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61.
van Oostrum J Calonder C Rechsteiner D Ehrat M Mestan J Fabbro D Voshol H 《Proteomics. Clinical applications》2009,3(4):412-422
Controlling aberrant protein kinase activity is a promising strategy for a variety of diseases, particularly cancer. Hence, the development of kinase inhibitors is currently a focal point for pharmaceutical research. In this study we utilize a chip-based reverse phase protein array (RPA) platform for profiling of kinase inhibitors in cell-based assays. In combination with the planar wave-guide technology the assay system has an absolute LOD down to the low zeptomole range. A431 cell lysates were analyzed for the activation state of key effectors in the epidermal growth factor (EGF) and insulin signaling pathways to validate this model for compound screening. A microtiter-plate format for growing, treating, and lysing cells was shown to be suitable for this approach, establishing the value of the technology as a screening tool for characterization of large numbers of kinase inhibitors against a wide variety of cellular signaling pathways. Moreover, the reverse array format allows rapid development of site-specific phosphorylation assays, since in contrast to ELISA type systems only a single antigen-specific antibody is required. 相似文献
62.
Ludovit Markus 《Journal of Intelligent and Robotic Systems》1994,11(1-2):109-116
A general method for solving the robot inverse kinematics problem is presented. The method is based upon the general elimination method to obtain the equivalent system of equations which are triangularized and the solutions of the inverse kinematics problem can be solved by backsubstitutions. 相似文献
63.
Hemminki Ari; Hoffren Anna-Marja; Takkinen Kristiina; Vehniainen Markus; Makinen Maija-Liisa; Pettersson Kim; Teleman Olle; Soderlund Hans; Teeri Tuula T. 《Protein engineering, design & selection : PEDS》1995,8(2):185-191
Europium chelates provide a non-radioactive alternative forsensitive labelling of antibodies for diagnostic immunoassays.Lysine residues at antibody surfaces are ready targets for labellingby an isothiocyanate derivative of the europium chelate (Eu3+).Here the labelling efficiency of a recombinant anti-human -fetoprotein(hAFP) Fab fragment has been improved by increasing its lysinecontent by protein engineering. Molecular modelling was usedto identify three light chain constant domain surface arginineresidues, R154, R187 and R210, which were mutated to lysineresidues. The mutations did not influence the affinity of thelysine-enriched Fab fragment and its labelling efficiency wasfound to be 40% higher than that of the wildtype Fab fragmentWith low degree of labelling, the affinities of the two Fabfragments were identical and comparable with that of the originalmonoclonal anti-hAFP IgG. With a higher degree of labellingthe affinities of both Fab fragments decreased more than thatof the intact IgG since more lysine residues are available forlabelling in the additional heavy chain constant domains ofthe larger molecule. Electrostatic adsorption and covalent immobilizationof the Fab fragments were characterized by BIAcoreTM and thelysine-enriched Fab fragment was found to be more efficientlyimmobilized to an activated carboxymethyl surface. 相似文献
64.
Erik Valentine Bachtiar Markus Rüggeberg Stefan Hering Michael Kaliske Peter Niemz 《Materials and Structures》2017,50(6):248
In this study, several theoretical models to numerically estimate shear properties of orthotropic materials are introduced. These approaches are based on the combination of Hankinson’s empirically derived formula with other empirical and analytical calculations. Next to shear moduli, which are estimated from the elastic moduli and Poisson’s ratios, shear strengths are also estimated from the in-axis strengths. The models are validated by mechanical tests on walnut wood (Juglans regia L.), for which a sufficient data set can be found in literature. The Arcan test is used to estimate the shear moduli, while the shear block test is used to estimate the shear strengths. The results show that the model, which is based on a combined use of Hankinson’s formula and tensor rotation, gives the best estimation of shear moduli as evaluated by the minimum differences to the experimentally obtained results. For the shear strengths, a combination of Hankinson’s formula and Norris’ failure criterion shows the best agreement in comparison to the experimental data. The theoretical calculations may be used for a time efficient estimation of shear modulus and strength in comparison to the very time-consuming experimental estimation. 相似文献
65.
66.
Mathematical models are important tools to study the excluded volume effects on reaction–diffusion systems, which are known to play an important role inside living cells. Detailed microscopic simulations with off‐lattice Brownian dynamics become computationally expensive in crowded environments. In this study, the authors therefore investigate to which extent on‐lattice approximations, the so‐called cellular automata models, can be used to simulate reactions and diffusion in the presence of crowding molecules. They show that the diffusion is most severely slowed down in the off‐lattice model, since randomly distributed obstacles effectively exclude more volume than those ordered on an artificial grid. Crowded reaction rates can be both increased and decreased by the grid structure and it proves important to model the molecules with realistic sizes when excluded volume is taken into account. The grid artefacts increase with increasing crowder density and they conclude that the computationally more efficient on‐lattice simulations are accurate approximations only for low crowder densities.Inspec keywords: reaction‐diffusion systems, cellular biophysics, biodiffusion, Brownian motion, cellular automata, molecular biophysics, molecular configurationsOther keywords: crowder density, grid artefacts, grid structure, crowded reaction rates, artificial grid, randomly distributed obstacles, crowding molecules, cellular automata models, on‐lattice approximations, crowded environments, off‐lattice Brownian dynamics, detailed microscopic simulations, living cells, mathematical models, off‐lattice reaction‐diffusion models, on‐lattice reaction‐diffusion models, excluded volume effects 相似文献
67.
Igor Solodov Markus Rahammer Nikolai Gulnizkij Marc Kreutzbruck 《Journal of Nondestructive Evaluation》2016,35(3):48
A selective acoustic activation of defects based on the concept of local defect resonance enables to enhance considerably the intensity of defect vibrations and makes it possible to reduce the input acoustic powers to the levels permissible for noncontact nondestructive inspection. Since for cm-size defects in composite materials, the LDR frequencies lie in the low kHz-range, the resonant noncontact activation shifts to an audible frequency range and can be provided by conventional sonic equipment. In this paper, the feasibility of the resonant noncontact inspection is validated for the most “problematic” methodologies of nonlinear, thermosonic and shearosonic NDE that usually require an elevated acoustic power and, therefore, a reliable contact between the specimen and the transducer. In contrast, the noncontact versions developed employ commercial loudspeakers which can simultaneously insonify large areas and be applied for a contactless sonic inspection of different materials and various scale components. 相似文献
68.
The Mann–Whitney effect is an intuitive measure for discriminating two survival distributions. Here we analyse various inference techniques for this parameter in a two-sample survival setting with independent right-censoring, where the survival times are even allowed to be discretely distributed. This allows for ties in the data and requires the introduction of normalized versions of Kaplan–Meier estimators from which adequate point estimates are deduced. Asymptotically exact inference procedures based on standard normal, bootstrap, and permutation quantiles are developed and compared in simulations. Here, the asymptotically robust and—under exchangeable data—even finitely exact permutation procedure turned out to be the best. Finally, all procedures are illustrated using a real data set. 相似文献
69.
A Review of Metal Fabricated with Laser‐ and Powder‐Bed Based Additive Manufacturing Techniques: Process,Nomenclature, Materials,Achievable Properties,and its Utilization in the Medical Sector 下载免费PDF全文
70.
Single point incremental forming: state-of-the-art and prospects 总被引:1,自引:0,他引:1
Joost R. Duflou Anne-Marie Habraken Jian Cao Rajiv Malhotra Markus Bambach Dave Adams Hans Vanhove Amirahmad Mohammadi Jack Jeswiet 《International Journal of Material Forming》2018,11(6):743-773
Incremental sheet metal forming in general and Single Point Incremental Forming (SPIF) specifically have gone through a period of intensive development with growing attention from research institutes worldwide. The result of these efforts is significant progress in the understanding of the underlying forming mechanisms and opportunities as well as limitations associated with this category of flexible forming processes. Furthermore, creative process design efforts have enhanced the process capabilities and process planning methods. Also, simulation capabilities have evolved substantially. This review paper aims to provide an overview of the body of knowledge with respect to Single Point Incremental Forming. Without claiming to be exhaustive, each section aims for an up-to-date state-of-the-art review with corresponding conclusions on scientific progress and outlook on expected further developments. 相似文献