Modelling multi-tier enterprise applications behaviour with design of experiments technique

Queueing network models are commonly used for performance modelling. However, through application development stage analytical models might not be able to continuously reflect performance, for example due to performance bugs or minor changes in the application code that cannot be readily reflected in the queueing model. To cope with this problem, a measurement-based approach adopting Design of Experiments (DoE) technique is proposed. The applicability of the proposed method is demonstrated on a complex 3-tier e-commerce application that is difficult to model with queueing networks

ІНТЕРПРЕТАЦІЯ РОМАНУ Е. М. ФОРСТЕРА «ДЕ АНГЕЛИ СТУПИТЬ СТРАШАТЬСЯ» (INTERPRETATION OF NOVEL by EM Forster «ДЕ АНГЕЛИ СТУПИТЬ СТРАШАТЬСЯ»)

У роботі проводиться аналітична інтерпретація одного з романів Едварда Моргана Форстера, мета даної статті – виявити основні дискусійні аспекти проблеми висвітлення митцем подій та проблематики роману; розглянути власні новації Форстера, які надають можливість назвати його одним з основоположників модернізму, та потрактування цих особливостей у науковій та літературно-критичній форстеріані. (The article deals with the analytical interpretation of one of the novels by Edward Morgan Forster, the purpose of this work is to determine the main controversial aspects of the problem of the author’s description the events and problems in the novel, to consider Forster’s innovation which gives opportunity to name him one of the Modernism founders and interpretation of these features in scientific and critical Forster studies.

Plurilingualism and the Second Language Teacher Education

В статье рассматривается процесс формирования профессиональной коммуникативной компетентности будущих учителей иностранного языка.The article aims at clarifying the premises of modelling educational outcomes of second language teachers'preparation by defining two core aspects of their professional competence architecture

The Simulation of the Trend of the Time Series in the form of the Spline of Third-Order With a Random Number of Data at the Moments of Measurement

The possibility of simulation of trend of a time series as a spline of third-order with a random number of data at the moments of measurement is discussed. Estimations of coefficients of the spline are obtained in the explicit form. The statistical characteristics of the received estimations are studied in details

Electrodeposition of Silicon from the Low-Melting LiCl-KCl-CsCl-K2SiF6Electrolytes

The possibility of silicon electrodeposition from the low-melting LiCl-KCl-CsCl-K2SiF6 electrolytes has been studied. The stability of a silicon-containing additive was studied by cyclic voltammetry, and the rate constant of the chemical reaction of SiF4 release at a temperature of 827 K was calculated. It is determined that the constants of velocity values in the melt based on eutectic composition are 2 orders of magnitude higher, which indicates a higher rate of formation of volatile compounds. Cyclic voltammetry was also used to study the electrochemical behavior of K2SiF6 in the melts under study. It was found that the silicon electroreduction at the cathode is not reversible and proceeds in one 4-electron reaction. The diffusion coefficient calculated by the Matsuda-Ayabe equation was 0.72·10-5 cm2·s-1 at temperature of 823 K. According to the obtained voltammograms, the parameters for the silicon electrodeposition were selected. At a potential of -0.4 V vs QRE, dendritic silicon deposits were obtained. © 2022 The Author(s). Published on behalf of The Electrochemical Society by IOP Publishing Limited. This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives 4.0 License (CC BYNC- ND, http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is not changed in any way and is properly cited. For permission for commercial reuse, please email: [email protected]. [DOI: 10.1149/1945-7111/ac5a1c]

Analysis of Requirements for Inhalation Toxicity Studies of Chemicals

Scientific relevance. Studies of the inhalation administration of chemicals are associated with challenges in designing experiments. The parameters to be selected include the experimental animal species, the inhalation chamber, and the mode of inhalation (dynamic or static).Aim. This study aimed to analyse the practical application of regulatory requirements to non-clinical studies of the inhalation toxicity of chemicals.Discussion. This review compares international and Russian standards for studying the inhalation toxicity of chemicals, including GOST 32542-2013, GOST 32643-2020, GOST 32636-2020, GOST 32383-2013, and GOST 2646-2014. The improvement of the legal and regulatory framework correlates with adopting the Good Laboratory Practice and the risk-based approach to categorising test substances into hazard classes. Hazard classes are determined in rodents without dose extrapolation to humans. The authors present the differences between the main guidelines on inhalation exposure in rodent studies of acute, subacute, subchronic, and chronic toxicity. The article describes current approaches to assessing the inhalation toxicity of chemicals, which allow researchers to replace animal studies with in vitro tests.Conclusions. According to the current regulatory standards, inhalation toxicity is studied in rats/mice, which have anatomical differences from humans. As an alternative to animal studies, researchers are developing and validating in vitro methods, which yet require regulatory review and approval

DETECTION AND DIFFERENTIATION OF NON-TUBERCULOUS MYCOBACTERIA AND M. TUBERCULOSIS COMPLEX BY REAL TIME PCR

Goal of the study: to define the design of primers and probes specific to DNA of non-tuberculous mycobacteria and evaluate their diagnostic value in case of simultaneous detection of non-tuberculous mycobacteria and M. tuberculosis complex by real time PCR.Materials and methods. Primer 3, Primer BLAST, Ugene Uni Pro were used to design primers and probes. Preliminary assessment of specificity and sensitivity of detection of non-tuberculous mycobacteria DNA was performed on cultures belonging to 18 types of non-tuberculous mycobacteria, 16 strains of M. tuberculosis complex and 14 types of microorganisms being none Mycobacterum. Analytic sensitivity was tested on 284 cultures of non-tuberculous mycobacteria and diagnostic sensitivity was tested on 124 sputum samples. The kit ofM-Sorb-Tub-Avtomat (ZAO Sintol) was used for DNA isolation. Cultures were subcultured on the liquid medium of Middlebrook 7H9 in Bactec MGIT 960. Cultures were identified with the use of standard microbiological techniques. Analysis of DNA isolated from cultures was performed by the reagent kit of GenoTypeCM/AS (Hain Lifescience, Germany).Results. 100% specificity and sensitivity of PCR was demonstrated in mycobacterial cultures and 100% specificity and 69-70% sensitivity was demonstrated in diagnostic material analysis

Experience with olaparib in a patient with luminal HER2-positive metastatic breast cancer

Hereditary breast cancer (BC) accounts for about 5-10% of cases. BRCA-associated tumors have been identified as a separate group of malignant neoplasms with distinctive clinical manifestations and specific treatment features. Understanding of biological mechanisms leading to cancer in BRCA1/2 mutation carriers and discovery of potential molecular targets, such as poly (ADP-ribose) polymerase (PARP), involved in base excision repair mechanisms, led to the development of a new class of targeted drugs belonging to the PARP inhibitors group. PARP inhibition leads to the preservation of single-stranded DNA breaks, the arrest of the replication fork, and the realization of the “synthetic lethality” phenomenon due to the inability to repair double-stranded DNA breaks by homologous recombination in cells with mutations in the BRCA1/2 genes. Two randomized trials OlympiAD and EMBRACA evaluated and proved the effectiveness of PARP inhibitors in patients with metastatic BRCA-mutated HER2-negative breast cancer in comparison with standard chemotherapy. At the same time, data on the potential use of PARP inhibitors for the treatment of BRCA-mutated HER2-positive breast cancer patients are extremely limited. This article presents a clinical example of the use of olaparib in a patient with BRCA-mutated HER2-positive metastatic breast cancer

The Role of TLR4 in the Paclitaxel Effects on Neuronal Growth In Vitro

Paclitaxel (Pac) is an antitumor agent that is widely used for treatment of solid cancers. While being effective as a chemotherapeutic agent, Pac in high doses is neurotoxic, specifically targeting sensory innervations. In view of these toxic effects associated with conventional chemotherapy, decreasing the dose of Pac has been recently suggested as an alternative approach, which might limit neurotoxicity and immunosuppression. However, it remains unclear if low doses of Pac retain its neurotoxic properties or might exhibit unusual effects on neuronal cells. The goal of this study was to analyze the concentration-dependent effect of Pac on isolated and cultured DRG neuronal cells from wild-type and TLR4 knockout mice. Three different morphological parameters were analyzed: the number of neurons which developed neurites, the number of neurites per cell and the total length of neurites per cell. Our data demonstrate that low concentrations of Pac (0.1 nM and 0.5 nM) do not influence the neuronal growth in cultures in both wild type and TLR4 knockout mice. Higher concentrations of Pac (1-100 nM) had a significant effect on DRG neurons from wild type mice, affecting the number of neurons which developed neurites, number of neurites per cell, and the length of neurites. In DRG from TLR4 knockout mice high concentrations of Pac showed a similar effect on the number of neurons which developed neurites and the length of neurites. At the same time, the number of neurites per cell, indicating the process of growth cone initiation, was not affected by high concentrations of Pac. Thus, our data showed that Pac in high concentrations has a significant damaging effect on axonal growth and that this effect is partially mediated through TLR4 pathways. Low doses of Pac are devoid of neuronal toxicity and thus can be safely used in a chemomodulation mode. © 2013 Ustinova et al

Анализ требований к проведению исследований ингаляционной токсичности химических веществ

Scientific relevance. Studies of the inhalation administration of chemicals are associated with challenges in designing experiments. The parameters to be selected include the experimental animal species, the inhalation chamber, and the mode of inhalation (dynamic or static).Aim. This study aimed to analyse the practical application of regulatory requirements to non-clinical studies of the inhalation toxicity of chemicals.Discussion. This review compares international and Russian standards for studying the inhalation toxicity of chemicals, including GOST 32542-2013, GOST 32643-2020, GOST 32636-2020, GOST 32383-2013, and GOST 2646-2014. The improvement of the legal and regulatory framework correlates with adopting the Good Laboratory Practice and the risk-based approach to categorising test substances into hazard classes. Hazard classes are determined in rodents without dose extrapolation to humans. The authors present the differences between the main guidelines on inhalation exposure in rodent studies of acute, subacute, subchronic, and chronic toxicity. The article describes current approaches to assessing the inhalation toxicity of chemicals, which allow researchers to replace animal studies with in vitro tests.Conclusions. According to the current regulatory standards, inhalation toxicity is studied in rats/mice, which have anatomical differences from humans. As an alternative to animal studies, researchers are developing and validating in vitro methods, which yet require regulatory review and approval.Актуальность. Изучение токсичности химических веществ при ингаляционном введении имеет ряд особенностей, вызывающих затруднения при планировании эксперимента. Параметрами выбора при этом являются: вид экспериментальных животных, тип ингаляционной установки и способ ингаляции (динамический или статический).Цель. Анализ практики применения нормативных требований к проведению доклинических исследований токсичности химических веществ при их ингаляционном введении.Обсуждение. Проведен сравнительный анализ требований международных и отечественных стандартов (ГОСТ 32542-2013, ГОСТ 32643-2020, ГОСТ 32636-2020, ГОСТ 32383-2013, ГОСТ 32646-2014) по исследованию ингаляционной токсичности химических веществ. Показано, что совершенствование нормативной правовой базы связано с внедрением правил надлежащей лабораторной практики и использованием риск-ориентированного подхода к определению классов опасности исследуемых веществ. Отмечено, что класс опасности вещества определяют у грызунов без переноса дозовой зависимости на человека. Выявлены различия основных правил проведения ингаляционного воздействия в исследованиях на грызунах при изучении острой, подострой, субхронической и хронической токсичности. Описаны современные подходы, позволяющие оценивать ингаляционную токсичность химических веществ и лекарственных средств с помощью тестов in vitro, заменяющих исследования на животных.Выводы. Согласно действующим нормативным документам объектом исследований ингаляционной токсичности являются крысы/мыши, которые имеют анатомические различия с человеком. В качестве альтернативы исследованиям на животных разрабатываются и валидируются методы in vitrо, которые требуют рассмотрения и утверждения регуляторными органами