TY - JOUR A1 - Schirra, Julian A1 - Watmuff, Jonathan A1 - Bauschat, J.-Michael T1 - Highly non-planar lifting systems: a relative assessment of existing potential-methodologies to accurately estimate the induced drag JF - 32nd AIAA Applied Aerodynamics Conference 2014 : June, 16-20 2014, Atlanta, Ga. Y1 - 2014 SN - 978-1-62410-288-2 U6 - http://dx.doi.org/10.2514/6.2014-2988 SP - Publ. online ER - TY - JOUR A1 - Wagner, Patrick A1 - Doll, Theodor A1 - Schöning, Michael Josef T1 - Engineering of functional interfaces / Patrick Wagner ; Theodor Doll ; Michael J. Schöning (eds.) JF - Physica status solidi (A) : Applications and materials science Y1 - 2014 U6 - http://dx.doi.org/10.1002/pssa.201470241 SN - 1521-396X (E-Book); 1862-6319 (E-Book); 0031-8965 (Print); 1862-6300 (Print) VL - 211 IS - 6 SP - 1339 EP - 1339 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Timme, Michael T1 - Wohnungseigentümergemeinschaft - Einstimmigkeitserfordernis bei Errichtung einer Mobilfunkantenne JF - Monatsschrift für Deutsches Recht : MDR : Zeitschrift für die Zivilrechts-Praxis N2 - Der BGH (BGH v. 25.1.2014 – V ZR 48/13, MDR 2014, 399) hatte darüber zu befinden, ob auf dem Dach eines Hauses, das im Eigentum einer Wohnungseigentümergemeinschaft steht, auch gegen den Willen eines einzelnen Eigentümers eine Mobilfunkantenne angebracht werden kann. Das Urteil führt in das Spannungsfeld einer Abwägung zwischen Mehrheits- und Individualinteressen innerhalb einer WEG. Insoweit betont der BGH den grundsätzlichen Vorrang der Individualinteressen, jedenfalls soweit es um Beeinträchtigungen geht, die verständlicherweise von einem Eigentümer abgelehnt werden können. Der BGH verlangt im Ergebnis im Zweifel eine allseitige Zustimmung. Das Urteil ist zu begrüßen, lässt aber für die Zukunft Abgrenzungsfragen offen. Y1 - 2014 SN - 0340-1812 VL - 68 (2014) IS - 11 SP - 634 EP - 635 PB - Verlag Dr. Otto Schmidt CY - Köln ER - TY - JOUR A1 - Whitehead, Mark A1 - Öhlschläger, Peter A1 - Almajhdi, Fahad N. A1 - Alloza, Leonor A1 - Marzábal, Pablo A1 - Meyers, Ann E. A1 - Hitzeroth, Inga I. A1 - Rybicki, Edward P. T1 - Human papillomavirus (HPV) type 16 E7 protein bodies cause tumour regression in mice JF - BMC cancer Y1 - 2014 U6 - http://dx.doi.org/10.1186/1471-2407-14-367 SN - 1471-2407 IS - 14:367 SP - 1 EP - 15 PB - BioMed Central CY - London ER - TY - JOUR A1 - Guo, Yuanyuan A1 - Seki, Kosuke A1 - Miyamoto, Ko-ichiro A1 - Wagner, Torsten A1 - Schöning, Michael Josef A1 - Yoshinobu, Tatsuo T1 - Novel photoexcitation method for light-addressable potentiometric sensor with higher spatial resolution JF - Applied physics express : APEX N2 - A novel photoexcitation method for the light-addressable potentiometric sensor (LAPS) is proposed to achieve a higher spatial resolution of chemical images. The proposed method employs a combined light source that consists of a modulated light probe, which generates the alternating photocurrent signal, and a ring of constant illumination surrounding it. The constant illumination generates a sheath of carriers with increased concentration which suppresses the spread of photocarriers by enhanced recombination. A device simulation was carried out to verify the effect of constant illumination on the spatial resolution, which demonstrated that a higher spatial resolution can be obtained. Y1 - 2014 U6 - http://dx.doi.org/10.7567/APEX.7.067301 SN - 1882-0786 (E-Journa); 1882-0778 (Print) VL - 7 IS - 6 SP - 067301-4 PB - IOP CY - Bristol ER - TY - JOUR A1 - Alebouyeh Samami, Behzad A1 - Pieper, Martin A1 - Breitbach, Gerd A1 - Hodapp, Josef T1 - Heat production in the windings of the stators of electric machines under stationary condition JF - Heat and mass transfer N2 - In electric machines due to high currents and resistive losses (joule heating) heat is produced. To avoid damages by overheating the design of effective cooling systems is required. Therefore the knowledge of heat sources and heat transfer processes is necessary. The purpose of this paper is to illustrate a good and effective calculation method for the temperature analysis based on homogenization techniques. These methods have been applied for the stator windings in a slot of an electric machine consisting of copper wires and resin. The key quantity here is an effective thermal conductivity, which characterizes the heterogeneous wire resin-arrangement inside the stator slot. To illustrate the applicability of the method, the analysis of a simplified, homogenized model is compared with the detailed analysis of temperature behavior inside a slot of an electric machine according to the heat generation. We considered here only the stationary situation. The achieved numerical results are accurate and show that the applied homogenization technique works in practice. Finally the results of simulations for the two cases, the original model of the slot and the homogenized model chosen for the slot (unit cell), are compared to experimental results. Y1 - 2014 U6 - http://dx.doi.org/10.1007/s00231-014-1371-8 SN - 0947-7411 (Print) ; 1432-1181 (E-Journal) VL - 50 SP - 1707 EP - 1716 PB - Springer CY - Heidelberg ER - TY - JOUR A1 - Wolf, Martin A1 - Biesen, Ina van der A1 - Greeb, Birgit T1 - Mein Freund, die Uni JF - Die neue Hochschule : DNH : für anwendungsbezogene Wissenschaft und Kunst Y1 - 2014 SN - 0340-448X N1 - Gedr. Ausgabe in der Bibliothek Eupener Str. vorhanden. VL - 2014 IS - 2 SP - 54 EP - 56 PB - HLB CY - Bonn ER - TY - JOUR A1 - Turaliyeva, M. A1 - Yeshibaev, A. A1 - Digel, Ilya A1 - Elibayeva, G. A1 - Sydykova, A. A1 - Uspabayeva, A. A1 - Dosybayeva, G. A1 - Zhylysbayeva, A. A1 - Lakhanova, K. T1 - Molecular-genetic identification of emerged novel invasive pathogens of Asiatic Elm Ulmus pumila L JF - Life science journal N2 - The dwarf elm Ulmus pumila L. (Ulmaceae) is one of indigenous species of flora in Kazakhstan and forms a basis of dendroflora in virtually all settlements of the region. In the past decade, multiple outbreaks of previously unknown diseases of the small-leaved elm have been registered. In our study, by the molecular-genetic analysis it was found that the pathogens responsible for the outbreaks are microfungi belonging to the genus Fusarium – F. solani and F. oxysporum. The nucleotide sequences (ITS regions) isolated from the diseased trees showed very high similarity with the GenBank control numbers EU625403.1 and FJ478128.1 (100.0 and 99.0 % respectively). Oncoming research will focus on the search of natural microbial antagonists of the discovered phytopathogens. Y1 - 2014 U6 - http://dx.doi.org/10.7537/marslsj1105s14.33 SN - 1097-8135 VL - 11 IS - Spec. iss. 5s SP - 171 EP - 175 PB - Marsland Press CY - New York ER - TY - JOUR A1 - Küppers, Tobias A1 - Steffen, Victoria A1 - Hellmuth, Hendrik A1 - O'Connell, Timothy A1 - Bongaerts, Johannes A1 - Maurer, Karl-Heinz A1 - Wiechert, Wolfgang T1 - Developing a new production host from a blueprint: Bacillus pumilus as an industrial enzyme producer JF - Microbial cell factories Y1 - 2014 U6 - http://dx.doi.org/10.1186/1475-2859-13-46 SN - 1475-2859 (E-Journal) VL - 13 SP - Article No. 46 PB - BioMed Central CY - London ER - TY - JOUR A1 - Fuest, Matthias A1 - Kotliar, Konstantin A1 - Walter, Peter A1 - Plange, Niklas T1 - Monitoring intraocular pressure changes after intravitreal Ranibizumab injection using rebound tonometry JF - Ophthalmic and physiological optics Y1 - 2014 U6 - http://dx.doi.org/10.1111/opo.12134 SN - 1475-1313 (E-Journal); 0275-5408 (Print) N1 - Special Issue: The Ageing Visual System VL - 34 IS - 4 SP - 438 EP - 444 PB - Wiley-Blackwell CY - Oxford ER - TY - JOUR A1 - Laack, Walter van T1 - Therefore Fermat is right JF - American journal of humanities and social sciences : AJHSS N2 - It was Fernat's idea to investigate how many numbers would fulfill the equation according to the Pythagorean Theorem if the exponent were increased to random, e.g. to a3 + b3 = c3. His question became therefore: are there two whole numbers the cubes of which add up to the volume of the cube of a third whole number? He posed this same question, of course, for all kinds of higher exponents, so that the equation could be generalized: is there an integral solution for the equation an + bn = cn, if the exponent n is higher than 2? Although in 1993, the English mathematician Andrew Wiles was able to produce an arithmetical proof for Fermat's famous theorem, I will show that there is a simple logical explanation which is also pragmatic and plausible and what is the result of a fundamental alternative idea how our world seems to be constructed. Y1 - 2014 SN - 2329-079X (E-Journal); 2329-0781 (Print) VL - 2 IS - 2 SP - 117 EP - 120 ER - TY - JOUR A1 - Pham, Phu Tinh A1 - Staat, Manfred T1 - FEM-based shakedown analysis of hardening structures JF - Asia Pacific journal on computational engineering N2 - This paper develops a new finite element method (FEM)-based upper bound algorithm for limit and shakedown analysis of hardening structures by a direct plasticity method. The hardening model is a simple two-surface model of plasticity with a fixed bounding surface. The initial yield surface can translate inside the bounding surface, and it is bounded by one of the two equivalent conditions: (1) it always stays inside the bounding surface or (2) its centre cannot move outside the back-stress surface. The algorithm gives an effective tool to analyze the problems with a very high number of degree of freedom. Our numerical results are very close to the analytical solutions and numerical solutions in literature. Y1 - 2014 U6 - http://dx.doi.org/10.1186/2196-1166-1-4 SN - 2196-1166 (E-Journal) IS - 1 SP - Article No. 4 PB - SpringerOpen CY - Berlin ER - TY - JOUR A1 - Poghossian, Arshak A1 - Schöning, Michael Josef T1 - Label-free sensing of biomolecules with field-effect devices for clinical applications JF - Electroanalysis N2 - Among the variety of transducer concepts proposed for label-free detection of biomolecules, the semiconductor field-effect device (FED) is one of the most attractive platforms. As medical techniques continue to progress towards diagnostic and therapies based on biomarkers, the ability of FEDs for a label-free, fast and real-time detection of multiple pathogenic and physiologically relevant molecules with high specificity and sensitivity offers very promising prospects for their application in point-of-care and personalized medicine for an early diagnosis and treatment of diseases. The presented paper reviews recent advances and current trends in research and development of different FEDs for label-free, direct electrical detection of charged biomolecules by their intrinsic molecular charge. The authors are mainly focusing on the detection of the DNA hybridization event, antibody-antigen affinity reaction as well as clinically relevant biomolecules such as cardiac and cancer biomarkers. Y1 - 2014 U6 - http://dx.doi.org/10.1002/elan.201400073 SN - 1521-4109 (E-Journal); 1040-0397 (Print) VL - 26 IS - 6 SP - 1197 EP - 1213 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Wu, Chunsheng A1 - Bronder, Thomas A1 - Poghossian, Arshak A1 - Werner, Frederik A1 - Bäcker, Matthias A1 - Schöning, Michael Josef T1 - Label-free electrical detection of DNA with a multi-spot LAPS: First step towards light-addressable DNA chips JF - Physica status solidi A : Applications and materials science N2 - A multi-spot (4 × 4 spots) light-addressable potentiometric sensor (MLAPS) consisting of an Al–p-Si–SiO2 structure has been applied for the label-free electrical detection of DNA (deoxyribonucleic acid) immobilization and hybridization by the intrinsic molecular charge for the first time. Single-stranded probe ssDNA molecules (20 bases) were covalently immobilized onto the silanized SiO2 gate surface. The unspecific adsorption of mismatch ssDNA on the MLAPS gate surface was blocked by bovine serum albumin molecules. To reduce the screening effect and to achieve a high sensor signal, the measurements were performed in a low ionic-strength solution. The photocurrent–voltage (I–V) curves were simultaneously recorded on all 16 spots after each surface functionalization step. Large shifts of I–V curves of 25 mV were registered after the DNA immobilization and hybridization event. In contrast, a small potential shift (∼5 mV) was observed in case of mismatch ssDNA, revealing good specificity of the sensor. The obtained results demonstrate the potential of the MLAPS as promising transducer platform for the multi-spot label-free electrical detection of DNA molecules by their intrinsic molecular charge. Y1 - 2014 U6 - http://dx.doi.org/10.1002/pssa.201330442 SN - 1521-396X (E-Journal); 1862-6319 (E-Journal); 0031-8965 (Print); 1862-6300 (Print) VL - 211 IS - 6 SP - 1423 EP - 1428 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Takenaga, Shoko A1 - Biselli, Manfred A1 - Schnitzler, Thomas A1 - Öhlschläger, Peter A1 - Wagner, Torsten A1 - Schöning, Michael Josef T1 - Toward multi-analyte bioarray sensors: LAPS-based on-chip determination of a Michaelis–Menten-like kinetics for cell culturing JF - Physica status solidi A : Applications and materials science N2 - The metabolic activity of Chinese hamster ovary (CHO) cells was observed using a light-addressable potentiometric sensor (LAPS). The dependency toward different glucose concentrations (17–200 mM) follows a Michaelis–Menten kinetics trajectory with Kₘ = 32.8 mM, and the obtained Kₘ value in this experiment was compared with that found in literature. In addition, the pH shift induced by glucose metabolism of tumor cells transfected with the HPV-16 genome (C3 cells) was successfully observed. These results indicate the possibility to determine the tumor cells metabolism with a LAPS-based measurement device. Y1 - 2014 U6 - http://dx.doi.org/10.1002/pssa.201330464 SN - 1521-396X (E); 1862-6319 (E-Journal); 0031-8965 (Print); 1862-6300 (Print) VL - 211 IS - 6 SP - 1410 EP - 1415 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Guo, Yuanyuan A1 - Miyamoto, Ko-ichiro A1 - Wagner, Torsten A1 - Schöning, Michael Josef A1 - Yoshinobu, Tatsuo T1 - Theoretical study and simulation of light-addressable potentiometric sensors JF - Physica status solidi (A) : applications and materials N2 - The light-addressable potentiometric sensor (LAPS) is a semiconductor-based potentiometric sensor using a light probe with an ability of detecting the concentration of biochemical species in a spatially resolved manner. As an important biomedical sensor, research has been conducted to improve its performance, for instance, to realize high-speed measurement. In this work, the idea of facilitating the device-level simulation, instead of using an equivalent-circuit model, is presented for detailed analysis and optimization of the performance of the LAPS. Both carrier distribution and photocurrent response have been simulated to provide new insight into both amplitude-mode and phase-mode operations of the LAPS. Various device parameters can be examined to effectively design and optimize the LAPS structures and setups for enhanced performance. Y1 - 2014 U6 - http://dx.doi.org/10.1002/pssa.201330354 SN - 0031-8965 VL - 211 IS - 6 SP - 1467 EP - 1472 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Bäcker, Matthias A1 - Kramer, F. A1 - Huck, Christina A1 - Poghossian, Arshak A1 - Bratov, A. A1 - Abramova, N. A1 - Schöning, Michael Josef T1 - Planar and 3D interdigitated electrodes for biosensing applications: The impact of a dielectric barrier on the sensor properties JF - Physica Status Solidi (A) - Applications and Materials Science N2 - Planar and three-dimensional (3D) interdigitated electrodes (IDE) with electrode digits separated by an insulating barrier of different heights were electrochemically characterized and compared in terms of their sensing properties. Due to the impact of the surface resistance, both types of IDE structures display a non-linear behavior in low-ionic strength solutions. The experimental data were fitted to an electrical equivalent circuit and interpreted taking into account the surface-charge-governed properties. The effect of a charged polyelectrolyte layer electrostatically assembled onto the sensor surface on the surface resistance in solutions with different KCl concentration is studied. In case of the same electrode footprint, 3D-IDEs show a larger cell constant and a higher sensitivity to molecular adsorption than that of planar IDEs. The obtained results demonstrate the potential of 3D-IDEs as a new transducer structure for a direct label-free sensing of charged molecules. Y1 - 2014 U6 - http://dx.doi.org/10.1002/pssa.201330416 SN - 1521-396X (E-Journal); 1862-6319 (E-Journal); 0031-8965 (Print); 1862-6300 (Print) VL - 211 IS - 6 SP - 1357 EP - 1363 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Huck, Christina A1 - Poghossian, Arshak A1 - Kerroumi, Iman A1 - Schusser, Sebastian A1 - Bäcker, Matthias A1 - Zander, Willi A1 - Schubert, Jürgen A1 - Buniatyan, Vahe V. A1 - Martirosyan, Norayr W. A1 - Wagner, Patrick A1 - Schöning, Michael Josef T1 - Multiparameter sensor chip with Barium Strontium Titanate as multipurpose material JF - Electroanalysis N2 - It is well known that biochemical and biotechnological processes are strongly dependent and affected by a variety of physico-chemical parameters such as pH value, temperature, pressure and electrolyte conductivity. Therefore, these quantities have to be monitored or controlled in order to guarantee a stable process operation, optimization and high yield. In this work, a sensor chip for the multiparameter detection of three physico-chemical parameters such as electrolyte conductivity, pH and temperature is realized using barium strontium titanate (BST) as multipurpose material. The chip integrates a capacitively coupled four-electrode electrolyte-conductivity sensor, a capacitive field-effect pH sensor and a thin-film Pt-temperature sensor. Due to the multifunctional properties of BST, it is utilized as final outermost coating layer of the processed sensor chip and serves as passivation and protection layer as well as pH-sensitive transducer material at the same time. The results of testing of the individual sensors of the developed multiparameter sensor chip are presented. In addition, a quasi-simultaneous multiparameter characterization of the sensor chip in buffer solutions with different pH value and electrolyte conductivity is performed. To study the sensor behavior and the suitability of BST as multifunctional material under harsh environmental conditions, the sensor chip was exemplarily tested in a biogas digestate. Y1 - 2014 U6 - http://dx.doi.org/10.1002/elan.201400076 SN - 1521-4109 (E-Journal); 1040-0397 (Print) VL - 26 IS - 5 SP - 980 EP - 987 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Heine, A. A1 - Herrmann, G. A1 - Selmer, Thorsten A1 - Terwesten, F. A1 - Buckel, W. A1 - Reuter, K. T1 - High resolution crystal structure of clostridium propionicum β-Alanyl-CoA:Ammonia Lyase, a new member of the "Hot Dog Fold" protein superfamily JF - Proteins N2 - Clostridium propionicum is the only organism known to ferment β-alanine, a constituent of coenzyme A (CoA) and the phosphopantetheinyl prosthetic group of holo-acyl carrier protein. The first step in the fermentation is a CoA-transfer to β-alanine. Subsequently, the resulting β-alanyl-CoA is deaminated by the enzyme β-alanyl-CoA:ammonia lyase (Acl) to reversibly form ammonia and acrylyl-CoA. We have determined the crystal structure of Acl in its apo-form at a resolution of 0.97 Å as well as in complex with CoA at a resolution of 1.59 Å. The structures reveal that the enyzme belongs to a superfamily of proteins exhibiting a so called “hot dog fold” which is characterized by a five-stranded antiparallel β-sheet with a long α-helix packed against it. The functional unit of all “hot dog fold” proteins is a homodimer containing two equivalent substrate binding sites which are established by the dimer interface. In the case of Acl, three functional dimers combine to a homohexamer strongly resembling the homohexamer formed by YciA-like acyl-CoA thioesterases. Here, we propose an enzymatic mechanism based on the crystal structure of the Acl·CoA complex and molecular docking. Proteins 2014; 82:2041–2053. © 2014 Wiley Periodicals, Inc. Y1 - 2014 U6 - http://dx.doi.org/10.1002/prot.24557 SN - 1097-0134 (E-Journal); 0887-3585 (Print) VL - 82 IS - 9 SP - 2041 EP - 2053 PB - Wiley-Liss CY - New York ER - TY - JOUR A1 - Frings, Michael T1 - Neuregelung des Verbraucherschutzes – Umsetzung der EU-Verbraucherrechterichtlinie JF - NWB : NWB Steuer- und Wirtschaftsrecht Y1 - 2014 SN - 0028-3460 (Print) IS - 14 SP - 1003 EP - 1018 PB - NWB-Verlag CY - Herne ER - TY - JOUR A1 - Frings, Michael T1 - Das Gesetz gegen unseriöse Geschäftspraktiken JF - NWB : NWB Steuer- und Wirtschaftsrecht Y1 - 2014 SN - 0028-3460 (Print) IS - 11 SP - 769 EP - 775 PB - NWB-Verlag CY - Herne ER - TY - JOUR A1 - Oberländer, Jan A1 - Kirchner, Patrick A1 - Boyen, Hans-Gerd A1 - Schöning, Michael Josef T1 - Detection of hydrogen peroxide vapor by use of manganese(IV) oxide as catalyst for calorimetric gas sensors JF - Physica status solidi A: Applications and materials science N2 - In this work, the catalyst manganese(IV) oxide (MnO2), of calorimetric gas sensors (to monitor the sterilization agent vaporized hydrogen peroxide) has been investigated in more detail. Chemical analyses by means of X-ray-induced photoelectron spectroscopy have been performed to unravel the surface chemistry prior and after exposure to hydrogen peroxide vapor at elevated temperature, as applied in the sterilization processes of beverage cartons. The surface characterization reveals a change in oxidation states of the metal oxide catalyst after exposure to hydrogen peroxide. Additionally, a cleaning effect of the catalyst, which itself is attached to the sensor surface by means of a polymer interlayer, could be observed. Y1 - 2014 U6 - http://dx.doi.org/10.1002/pssa.201330359 SN - 1521-396X (E-Journal); 1862-6319 (E-Journal); 0031-8965 (Print); 1862-6300 (Print) VL - 211 IS - 6 SP - 1372 EP - 1376 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Huck, Christina A1 - Poghossian, Arshak A1 - Bäcker, Matthias A1 - Chaudhuri, S. A1 - Zander, W. A1 - Schubert, J. A1 - Begoyan, V. K. A1 - Buniatyan, V. V. A1 - Wagner, P. A1 - Schöning, Michael Josef T1 - Capacitively coupled electrolyte-conductivity sensor based on high-k material of barium strontium titanate JF - Sensors and actuators. B: Chemical Y1 - 2014 U6 - http://dx.doi.org/10.1016/j.snb.2014.02.103 SN - 1873-3077 (E-Journal); 0925-4005 (Print) IS - 198 SP - 102 EP - 109 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Funke, Harald A1 - Dickhoff, J. A1 - Keinz, Jan A1 - Anis, H. A. A1 - Parente, A. A1 - Hendrick, P. T1 - Experimental and numerical study of the micromix combustion principle applied for hydrogen and hydrogen-rich syngas as fuel with increased energy density for industrial gas turbine applications JF - Energy procedia N2 - The Dry Low NOx (DLN) Micromix combustion principle with increased energy density is adapted for the industrial gas turbine APU GTCP 36-300 using hydrogen and hydrogen-rich syngas with a composition of 90%-Vol. hydrogen (H₂) and 10%-Vol. carbon-monoxide (CO). Experimental and numerical studies of several combustor geometries for hydrogen and syngas show the successful advance of the DLN Micromix combustion from pure hydrogen to hydrogen-rich syngas. The impact of the different fuel properties on the combustion principle and aerodynamic flame stabilization design laws, flow field, flame structure and emission characteristics is investigated by numerical analysis using a hybrid Eddy Break Up combustion model and validated against experimental results. Y1 - 2014 U6 - http://dx.doi.org/10.1016/j.egypro.2014.12.201 SN - 1876-6102 (E-Journal) IS - 61 SP - 1736 EP - 1739 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Leinhos, Marcel A1 - Schusser, Sebastian A1 - Bäcker, Matthias A1 - Poghossian, Arshak A1 - Schöning, Michael Josef T1 - Micromachined multi-parameter sensor chip for the control of polymer-degradation medium JF - Physica Status Solidi (A) : special issue on engineering and functional interfaces N2 - It is well known that the degradation environment can strongly influence the biodegradability and kinetics of biodegradation processes of polymers. Therefore, besides the monitoring of the degradation process, it is also necessary to control the medium in which the degradation takes place. In this work, a micromachined multi-parameter sensor chip for the control of the polymer-degradation medium has been developed. The chip combines a capacitive field-effect pH sensor, a four-electrode electrolyte-conductivity sensor and a thin-film Pt-temperature sensor. The results of characterization of individual sensors are presented. In addition, the multi-parameter sensor chip together with an impedimetric polymer-degradation sensor was simultaneously characterized in degradation solutions with different pH and electrolyte conductivity. The obtained results demonstrate the feasibility of the multi-parameter sensor chip for the control of the polymer-degradation medium. Y1 - 2014 U6 - http://dx.doi.org/10.1002/pssa.201330364 SN - 1521-396X (E-Journal); 1862-6319 (E-Journal); 0031-8965 (Print); 1862-6300 (Print) VL - 211 IS - 6 SP - 1346 EP - 1351 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Sawada, Kazuaki A1 - Nakazawa, Hirokazu A1 - Takenaga, Shoko A1 - Hizawa, Takeshi A1 - Futagawa, Masato A1 - Dasai, Fumihiro A1 - Sakurai, Takashi A1 - Okumura, Koichi A1 - Hattori, Toshiaki A1 - Ishida, Makoto T1 - Multimodal bioimage sensor JF - IEICE transactions on fundamentals of electronics, communidations and computer sciences N2 - To visualize the biochemical distribution two-dimensionally, we invented a solid-state-type ion image sensor that indicates the chemical activity of solutions and cells. The device, which consists of a CCD array covered with a functionalized membrane to detect charge accumulation, is highly sensitive to changes in the concentration and two-dimensional distribution of ions and biomaterials. Y1 - 2014 U6 - http://dx.doi.org/10.1587/transfun.E97.A.726 SN - 0916-8508 (Print) ; 1745-1337 (Online) VL - E97-A (2014) IS - 3 SP - 726 EP - 733 PB - IEICE CY - Tokyo ER - TY - JOUR A1 - Arinkin, Vladimir A1 - Digel, Ilya A1 - Porst, Dariusz A1 - Temiz Artmann, Aysegül A1 - Artmann, Gerhard T1 - Phenotyping date palm varieties via leaflet cross-sectional imaging and artificial neural network application JF - BMC bioinformatics N2 - Background True date palms (Phoenix dactylifera L.) are impressive trees and have served as an indispensable source of food for mankind in tropical and subtropical countries for centuries. The aim of this study is to differentiate date palm tree varieties by analysing leaflet cross sections with technical/optical methods and artificial neural networks (ANN). Results Fluorescence microscopy images of leaflet cross sections have been taken from a set of five date palm tree cultivars (Hewlat al Jouf, Khlas, Nabot Soltan, Shishi, Um Raheem). After features extraction from images, the obtained data have been fed in a multilayer perceptron ANN with backpropagation learning algorithm. Conclusions Overall, an accurate result in prediction and differentiation of date palm tree cultivars was achieved with average prediction in tenfold cross-validation is 89.1% and reached 100% in one of the best ANN. Y1 - 2014 U6 - http://dx.doi.org/10.1186/1471-2105-15-55 SN - 1471-2105 VL - 15 IS - 55 SP - 1 EP - 8 ER - TY - JOUR A1 - Schroeter, Rebecca A1 - Hoffmann, Tamara A1 - Voigt, Birgit A1 - Meyer, Hanna A1 - Bleisteiner, Monika A1 - Muntel, Jan A1 - Jürgen, Britta A1 - Albrecht, Dirk A1 - Becher, Dörte A1 - Lalk, Michael A1 - Evers, Stefan A1 - Bongaerts, Johannes A1 - Maurer, Karl-Heinz A1 - Putzer, Harald A1 - Hecker, Michael A1 - Schweder, Thomas A1 - Bremer, Erhard T1 - Stress responses of the industrial workhorse Bacillus licheniformis to osmotic challenges JF - PLoS ONE N2 - The Gram-positive endospore-forming bacterium Bacillus licheniformis can be found widely in nature and it is exploited in industrial processes for the manufacturing of antibiotics, specialty chemicals, and enzymes. Both in its varied natural habitats and in industrial settings, B. licheniformis cells will be exposed to increases in the external osmolarity, conditions that trigger water efflux, impair turgor, cause the cessation of growth, and negatively affect the productivity of cell factories in biotechnological processes. We have taken here both systems-wide and targeted physiological approaches to unravel the core of the osmostress responses of B. licheniformis. Cells were suddenly subjected to an osmotic upshift of considerable magnitude (with 1 M NaCl), and their transcriptional profile was then recorded in a time-resolved fashion on a genome-wide scale. A bioinformatics cluster analysis was used to group the osmotically up-regulated genes into categories that are functionally associated with the synthesis and import of osmostress-relieving compounds (compatible solutes), the SigB-controlled general stress response, and genes whose functional annotation suggests that salt stress triggers secondary oxidative stress responses in B. licheniformis. The data set focusing on the transcriptional profile of B. licheniformis was enriched by proteomics aimed at identifying those proteins that were accumulated by the cells through increased biosynthesis in response to osmotic stress. Furthermore, these global approaches were augmented by a set of experiments that addressed the synthesis of the compatible solutes proline and glycine betaine and assessed the growth-enhancing effects of various osmoprotectants. Combined, our data provide a blueprint of the cellular adjustment processes of B. licheniformis to both sudden and sustained osmotic stress. Y1 - 2014 U6 - http://dx.doi.org/10.1371/journal.pone.0080956 SN - 1932-6203 VL - 8 IS - 11 PB - PLOS CY - San Francisco ER - TY - JOUR A1 - Wang, Ren-Qi A1 - Druckenmüller, Katharina A1 - Elbers, Gereon A1 - Guenther, Klaus A1 - Croué, Jean-Philippe T1 - Analysis of aquatic-phase natural organic matter by optimized LDI-MS method JF - Journal of mass spectrometry N2 - The composition and physiochemical properties of aquatic-phase natural organic matter (NOM) are most important problems for both environmental studies and water industry. Laser desorption/ionization (LDI) mass spectrometry facilitated successful examinations of NOM, as humic and fulvic acids in NOM are readily ionized by the nitrogen laser. In this study, hydrophobic NOMs (HPO NOMs) from river, reservoir and waste water were characterized by this technique. The effect of analytical variables like concentration, solvent composition and laser energy was investigated. The exact masses of small molecular NOM moieties in the range of 200–1200 m/z were determined in reflectron mode. In addition, spectra of post-source-decay experiments in this range showed that some compounds from different natural NOMs had the same fragmental ions. In the large mass range of 1200–15 000 Da, macromolecules and their aggregates were found in HPO NOMs from natural waters. Highly humic HPO exhibited mass peaks larger than 8000 Da. On the other hand, the waste water and reservoir water mainly had relatively smaller molecules of about 2000 Da. The LDI-MS measurements indicated that highly humic river waters were able to form large aggregates and membrane foulants, while the HPO NOMs from waste water and reservoir water were unlikely to form large aggregates. Copyright © 2014 John Wiley & Sons, Ltd. Y1 - 2014 U6 - http://dx.doi.org/10.1002/jms.3321 SN - 1096-9888 VL - 49 IS - 2 SP - 154 EP - 160 PB - Wiley CY - Bognor Regis ER - TY - JOUR A1 - Goedhuys, Micheline A1 - Janz, Norbert A1 - Mohnen, Pierre T1 - Knowledge-based productivity in “low-tech” industries: evidence from firms in developing countries JF - Industrial and corporate change N2 - Using firm-level data from five developing countries—Brazil, Ecuador, South Africa, Tanzania, and Bangladesh—and three industries—food processing, textiles, and the garments and leather products—this article examines the importance of various sources of knowledge for explaining productivity and formally tests whether sector- or country-specific characteristics dominate these relationships. Knowledge sources driving productivity appear mainly sector specific. Also differences in the level of development affect the effectiveness of knowledge sources. In the food processing sector, firms with higher educated managers are more productive, and in least-developed countries, additionally those with technology licenses and imported machinery and equipment. In the capital-intensive textiles sector, productivity is higher in firms that conduct R&D. In the garments and leather products sector, higher education of the managers, licensing, and R&D raise productivity. Y1 - 2014 U6 - http://dx.doi.org/10.1093/icc/dtt006 SN - 1464-3650 (E-Journal); 0960-6491 (Print) VL - 23 IS - 1 SP - 1 EP - 23 PB - Oxford University Press CY - Oxford ER - TY - JOUR A1 - Beck, Daniel A1 - Buchleitner, Martin A1 - Ferrein, Alexander A1 - Niemüller, Tim A1 - Steinbauer, Gerald T1 - Mostly Harmless & AllemaniACs - mixed innovations Y1 - 2014 SP - 1 EP - 8 ER - TY - JOUR A1 - Moseley, Fiona A1 - Halamek, Jan A1 - Kramer, Friederike A1 - Poghossian, Arshak A1 - Schöning, Michael Josef A1 - Katz, Evgeny T1 - An enzyme-based reversible CNOT logic gate realized in a flow system JF - Analyst N2 - An enzyme system organized in a flow device was used to mimic a reversible Controlled NOT (CNOT) gate with two input and two output signals. Reversible conversion of NAD⁺ and NADH cofactors was used to perform a XOR logic operation, while biocatalytic hydrolysis of p-nitrophenyl phosphate resulted in an Identity operation working in parallel. The first biomolecular realization of a CNOT gate is promising for integration into complex biomolecular networks and future biosensor/biomedical applications. Y1 - 2014 U6 - http://dx.doi.org/10.1039/C4AN00133H SN - 1364-5528 (E-Journal) ; 0003-2654 (Print) VL - 139 IS - 8 SP - 1839 EP - 1842 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Laack, Walter van T1 - Nature is much smarter than expected: the Genetic Code is not degenerate JF - American journal of humanities and social sciences N2 - In any books about genetics it can still today be read that our genetic code is called “degenerate” because it is still believed that 43 = 64 triplets encode the 20 essential amino acids. Indeed we have to assume the inverse law, what means that 34 = 81 exact code positions are really effective for our genetic code and encode the amino acids, compiled to proteins. This very important discovery leads to two completely new results that are limits-overlooking: 1) 34 (=81) genetic code positions mean exactly the same number as there are stable and naturally existing chemical elements in our universe. This famous argument should now lead to some alternative, as well as new fundamental conclusions about our existence. 2) A genetic code positioning system shows that nature is much smarter than expected: mutations are made less dangerous than believed, because they won't be that easily able any more to cause severe damages in the protein-synthesis. This should also lead to some alternative views upon evolution of life. Y1 - 2014 SN - 2329-0781 (Print) ; 2329-079X (Online) VL - Vol. 2 IS - No. 1 SP - 10 EP - 12 ER - TY - JOUR A1 - Handtke, Stefan A1 - Schroeter, Rebecca A1 - Jürgen, Britta A1 - Methling, Karen A1 - Schlüter, Rabea A1 - Albrecht, Dirk A1 - Hijum, Sacha A. F. T. van A1 - Bongaerts, Johannes A1 - Maurer, Karl-Heinz A1 - Lalk, Michael A1 - Schweder, Thomas A1 - Hecker, Michael A1 - Voigt, Birgit T1 - Bacillus pumilus reveals a remarkably high resistance to hydrogen peroxide provoked oxidative stress JF - PLOS one N2 - Bacillus pumilus is characterized by a higher oxidative stress resistance than other comparable industrially relevant Bacilli such as B. subtilis or B. licheniformis. In this study the response of B. pumilus to oxidative stress was investigated during a treatment with high concentrations of hydrogen peroxide at the proteome, transcriptome and metabolome level. Genes/proteins belonging to regulons, which are known to have important functions in the oxidative stress response of other organisms, were found to be upregulated, such as the Fur, Spx, SOS or CtsR regulon. Strikingly, parts of the fundamental PerR regulon responding to peroxide stress in B. subtilis are not encoded in the B. pumilus genome. Thus, B. pumilus misses the catalase KatA, the DNA-protection protein MrgA or the alkyl hydroperoxide reductase AhpCF. Data of this study suggests that the catalase KatX2 takes over the function of the missing KatA in the oxidative stress response of B. pumilus. The genome-wide expression analysis revealed an induction of bacillithiol (Cys-GlcN-malate, BSH) relevant genes. An analysis of the intracellular metabolites detected high intracellular levels of this protective metabolite, which indicates the importance of bacillithiol in the peroxide stress resistance of B. pumilus. Y1 - 2014 U6 - http://dx.doi.org/10.1371/journal.pone.0085625 SN - 1932-6203 VL - 9 IS - 1 PB - PLOS CY - San Francisco ER - TY - JOUR A1 - Miyamoto, Ko-ichiro A1 - Itabashi, Akinori A1 - Wagner, Torsten A1 - Schöning, Michael Josef A1 - Yoshinobu, Tatsuo T1 - High-speed chemical imaging inside a microfluidic channel JF - Sensors and actuators. B: Chemical N2 - In this study, a high-speed chemical imaging system was developed for visualization of the interior of a microfluidic channel. A microfluidic channel was constructed on the sensor surface of the light-addressable potentiometric sensor (LAPS), on which the ion concentrations could be measured in parallel at up to 64 points illuminated by optical fibers. The temporal change of pH distribution inside the microfluidic channel was recorded at a maximum rate of 100 frames per second (fps). The high frame rate allowed visualization of moving interfaces and plugs in the channel even at a flow velocity of 111 mm/s, which suggests the feasibility of plug-based microfluidic devices for flow-injection analysis (FIA). Y1 - 2014 U6 - http://dx.doi.org/10.1016/j.snb.2013.12.090 SN - 1873-3077 (E-Journal); 0925-4005 (Print) VL - 194 SP - 521 EP - 527 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Rau, Christoph A1 - Alexopoulos, Spiros A1 - Breitbach, Gerd A1 - Hoffschmidt, Bernhard A1 - Latzke, Markus A1 - Sattler, Johannes, Christoph T1 - Transient simulation of a solar-hybrid tower power plant with open volumetric receiver at the location Barstow JF - Energy procedia : proceedings of the SolarPACES 2013 International Conference N2 - In this work the transient simulations of four hybrid solar tower power plant concepts with open-volumetric receiver technology for a location in Barstow-Daggett, USA, are presented. The open-volumetric receiver uses ambient air as heat transfer fluid and the hybridization is realized with a gas turbine. The Rankine cycle is heated by solar-heated air and/or by the gas turbine's flue gases. The plant can be operated in solar-only, hybrid parallel or combined cycle-only mode as well as in any intermediate load levels where the solar portion can vary between 0 to 100%. The simulated plant is based on the configuration of a solar-hybrid power tower project, which is in planning for a site in Northern Algeria. The meteorological data for Barstow-Daggett was taken from the software meteonorm. The solar power tower simulation tool has been developed in the simulation environment MATLAB/Simulink and is validated. Y1 - 2014 U6 - http://dx.doi.org/10.1016/j.egypro.2014.03.157 SN - 1876-6102 VL - 49 SP - 1481 EP - 1490 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Kronhardt, Valentina A1 - Alexopoulos, Spiros A1 - Reißel, Martin A1 - Sattler, Johannes, Christoph A1 - Hoffschmidt, Bernhard A1 - Hänel, Matthias A1 - Doerbeck, Till T1 - High-temperature thermal storage system for solar tower power plants with open-volumetric air receiver simulation and energy balancing of a discretized model JF - Energy procedia N2 - This paper describes the modeling of a high-temperature storage system for an existing solar tower power plant with open volumetric receiver technology, which uses air as heat transfer medium (HTF). The storage system model has been developed in the simulation environment Matlab/Simulink®. The storage type under investigation is a packed bed thermal energy storage system which has the characteristics of a regenerator. Thermal energy can be stored and discharged as required via the HTF air. The air mass flow distribution is controlled by valves, and the mass flow by two blowers. The thermal storage operation strategy has a direct and significant impact on the energetic and economic efficiency of the solar tower power plants. Y1 - 2014 U6 - http://dx.doi.org/10.1016/j.egypro.2014.03.094 SN - 1876-6102 (E-Journal) ; 1876-6102 (Print) VL - 49 SP - 870 EP - 877 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Heinze, Daniel A1 - Mang, Thomas A1 - Peter, Karin A1 - Möller, Martin A1 - Weichold, Oliver T1 - Synthesis of low molecular weight poly(vinyl acetate) and its application as plasticizer JF - Journal of applied polymer science N2 - Poly(vinyl acetate), PVAc, with a degree of polymerization Xn = 10 was prepared by chain-transfer radical polymerization using carbon tetrachloride and used as oligomeric plasticizer for commercial PVAc. However, the chlorinated chain ends cause a low thermal stability requiring mild Cl/H substitution. The product exhibits high thermal stability and excellent melt-compounding properties. Blends of oligomeric and commercial PVAc show single glass transition temperatures which decrease with higher oligomer content and exhibit small negative deviations from Fox' linear additivity rule. This indicates plasticization and miscibility being mainly due to entropic effects. Injection-moulded thick specimens show ductile behaviour at oligomer contents >10 wt %, while sheets with a thickness of 0.2–0.5 mm appear flexible already at 7.5 wt %. The oxygen permeability coefficients are an order of magnitude lower than those of low-density polyethylene. Due to the sum of their properties, the plasticized sheets present a promising alternative in the preparation of barrier materials. Y1 - 2014 U6 - http://dx.doi.org/10.1002/app.40226 SN - 1097-4628 (E-Journal); 0021-8995 (Print) VL - 131 IS - 9 SP - Article No. 40226 PB - Wiley CY - New York ER - TY - JOUR A1 - Dikta, Gerhard T1 - Asymptotically efficient estimation under semi-parametric random censorship models JF - Journal of multivariate analysis N2 - We study the estimation of some linear functionals which are based on an unknown lifetime distribution. The observations are assumed to be generated under the semi-parametric random censorship model (SRCM), that is, a random censorship model where the conditional expectation of the censoring indicator given the observation belongs to a parametric family. Under this setup a semi-parametric estimator of the survival function was introduced by the author. If the parametric model assumption is correct, it is known that the estimated functional which is based on this semi-parametric estimator is asymptotically at least as efficient as the corresponding one which rests on the nonparametric Kaplan–Meier estimator. In this paper we show that the estimated functional which is based on this semi-parametric estimator is asymptotically efficient with respect to the class of all regular estimators under this semi-parametric model. Y1 - 2014 U6 - http://dx.doi.org/10.1016/j.jmva.2013.10.002 SN - 1095-7243 (E-Journal); 0047-259X (Print) VL - 124 SP - 10 EP - 24 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Bandodkar, Amay J. A1 - Molinnus, Denise A1 - Mirza, Omar A1 - Guinovart, Tomas A1 - Windmiller, Joshua R. A1 - Valdes-Ramirez, Gabriela A1 - Andrade, Francisco J. A1 - Schöning, Michael Josef A1 - Wang, Joseph T1 - Epidermal tattoo potentiometric sodium sensors with wireless signal transduction for continuous non-invasive sweat monitoring JF - Biosensors and bioelectronics N2 - This article describes the fabrication, characterization and application of an epidermal temporary-transfer tattoo-based potentiometric sensor, coupled with a miniaturized wearable wireless transceiver, for real-time monitoring of sodium in the human perspiration. Sodium excreted during perspiration is an excellent marker for electrolyte imbalance and provides valuable information regarding an individual's physical and mental wellbeing. The realization of the new skin-worn non-invasive tattoo-like sensing device has been realized by amalgamating several state-of-the-art thick film, laser printing, solid-state potentiometry, fluidics and wireless technologies. The resulting tattoo-based potentiometric sodium sensor displays a rapid near-Nernstian response with negligible carryover effects, and good resiliency against various mechanical deformations experienced by the human epidermis. On-body testing of the tattoo sensor coupled to a wireless transceiver during exercise activity demonstrated its ability to continuously monitor sweat sodium dynamics. The real-time sweat sodium concentration was transmitted wirelessly via a body-worn transceiver from the sodium tattoo sensor to a notebook while the subjects perspired on a stationary cycle. The favorable analytical performance along with the wearable nature of the wireless transceiver makes the new epidermal potentiometric sensing system attractive for continuous monitoring the sodium dynamics in human perspiration during diverse activities relevant to the healthcare, fitness, military, healthcare and skin-care domains. Y1 - 2014 U6 - http://dx.doi.org/10.1016/j.bios.2013.11.039 SN - 1873-4235 (E-Journal); 0956-5663 (Print) VL - 54 SP - 603 EP - 609 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Winckler, Silvia A1 - Krueger, Rolf A1 - Schnitzler, Thomas A1 - Zang, Werner A1 - Fischer, Rainer A1 - Biselli, Manfred T1 - A sensitive monitoring system for mammalian cell cultivation processes: a PAT approach JF - Bioprocess and biosystems engineering N2 - Biopharmaceuticals such as antibodies are produced in cultivated mammalian cells, which must be monitored to comply with good manufacturing practice. We, therefore, developed a fully automated system comprising a specific exhaust gas analyzer, inline analytics and a corresponding algorithm to precisely determine the oxygen uptake rate, carbon dioxide evolution rate, carbon dioxide transfer rate, transfer quotient and respiratory quotient without interrupting the ongoing cultivation, in order to assess its reproducibility. The system was verified using chemical simulation experiments and was able to measure the respiratory activity of hybridoma cells and DG44 cells (derived from Chinese hamster ovary cells) with satisfactory results at a minimum viable cell density of ~2.0 × 10⁵ cells ml⁻¹. The system was suitable for both batch and fed-batch cultivations in bubble-aerated and membrane-aerated reactors, with and without the control of pH and dissolved oxygen. Y1 - 2014 U6 - http://dx.doi.org/10.1007/s00449-013-1062-8 SN - 1615-7591 (Print) 1615-7605 (Online) VL - 37 IS - 5 SP - 901 EP - 912 PB - Springer CY - Berlin, Heidelberg ER - TY - JOUR A1 - Jens, Otto A1 - Kaldenhoff, E. A1 - Kirschner-Hermanns, R. A1 - Mühl, Thomas A1 - Klinge, Uwe T1 - Elongation of textile pelvic floor implants under load is related to complete loss of effective porosity, thereby favoring incorporation in scar plates JF - Journal of biomedical materials research. Part A N2 - Use of textile structures for reinforcement of pelvic floor structures has to consider mechanical forces to the implant, which are quite different to the tension free conditions of the abdominal wall. Thus, biomechanical analysis of textile devices has to include the impact of strain on stretchability and effective porosity. Prolift® and Prolift + M®, developed for tension free conditions, were tested by measuring stretchability and effective porosity applying mechanical strain. For comparison, we used Dynamesh-PR4®, which was designed for pelvic floor repair to withstand mechanical strain. Prolift® at rest showed moderate porosity with little stretchability but complete loss of effective porosity at strain of 4.9 N/cm. Prolift + M® revealed an increased porosity at rest, but at strain showed high stretchability, with subsequent loss of effective porosity at strain of 2.5 N/cm. Dynamesh PR4® preserved its high porosity even under strain, but as consequence of limited stretchability. Though in tension free conditions Prolift® and Prolift + M® can be considered as large pore class I meshes, application of mechanical strain rapidly lead to collapse of pores. The loss of porosity at mechanical stress can be prevented by constructions with high structural stability. Assessment of porosity under strain was found helpful to define requirements for pelvic floor devices. Clinical studies have to prove whether devices with high porosity as well as high structural stability can improve the patients' outcome. Y1 - 2014 U6 - http://dx.doi.org/10.1002/jbm.a.34767 SN - 1552-4965 VL - 102 IS - 4 SP - 1079 EP - 1084 PB - Wiley CY - New York ER -