Amyloid-β (Aβ) oligomers represent a promising biomarker for the early diagnosis of Alzheimer's disease (AD). However, state-of-the-art methods for immunodetection of Aβ oligomers in body fluids show a large variability and lack a reliable and stable standard that enables the reproducible quantitation of Aβ oligomers. At present, the only available standard applied in these assays is based on a random aggregation process of synthetic Aβ and has neither a defined size nor a known number of epitopes. In this report, we generated a highly stable standard in the size range of native Aβ oligomers that exposes a defined number of epitopes. The standard consists of a silica nanoparticle (SiNaP), which is functionalized with Aβ peptides on its surface (Aβ-SiNaP). The different steps of Aβ-SiNaP synthesis were followed by microscopic, spectroscopic and biochemical analyses. To investigate the performance of Aβ-SiNaPs as an appropriate standard in Aβ oligomer immunodetection, Aβ-SiNaPs were diluted in cerebrospinal fluid and quantified down to a concentration of 10 fM in the sFIDA (surface-based fluorescence intensity distribution analysis) assay. This detection limit corresponds to an Aβ concentration of 1.9 ng l-1 and lies in the sensitivity range of currently applied diagnostic tools based on Aβ oligomer quantitation. Thus, we developed a highly stable and well-characterized standard for the application in Aβ oligomer immunodetection assays that finally allows the reproducible quantitation of Aβ oligomers down to single molecule level and provides a fundamental improvement for the worldwide standardization process of diagnostic methods in AD research.

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Still, there is need for significant improvements in reliable and accurate diagnosis for Alzheimer's disease (AD) at early stages. It is widely accepted that changes in the concentration and conformation of amyloid-β (Aβ) appear several years before the onset of first symptoms of cognitive impairment in AD patients. Because Aβ oligomers are possibly the major toxic species in AD, they are a promising biomarker candidate for the early diagnosis of the disease. To date, a variety of oligomer-specific assays have been developed, many of them ELISAs. Here, we demonstrate the sFIDA assay, a technology highly specific for Aβ oligomers developed toward single particle sensitivity. By spiking stabilized Aβ oligomers to buffer and to body fluids from control donors, we show that the sFIDA readout correlates with the applied concentration of stabilized oligomers diluted in buffer, cerebrospinal fluid (CSF), and blood plasma over several orders of magnitude. The lower limit of detection was calculated to be 22 fM of stabilized oligomers diluted in PBS, 18 fM in CSF, and 14 fM in blood plasma.

This research investigates the stability of a two-wheeled vehicle model on the basis of numerical determination of full range of eigenvalues of a linear approximation matrix in the vicinity of the rectilinear driving mode. The received result was checked by numerical integration of the initial equations system of the disturbed motion of the model. The discrepancy of two research techniques is explained by the specialty of the considered mathematical model in which two pairs of complex conjugate eigenvalues close to each other are realized, that explains the emergence of standard derivations at calculating their numerical determination. The model is asymptotically stable in the range much wider than an operational interval (up to 100 m/s). In order to provide more intensive dampening of initial disturbances, it is possible to introduce additional resilient and damping elements between the trucks and the body in the design of the wheeled vehicle that will counteract the yaw mode of trucks.

A method is proposed for determining the number of damaged stator windings in the presence of an asymmetric power supply system for an induction electric motor based on the Park vector hodograph. As a result of the experiments on the simulation model, it was found that with the symmetry of the system of supply voltages and stator windings, the hodograph of the Park vector describes a circle; in all other cases it is an ellipse. It has been established that the presence of asymmetry in the supply voltage system is indicated by the angle of inclination of the ellipse, and the indicator of the presence of the asymmetry of the stator windings is the angle of ellipticity. In order to identify the presence of asymmetry of the stator windings in the conditions of asymmetry of the supply voltage system, an algorithm for recalculating the ellipse parameters for the condition of the symmetry of the supply voltage system was proposed. Recalculation errors did not exceed 6%. It has been established that the dependence of the increment of the amplitudes of the phase and angles of the phase currents of the stator on the number of damaged turns of the stator winding is linear. Based on this fact, an algorithm for determining the number of damaged turns was proposed. The results of this work can be used to build systems for diagnosing the interturn short circuit of the stator of an induction electric motor built into the drive.