TY - JOUR A1 - Smith, Wayne A1 - Kotliar, Konstantin A1 - Lammertyn, Leandi A1 - Ramoshaba, Nthai E. A1 - Vilser, Walthard A1 - Huisman, Hugo W. A1 - Schutte, Aletta E. T1 - Retinal vessel caliber and caliber responses in true normotensive black and white adults: The African-PREDICT study JF - Microvascular Research N2 - Purpose Globally, a detrimental shift in cardiovascular disease risk factors and a higher mortality level are reported in some black populations. The retinal microvasculature provides early insight into the pathogenesis of systemic vascular diseases, but it is unclear whether retinal vessel calibers and acute retinal vessel functional responses differ between young healthy black and white adults. Methods We included 112 black and 143 white healthy normotensive adults (20–30 years). Retinal vessel calibers (central retinal artery and vein equivalent (CRAE and CRVE)) were calculated from retinal images and vessel caliber responses to flicker light induced provocation (FLIP) were determined. Additionally, ambulatory blood pressure (BP), anthropometry and blood samples were collected. Results The groups displayed similar 24 h BP profiles and anthropometry (all p > .24). Black participants demonstrated a smaller CRAE (158 ± 11 vs. 164 ± 11 MU, p < .001) compared to the white group, whereas CRVE was similar (p = .57). In response to FLIP, artery maximal dilation was greater in the black vs. white group (5.6 ± 2.1 vs. 3.3 ± 1.8%; p < .001). Conclusions Already at a young age, healthy black adults showed narrower retinal arteries relative to the white population. Follow-up studies are underway to show if this will be related to increased risk for hypertension development. The reason for the larger vessel dilation responses to FLIP in the black population is unclear and warrants further investigation. Y1 - 2020 U6 - http://dx.doi.org/10.1016/j.mvr.2019.103937 SN - 0026-2862 VL - 128 IS - Article 103937 PB - Elsevier CY - Amsterdam ER - TY - CHAP A1 - Finger, Felix A1 - de Vries, Reynard A1 - Vos, Roelof A1 - Braun, Carsten A1 - Bil, Cees T1 - A comparison of hybrid-electric aircraft sizing methods T2 - AIAA Scitech 2020 Forum Y1 - 2020 U6 - http://dx.doi.org/10.2514/6.2020-1006 N1 - AIAA Scitech 2020 Forum, Driving aerospace solutions for global challenges, Orlando, 06. - 10. January 2020 ER - TY - JOUR A1 - Rausch, Valentin A1 - Kahmann, Stephanie Lucina A1 - Baltschun, Christoph A1 - Staat, Manfred A1 - Müller, Lars P. A1 - Wegmann, Kilian T1 - Pressure distribution to the distal biceps tendon at the radial tuberosity: a biomechanical study JF - The Journal of Hand Surgery N2 - Purpose Mechanical impingement at the narrow radioulnar space of the tuberosity is believed to be an etiological factor in the injury of the distal biceps tendon. The aim of the study was to compare the pressure distribution at the proximal radioulnar space between 2 fixation techniques and the intact state. Methods Six right arms and 6 left arms from 5 female and 6 male frozen specimens were used for this study. A pressure transducer was introduced at the height of the radial tuberosity with the intact distal biceps tendon and after 2 fixation methods: the suture-anchor and the cortical button technique. The force (N), maximum pressure (kPa) applied to the radial tuberosity, and the contact area (mm²) of the radial tuberosity with the ulna were measured and differences from the intact tendon were detected from 60° supination to 60° pronation in 15° increments with the elbow in full extension and in 45° and 90° flexion of the elbow. Results With the distal biceps tendon intact, the pressures during pronation were similar regardless of extension and flexion and were the highest at 60° pronation with 90° elbow flexion (23.3 ± 53.5 kPa). After repair of the tendon, the mean peak pressure, contact area, and total force showed an increase regardless of the fixation technique. Highest peak pressures were found using the cortical button technique at 45° flexion of the elbow and 60° pronation. These differences were significantly different from the intact tendon. The contact area was significantly larger in full extension and 15°, 30°, and 60° pronation using the cortical button technique. Conclusions Pressures on the distal biceps tendon at the radial tuberosity increase during pronation, especially after repair of the tendon. Clinical relevance Mechanical impingement could play a role in both the etiology of primary distal biceps tendon ruptures and the complications occurring after fixation of the tendon using certain techniques. Y1 - 2020 U6 - http://dx.doi.org/10.1016/j.jhsa.2020.01.006 SN - 0363-5023 VL - 45 IS - 8 SP - 776.e1 EP - 776.e9 PB - Elsevier CY - Amsterdam ER - TY - CHAP A1 - Finger, Felix A1 - Braun, Carsten A1 - Bil, Cees T1 - Comparative assessment of parallel-hybrid-electric propulsion systems for four different aircraft T2 - AIAA SciTech Forum 2020, 06.01.2020 - 10.01.2020, Orlando Y1 - 2020 U6 - http://dx.doi.org/10.2514/6.2020-1502 ER - TY - CHAP A1 - Kreyer, Jörg A1 - Müller, Marvin A1 - Esch, Thomas T1 - A Map-Based Model for the Determination of Fuel Consumption for Internal Combustion Engines as a Function of Flight Altitude T2 - Deutscher Luft- und Raumfahrtkongress 2019, „Luft- und Raumfahrt – technologische Brücke in die Zukunft“, Darmstadt, 30. September bis 2. Oktober 2019 Y1 - 2020 U6 - http://dx.doi.org/10.25967/490162 PB - Deutsche Gesellschaft für Luft- und Raumfahrt - Lilienthal-Oberth e.V CY - Bonn ER - TY - JOUR A1 - Jildeh, Zaid B. A1 - Kirchner, Patrick A1 - Oberländer, Jan A1 - Vahidpour, Farnoosh A1 - Wagner, Patrick H. A1 - Schöning, Michael Josef T1 - Development of a package-sterilization process for aseptic filling machines: A numerical approach and validation for surface treatment with hydrogen peroxide JF - Sensor and Actuators A: Physical N2 - Within the present work a sterilization process by a heated gas mixture that contains hydrogen peroxide (H₂O₂) is validated by experiments and numerical modeling techniques. The operational parameters that affect the sterilization efficacy are described alongside the two modes of sterilization: gaseous and condensed H₂O₂. Measurements with a previously developed H₂O₂ gas sensor are carried out to validate the applied H₂O₂ gas concentration during sterilization. We performed microbiological tests at different H₂O₂ gas concentrations by applying an end-point method to carrier strips, which contain different inoculation loads of Geobacillus stearothermophilus spores. The analysis of the sterilization process of a pharmaceutical glass vial is performed by numerical modeling. The numerical model combines heat- and advection-diffusion mass transfer with vapor–pressure equations to predict the location of condensate formation and the concentration of H₂O₂ at the packaging surfaces by changing the gas temperature. For a sterilization process of 0.7 s, a H₂O₂ gas concentration above 4% v/v is required to reach a log-count reduction above six. The numerical results showed the location of H₂O₂ condensate formation, which decreases with increasing sterilant-gas temperature. The model can be transferred to different gas nozzle- and packaging geometries to assure the absence of H₂O₂ residues. Y1 - 2020 U6 - http://dx.doi.org/10.1016/j.sna.2019.111691 SN - 0924-4247 VL - 303 IS - 111691 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Capitain, Charlotte A1 - Ross-Jones, Jesse A1 - Möhring, Sophie A1 - Tippkötter, Nils T1 - Differential scanning calorimetry for quantification of polymer biodegradability in compost JF - International Biodeterioration & Biodegradation N2 - The objective of this study is the establishment of a differential scanning calorimetry (DSC) based method for online analysis of the biodegradation of polymers in complex environments. Structural changes during biodegradation, such as an increase in brittleness or crystallinity, can be detected by carefully observing characteristic changes in DSC profiles. Until now, DSC profiles have not been used to draw quantitative conclusions about biodegradation. A new method is presented for quantifying the biodegradation using DSC data, whereby the results were validated using two reference methods. The proposed method is applied to evaluate the biodegradation of three polymeric biomaterials: polyhydroxybutyrate (PHB), cellulose acetate (CA) and Organosolv lignin. The method is suitable for the precise quantification of the biodegradability of PHB. For CA and lignin, conclusions regarding their biodegradation can be drawn with lower resolutions. The proposed method is also able to quantify the biodegradation of blends or composite materials, which differentiates it from commonly used degradation detection methods. Y1 - 2020 U6 - http://dx.doi.org/10.1016/j.ibiod.2020.104914 SN - 0964-8305 VL - 149 SP - In Press, Article number 104914 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Mennicken, Max A1 - Peter, Sophia K. A1 - Kaulen, Corinna A1 - Simon, Ulrich A1 - Karthäuser, Silvia T1 - Transport through Redox-Active Ru-Terpyridine Complexes Integrated in Single Nanoparticle Devices JF - The Journal of Physical Chemistry C N2 - Transition metal complexes are electrofunctional molecules due to their high conductivity and their intrinsic switching ability involving a metal-to-ligand charge transfer. Here, a method is presented to contact reliably a few to single redox-active Ru-terpyridine complexes in a CMOS compatible nanodevice and preserve their electrical functionality. Using hybrid materials from 14 nm gold nanoparticles (AuNP) and bis-{4′-[4-(mercaptophenyl)-2,2′:6′,2″-terpyridine]}-ruthenium(II) complexes a device size of 30² nm² inclusive nanoelectrodes is achieved. Moreover, this method bears the opportunity for further downscaling. The Ru-complex AuNP devices show symmetric and asymmetric current versus voltage curves with a hysteretic characteristic in two well separated conductance ranges. By theoretical approximations based on the single-channel Landauer model, the charge transport through the formed double-barrier tunnel junction is thoroughly analyzed and its sensibility to the molecule/metal contact is revealed. It can be verified that tunneling transport through the HOMO is the main transport mechanism while decoherent hopping transport is present to a minor extent. Y1 - 2020 U6 - http://dx.doi.org/10.1021/acs.jpcc.9b11716 SN - 1932-7455 VL - 124 IS - 8 SP - 4881 EP - 4889 PB - ACS Publications CY - Washington, DC ER - TY - JOUR A1 - Rupp, Matthias A1 - Rieke, Christian A1 - Handschuh, Nils A1 - Kuperjans, Isabel T1 - Economic and ecological optimization of electric bus charging considering variable electricity prices and CO₂eq intensities JF - Transportation Research Part D: Transport and Environment N2 - In many cities, diesel buses are being replaced by electric buses with the aim of reducing local emissions and thus improving air quality. The protection of the environment and the health of the population is the highest priority of our society. For the transport companies that operate these buses, not only ecological issues but also economic issues are of great importance. Due to the high purchase costs of electric buses compared to conventional buses, operators are forced to use electric vehicles in a targeted manner in order to ensure amortization over the service life of the vehicles. A compromise between ecology and economy must be found in order to both protect the environment and ensure economical operation of the buses. In this study, we present a new methodology for optimizing the vehicles’ charging time as a function of the parameters CO₂eq emissions and electricity costs. Based on recorded driving profiles in daily bus operation, the energy demands of conventional and electric buses are calculated for the passenger transportation in the city of Aachen in 2017. Different charging scenarios are defined to analyze the influence of the temporal variability of CO₂eq intensity and electricity price on the environmental impact and economy of the bus. For every individual day of a year, charging periods with the lowest and highest costs and emissions are identified and recommendations for daily bus operation are made. To enable both the ecological and economical operation of the bus, the parameters of electricity price and CO₂ are weighted differently, and several charging periods are proposed, taking into account the priorities previously set. A sensitivity analysis is carried out to evaluate the influence of selected parameters and to derive recommendations for improving the ecological and economic balance of the battery-powered electric vehicle. In all scenarios, the optimization of the charging period results in energy cost savings of a maximum of 13.6% compared to charging at a fixed electricity price. The savings potential of CO₂eq emissions is similar, at 14.9%. From an economic point of view, charging between 2 a.m. and 4 a.m. results in the lowest energy costs on average. The CO₂eq intensity is also low in this period, but midday charging leads to the largest savings in CO₂eq emissions. From a life cycle perspective, the electric bus is not economically competitive with the conventional bus. However, from an ecological point of view, the electric bus saves on average 37.5% CO₂eq emissions over its service life compared to the diesel bus. The reduction potential is maximized if the electric vehicle exclusively consumes electricity from solar and wind power. Y1 - 2020 U6 - http://dx.doi.org/10.1016/j.trd.2020.102293 SN - 1361-9209 VL - 81 IS - Article 102293 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Cosma, Cosmin A1 - Kessler, Julia A1 - Gebhardt, Andreas A1 - Campbell, Ian A1 - Balc, Nicolae T1 - Improving the Mechanical Strength of Dental Applications and Lattice Structures SLM Processed JF - Materials N2 - To manufacture custom medical parts or scaffolds with reduced defects and high mechanical characteristics, new research on optimizing the selective laser melting (SLM) parameters are needed. In this work, a biocompatible powder, 316L stainless steel, is characterized to understand the particle size, distribution, shape and flowability. Examination revealed that the 316L particles are smooth, nearly spherical, their mean diameter is 39.09 μm and just 10% of them hold a diameter less than 21.18 μm. SLM parameters under consideration include laser power up to 200 W, 250–1500 mm/s scanning speed, 80 μm hatch spacing, 35 μm layer thickness and a preheated platform. The effect of these on processability is evaluated. More than 100 samples are SLM-manufactured with different process parameters. The tensile results show that is possible to raise the ultimate tensile strength up to 840 MPa, adapting the SLM parameters for a stable processability, avoiding the technological defects caused by residual stress. Correlating with other recent studies on SLM technology, the tensile strength is 20% improved. To validate the SLM parameters and conditions established, complex bioengineering applications such as dental bridges and macro-porous grafts are SLM-processed, demonstrating the potential to manufacture medical products with increased mechanical resistance made of 316L. Y1 - 2020 U6 - http://dx.doi.org/10.3390/ma13040905 SN - 1996-1944 VL - 13 IS - 4 SP - 1 EP - 18 PB - MDPI CY - Basel ER - TY - CHAP A1 - Azat, Seitkhan A1 - Kerimkulova, Almagul R. A1 - Mansurov, Zulkhair A. A1 - Adekenov, Sergazy A1 - Artmann, Gerhard T1 - The Use of Fusicoccin as Anticancer Compound T2 - Carbon Nanomaterials in Biomedicine and the Environment N2 - The problem of creation and use of sorption materials is of current interest for the practice of the modern medicine and agriculture. Practical importance is production of a biostimulant using a carbon sorbent for a significant increase in productivity, which is very relevant for the regions of Kazakhstan. It is known that a plant phytohormone—fusicoccin—in nanogram concentrations transforms cancer cells to the state of apoptosis. In this regard, there is a scientific practical interest in the development of a highly efficient method for producing fusicoccin from extract of germinated wheat seeds. According to the results of computer modeling, cleaning composite components of fusicoccin using microporous carbon adsorbents not suitable as the size of the molecule of fusicoccin more than micropores and the optimum pore size for purification of constituents of fusicoccin was determined by computer simulation. Y1 - 2020 SN - 978-0-429-42864-7 U6 - http://dx.doi.org/10.1201/9780429428647-8 SP - 149 EP - 172 PB - Jenny Stanford Publishing CY - New York ER - TY - JOUR A1 - Vögele, Stefan A1 - Grajewski, Matthias A1 - Govorukha, Kristina A1 - Rübbelke, Dirk T1 - Challenges for the European steel industry: Analysis, possible consequences and impacts on sustainable development JF - Applied Energy N2 - The steel industry in the European Union (EU), important for the economy as a whole, faces various challenges. These are inter alia volatile prices for relevant input factors, uncertainties concerning the regulation of CO₂-emissions and market shocks caused by the recently introduced additional import duties in the US, which is an important sales market. We examine primary and secondary effects of these challenges on the steel industry in the EU and their impacts on European and global level. Developing and using a suitable meta-model, we analyze the competitiveness of key steel producing countries with respect to floor prices depending on selected cost factors and draw conclusions on the impacts in the trade of steel on emissions, energy demand, on the involvement of developing countries in the value chain as well on the need for innovations to avoid relocations of production. Hence, our study contributes to the assessment of sustainable industrial development, which is aimed by the Sustainability Development Goal “Build resilient infrastructure, promote inclusive and sustainable industrialization and foster innovation countries”. By applying information on country-specific Human Development Indexes (reflecting aspects of life expectancy, education, and per capita income), we show that relocating energy-intensive industries from the EU may not only increase global energy demand and CO₂-emissions, but may also be to the disadvantage of developing countries. Y1 - 2020 U6 - http://dx.doi.org/10.1016/j.apenergy.2020.114633 SN - 0306-2619 VL - 264 IS - Article number: 114633 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Knox, Ronald A1 - Bruggemann, Andrea A1 - Gossmann, Matthias A1 - Thomas, Ulrich A1 - Horváth, András A1 - Dragicevic, Elena A1 - Stoelzle-Feix, Sonja A1 - Fertig, Niels A1 - Jung, Alexander A1 - Raman, Aravind Hariharan A1 - Staat, Manfred A1 - Linder, Peter T1 - Combining physiological relevance and throughput for in vitro cardiac contractility measurement JF - Biophysical Journal N2 - Despite increasing acceptance of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in safety pharmacology, controversy remains about the physiological relevance of existing in vitro models for their mechanical testing. We hypothesize that existing signs of immaturity of the cell models result from an improper mechanical environment. We cultured hiPSC-CMs in a 96-well format on hyperelastic silicone membranes imitating their native mechanical environment, resulting in physiological responses to compound stimuli.We validated cell responses on the FLEXcyte 96, with a set of reference compounds covering a broad range of cellular targets, including ion channel modulators, adrenergic receptor modulators and kinase inhibitors. Acute (10 - 30 min) and chronic (up to 7 days) effects were investigated. Furthermore, the measurements were complemented with electromechanical models based on electrophysiological recordings of the used cell types.hiPSC-CMs were cultured on freely-swinging, ultra-thin and hyperelastic silicone membranes. The weight of the cell culture medium deflects the membranes downwards. Rhythmic contraction of the hiPSC-CMs resulted in dynamic deflection changes which were quantified by capacitive distance sensing. The cells were cultured for 7 days prior to compound addition. Acute measurements were conducted 10-30 minutes after compound addition in standard culture medium. For chronic treatment, compound-containing medium was replaced daily for up to 7 days. Electrophysiological properties of the employed cell types were recorded by automated patch-clamp (Patchliner) and the results were integrated into the electromechanical model of the system.Calcium channel agonist S Bay K8644 and beta-adrenergic stimulator isoproterenol induced significant positive inotropic responses without additional external stimulation. Kinase inhibitors displayed cardiotoxic effects on a functional level at low concentrations. The system-integrated analysis detected alterations in beating shape as well as frequency and arrhythmic events and we provide a quantitative measure of these. Y1 - 2020 U6 - http://dx.doi.org/10.1016/j.bpj.2019.11.3104 SN - 0006-3495 N1 - Raman, Arayind Hariharan im Artikel unter dem Namen: Raman, Alexander H. VL - 118 IS - Issue 3, Supplement 1 SP - 570a PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Dadfar, Dryed Mohammadali A1 - Camozzi, Denise A1 - Darguzyte, Milita A1 - Roemhild, Karolin A1 - Varvarà, Paola A1 - Metselaar, Josbert A1 - Banala, Srinivas A1 - Straub, Marcel A1 - Güver, Nihan A1 - Engelmann, Ulrich M. A1 - Slabu, Ioana A1 - Buhl, Miriam A1 - Leusen, Jan van A1 - Kögerler, Paul A1 - Hermanns-Sachweh, Benita A1 - Schulz, Volkmar A1 - Kiessling, Fabian A1 - Lammers, Twan T1 - Size-isolation of superparamagnetic iron oxide nanoparticles improves MRI, MPI and hyperthermia performance JF - Journal of Nanobiotechnology N2 - Superparamagnetic iron oxide nanoparticles (SPION) are extensively used for magnetic resonance imaging (MRI) and magnetic particle imaging (MPI), as well as for magnetic fluid hyperthermia (MFH). We here describe a sequential centrifugation protocol to obtain SPION with well-defined sizes from a polydisperse SPION starting formulation, synthesized using the routinely employed co-precipitation technique. Transmission electron microscopy, dynamic light scattering and nanoparticle tracking analyses show that the SPION fractions obtained upon size-isolation are well-defined and almost monodisperse. MRI, MPI and MFH analyses demonstrate improved imaging and hyperthermia performance for size-isolated SPION as compared to the polydisperse starting mixture, as well as to commercial and clinically used iron oxide nanoparticle formulations, such as Resovist® and Sinerem®. The size-isolation protocol presented here may help to identify SPION with optimal properties for diagnostic, therapeutic and theranostic applications. Y1 - 2020 U6 - http://dx.doi.org/10.1186/s12951-020-0580-1 SN - 1477-3155 VL - 18 IS - Article number 22 SP - 1 EP - 13 PB - Nature Portfolio ER - TY - JOUR A1 - Abel, Alexander A1 - Kahmann, Stephanie Lucina A1 - Mellon, Stephen A1 - Staat, Manfred A1 - Jung, Alexander T1 - An open-source tool for the validation of finite element models using three-dimensional full-field measurements JF - Medical Engineering & Physics N2 - Three-dimensional (3D) full-field measurements provide a comprehensive and accurate validation of finite element (FE) models. For the validation, the result of the model and measurements are compared based on two respective point-sets and this requires the point-sets to be registered in one coordinate system. Point-set registration is a non-convex optimization problem that has widely been solved by the ordinary iterative closest point algorithm. However, this approach necessitates a good initialization without which it easily returns a local optimum, i.e. an erroneous registration. The globally optimal iterative closest point (Go-ICP) algorithm has overcome this drawback and forms the basis for the presented open-source tool that can be used for the validation of FE models using 3D full-field measurements. The capability of the tool is demonstrated using an application example from the field of biomechanics. Methodological problems that arise in real-world data and the respective implemented solution approaches are discussed. Y1 - 2020 U6 - http://dx.doi.org/10.1016/j.medengphy.2019.10.015 SN - 1350-4533 VL - 77 SP - 125 EP - 129 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Gerhards, Michael A1 - Sander, Volker A1 - Zivkovic, Miroslav A1 - Belloum, Adam A1 - Bubak, Marian T1 - New approach to allocation planning of many‐task workflows on clouds JF - Concurrency and Computation: Practice and Experience N2 - Experience has shown that a priori created static resource allocation plans are vulnerable to runtime deviations and hence often become uneconomic or highly exceed a predefined soft deadline. The assumption of constant task execution times during allocation planning is even more unlikely in a cloud environment where virtualized resources vary in performance. Revising the initially created resource allocation plan at runtime allows the scheduler to react on deviations between planning and execution. Such an adaptive rescheduling of a many-task application workflow is only feasible, when the planning time can be handled efficiently at runtime. In this paper, we present the static low-complexity resource allocation planning algorithm (LCP) applicable to efficiently schedule many-task scientific application workflows on cloud resources of different capabilities. The benefits of the presented algorithm are benchmarked against alternative approaches. The benchmark results show that LCP is not only able to compete against higher complexity algorithms in terms of planned costs and planned makespan but also outperforms them significantly by magnitudes of 2 to 160 in terms of required planning time. Hence, LCP is superior in terms of practical usability where low planning time is essential such as in our targeted online rescheduling scenario. Y1 - 2020 U6 - http://dx.doi.org/10.1002/cpe.5404 SN - 1532-0634 VL - 32 IS - 2 Article e5404 SP - 1 EP - 16 PB - Wiley CY - Chichester ER - TY - JOUR A1 - Tran, Ngoc Trinh A1 - Staat, Manfred T1 - Direct plastic structural design under lognormally distributed strength by chance constrained programming JF - Optimization and Engineering N2 - We propose the so-called chance constrained programming model of stochastic programming theory to analyze limit and shakedown loads of structures under random strength with a lognormal distribution. A dual chance constrained programming algorithm is developed to calculate simultaneously both the upper and lower bounds of the plastic collapse limit and the shakedown limit. The edge-based smoothed finite element method (ES-FEM) is used with three-node linear triangular elements. Y1 - 2020 U6 - http://dx.doi.org/10.1007/s11081-019-09437-2 SN - 1573-2924 VL - 21 IS - 1 SP - 131 EP - 157 PB - Springer Nature CY - Cham ER -