Asymmetry of Cell Division in CFSE-Based Lymphocyte Proliferation Analysis

Flow cytometry-based analysis of lymphocyte division using carboxyfluorescein succinimidyl ester (CFSE) dye dilution permits acquisition of data describing cellular proliferation and differentiation. For example, CFSE histogram data enable quantitative insight into cellular turnover rates by applying mathematical models and parameter estimation techniques. Several mathematical models have been developed using different types of deterministic or stochastic approaches. However, analysis of CFSE proliferation assays is based on the premise that the label is halved in the two daughter cells. Importantly, asymmetry of protein distribution in lymphocyte division is a basic biological feature of cell division with the degree of the asymmetry depending on various factors. Here, we review the recent literature on asymmetric lymphocyte division and CFSE-based lymphocyte proliferation analysis. We suggest that division- and label-structured mathematical models describing CFSE-based cell proliferation should take into account asymmetry and time-lag in cell proliferation. Utilization of improved modeling algorithms will permit straightforward quantification of essential parameters describing the performance of activated lymphocytes

Numerical bifurcation analysis of delay differential equations

AbstractNumerical methods for the bifurcation analysis of delay differential equations (DDEs) have only recently received much attention, partially because the theory of DDEs (smoothness, boundedness, stability of solutions) is more complicated and less established than the corresponding theory of ordinary differential equations. As a consequence, no established software packages exist at present for the bifurcation analysis of DDEs. We outline existing numerical methods for the computation and stability analysis of steady-state solutions and periodic solutions of systems of DDEs with several constant delays

Das Strafvollzugssystem der Russischen Föderation: Bestrafung statt Resozialisierung?

Aleksej Nawalnyj verbüßt seine Haftstrafe in einer Besserungsarbeitskolonie mit allgemeinem Strafvollzug. Dies ist der häufigste Typ der Justizvollzugsanstalt in Russland und ist mit westlichen Gefängnissen nicht vergleichbar. Denn das russische Strafvollzugssystem ist komplex und unterscheidet sich grundlegend vom dem im Westen. In der folgenden Analyse wird die Entwicklung der Häftlingszahlen, der Anstieg politisch motivierter Verfahren sowie die verschiedenen Typen von Justizvollzugsanstalten in Russland besprochen

Numerical modelling of label-structured cell population growth using CFSE distribution data

<p>Abstract</p> <p>Background</p> <p>The flow cytometry analysis of CFSE-labelled cells is currently one of the most informative experimental techniques for studying cell proliferation in immunology. The quantitative interpretation and understanding of such heterogenous cell population data requires the development of distributed parameter mathematical models and computational techniques for data assimilation.</p> <p>Methods and Results</p> <p>The mathematical modelling of label-structured cell population dynamics leads to a hyperbolic partial differential equation in one space variable. The model contains fundamental parameters of cell turnover and label dilution that need to be estimated from the flow cytometry data on the kinetics of the CFSE label distribution. To this end a maximum likelihood approach is used. The Lax-Wendroff method is used to solve the corresponding initial-boundary value problem for the model equation. By fitting two original experimental data sets with the model we show its biological consistency and potential for quantitative characterization of the cell division and death rates, treated as continuous functions of the CFSE expression level.</p> <p>Conclusion</p> <p>Once the initial distribution of the proliferating cell population with respect to the CFSE intensity is given, the distributed parameter modelling allows one to work directly with the histograms of the CFSE fluorescence without the need to specify the marker ranges. The label-structured model and the elaborated computational approach establish a quantitative basis for more informative interpretation of the flow cytometry CFSE systems.</p

A Systems Immunology Approach to Plasmacytoid Dendritic Cell Function in Cytopathic Virus Infections

Plasmacytoid dendritic cell (pDC)-mediated protection against cytopathic virus infection involves various molecular, cellular, tissue-scale, and organism-scale events. In order to better understand such multiscale interactions, we have implemented a systems immunology approach focusing on the analysis of the structure, dynamics and operating principles of virus-host interactions which constrain the initial spread of the pathogen. Using high-resolution experimental data sets coming from the well-described mouse hepatitis virus (MHV) model, we first calibrated basic modules including MHV infection of its primary target cells, i.e. pDCs and macrophages (Mφs). These basic building blocks were used to generate and validate an integrative mathematical model for in vivo infection dynamics. Parameter estimation for the system indicated that on a per capita basis, one infected pDC secretes sufficient type I IFN to protect 103 to 104 Mφs from cytopathic viral infection. This extremely high protective capacity of pDCs secures the spleen's capability to function as a ‘sink’ for the virus produced in peripheral organs such as the liver. Furthermore, our results suggest that the pDC population in spleen ensures a robust protection against virus variants which substantially down-modulate IFN secretion. However, the ability of pDCs to protect against severe disease caused by virus variants exhibiting an enhanced liver tropism and higher replication rates appears to be rather limited. Taken together, this systems immunology analysis suggests that antiviral therapy against cytopathic viruses should primarily limit viral replication within peripheral target organs

Effect of tetracaine on DMPC and DMPC + cholesterol biomembrane models: Liposomes and monolayers

“NOTICE: this is the author’s version of a work that was accepted for publication in Colloids and Surfaces B: Biointerfaces. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Colloids and Surfaces B: Biointerfaces, [Vol. 16, (April 2014)] DOI 10.1016/j.colsurfb.2013.12.042 ""Different types of lipid bilayers/monolayers have been used to simulate the cellular membranes in the investigation of the interactions between drugs and cells. However, to our knowledge, very few studies focused on the influence of the chosen membrane model upon the obtained results. The main objective of this work is to understand how do the nature and immobilization state of the biomembrane models influence the effect of the local anaesthetic tetracaine (TTC) upon the lipid membranes. The interaction of TTC with different biomembrane models of dimyristoylphosphatidylcholine (DMPC) with and without cholesterol (CHOL) was investigated through several techniques. A quartz crystal microbalance with dissipation (QCM-D) was used to study the effect on immobilized liposomes, while phosphorus nuclear magnetic resonance (31P-NMR) and differential scanning calorimetry (DSC) were applied to liposomes in suspension. The effect of TTC on Langmuir monolayers of lipids was also investigated through surface pressure-area measurements at the air-water interface. The general conclusion was that TTC has a fluidizing effect on the lipid membranes and, above certain concentrations, induced membrane swelling or even solubilization. However, different models led to variable responses to the TTC action. The intensity of the disordering effect caused by TTC increased in the following order: supported liposomes < liposomes in solution < Langmuir monolayers. This means that extrapolation of the results obtain in in vitro studies of the lipid/anaesthetic interactions to in vivo conditions should be done carefully.

Анализ эффективности применения поощрений для трудовой мотивации специалистов аптечного предприятия

In the paper organization of nonfinancial incentives for pharmacists were analyzed and improvement references in staff management were designed. Through the comparative investigation of pharmaceutical specialists’ encouragements it was found that pharmaceutical enterprises practise some of and not always regular nonfinancial incentives where limited list of encouragements is included. Integration of factor and cluster analyses and further two-dimentional data analysis found no correlation between applied encouragements system and pharmacists needs that resulted in essential job motivation weakening. Nonfinancial methods preference is in lesser financial load that is why their application area much wider than in financial methods. In the event that complex application of pecuniary and non-pecuniary job stimulation methods a synergetic effect producing sizable working efficiency rise has been found.Представлены анализ состояния организации немонетарного стимулирования сотрудников аптечных предприятий и разработка рекомендаций по совершенствованию этого направления управления персоналом. Проведен сравнительный анализ поощрений фармацевтических специалистов, в результате которого установлено, что аптечные предприятия имеют некоторую и не всегда регулярную практику немонетарной мотивации, в рамках которой используется ограниченный перечень поощрений. В результате объединения факторного и кластерного анализов и последующего двумерного анализа данных выявлено отсутствие взаимосвязи между применяемой системой поощрений и потребностями специалистов аптек, что приводит к существенному ослаблению мотивации к трудовой деятельности. Преимущество нематериальных методов состоит в меньшей финансовой нагрузке, поэтому направления их применения гораздо шире, чем у финансовых методов. В случае комплексного использования материальных и нематериальных методов стимулирования труда работников аптечных предприятий наблюдается синергический эффект, дающий значительный рост производительности труда

Electronic Educational Resources as a Strategic Innovation

В статье рассматривается понятие электронных образовательных ресурсов (ЭОР), описаны дидактические функции данного вида ресурсов, приведены основные типы ЭОР на занятиях по иностранному языку, а также выделены недостатки ЭОР.This article discusses the concept of electronic educational resources (EER), describes the didactic functions of this type of resources, presents the main types of EER in foreign language classes, and highlights the disadvantages of EER

Synchronization in a System of Globally Coupled Oscillators with Time Delay

We study the synchronization phenomena in a system of globally coupled oscillators with time delay in the coupling. The self-consistency equations for the order parameter are derived, which depend explicitly on the amount of delay. Analysis of these equations reveals that the system in general exhibits discontinuous transitions in addition to the usual continuous transition, between the incoherent state and a multitude of coherent states with different synchronization frequencies. In particular, the phase diagram is obtained on the plane of the coupling strength and the delay time, and ubiquity of multistability as well as suppression of the synchronization frequency is manifested. Numerical simulations are also performed to give consistent results