Development of a technology for the preparation of a dry nutrient medium for anthrax vaccine production

Currently, submerged cultivation of the Bacillus anthracis STI-1 strain for live anthrax vaccine production requires liquid nutrient media, which have disadvantages of a short shelf life (no more than one month) and a narrow range of storage temperatures (2–8 °С). Dry media, in contrast, have a number of indisputable advantages: such media are transportable and easy to use, have a standard capability to retain properties, and can be stored without preservatives at 2–30 °С for 2–5 years. The aim of this work was to develop a technology for the preparation of a dry nutrient medium for anthrax vaccine production. Materials and methods: The study used the Bacillus anthracis STI-1 vaccine strain and a nutrient medium for its cultivation, containing a 70:30 mixture of an enzymatic digest of casein and a pre-processed corn extract solution. Drying of the nutrient medium was carried out on a spray-drying unit. The authors evaluated physicochemical parameters of experimental medium batches. The shelf life was determined by an accelerated stability study. The dry nutrient medium was used to produce a live anthrax vaccine. Quality attributes of the vaccine were assessed for compliance with regulatory requirements. Results: The authors developed the dry media production technology. According to it, the liquid nutrient medium is fed to the drying unit at a rate of 20–25 dm3/h. The spray air pressure is 0.02 MPa. Temperatures at the drying chamber inlet and outlet are 118–122 °С and 85–90 °С, respectively. The technology was used to obtain 3 experimental batches of the dry medium. The study results demonstrate that the technology is reproducible, and the tested quality attributes of experimental medium batches are consistent with the requirements. According to the accelerated stability study, the shelf life of the dry nutrient medium at 2–30 °С is at least 3 years. Experiments demonstrated the possibility of using the dry nutrient medium for live anthrax vaccine production. Critical quality attributes of the vaccine obtained with the medium met regulatory requirements. Conclusions: The developed technology allows for the production of a standard dry nutrient medium with a prolonged shelf life, which is convenient for live anthrax vaccine production

Black hole spin-orbit misalignment in the x-ray binary MAXI J1820+070

The observational signatures of black holes in x-ray binary systems depend on their masses, spins, accretion rate, and the misalignment angle between the black hole spin and the orbital angular momentum. We present optical polarimetric observations of the black hole x-ray binary MAXI J1820+070, from which we constrain the position angle of the binary orbital. Combining this with previous determinations of the relativistic jet orientation. which traces the black hole spin, and the inclination of the orbit, we determine a lower limit of 40 degrees on the spin-orbit misalignment angle. The misalignment must originate from either the binary evolution or black hole formation stages. If other x-ray binaries have similarly large misalignments, these would bias measurements of black hole masses and spins from x-ray observations

Разработка технологии приготовления сухой питательной среды для производства сибиреязвенной вакцины

Currently, submerged cultivation of the Bacillus anthracis STI-1 strain for live anthrax vaccine production requires liquid nutrient media, which have disadvantages of a short shelf life (no more than one month) and a narrow range of storage temperatures (2–8 °С). Dry media, in contrast, have a number of indisputable advantages: such media are transportable and easy to use, have a standard capability to retain properties, and can be stored without preservatives at 2–30 °С for 2–5 years. The aim of this work was to develop a technology for the preparation of a dry nutrient medium for anthrax vaccine production. Materials and methods: The study used the Bacillus anthracis STI-1 vaccine strain and a nutrient medium for its cultivation, containing a 70:30 mixture of an enzymatic digest of casein and a pre-processed corn extract solution. Drying of the nutrient medium was carried out on a spray-drying unit. The authors evaluated physicochemical parameters of experimental medium batches. The shelf life was determined by an accelerated stability study. The dry nutrient medium was used to produce a live anthrax vaccine. Quality attributes of the vaccine were assessed for compliance with regulatory requirements. Results: The authors developed the dry media production technology. According to it, the liquid nutrient medium is fed to the drying unit at a rate of 20–25 dm3/h. The spray air pressure is 0.02 MPa. Temperatures at the drying chamber inlet and outlet are 118–122 °С and 85–90 °С, respectively. The technology was used to obtain 3 experimental batches of the dry medium. The study results demonstrate that the technology is reproducible, and the tested quality attributes of experimental medium batches are consistent with the requirements. According to the accelerated stability study, the shelf life of the dry nutrient medium at 2–30 °С is at least 3 years. Experiments demonstrated the possibility of using the dry nutrient medium for live anthrax vaccine production. Critical quality attributes of the vaccine obtained with the medium met regulatory requirements. Conclusions: The developed technology allows for the production of a standard dry nutrient medium with a prolonged shelf life, which is convenient for live anthrax vaccine production.В настоящее время при производстве вакцины сибиреязвенной живой для глубинного выращивания штамма Bacillus anthracis СТИ-1 используется жидкая питательная среда, недостатками которой являются малый срок годности — не более одного месяца и узкий диапазон температуры ее хранения: от 2 до 8 °С. Сухие питательные среды (ПС) обладают рядом неоспоримых преимуществ: их можно хранить от 2 до 5 лет при температуре от 2 до 30 °С без консервантов; они транспортабельны, удобны в применении и стандартны в сохранении свойств. Цель работы: разработка технологии приготовления сухой ПС для производства сибиреязвенной вакцины. Материалы и методы: в исследованиях использовали вакцинный штамм B. anthracis СТИ-1 и ПС, состоящую из смеси ферментативного гидролизата казеина и раствора обработанного кукурузного экстракта в соотношении 70 и 30%, для культивирования сибиреязвенного микроба. Обезвоживание ПС осуществляли на установке распылительного типа. Экспериментальные серии сухой ПС оценивали по физико-химическим показателям на соответствие требованиям нормативной документации. Срок годности определяли методом «ускоренного старения». С использованием сухой ПС готовили вакцину сибиреязвенную живую и проводили оценку показателей качества препарата на соответствие требованиям нормативной документации. Результаты: разработана технология приготовления сухой ПС (скорость подачи ПС на сушку от 20 до 25 дм3/ч, давление сжатого воздуха в распылителе 0,02 МПа, температура воздуха на входе в сушильную камеру от 118 до 122 °С, температура воздуха на выходе — от 85 до 90 °С). По этой технологии получены 3 серии экспериментальной сухой ПС. Показано, что разработанная технология воспроизводима, а экспериментальные серии сухой ПС по изученным показателям отвечают предъявляемым требованиям. Срок годности сухой ПС, установленный с использованием метода «ускоренного старения», не менее 3 лет при температуре хранения от 2 до 30 °С. Экспериментально подтверждена возможность использования сухой ПС в технологии производства сибиреязвенной вакцины. Приготовленный препарат по основным показателям качества отвечает требованиям нормативной документации. Выводы: разработанная технология позволяет получить сухую ПС стандартную с увеличенным сроком хранения и удобную при использовании в производстве вакцины сибиреязвенной живой

Optical polarimetry: Methods, Instruments and Calibration Techniques

In this chapter we present a brief summary of methods, instruments and calibration techniques used in modern astronomical polarimetry in the optical wavelengths. We describe the properties of various polarization devices and detectors used for optical broadband, imaging and spectropolarimetry, and discuss their advantages and disadvantages. The necessity of a proper calibration of the raw polarization data is emphasized and methods of the determination and subtraction of instrumental polarization are considered. We also present a few examples of high-precision measurements of optical polarization of black hole X-ray binaries and massive binary stars made with our DiPol-2 polarimeter, which allowed us to constrain the sources of optical emission in black hole X-ray binaries and measure orbital parameters of massive stellar binaries.Comment: 33 pages, 14 figure; to be published in Astrophysics and Space Science Library 460, Astronomical Polarisation from the Infrared to Gamma Ray

Software for the frontiers of quantum chemistry:An overview of developments in the Q-Chem 5 package

This article summarizes technical advances contained in the fifth major release of the Q-Chem quantum chemistry program package, covering developments since 2015. A comprehensive library of exchange–correlation functionals, along with a suite of correlated many-body methods, continues to be a hallmark of the Q-Chem software. The many-body methods include novel variants of both coupled-cluster and configuration-interaction approaches along with methods based on the algebraic diagrammatic construction and variational reduced density-matrix methods. Methods highlighted in Q-Chem 5 include a suite of tools for modeling core-level spectroscopy, methods for describing metastable resonances, methods for computing vibronic spectra, the nuclear–electronic orbital method, and several different energy decomposition analysis techniques. High-performance capabilities including multithreaded parallelism and support for calculations on graphics processing units are described. Q-Chem boasts a community of well over 100 active academic developers, and the continuing evolution of the software is supported by an “open teamware” model and an increasingly modular design

N-methyl D-aspartate (NMDA) receptors in rat and human heart

This study focuses on the investigation of expression and function of N-methyl D-aspartate receptors (NMDARs) in rat myocardium and on the role these receptors play in control of autonomous heart function. NMDARs are ionotropic glutamate receptors mediating Ca2+ uptake upon their activation by co-agonists glutamate and glycine. We have detected the presence of gene transcripts of the NR1, 2A, B, C and D and 3A subunits. Expression of the NMDAR subunits and activity of the receptor complex varied substantially within the heart. In hearts of young animals maximal expression and the highest density of active NMDAR units was found in the atria and in septum. In senescent hearts up-regulation in NR2B abundance and the receptor activity was observed in the ventricles. Activation of the NMDARs in isolated ventricular myocytes resulted in an increase in the intracellular Ca2+ levels and initiation of Ca2+ transients which could be suppressed by co-administration of antagonist of the NMDAR, MK-801. Perfusion of rat hearts with autologous blood supplemented with NMDA agonists was associated with induction of tachycardia and sinus arrhythmia, and a positive inotropic effect whereas intracoronary administration of the NMDAR antagonists exerted an anti-arrhythmic effect and resulted in bradycardia. We have performed pilot studies exploring expression levels of the NMDAR subunits in biopsies collected from all four chambers of human patients undergoing mitral valve replacement surgery. Expression of NR1, NR2A, B, C and D, NR3A and B was shown. Development of decompensated hypertrophy was associated with an increase in expression. The obtained data reveal that NMDARs are expressed in rat heart and are active players in calcium handling contributing to the pacemaker function and contractile force control

N-methyl D-aspartate receptor in human heart function

N-methyl D-aspartate receptors (NMDARs) are ionotropic glutamate receptors highly abundant in the brain and present in the lung, kidneys, red blood cells and in the heart of a variety of species including humans. Upon stimulation with glutamate and glycine these non-selective ion channels mediate calcium uptake and depolarize the membrane, both processes having crucial impact on heart function. Channels are hetero-tetramers consisting of glutamate-binding (NR2A,B,C or D) and glycine-binding (NR1, 3A and 3B) subunits. Subunit composition defines the agonist-, antagonist and ion permeability preferences, amplitude and deactivation time of the receptors. In rat heart NR2D and NR3A expression was recently shown to dominate. In human heart only NR1 was reported to be expressed so far. In this study we have explored the expression pattern of all known NMDAR subunits in four chambers of human heart and performed co-variance analysis of the transcript levels relating them to the loss of cardiac rhythmicity and hypertrophic remodeling