Analytical Model of the Frictional Heating in a Railway Brake Disc at Single Braking with Experimental Verification.

A one-dimensional thermal problem of friction was formulated, taking into account the contact pressure increase at the beginning of the process. The obtained solution to this problem allows for the quick calculation of the transient temperature distribution in a railway brake disc during single braking application. In order to validate the developed model, the experimental tests were performed for two friction pairs consisting of the cast iron brake disc and pads comprising two composite materials. Theoretical results were compared with the data measured by thermocouples embedded in the brake disc during the full-size dynamometer tests. The maximum temperature values found based on the analytical solution are convergent with the corresponding empirical data. The consistency of the results obtained for two friction couples demonstrates the usefulness of the proposed computational model.

Research into the Strength of an Open Wagon with Double Sidewalls Filled with Aluminium Foam.

The research is concerned with the use of double walls filled with aluminium foam for an open wagon in order to decrease the dynamic stresses during the operational modes. The research presents the strength calculation for the bearing structure of an open wagon with consideration of the engineering solutions proposed. It was found that the maximum equivalent stresses appeared in the bottom section of the centre sill behind the back support; they amounted to about 315 MPa and did not exceed the allowable values. The maximum displacements were detected in the middle section of the centre sill and amounted to 9.6 mm. The maximum deformations were 1.17 × 10-2. The research also presents the strength calculation for a weld joint in the maximum loaded zones of the bearing structure of an open wagon and gives the results of a modal analysis of the bearing structure of the improved open wagon. It was found that the critical oscillation frequencies did not exceed the allowable values. The results of the research may be useful for those who are concerned about designing innovative rolling stock units and improving the operational efficiency of railway transport.

Dynamics and Strength of Circular Tube Open Wagons with Aluminum Foam Filled Center Sills.

The study deals with an application of aluminum foam as an energy-absorbing material for the carrying structure of a rail car. The material is particularly recommended for circular tube carrying structures. The authors conducted mathematical modeling of dynamic loads on the carrying structure of an open wagon that faces shunting impacts with consideration of the center sill filled with aluminum foam. It was established that the maximum accelerations on the carrying structure of an open wagon were 35.7 m/s2, which was 3.5% lower in comparison with those for a circular tube structure without a filler. The results obtained were proved by computer modeling. The strength of the carrying structure of an open wagon was also calculated. It was established that aluminum foam applied as a filler for the center sill decreased the maximum equivalent stresses in the carrying structure of an open wagon by about 5% and displacements by 12% in comparison with those involving the circular tube carrying structure of an open wagon without a filler. The natural frequencies and the oscillation modes of the carrying structure of an open wagon were defined. The designed models of the dynamic loading of the carrying structure of an open wagon were verified with an F-test.

Analysis of anticoagulants for blood-based quantitation of amyloid ß oligomers in the sFIDA assay.

Early diagnostics at the preclinical stage of Alzheimer's disease is of utmost importance for drug development in clinical trials and prognostic guidance. Since soluble Aß oligomers are considered to play a crucial role in the disease pathogenesis, several methods aim to quantify Aß oligomers in body fluids such as cerebrospinal fluid (CSF) and blood plasma. The highly specific and sensitive method surface-based fluorescence intensity distribution analysis (sFIDA) has successfully been established for oligomer quantitation in CSF samples. In our study, we explored the sFIDA method for quantitative measurements of synthetic Aß particles in blood plasma. For this purpose, EDTA-, citrate- and heparin-treated blood plasma samples from five individual donors were spiked with Aß coated silica nanoparticles (Aß-SiNaPs) and were applied to the sFIDA assay. Based on the assay parameters linearity, coefficient of variation and limit of detection, we found that EDTA plasma yields the most suitable parameter values for quantitation of Aß oligomers in sFIDA assay with a limit of detection of 16 fM.

sFIDA automation yields sub-femtomolar limit of detection for Aß aggregates in body fluids.

OBJECTIVES: Alzheimer's disease (AD) is a neurodegenerative disorder with yet non-existent therapeutic and limited diagnostic options. Reliable biomarker-based AD diagnostics are of utmost importance for the development and application of therapeutic substances. We have previously introduced a platform technology designated 'sFIDA' for the quantitation of amyloid ß peptide (Aß) aggregates as AD biomarker. In this study we implemented the sFIDA assay on an automated platform to enhance robustness and performance of the assay. DESIGN AND METHODS: In sFIDA (surface-based fluorescence intensity distribution analysis) Aß species are immobilized by a capture antibody to a glass surface. Aß aggregates are then multiply loaded with fluorescent antibodies and quantitated by high resolution fluorescence microscopy. As a model system for Aß aggregates, we used Aß-conjugated silica nanoparticles (Aß-SiNaPs) diluted in PBS buffer and cerebrospinal fluid, respectively. Automation of the assay was realized on a liquid handling system in combination with a microplate washer. RESULTS: The automation of the sFIDA assay results in improved intra-assay precision, linearity and sensitivity in comparison to the manual application, and achieved a limit of detection in the sub-femtomolar range. CONCLUSIONS: Automation improves the precision and sensitivity of the sFIDA assay, which is a prerequisite for high-throughput measurements and future application of the technology in routine AD diagnostics.

Biofunctionalized Silica Nanoparticles: Standards in Amyloid-ß Oligomer-Based Diagnosis of Alzheimer's Disease.

Amyloid-ß (Aß) oligomers represent a promising biomarker for the early diagnosis of Alzheimer's disease (AD). However, state-of-the-art methods for immunodetection of Aß oligomers in body fluids show a large variability and lack a reliable and stable standard that enables the reproducible quantitation of Aß oligomers. At present, the only available standard applied in these assays is based on a random aggregation process of synthetic Aß 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 Aß oligomers that exposes a defined number of epitopes. The standard consists of a silica nanoparticle (SiNaP), which is functionalized with Aß peptides on its surface (Aß-SiNaP). The different steps of Aß-SiNaP synthesis were followed by microscopic, spectroscopic and biochemical analyses. To investigate the performance of Aß-SiNaPs as an appropriate standard in Aß oligomer immunodetection, Aß-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 Aß concentration of 1.9 ng l-1 and lies in the sensitivity range of currently applied diagnostic tools based on Aß oligomer quantitation. Thus, we developed a highly stable and well-characterized standard for the application in Aß oligomer immunodetection assays that finally allows the reproducible quantitation of Aß oligomers down to single molecule level and provides a fundamental improvement for the worldwide standardization process of diagnostic methods in AD research.

Application of an Amyloid Beta Oligomer Standard in the sFIDA Assay.

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-ß (Aß) appear several years before the onset of first symptoms of cognitive impairment in AD patients. Because Aß 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 Aß oligomers developed toward single particle sensitivity. By spiking stabilized Aß 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.