bacillus subtilis, (ii) making Vaccinia virus oncolytic by switching on its viral replication mainly in cancer cells and triggering cancer cell apoptosis and (iii) optogenetic control of nucleotide processing protein networks to operate DNA storage. Multilevel communication between components is critical for efficient network switching, as demonstrated by a general census on prokaryotic and eukaryotic networks and comparing design with synthetic networks using PRO-Simat. The tool is available at https://prosimat.heinzelab.de/ as a web-based query server.}, language = {en} }