On Stability For Nonstationary M/M/N/N + R Queue

We consider nonstationary M/M/N/N + R queueing model and obtain the first bounds of stability

Исследование противогриппозной активности комплексов миРНК против клеточных генов FLT4, Nup98 и Nup205 на модели in vitro

Objectives. Evaluation of changes in the viral activity of influenza A/WSN/33 after complex knockdown of combinations of cellular genes FLT4, Nup98 and Nup205 in human lung cell culture A549. Methods. The work was carried out using the equipment of the Center for Collective Use of the I. Mechnikov Research Institute of Vaccines and Sera, Russia. The authors performed transfection of combinations of small interfering ribonucleic acid (siRNA) complexes that cause simultaneous disruption of the expression of cellular genes FLT4, Nup98, and Nup205. Within three days from the moment of transfection and infection, the supernatant fluid and cell lysate were taken for subsequent viral reproduction intensity determination using the titration method for cytopathic action. The dynamics of changes in the concentration of viral ribonucleic acid (vRNA) was determined by real-time reverse transcription polymerase chain reaction (real-time RT-PCR). The nonparametric Mann–Whitney test was used to calculate statistically significant differences between groups.Results. Using all of the combinations of siRNA complexes, cell viability did not decrease below the threshold level of 70%. In cells treated with complex FLT4.2 + Nup98.1 + Nup205 at the multiplicity of infection (MOI) equal to 0.1, a significant decrease in viral reproduction by 1.5 lg was noted on the first day in relation to nonspecific and viral controls. The use of siRNA complexes at MOI 0.01 resulted in a more pronounced antiviral effect. The viral titer in cells treated with siRNA complexes FLT4.2 + Nup98.1 and Nup98.1 + Nup205 decreased by 1.5 lg on the first day. In cells treated with complexes FLT4.2 + Nup205 and FLT4.2 + Nup98.1 + Nup205, it decreased by 1.8 and 2.0 lg on the first day and by 1.8 and 2.5 lg on the second day, respectively, in relation to nonspecific and viral controls. When conducting real-time RT-PCR, a significant decrease in the concentration of vRNA was noted. At MOI 0.1, a 295, 55, and 63-fold decrease in the viral load was observed with the use of siRNA complexes FLT4.2 + Nup98.1, Nup98.1 + Nup205, and FLT4.2 + Nup98.1 + Nup205, respectively. On the second day, a decrease in vRNA was also observed in cells treated with complex A. A 415-fold decrease in vRNA on the third day was noted in cells treated with complex FLT4.2 + Nup205. At MOI 0.01, the concentration of vRNA decreased 9.5 times when using complex B relative to nonspecific and viral control.Conclusions. The study showed a pronounced antiviral effect of siRNA combinations while simultaneously suppressing the activity of cellular genes (FLT4, Nup98, and Nup205), whose expression products are playing important role in the viral reproduction process, and obtained original designs of siRNA complexes. The results obtained are of great importance for the creation of emergence prophylactic and therapeutic drugs, whose action is based on the mechanism of RNA interference.Цели. Оценка изменения вирусной активности гриппа A/WSN/33 после комплексного нокдауна комбинаций клеточных генов FLT4, Nup98 и Nup205 в культуре легочных кле­ток человека А549.Методы. Работа выполнена с использованием оборудования центра коллективного поль­зования Научно-исследовательского института вакцин и сывороток им И.И. Мечникова (Россия). Авторами выполнялась трансфекция комбинаций комплексов миРНК, вызыва­ющих одновременное нарушение экспрессии клеточных генов FLT4, Nup98 и Nup205. В течение трех дней с момента трансфекции и заражения проводился отбор надосадоч­ной жидкости и клеточного лизата для последующего определения интенсивности ви­русной репродукции по методу титрования по цитопатическому действию. Динамику изменения концентрации вирусной рибонуклеиновой кислоты (вРНК) определяли мето­дом обратной транскрипции и полимеразной цепной реакции в режиме реального вре­мени (ОТ-ПЦР-РВ). Для вычисления статистически значимых различий между группами использовали непараметрический критерий Манна-Уитни.Результаты. При использовании всех комбинаций комплексов малых интерферирую­щих РНК (миРНК) жизнеспособность клеток не снижалась ниже порогового уровня в 70%. В клетках, обработанных комплексом FLT4.2 + Nup98.1 + Nup205 при множественности заражения (Multiplicity of infection, MOI) 0.1 достоверное снижение вирусной репродукции на 1.5 lg отмечалось на первые сутки по отношению к неспецифическому и вирусному контролям. Использование комплексов миРНК при MOI 0.01 приводило к более выражен­ному противовирусному эффекту. Вирусный титр в клетках, обработанных комплек­сами миРНК FLT4.2 + Nup98.1 и Nup98.1 + Nup205 снижался на первые сутки на 1.5 lg. В клетках, обработанных комплексами FLT4.2 + Nup205 и FLT4.2 + Nup98.1 + Nup205 снижался на 1.8 и 2 lg на первые сутки и на 1.8 и 2.5 lg на вторые сутки соответствен­но по отношению к неспецифическому и вирусному контролям. При проведении ОТ-ПЦР-РВ отмечено достоверное снижение концентрации вирусной РНК. При MOI 0.1 снижение ви­русной в 295, 55 и 63 раза отмечался при использовании комплексов миРНК FLT4.2 + Nup98.1, Nup98.1 + Nup205 и FLT4.2 + Nup98.1 + Nup205 соответственно. На вторые сутки сниже­ние вирусной РНК также отмечалось в клетках, обработанных комплексом FLT4.2 + Nup98.1. Снижение вРНК на третьи сутки в 415 раз отмечалось в клетках, обработанных ком­плексом FLT4.2 + Nup205. При MOI 0.01 концентрация вРНК снизилась в 9.5 раз при ис­пользовании комплекса Nup98.1 + Nup205 относительно неспецифического и вирусного контроля.Выводы. В ходе исследования был показан выраженный противовирусный эффект ком­бинаций миРНК при одновременном подавлении активности клеточных генов (FLT4, Nup98 и Nup205), чьи продукты экспрессии играют важное участие в процессе вирусной репродукции, а также получены оригинальные конструкции комплексов миРНК. Полу­ченные результаты имеют важное значение для создания препаратов для экстренной профилактики и терапии, чье действие основано на механизме РНК-интерференции

Two-sided truncations for a class of continuous-time markov chains

We consider nonstationary Markovian queueing models with batch arrivals and group services. We study the mathematical expectation of the respective queue-length process and obtain the bounds on the rate of convergence and error of truncation of the process. © Springer International Publishing AG 2017

Two-sided truncations for a class of continuous-time markov chains

We consider nonstationary Markovian queueing models with batch arrivals and group services. We study the mathematical expectation of the respective queue-length process and obtain the bounds on the rate of convergence and error of truncation of the process. © Springer International Publishing AG 2017

Some results for inhomogeneous birth-and-death process with application to staffing problem in telecommunication service systems

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Ergodicity and truncation bounds for inhomogeneous birth and death processes with additional transitions from and to origin

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Some results for inhomogeneous birth-and-death process with application to staffing problem in telecommunication service systems

This paper proposes some analytical results that may facilitate long-term staffing problem in high-level telecommunication service systems (such as information call centers) in which rates of processes, that govern their behaviour, depend on time. We assume that except for arrivals of requests and their service there happen periodic system breakdowns (possibly with very long inter-breakdown periods). The staffing objective is immediate service of a given percentage of incoming requests. A natural model for such a time-varying processes is an innhomogeneous birth-death process for which we propose some general theoretical results concerning its ergodicity conditions and limiting behaviour. As an example we show that if the service system is modelled by multiserver queue Mt/Mt/S with state-dependent periodic arrivals, services and breakdown rates, then using obtained results one can calculate the quantities needed for the solution of optimization problem. Accuracy of approximation is briefly discussed. © 2015 IEEE

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On Stability For Nonstationary M/M/N/N + R Queue

We consider nonstationary M/M/N/N + R queueing model and obtain the first bounds of stability