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Non-invasive prenatal testing (NIPT) is a molecular genetic method of cell-free fetal DNA fetal chromosomal abnormalities risks assessing. Currently, NIPT is quite widespread throughout the world, and its clinical efficacy high sensitivity and specificity has been repeatedly proven. At the same time, the decision to include NIPT in the algorithm of prenatal diagnostics carried out with public funds depends on its cost-effectiveness, which should be assessed separately for each country or territory due to different costs and different models of inclusion. This article presents the different countries approaches to the assessment of the medical and economic efficiency of NIPT.

A microwave system in the form of a quasi-optical (QO) transmission line is proposed as an interaction circuit of an amplifier or an oscillator based on the cyclotron resonance maser (CRM) instability. The circuit consists of periodically spaced along the horizontal ${z}$ -axis focusing mirrors, which transport the Gaussian wave beam along a zigzag path with vertical and inclined segments. A beam of electrons having sufficiently high perpendicular velocities is guided by a static B-field along the ${z}$ -axis so that the e-beam periodically crosses the wave beam. The CRM instability occurs in regions where an electromagnetic wave having a Bz-component, as in a gyrotron, propagates strictly across the e-beam resulting in the interaction with minimal sensitivity to particle velocity spread. Three-dimensional Particle-In-Cell (3-D PIC) simulations demonstrate the attractiveness of this “zigzag” CRM for the implementation of relatively broadband amplifiers or oscillators with unique (more than an octave bandwidth) frequency tunability at wavelengths of 1–2 mm.

To cover the so-called terahertz gap in powerful sources of coherent electromagnetic waves, a second-harmonic gyrotron operating in a 10 T liquid helium-free superconducting magnet has been designed, manufactured, and tested. With an operating voltage of 15 kV and a beam current of 0.6 A, the gyrotron generated coherent continuous-wave radiation at a frequency of 0.526 Terahertz with an output power of 250 Watts and an efficiency of 2.7%.

Steroid metabolism in humans originates from cholesterol and involves several enzyme reactions including dehydrogenation, hydroxylation, and carbon–carbon bond cleavage that occur at regio- and stereo-specific points in the four-membered ring structure. Cytochrome P450s occur at critical junctions that control the production of the male sex hormones (androgens), the female hormones (estrogens) as well as the mineralocorticoids and glucocorticoids. An important branch point in human androgen production is catalyzed by cytochrome P450 CYP17A1 and involves an initial Compound I-mediated hydroxylation at the 17-position of either progesterone (PROG) or pregnenolone (PREG) to form 17-hydroxy derivatives, 17OH-PROG and 17OH-PREG, with approximately similar efficiencies. Subsequent processing of the 17-hydroxy substrates involves a C(17)–C(20) bond scission (lyase) activity that is heavily favored for 17OH-PREG in humans. The mechanism for this lyase reaction has been debated for several decades, some workers favoring a Compound I-mediated process, with others arguing that a ferric peroxo- is the active oxidant. Mutations in CYP17A1 can have profound clinical manifestations. For example, the replacement of the glutamic acid side with a glycine chain at position 305 in the CYP17A1 structure causes a clinically relevant steroidopathy; E305G CYP17A1 displays a dramatic decrease in the production of dehydroepiandrosterone from pregnenolone but surprisingly increases the activity of the enzyme toward the formation of androstenedione from progesterone. To better understand the functional consequences of this mutation, we self-assembled wild-type and the E305G mutant of CYP17A1 into nanodiscs and examined the detailed catalytic mechanism. We measured substrate binding, spin state conversion, and solvent isotope effects in the hydroxylation and lyase pathways for these substrates. Given that, following electron transfer, the ferric peroxo- species is the common intermediate for both mechanisms, we used resonance Raman spectroscopy to monitor the positioning of important hydrogen-bonding interactions of the 17-OH group with the heme-bound peroxide. We discovered that the E305G mutation changes the orientation of the lyase substrate in the active site, which alters a critical hydrogen bonding of the 17-alcohol to the iron-bound peroxide. The observed switch in substrate specificity of the enzyme is consistent with this result if the hydrogen bonding to the proximal peroxo oxygen is necessary for a proposed nucleophilic peroxoanion-mediated mechanism for CYP17A1 in carbon–carbon bond scission.

The rapidly growing cultural globalization, while strengthening the foundations of totalitarianism in social management, reveals the effect of losing the already not very bright identity of 'an ordinary' (and sometimes also 'historically young') provincial Russian city, even if this city has a significant name in history. This process is objective, natural, and needs to be understood. Understanding its basis is a necessary condition for managing its flow.Urban monumental sculpture is an important area that can be explored to aid this understanding.The subject of research is the historical evolution of the monumental and sculptural decoration of 'the capital of the Kuban Cossacks: Ekaterinodar/Krasnodar. The purpose of the study is to understand the processes that determine the historical variability of the 'soul of the city"', i.e. the most important indicator of its identity.The analysis shows that the essential basis of the process is the combination of the determining aspects of the 'spirit of citizens' and the 'spirit of the city administration'. In different historical periods, the juxtaposition of opposites changed. If the relative unity of 'administrative spirit of the city' and 'elements of the aggregate of the souls of the citizens is typical for the beginning of the city history, if the Soviet historical period is typical of the severe suppression of administrative-command management of manifestations of 'soul of people, the XXI century is characterized by the eclectic parallelism of opposite worlds. One of the worlds is filled with the 'spirit of the empty official pomposity', while the other shows the 'lightheadedness eclectic incarnation of sentiment'.Spontaneously, in such conditions, the identity of the city and the spirit of the historical center of culture of the Kuban Cossacks can no longer be restored. The development trend of the 'soul of the city', which is involved in the active processes of economic and cultural globalization, does not contain any other way of forming a 'Cossack identity', except through the artificial creation of its simulacrum.

We developed an efficient and sensitive probe for drug–drug interactions mediated by human CYP3A4 by using midazolam (MDZ) as a probe substrate. Using global analysis of four parameters over several experimental data sets, we demonstrate that the first MDZ molecule (MDZ1) binds with high affinity at the productive site near the heme iron and gives only hydroxylation at the 1 position (1OH). The second midazolam molecule (MDZ2) binds at an allosteric site at the membrane surface and perturbs the position and mobility of MDZ1 such that the minor hydroxylation product at the 4 position (4OH) is formed in a 1:2 ratio (35%). No increase in catalytic rate is observed after the second MDZ binding. Hence, the site of the 1OH:4OH metabolism ratio is a sensitive probe for drugs, such as progesterone, that bind with high affinity to the allosteric site and serve as effectors. We observe similar changes in the MDZ 1OH:4OH ratio in the presence of progesterone (PGS), suggesting a direct communication between the active and allosteric sites. Mutations introduced into the F–F′ loop indicate that residues F213 and D214 are directly involved in allosteric interactions leading to MDZ homotropic cooperativity, and these same residues, together with L211, are involved in heterotropic allosteric interactions in which PGS is the effector and MDZ the substrate. Molecular dynamics simulations provide a mechanistic picture of the origin of this cooperativity. These results show that the midazolam can be used as a sensitive probe for drug–drug interactions in human P450 CYP3A4.

The issues of designing the route network of urban passenger transport and the need for the device of travel pockets for it are considered. It is proposed to use mathematical statistics formulas to calculate the probability of the number of simultaneous appearance of public transport units at a stop. The procedure for calculating the length of the entrance pocket at the stop using the results of visual observation of the entrance to the stop of passenger transport units is given. The length of the entry pocket iscalculated for the simultaneous appearance at the stop of two buses of large and one bus of small capacity, which was 68 m.

CYP17A1 is an essential human steroidogenic enzyme, which catalyzes two sequential reactions leading to the formation of androstenedione from progesterone and dehydroepiandrosterone from pregnenolone. The second reaction is the C17-C20 bond scission, which is strongly dependent on the presence of cytochrome b5 and displays a heretofore unexplained more pronounced acceleration when 17OH-progesteone (17OH-PROG) is a substrate. The origin of the stimulating effect of cytochrome b5 on C-C bond scission catalyzed by CYP17A1 is still debated as mostly due to either the acceleration of the electron transfer to the P450 oxy complex or allosteric effects of cytochrome b5 favoring active site conformations that promote lyase activity. Using resonance Raman spectroscopy, we compared the effect of Mn-substituted cytochrome b5 (Mn-Cytb5) on the oxy complex of CYP17A1 with both proteins co-incorporated in lipid nanodiscs. For CYP17A1 with 17OH-PROG, a characteristic shift of the Fe-O mode is observed in the presence of Mn-b5, indicating reorientation of a hydrogen bond between the 17OH group of the substrate from the terminal to the proximal oxygen atom of the Fe-O-O moiety, a configuration favorable for the lyase catalysis. For 17OH-pregnenolone, no such shift is observed, the favorable H-bonding orientation being present even without Mn-Cytb5. These new data provide a precise allosteric interpretation for the more pronounced acceleration seen for the 17OH-PROG substrate.

Nonlinear dynamics of a gyrotron with high-order operating mode, driven by an external signal with harmonic or stepwise modulation of its parameters or by two monochromatic signals, was studied theoretically. Conditions for locking and control of the radiation frequency were found. Exit from the locking regime is accompanied by the beats of the operating mode or excitation of spurious modes. Simulations were performed using a megawatt-power TE28.12 mode gyrotron as the example (Chirkov et al., Appl Phys Lett 106(26), 2015).

The last decade has contributed to the rapid progress in the gyrotron development. Megawatt-class, continuous wave gyrotrons are employed as high-power millimeter (mm)-wave sources for electron cyclotron heating (ECH) and current drive in the tokamaks and stellarators. The progress in gyrotron development pushes ECH from a minor to a major heating method. Also gyrotron based technological complexes successfully applied in electron cyclotron resonance ion sources, for microwave ceramic sintering and diamond disk production. The paper describes the main features of high frequency gyrotrons. Some data about pulsed and CW tubes, working in the terahertz frequency range, are given. These gyrotrons operate (in some specific combinations) at very low voltage and beam current, demonstrate an extremely narrow frequency spectrum or wide frequency tuning. Although in comparison with the classical microwave tubes the gyrotrons are characterized by greater volume and weight due to the presence of bulky parts (such as superconducting magnets and massive collectors where the energy of the spent electron beam is dissipated) they can easily be embedded in a sophisticated laboratory equipment (e.g., spectrometers, technological systems, etc.). All these advantageous features have opened the road to many novel and prospective applications of gyrotrons.

The influence of the magnetic-field profile in the gyrotron interaction space on the generation efficiency and frequency was experimentally studied. A profiled magnetic field was created by a system of several low-inductance coils. It is shown that it is possible to increase the generation efficiency by ~1.3 times, which is comparable with the results that are obtained using single-stage recuperation of the residual electron-beam energy. In this case, the proposed method is easier to implement and can be used jointly with the recuperation. It is also demonstrated that it is possible to control the generation frequency within a range of at least twice the width of the radiation spectrum with characteristic times of the order of milliseconds. This allows one to believe that the gyrotron frequency-stabilization circuit can be successfully performed using small changes in the magnetic field.

Human cytochrome P450 CYP17A1 first catalyzes hydroxylation at the C17 position of either pregnenolone (PREG) or progesterone (PROG), and a subsequent C(17)–C(20) bond scission to produce dehydroepiandrosterone (DHEA) or androstenedione (AD). In the T306A mutant, replacement of the Threonine 306 alcohol functionality, essential for efficient proton delivery in the hydroxylase reaction, has only a small effect on the lyase activity. In this work, resonance Raman spectroscopy is employed to provide crucial structural insight, confirming that this mutant, with its disordered proton shuttle, fails to generate essential hydroxylase pathway intermediates, accounting for the loss in hydroxylase efficiency. Significantly, a corresponding spectroscopic study with the susceptible lyase substrate, 17-OH PREG, not only reveals an initially trapped peroxo-iron intermediate experiencing an H-bond interaction of the 17-OH group with the proximal oxygen of the Fe-O(p)-O(t) fragment, facilitating peroxo- attack on the C(20) carbon, but also unequivocally shows the presence of the subsequent hemiketal intermediate of the lyase reaction.

We study the oscillation regimes for the model of a gyrotron with a fixed Gaussian longitudinal field structure and three modes of an equidistant spectrum (an operation mode and two satellites symmetrically spaced by frequency) during autonomous operation and under the action of an external monochromatic signal. The two-parameter (dimensionless current and the cyclotronresonance mismatch for an operating mode) plane is partitioned into the regions corresponding to various regimes. It is shown that the presence of a maximum at the leading edge of the voltage pulse can lead to excitation of the parasitic modes in the process of the power-source switch-on and to quenching of oscillation of the operating mode. These undesirable effects can be suppressed by locking the operation-mode frequency by an external monochromatic signal, which provides oscillation at the operation mode.

As part of the creation of a unique T-15MD tokamak with a magnetic field of 2 T and an aspect ratio of 2.2, the first one of a series (8 pieces) of microwave setups of a megawatt power level for electron–cyclotron plasma heating and current drive was developed and successfully tested. The setup includes a gyrotron, power supplies, a microwave radiation transmission line, and a fast (response time is no more than 10 μs) gyrotron emergency protection system. The generation regime was experimentally demonstrated with the parameters 1 MW/30 s/82.6 GHz for an efficiency of 57%.

In this article, construction schemes direct and indirect control systems were analyzed, and new construction, providing high operating characteristics for optic filters, was introduced. Authors introduce the original decision for creation modern broadband optic control system. Based on the proposed method, approbation of created system was made, and output characteristics control system – spectral transmission dependencies were introduced as a result. Spectral transmission dependencies of interference optical filters, made with different optical control systems were analyzed. Conclusions and prognoses about further developments of direct broadband optic control system for thickness sprayed coatings were made.

We show that during phase locking of the oscillations of a megawatt-level gyrotron by a relatively weak external monochromatic signal, the phase and frequency modulation of the gyrotron radiation due to the low-frequency fluctuations of the accelerating voltage and current decreases severalfold compared to the autonomous regime. The calculations were performed using the example of two megawatt-level gyrotrons, namely, a gyrotron developed at the Institute of Applied Physics of the Russian Academy of Sciences and operated at the TE28,12 mode with a frequency of 170 GHz [1] and a gyrotron with twice as high frequency and operation-mode indices (345 GHz and TE56,24), whose ability to generate a megawatt power in the case of frequency and phase locking by an external signal is shown theoretically [2].

Based on the analysis of electron–wave interaction, we study the possibility of developing a gyrotron that is able to provide a megawatt output power in quasi-continuous (long-pulse) oscillations at both first and second gyrofrequency harmonics. For selective excitation at the second cyclotron harmonic when the operating current is significantly higher than its starting value, we propose to lock the gyrotron by a weak (several percent power) monochromatic incoming signal which suppresses spurious oscillations at the fundamental cyclotron resonance in the gyrotron start-up process. Simulations of a two-frequency gyrotron with an output power of 1 MW at the first cyclotron harmonic (19 GHz) and 0.8 MW at the second one (38 GHz) based on a nonstationary self-consistent system of equations are presented. Such a source of radiation is of interest for plasma-heating systems in spherical tokamaks.

Influence of the density of mode spectrum in the gyrotron cavity on the possibility of stable single-mode operation has been investigated for high-order modes. Interaction of the operating mode wit...

The results of experimental investigation into the dielectric losses in GaAs, InP:Fe, and Si semiconductor crystals in the millimeter wavelength range (80–260 GHz) using the original precise method of measuring the reflectance and dielectric-loss tangent tanδ based on open high-quality Fabry–Perot cavities are presented. It is shown that the losses in the frequency range from 100 to 260 GHz in ultrapure semiconductor single-crystal GaAs substrates are mainly determined by lattice absorption, while the main loss mechanism in single-crystal silicon is absorption by free carriers; herewith, tan δ ≈ (1–2) × 10–4 even for a noticeable, at a level of 1012 cm–3, free carrier concentration. In contrast with GaAs and Si, tanδ in compensated InP:Fe crystals is almost independent of frequency in the range from 100 to 260 GHz, which is associated with the material conductivity and optimization of microwave semiconductor devices, in particular, frequency-multiplication devices and devices of the controlled emission output of continuous and pulsed gyrotrons.

We propose a robust way of advancement of the gyrotrons into the region of terahertz frequencies and MW-level power of radiation while retaining high efficiency and high stability of the frequency. These gyrotrons may be used for electron cyclotron resonance heating and current drive systems (ECRH&CD) in future fusion setups, in large complexes of coherently radiating gyrotrons for THz data and energy transmission, for THz particles acceleration. We at first demonstrate the advantages of this way at the example of the gyrotron with very-high-order operating mode TE56.24, driven by a relatively weak external monochromatic signal, and show that in the phase- and frequency-locking mode a significant enhancement of radiation parameters – frequency, power and efficiency – can be achieved.

Experimental details are discussed and millimeter wave measurements presented of a W-band gyrotron traveling-wave tube (gyro-TWT) that uses a helically corrugated interaction waveguide operating at the second electron cyclotron harmonic. A method for increasing the gain by using an interaction circuit with two sections separated by a long sub-cutoff drift section has been experimentally verified. A 10-mW driving source was sufficient to enable an amplified signal output power of 3 kWs. The continuous-wave (CW) operation with a single-stage depressed collector and deposited beam power of about 20 kW is believed to be the first demonstration of its kind for a W-band gyro-TWT.

The article presents an analysis of the structural safety elements of cars that are used in the construction of vehicles. A description of the elements that affect the level of vehicle safety is given. The influence of structural safety elements of a car on the likelihood of an emergency is considered.

A car hitting a pedestrian is the most dangerous type of traffic accident. To study the impact, various techniques are used, they are improved depending on the direction of movement of the car and pedestrian. A collision with a pedestrian who came out from behind an oncoming obstacle is considered, a variant of the engineering calculation of the removal of the car from the place of impact is given.

We discovered a specific property of the eigenmodes of a cylindrical waveguide, due to which efficient mode excitation at ultrahigh (s=4n+1, n is integer) multiples of the gyrofrequency can be provided by a polyhelical weakly relativistic electron beam, standardly used for gyrotron operation. In the proof-of-principle experiment with a V-band gyrotron driven by a 25-keV, 2-A beam, about 100 mW radiation power at the fifth cyclotron harmonic (0.22 THz) has been detected in the cw regime. Based on the gyrotron theory, we demonstrate in simulations that, using parameters of existing gyrotrons, this method can be applied for producing cw radiation at a power level of up to several watts in the terahertz gap.

We consider the influence of an external quasi-monochromatic signal on a multimode gyrotron in the case where the signal frequency is close to the frequency of the operating mode of the gyrotron. The influence of the mode competition on the generation regime at a harmonic frequency modulation is studied. The calculations were performed for a high-power 170 GHz gyrotron developed at the Institute of Applied Physics of the Russian Academy of Sciences (IAP RAS). Depending on the parameters of the gyrotron and the external signal, various generation regimes were determined, including locking of the operating-mode frequency when the radiation frequency is close to the frequency of the external signal, beats of the frequency and amplitude of the operating mode, and excitation of spurious modes.

The radiation-frequency locking by an external signal is experimentally studied for a megawatt gyrotron. An external signal from a magnetron is applied to the operation space of the gyrotron at a frequency of 35 GHz via a synthesized two-mirror quasioptical converter developed at the Institute of Applied Physics of the Russian Academy of Sciences. The radiation spectra are measured for both the frequency locking regime and the frequency beats. The locking region is constructed on the plane of two parameters, namely, the external-signal power and frequency. The experimental and theoretical results are compared to show a good agreement.

The gyrotron traveling-wave tube (gyro-TWT) is a wideband version of gyrotron amplifiers, which produce pulsed or continuous-wave radiation in the millimeter-wavelength band at a power level that exceeds the powers produced by conventional TWTs with slow-wave structures and rectilinear beams by 1–2 orders of magnitude. Since 1996, researchers at the Institute of Applied Physics of the Russian Academy of Sciences (IAP RAS) have been developing the concept of the gyro-TWT based on the use of a waveguide with a helically corrugated surface, which changes the dispersion of one of the eigenmodes in a circular waveguide radically. In this paper, we discuss several problems that arise in implementation of such devices, which many years of experimental studies have revealed, present the parameters of gyro-TWTs developed with allowance for specific applications of their end users, and discuss lines of further perfection of such amplifiers.

This review is devoted to the analysis of information on protein-markers of chronic heart failure (CHF). The review contains current information about protein predictors of cardiovascular disease and concomitant CHF. The methodology of proteomic analysis is considered. The following conclusions were made: 1. The method of controlling the expression of individual genome sections proteomic analysis is a method of early, preclinical diagnosis of diseases, because it allows to identify the initial stages of the pathological genome in the phenotype. 2. The study of CHF protein markers is at the primary stage of accumulation of factual material, making this research direction promising. 3. In many ways, in addition to the prognostic effect of pathological protein-markers, the detection allows to understand the pathogenesis of the disease, its implementation at the molecular level. 4. In turn, determining exact molecular mechanisms of the pathological process development helps finding new treatment modalities. 5. Changes in the number of pathological protein-markers dynamics allows to predict the severity and outcome of the disease.

An original design is proposed that makes it possible to create a two-channel optoelectronic instrument for diagnostics of the shape and quality of intraocular lenses. This instrument consists of a collimation-type channel and a channel based on a Shack–Hartmann wavefront sensor. The hardware characteristics of the instrument are examined, i.e., the radius of curvature of the wavefront in the plane of the lens raster, and the dynamic range to which possible measurable aberrations of the intraocular lenses are restricted. A methodology is proposed for diagnostics of the design parameters of intraocular lenses. The systematic error of the output parameter of the instrument being developed is examined within the framework of precision calculations. The calculations that were performed made it possible to transfer to the design stages of an optoelectronic instrument based on the wavefront sensor for monitoring the parameters of the shape of intraocular lenses.

When subjected to γ-irradiation at cryogenic temperatures the oxygenated complexes of Cytochrome P450 17A1 bound with either of the lyase substrates, 17-OH PREG or 17-OH PROG are shown here to generate the corresponding lyase products, dehydroepiandrosterone (DHEA) and androstenedione (AD) respectively. The current study uses gas chromatography-mass spectrometry (GC/MS) to document the presence of the initial substrates and products in extracts of the processed samples. A rapid and efficient method for the simultaneous determination of residual substrate and products by GC/MS is described without derivatization of the products. It is also shown that no lyase products were detected for similarly treated control samples containing no nanodisc associated CYP17 enzyme, demonstrating that the product is formed during the enzymatic reaction and not by GC/MS conditions nor the conditions produced by the cryoradiolysis process.

We theoretically study the possibility of high-power (MW-level) generation in second-harmonic gyrotrons based on the frequency-locking by a weak (several percent of the power) external monochromatic signal. Such a signal can suppress the generation of the parasitic fundamental harmonic during the start-up process. Within the frame of multimode self-consistent non-stationary model, we demonstrate the applicability of the described approach to provide 0.65 MW output radiation in a 230 GHz 2nd-harmonic gyrotron with TE 31,8 operating mode.