Retention of Activity by Antibodies Immobilized on Gold Nanoparticles of Different Sizes: Fluorometric Method of Determination and Comparative Evaluation

Antibody–nanoparticle conjugates are widely used analytical reagents. An informative parameter reflecting the conjugates’ properties is the number of antibodies per nanoparticle that retain their antigen-binding ability. Estimation of this parameter is characterized by a lack of simple, reproducible methods. The proposed method is based on the registration of fluorescence of tryptophan residues contained in proteins and combines sequential measurements of first the immobilized antibody number and then the bound protein antigen number. Requirements for the measurement procedure have been determined to ensure reliable and accurate results. Using the developed technique, preparations of spherical gold nanoparticles obtained by the most common method of citrate reduction of gold salts (the Turkevich–Frens method) and varying in average diameter from 15 to 55 nm have been characterized. It was shown that the number of antibodies (immunoglobulins G) bound by one nanoparticle ranged from 30 to 194 during adsorptive unoriented monolayer immobilization. C-reactive protein was considered as the model antigen. The percentage of antibody valences that retained their antigen-binding properties in the conjugate increased from 17 to 34% with an increase in the diameter of gold nanoparticles. The proposed method and the results of the study provide tools to assess the capabilities of the preparations of gold nanoparticles and their conjugates as well as the expediency of seeking the best techniques for various practical purposes.

Dynamic Mode Decomposition and Its Variants

Dynamic mode decomposition (DMD) is a factorization and dimensionality reduction technique for data sequences. In its most common form, it processes high-dimensional sequential measurements, extracts coherent structures, isolates dynamic behavior, and reduces complex evolution processes to their dominant features and essential components. The decomposition is intimately related to Koopman analysis and, since its introduction, has spawned various extensions, generalizations, and improvements. It has been applied to numerical and experimental data sequences taken from simple to complex fluid systems and has also had an impact beyond fluid dynamics in, for example, video surveillance, epidemiology, neurobiology, and financial engineering. This review focuses on the practical aspects of DMD and its variants, as well as on its usage and characteristics as a quantitative tool for the analysis of complex fluid processes. Expected final online publication date for the Annual Review of Fluid Mechanics, Volume 54 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Validation of blood pressure measurement by the complex for daily monitoring of ECG and blood pressure “Medicom-Combi" by oscillometric and auscultatory methods in pediatric population (according to the BHS-93 protocol)

Purpose. To assess the accuracy of blood pressure (BP) measurement by the complex for daily monitoring of ECG and blood pressure «MedicomCombi» in comparison with a mercury sphygmomanometer in pediatric patients.Materials and methods. The recruitment of study participants was carried out in accordance with the criteria outlined in the international protocol BHS-93 for the pediatric population. During the tests, repeated sequential measurements of blood pressure were carried out by experts (using mercury sphygmomanometers) and the tested complex (by oscillometric and auscultatory methods).Results. The mean SBP, determined by the oscillometric method, was 116.0 ± 13.6 mm Hg, DBP - 69.0 ± 11.8 mm Hg. The mean SBP according to the auscultatory method was 116.0 ± 14.6 mm Hg, DBP - 70.4 ± 11.9 mm Hg. In 66% of cases for SBP and in 62% of cases for DBP, the difference between expert and test measurements by the oscillometric method did not exceed 5 mm Hg. In 100% of cases for SBP and in 96% of cases for DBP, the differences were within 10 mm Hg. The average differences between the experts and the tested complex were - 0.2 ± 5.7 mm Hg for SBP and 1.6 ± 6.1 for DBP. In 68 % of cases for SBP and in 65 % of cases for DBP, the difference between expert and test measurements by the auscultatory method was no more than 5 mm Hg. In 100% of cases for SBP and in 95% of cases for DBP, the differences did not exceed 10 mm Hg. The average differences between the experts and the tested complex were - 0.3 ± 4.7 mm Hg for SBP and 0.1 ± 5.7 for DBP.Conclusion. The complex for daily monitoring of ECG and blood pressure «Medicom-Combi» has demonstrated compliance with the accuracy requirements specified in the BHS 1993 protocol (class «А/А»), and can be recommended for measuring blood pressure by oscillometric and auscultatory methods in pediatric practice.

Utility of single versus sequential measurements of risk factors for prediction of stroke in Chinese adults

Absolute risks of stroke are typically estimated using measurements of cardiovascular disease risk factors recorded at a single visit. However, the comparative utility of single versus sequential risk factor measurements for stroke prediction is unclear. Risk factors were recorded on three separate visits on 13,753 individuals in the prospective China Kadoorie Biobank. All participants were stroke-free at baseline (2004–2008), first resurvey (2008), and second resurvey (2013–2014), and were followed-up for incident cases of first stroke in the 3 years following the second resurvey. To reflect the models currently used in clinical practice, sex-specific Cox models were developed to estimate 3-year risks of stroke using single measurements recorded at second resurvey and were retrospectively applied to risk factor data from previous visits. Temporal trends in the Cox-generated risk estimates from 2004 to 2014 were analyzed using linear mixed effects models. To assess the value of more flexible machine learning approaches and the incorporation of longitudinal data, we developed gradient boosted tree (GBT) models for 3-year prediction of stroke using both single measurements and sequential measurements of risk factor inputs. Overall, Cox-generated estimates for 3-year stroke risk increased by 0.3% per annum in men and 0.2% per annum in women, but varied substantially between individuals. The risk estimates at second resurvey were highly correlated with the annual increase of risk for each individual (men: r = 0.91, women: r = 0.89), and performance of the longitudinal GBT models was comparable with both Cox and GBT models that considered measurements from only a single visit (AUCs: 0.779–0.811 in men, 0.724–0.756 in women). These results provide support for current clinical guidelines, which recommend using risk factor measurements recorded at a single visit for stroke prediction.

NOMA: a high-throughput microchip for robust sequential measurements of secretions from the same single-cells

Despite advances in single-cell secretion analysis technologies, lacking simple methods to reliably keep the live single-cells traceable for longitudinal detection poses a significant obstacle. Here we developed the high-density NOMA (narrow-opening microwell array) microchip that realized the retention of ≥97% of trapped single cells during repetitive detection procedures, regardless of adherent or suspension cells. We demonstrated its use to decode the correlation of protein abundance between secreted extracellular vesicles (EVs) and its donor cells at the same single-cell level, in which we found that these two were poorly correlated with each other. We further applied it in monitoring single-cell protein secretions sequentially from the same single cells. Notably, we observed the digital protein secretion patterns dominate the protein secretion. We also applied the microchip for longitudinally tracking of the single-cell integrative secretions over days, which revealed the presence of “super secretors” within the cell population that could be more persistent to secrete protein or extracellular vesicle for an extended period. The NOMA platform reported here is simple, robust, and easy to operate for realizing sequential measurements from the same single cells, representing a novel and informative tool to inspire new observations in biomedical research.

Navigation Along Windborne Plumes of Pheromone and Resource-Linked Odors

Many insects locate resources such as a mate, a host, or food by flying upwind along the odor plumes that these resources emit to their source. A windborne plume has a turbulent structure comprised of odor filaments interspersed with clean air. As it propagates downwind, the plume becomes more dispersed and dilute, but filaments with concentrations above the threshold required to elicit a behavioral response from receiving organisms can persist for long distances. Flying insects orient along plumes by steering upwind, triggered by the optomotor reaction. Sequential measurements of differences in odor concentration are unreliable indicators of distance to or direction of the odor source. Plume intermittency and the plume's fine-scale structure can play a role in setting an insect's upwind course. The prowess of insects in navigating to odor sources has spawned bioinspired virtual models and even odor-seeking robots, although some of these approaches use mechanisms that are unnecessarily complex and probably exceed an insect's processing capabilities.