Protein's Protein Corona: Nanoscale Size Evolution of Human Immunoglobulin G Aggregates Induced by Serum Albumin.

Nanoparticles are readily coated by proteins in biological systems. The protein layers on the nanoparticles, which are called the protein corona, influence the biological impacts of the nanoparticles, including internalization into cells and cytotoxicity. This study expands the scope of the nanoparticle's protein corona for exogenous artificial nanoparticles to that for exogenous proteinaceous nanoparticles. Specifically, this study addresses the formation of protein coronas on nanoscale human antibody aggregates with a radius of approximately 20-40 nm, where the antibody aggregates were induced by a pH shift from low to neutral pH. The size of the human immunoglobulin G (hIgG) aggregates grew to approximately 25 times the original size in the presence of human serum albumin (HSA). This size evolution was ascribed to the association of the hIgG aggregates, which was triggered by the formation of the hIgG aggregate's protein corona, i.e., protein's protein corona, consisting of the adsorbed HSA molecules. Because hIgG aggregate association was significantly reduced by the addition of 30-150 mM NaCl, it was attributed to electrostatic attraction, which was supported by molecular dynamics (MD) simulations. Currently, the use of antibodies as biopharmaceuticals is concerning because of undesired immune responses caused by antibody aggregates that are typically generated by a pH shift during the antibody purification process. The present findings suggest that nanoscale antibody aggregates form protein coronas induced by HSA and the resulting nanoscale antibody-HSA complexes are stable in blood containing approximately 150 mM salt ions, at least in terms of the size evolution. Mechanistic insights into protein corona formation on nanoscale antibody aggregates are useful for understanding the unintentional biological impacts of antibody drugs.

Regional heterogeneity of afterload sensitivity in myocardial strain.

PURPOSE: The peak systolic strain decreases due to afterload augmentation. However, its deterioration (i.e., afterload sensitivity) may be different within the left ventricular (LV) segments. We investigated how afterload influences regional strain and whether there is regional heterogeneity of afterload sensitivity. METHODS: Afterload was increased by aortic banding in 20 open-chest dogs. Short-axis images were acquired at baseline and during banding. Circumferential strain was analyzed in six segments, and the absolute decrease in the peak systolic strain during banding (Δε) was calculated for each segment. To assess the effect of the compensatory preload recruitment during banding, the endocardial lengths of the septum and free wall were measured at end-diastole, and the rate of increase due to banding was calculated. RESULTS: LV systolic pressure was significantly increased during banding (100 ± 14 vs. 143 ± 18 mmHg, P < 0.001). The peak systolic strain in all segments was significantly decreased during banding. Δɛ in the anterior segment, which is a part of the free wall, was significantly lower than that in the inferoseptal segment (2.6 ± 4.7 vs. 6.5 ± 3.5%, P = 0.035). The rate of increase in endocardial length in the free wall was significantly larger than that in the septum (15.6 ± 10.4 vs. 8.1 ± 7.4%, P = 0.014). CONCLUSION: The decrease in septal strain during afterload augmentation was larger than that in free wall strain, indicating that there was regional heterogeneity of afterload sensitivity in circumferential strain. The larger compensatory preload recruitment in the free wall than in the septum is implicated as a cause of the heterogeneity.

A discrimination method for paper by Fourier transform and cross correlation.

A non-destructive method for discriminating between different types of paper has been proposed, using image analysis, Fourier transformation, and cross-correlation matching. A fast Fourier transform (FFT) is used to extract the periodicity in the structure of paper that results from the manufacturing processes. The light-transmission images of the paper to be Fourier transformed are obtained from a flatbed image scanner. The similarity between the power spectrum of the FFT of the sample and that of a reference is quantified using a cross-correlation matching method. An advantage of using frequency analysis is that periodicity can be detected even if the sample is damaged or is printed on. The technique works on samples as small as 2 cm2.