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The aim of the study was to create a patient-derived xenograft (PDX) model of human colorectal cancer and to determine its histologic and molecular characteristics, such as the status of KRAS, NRAS, and BRAF genes and the presence of microsatellite instability.Materials and methods. First generation xenograft models in vivo were created using tumors from patients with colorectal cancer (n = 4) and immunodeficient Balb/c Nude mice (n = 20); second, third, and fourth generation models were created in the same mouse line (n = 3 for each generation). A caliper was used to measure subcutaneous xenografts; their size was calculated by the ellipsoid formula. Cryopreservation involved immersing the samples in a freezing medium (80% RPMI 1640, 10% fetal bovine serum, 10% dimethyl sulfoxide (DMSO)) and storing them at –80 °C. The histologic analysis was performed according to the standard technique (preparation of paraffin blocks and staining of microsections with hematoxylin and eosin). Mutations in the KRAS, NRAS, and BRAF genes were determined by direct Sanger sequencing; microsatellite instability was determined by the fragment analysis at five loci: Bat-25, Bat-26, NR21, NR24, and NR27.Results. Stable, transplantable xenografts of colorectal cancer were obtained from two out of four patients. The average waiting time from the implantation to the growth of the first generation xenograft was 28 days. The latency phase after cryopreservation was comparable to that at the creation of the first generation PDX model. The model reproduced the histotype, grade and mutational status of the KRAS, NRAS, and BRAF genes, as well as microsatellite instability of the donor tumor.Conclusion. The developed model of human colorectal cancer was characterized in terms of growth dynamics, cryopreservation tolerance, and histologic and molecular genetic parameters.

Influenza viruses cause acute respiratory infections, especially in the autumn-winter period. They are characterized by a high mutation frequency and cause annual seasonal epidemics. The detection of antibodies that neutralize the virus is an important criterion in the assessment of population immunity and the influenza vaccine effectiveness. In this study, a method for determining the titer of virus-neutralizing antibodies in blood serum has been developed. A new test called the luciferase neutralization assay uses a bioluminescent signal for detection. The assay is based on engineered influenza reporter viruses with various surface antigens and a nanoluciferase reporter protein in the NS1 reading frame. Using the developed method, we studied paired sera of volunteers obtained before and after vaccination. The proposed assay was compared with the conventional antibody assessment methods (microneutralization and hemagglutination inhibition assay); a high degree of correlation was observed. At the same time, the use of the luciferase neutralization assay made it possible to reduce the time required for the analysis and to simplify the detection procedure.The online version contains supplementary material available at 10.1134/S0003683822070067.

The paper is devoted to the consideration of the question of whether the Russian system of scientific attestation retains its integrity. The elimination of the monopoly of the Higher Attestation Commission (HAC) in matters of control over the activities of dissertation councils and procedures for defending dissertations made it possible to increase the variety of rules and practices of scientific attestation. Many scientific and educational organizations have developed their own regulations governing the corresponding activities. At the level of legislation, the instruction was fixed for the self-awarding of academic degrees to set requirements not lower than how they are formulated in federal acts. The question of how exactly this instruction is implemented is of research interest. In addition, it is important to understand whether applicants can receive equal rights and opportunities in different parts of the modern system. During the study, three existing subsystems were identified, together forming a single system. The first of them consists of ordinary and special dissertation councils, regulated directly by the Higher Attestation Commission and the Ministry of Science and Higher Education of Russia. The second subsystem is a collection of leading scientific and educational organizations that independently award academic degrees. Finally, the third subsystem consists of spiritual educational organizations, empowered to award theological degrees, which at the level of federal state educational standards are recognized as like other academic degrees. In all three subsystems, options for the defence of dissertations in permanent, one-time and joint dissertation councils were considered. Comparative analysis of regulatory and legal acts made it possible to highlight the similarities and differences of these subsystems, as well as to identify possible options for their development.

Cognitive impairments in schizophrenia are currently regarded as the third key group of symptoms, along with negative and productive psychopathological symptomatology. They are encountered in a majority of patients and determine the functional outcome of illness. This article presents a review of the literature on modeling of cognitive impairments in schizophrenia in animals. Pharmacological, ontogenetic, and genetic models are discussed, along with their mechanisms and characteristic manifestations, and methods of evaluating cognitive functions in rodents. There is now a multitude of methods for modeling individual cognitive impairments typical of schizophrenia patients in animals. These models are required for further development of psychopharmacology and studies of pathophysiological mechanisms, though none as yet allows the whole set and heterogenous structure of cognitive defi cit seen in patients to be reproduced. Particular attention is paid to ontogenetic models which can be used to study risk factors for the development of schizophrenia and early interventions in states posing high risks of developing psychosis.

The optical properties of three-dimensional quantum-size InGaPAs islands, which are formed by substitution of phosphorous by arsenic in an InGaPAs layer deposited on GaAs directly during the epitaxial growth, are studied by photoluminescence (PL) spectroscopy. The PL line of the formed array of island lies in the range of 950–1000 nm at room temperature. The PL studies in the temperature range of 78–300 K indicate significant inhomogeneity of the island array, existence of nonradiative recombination centers, and transport of carriers between islands. The photoluminescence excitation spectra exhibit a line related to the absorption in the residual two-dimensional InGaPAs layer. Annealing of the structures allowed us to increase the PL intensity at room temperature up to 300% with a slight short-wavelength shift of the island emission line and to improve the homogeneity inside the island array.

Influenza viruses cause an acute respiratory infection, especially in the autumn-winter period. They are characterized by a high mutation frequency and cause annual seasonal epidemics. The detection of virus-neutralizing antibodies is an important criterion in the assessment of population immunity and the influenza vaccine effectiveness. In this study, a method for determining the titer of virus-neutralizing antibodies in blood serum has been developed. A new test, called the luciferase neutralization assay, uses measurement of a bioluminescent signal as a detection method. The influenza A reporter viruses of various subtypes were constructed that encode the nanoluciferase protein in the non-structural NS1 protein reading frame. The developed method was used to compare paired sera of volunteers before and after their immunization with a seasonal influenza vaccine. The proposed method was also compared with certified antibody assay methods: neutralization reaction and hemagglutination inhibition reaction. The tests showed a high correlation, while the luciferase neutralization assay reduced the time and simplified the detection procedure. microneutralization, reporter virus, influenza virus, bioluminescence, nanoluciferase The study was supported by the grant of the President of the Russian Federation for young PhDs (no. 075-15-2019-226); and also by the grant of the Government of Saint-Petersburg for undergraduate and graduate students (September 25, 2018, no 124).

A new method for the formation of three-dimensional quantum-dimensional InGaP(As) islands is proposed, which consists in replacing phosphorus with arsenic in an InGaP layer deposited on GaAs directly during epitaxial growth. It is shown that the replacement of phosphorus with arsenic results in formation of three-dimensional islands in the thin InGaP layer. At room temperature, these islands emit light in the spectral range of 0.95–0.97 µm. The estimated density of the islands is 1.3 × 1010 cm–2.

An investigation has been performed of 1.55-μm vertical-cavity surface-emitting lasers based on heterostructures with a buried tunnel junction (BTJ) with a height difference of 15 nm. The devices are obtained by wafer fusion of heterostructures grown by molecular beam epitaxy and provide single-mode lasing at a BTJ diameter of up to 8 μm. A decrease in the BTJ size leads to a sharp increase in the threshold current, the output optical power, and the resonance frequency at the lasing threshold. Stable single-mode lasing takes place due to the smoothed boundary of the buried surface relief, which induces a gradual change in the profile of the effective refractive index in the lateral direction with the effective current confinement retained. This makes it possible to reduce significantly the transverse optical confinement factor for the higher-order modes even at a large BTJ size. However, at a small BTJ size, it leads to the formation of a saturable absorber in unpumped parts of the active region.

We have created a quantum-cascade laser with 7–8 μm wavelength and surface radiation output through a lattice formed by focused ion beam etching of the upper cladding of the waveguide. The active area of the quantum-cascade laser heterostructure was formed on the basis of the solid alloy heteropair In0.53Ga0.47As/Al0.48In0.52As with two-phonon depletion of the cascade lower level. We demonstrate laser generation in the spectral band 7–8 μm for the created lasers with the selective ring resonator. The studies of the generation spectra for the temperatures in 8–77 K range have shown, that the mode spacing in the generation spectra of these lasers correspond to the whispering-gallery modes.

We have studied heterostructures based on short-period InGaAs/InGaAlAs superlattices (SLs) manufactured by molecular-beam epitaxy on InP substrates, intended for use as active regions in vertical-cavity surface-emitting lasers operating in a 1.3-μm spectral range. The heterostructures were characterized by measuring photoluminescence (PL) emission and X-ray diffraction. It is established that variation of the ratio of quantum-well and barrier-layer thicknesses in the SL allows controlled shift of the PL peak position for lasing in the 1.3-μm range at almost constant PL efficiency.

Quantum-cascade room-temperature 4.5 – 4.6 μm lasers with different numbers of quantum cascades are developed and studied. It is shown that losses at the metallised sidewalls of the ridge waveguide considerably increase the threshold current density. It is demonstrated that the current density needed to overcome the internal and outcoupling losses in lasers with 30 quantum cascades is an order of magnitude lower than in lasers with 15 quantum cascades.

Near- and far-fields of quantum-cascade lasers emitting in the spectral range near 8 μm have been studied. For all laser samples with a ridge width of 20 and 50 μm, lasing on the fundamental waveguide mode with a divergence of ~50° was observed for all laser samples with a ridge width of 20 and 50 μm along the “fast” axis. Along the “slow” axis, a multimode lasing and a competition between the fundamental and higher waveguide modes, which is manifested for lasers with a ridge width of 50 μm in an increase in the emission divergence from ~10° near the threshold to >50° when the lasing threshold is exceeded by a factor of 2–3. The divergence along the “slow” axis for lasers with ridge width of 22 μm remained invariable in the whole range of pumping currents and equaled ~50°. That there is a substantial contribution from the fundamental mode to the total emission intensity of quantum-cascade lasers, which is apparent from the far-field intensity distribution pattern, cannot be established exclusively on the basis of results obtained in near-field measurements.

The results are presented of a study and optimization of the conditions under which heterointerfaces of the GaAs–InGaAsP type are formed via the direct intermolecular wafer bonding (fusion) of a heterostructure of an active region on an InP substrate and distributed Bragg reflectors on GaAs substrates upon the fabrication of hybrid heterostructures for long-wavelength vertical-cavity surface-emitting lasers (VCSELs). The heterostructures are grown by solid-source molecular-beam epitaxy. It is shown that, in the case of the incomplete removal of oxide films during preparation of the wafers before fusion and/or in the presence of adsorbed water on the wafer surfaces, the fused interface contains a large number of amorphous inclusions, which are most likely oxides of Group-III elements. Optimization of the conditions in which a buried tunnel junction is formed on the surface of the heterostructure on an InP wafer made it possible to reduce the surface roughness to 1 nm and to ensure that the thickness of the GaAs–InGaAsP fused interface does not exceed 5 nm, with no dislocations or other extended defects found at the fused heterointerfaces. The 1.55-μm VCSELs fabricated from the hybrid heterostructures created using the developed technology demonstrate efficient lasing under continuous-wave pumping in a wide temperature range, which is indicative of the high optical quality of the fused heterointerfaces in the VCSEL structure.

Recommendations are given on designing thermosiphons (TS) prepared on the basis of the experience that the authors gained in designing more than 4000 TSs for heat-recovery steam generators and the results of long-term investigations and tests carried out to study thermohydraulic and corrosion processes in vertical and inclined TSs filled with steam-water mixture. The results of similar studies performed by other authors are analyzed. References are given to the regulations on the design of heat transfer equipment for thermal and nuclear power stations. The requirements for TS construction materials, the degree of TS filling with water, and the TS vacuum level are outlined. Whether the evacuation of TS may be abandoned was assessed. Measures are proposed to prevent depressurization on water freezing in TSs. Recommendations are given on the calculation of thermohydraulic characteristics and steam-and-gas distribution in vertical or inclined TSs. The conditions of displacement by a steam flow of noncondensable gases, including air, to the top of the condensation zone in a thermosiphon are considered. Various regimes of axial heat transport and heat transfer are described for pure steam condensation (including film condensation, bubble condensation, distribution of different regimes of steam condensation, and condensate cooling along the height of the condensation zone during “flooding”). Heat transfer in the steam condensation from an air-steam mixture (the diffusion component of thermal resistance), maximum power, and the conditions for poorer cooling of the TS heating zone (“flooding,” steam separation at the upper generatrix of the heating zone in an inclined thermosiphon) are examined. Thermosiphons feature a countercurrent flow of steam and its condensate in a single flow with the same mass flowrates. Hence, a special case of “flooding” affecting the maximum power of the thermosiphon, the effect of the incoming steam flow on the heat transfer rate during film condensation, steam-and-gas distribution in a top-plugged channel, corrosion processes in thermosiphons, and hydrogen diffusion through the thermosiphon wall should also be studied.

The results of experiments aimed at fabricating and studying the properties of photodetector structures based on single-layer graphene produced by chemical vapor deposition are presented. The configuration of a Ta2O5 vertical microcavity with a resonance wavelength of about 850 nm and a lower dielectric SiO2/Ta2O5 distributed Bragg reflector is taken as the base structure. The conditions for the transfer and fabrication of mesas in the graphene layer on the microcavity surface are optimized. The diagnostics by Raman spectroscopy of the structural quality of graphene after fabrication of the mesas in the graphene layer and contact pads are indicative of the single-layer structure of graphene with a low intensity of features in its spectrum, responsible for imperfection of the structure. The photocurrent is measured under local optical pumping.

In this work, the effect of the irradiation intensity on the radiation hardness of CMOS integrated circuits (ICs) was studied. We investigated 3 types of ICs manufactured according to design rules from 0.8 to 3 microns, and used in various information transmission systems: 1586IN4, HEF4093BT and MC14504B. The U-31/33 accelerator of electrons has been used for the study in both gamma-ray mode (for moderate intensity) and pulse electron generation mode (for high intensity). As a result, it was revealed that an increase in the intensity of exposure by 4 orders of magnitude might result in a radiation hardness decrease up to factor of 30. This circumstance has to be taken into account when testing CMOS ICs for radiation hardness to high intensity effects. The obtained experimental data confirm theoretical understanding of the influence of increased irradiation intensity on the dose hardness of CMOS ICs.

A design of a tunnel junction (TJ) based on n++-InGaAs/p++-InGaAs/p++-InAlGaAs layers for vertical-cavity surface-emission lasers (VCSELs) for the 1.55-μm spectral range fabricated by wafer fusion of an InAlGaAsP/InP optical cavity and wafers with AlGaAs/GaAs distributed Bragg reflectors has been suggested and tested. The presence of the oxidation-resistant InGaAs layers makes it possible to employ the molecular-beam epitaxy in all stages of the fabrication technology of VCSELs, including the overgrowth of the surface profile in the TJ layer. Owing to the Burstein–Moss effect and to the thickness minimization of the p++-InGaAs layer, it was possible to avoid a buildup of the internal optical loss. As a result, the characteristics of the thus fabricated devices are comparable with those of VCSELs having an n++-/p++-InAlGaAs TJ and a similar level of the mirror losses.

A cavity scheme based on a half-ring with different radii is proposed and fabricated for 7–8 μm quantum-cascade lasers. A quantum-cascade laser with a half-ring cavity radius of 191 μm demonstrated lasing with a spectral width of 474 nm (82 cm–1) at low temperatures. The free spectral range in these lasers was determined by the whispering gallery modes typical for ring cavities. The laser bandwidth at room temperature was 190 nm (31 cm–1), which may be related to an increase in the internal losses with increasing temperature. An increase in the cavity radius to 291 μm made it possible to achieve room-temperature lasing with whispering gallery modes and a bandwidth of 249 nm (40 cm–1) by reducing losses on the mirrors.

We have studied the spectral and dynamic characteristics of quantum cascade lasers emitting in the long-wavelength infrared range. It is shown that lasers with a short cavity (~1 mm) make it possible to obtain frequency combs in a very wide spectral range. We have investigated the spectral dynamics in the frequency comb generation regime. It is demonstrated that the intensity of longitudinal laser modes varies during a pump pulse propagation. We have observed simultaneous generation of all longitudinal modes of a frequency comb over a pump pulse segment with a constant amplitude.

The temperature characteristics of arched-cavity quantum-cascade lasers with different geometrical dimensions emitting in the spectral range of 7–8 μm are studied. The laser heterostructure was grown by molecular-beam epitaxy. The active region consisted of 50 cascades based on a heteropair of In0.53Ga0.47As/Al0.48In0.52As solid alloys. Single-mode lasing is demonstrated for lasers with the semicircular cavity segment 100 μm in diameter and the linear segment 1 mm long. The maximum side-mode suppression ratio at a temperature of 290 K was 26 dB, and the emission wavelength was 7.73 μm.

A pronounced stratification of the temperature (density) of the fluid over the cross section of the heating zone occurs in a thermosyphon that is slightly inclined to the horizontal and has a high degree of water filling, which leads to the onset of natural circulation of the medium along the length of the thermosiphon. In this case, there is an upward flow of water or a steam–water mixture in the upper part of the thermosiphon and a downward flow in the lower part. In experiments with a full-scale thermosiphon, the natural circulation in question increased the axial heat transfer through nonboiling water along all thermosiphon zones by three to seven times as compared to the heat transfer in a vertical thermosiphon. The estimated mass flow rate of natural circulation along the heating zone ranged from 25 to 105 kg/(m2 s). The heat-transfer coefficient and friction factor are estimated at the boundary of countercurrent water flows induced by natural circulation. The conditions of poorer cooling of the thermosiphon heating zone due to steam separation at its upper generatrix are examined. A decrease in the mass filling of the thermosiphon, i.e., an increase in the average void fraction of the medium in it, successively leads to the onset of bubbling steam condensation within the transport section and then in the cooling zone, with a decrease in the length of the upper section of nonboiling water. A transition to film condensation of steam occurs at the limit along the entire length of the cooling zone with a countercurrent steam flow and a near-wall film of its condensate above the level of the steam–water mixture in the thermosiphon.

The method of molecular-beam epitaxy was used to fabricate an elastically balanced heterostructure of a quantum-cascade laser for the spectral range of 4.6 μm based on a heteropair of solid alloys, In0.67Ga0.33As/In0.36Al0.64As, and indium phosphide layers serving as waveguide cladding layers. An X-ray diffraction analysis demonstrated the high uniformity of the composition and thickness of layers in cascades of the heterostructure over the substrate area. Lasers with four cleaved facets show lasing at room temperature at a wavelength close to 4.6 μm with a comparatively low threshold current density of 1.1 kA/cm2.

Single-mode lasing of quantum-cascade lasers with a distributed Bragg reflector formed by ion-beam etching in layers of the upper waveguide cladding is demonstrated. The active region is formed based on an In0.53Ga0.47As/Al0.48In0.52As solid-alloy heteropair with two-phonon depletion of the lower level in the cascade. Single-mode lasing at a temperature of 280 K corresponds to the emission wavelength of 7.74 μm, and the side-mode suppression ratio is 24 dB.