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The properties of circularly polarized light has recently been used to selectively reflect chiral metasurfaces. Here we report the more complete basic functionalities of reflectors and absorbers that display various optical phenomena under circularly polarized light at normal incidence as before. For the chiral metamirrors we designed, the circular dichroism in about 0.4 reflection is experimentally observed in visible wavelengths. The experimental results also show high reflectance for right-handed circular polarization with preserved handedness and strongly absorbed left-handed circular polarization at chiroptical resonant wavelengths. By combining a nanobrick and wire grating for our design, we find and offer a new structure to demonstrate the superposition concept of the phase in the same plane that is helpful in effectively designing chiral metamirrors, and could advance development of their ultracompact optical components.

Light-trapping devices have always been a topic of intense interest among researchers. One such device that has gained attention is the hot-electron photodetector with a tunable detection wavelength. Photodetectors based on plasmon nanostructures that provide excitation of surface plasmon polaritons are challenging to manufacture. To address this issue, a planar hot-electron photodetector based on a Tamm plasmon polariton localized in a metal-semiconductor-multilayer mirror structure has been proposed in this study. The parameters and materials of the structure were adjusted to ensure perfect absorption at the resonance wavelength. As a result, the photoresponsivity of the proposed device can reach 42.6 mA W -1 at 905 nm. For the first time, the photosensitivity was calculated analytically by solving the dispersion law for the Tamm plasmon polariton.

A photonic crystal microcavity with the liquid crystal resonant layer tunable by heating has been implemented. The multiple vanishing resonant lines corresponding to optical bound states in the continuum are observed. The abrupt change in the resonant linewidth near the vanishing point can be used for temperature sensing.

The microcavity in the form of a liquid crystal defect layer embedded in a one-dimensional photonic crystal is considered. The microcavity mode has a tunable radiation decay rate in the vicinity of a bound state in the continuum. It is demonstrated that coupling between the microcavity mode and a Tamm plasmon polariton results in hybrid Tamm-microcavity modes with a tunable Q factor. The measured spectral features of hybrid modes are explained in the framework of the temporal coupled mode theory.

Benzo[a]pyrene (BaP) is one of the priority pollutants in the urban environment. For the first time, the accumulation of BaP in road dust on different types of Moscow roads has been determined. The average BaP content in road dust is 0.26 mg/kg, which is 53 times higher than the BaP content in the background topsoils (Umbric Albeluvisols) of the Moscow Meshchera lowland, 50 km east of the city. The most polluted territories are large roads (0.29 mg/kg, excess of the maximum permissible concentration (MPC) in soils by 14 times) and parking lots in the courtyards (0.37 mg/kg, MPC excess by 19 times). In the city center, the BaP content in the dust of courtyards reaches 1.02 mg/kg (MPC excess by 51 times). The accumulation of BaP depends on the parameters of street canyons formed by buildings along the roads: in short canyons (< 500 m), the content of BaP reaches maximum. Relatively wide canyons accumulate BaP 1.6 times more actively than narrow canyons. The BaP accumulation in road dust significantly increases on the Third Ring Road (TRR), highways, medium and small roads with an average height of the canyon > 20 m. Public health risks from exposure to BaP-contaminated road dust particles were assessed using the US EPA methodology. The main BaP exposure pathway is oral via ingestion (> 90% of the total BaP intake). The carcinogenic risk for adults is the highest in courtyard areas in the south, southwest, northwest, and center of Moscow. The minimum carcinogenic risk is characteristic of the highways and TRR with predominance of nonstop traffic., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

A photonic crystal microcavity with a tunable quality factor (Q factor) has been implemented on the basis of a bound state in the continuum using the advanced liquid crystal cell technology platform. It has been shown that the Q factor of the microcavity changes from 100 to 360 in the voltage range of 0.6 V.

Recently, two-dimensional materials have attracted attention owing to their special optical characteristics and miniaturization, with low thickness as well as extremely high responsivity. Additionally, Tamm plasmon polariton (TPP) resonance can be observed by combining a metal film and a one-dimensional (1D) photonic crystal (PC), where an electric field confinement is located at the metal-1D PC interface. In this study, a graphene layer combined with a TPP is proposed as a wavelength- and angle-selective photodetector. The graphene layer is located where the strong field confinement occurs, and the photocurrent response is significantly enhanced with increasing absorption by over four times (from 62.5 μA⋅W -1 to 271 μA⋅W -1 and undetected state to 330 μA⋅W -1 in two different samples). Moreover, the graphene-TPP photodetector has wavelength and angle selectivity, which can be applied in LiDAR detecting, sun sensors, laser beacon tracking, and navigational instruments in the future.

Medical care refers to a risky type of activity, since as a result of its provision, harm to the patient's health may be caused and prerequisites for the onset of legal (civil, disciplinary, administrative and criminal) liability may arise. The legal liability of a pathologist in the event of an incorrect diagnosis by the attending physician on the basis of an incorrect conclusion of the pathologist may occur due to violations due to low qualifications, frivolity, negligence, failure to comply with the rules, procedures for providing medical care, job descriptions, official duties. If the incorrect conclusion of the pathologist was of an objective nature (for example, in the case of an incorrect interpretation of a diagnostically difficult case), it should go beyond the scope of punishable shortcomings in the activities of the pathologist. The financial responsibility of a pathologist may occur when its burden is placed on a medical organization for harm caused to the life or health of a patient, due to the establishment, among other things, of the legality of the actions (inaction) of a medical worker with whom the medical organization is in an employment relationship. A medical organization, in case of satisfaction of the patient's claims by the court, as a rule, in a regression procedure, may involve the relevant medical worker who caused the harm in the issue of compensation, compensate for their financial and reputational losses. The most important thing in such cases is to resolve the issue of establishing the grounds for bringing a medical worker to responsibility.

We consider Tamm plasmon polariton in a subwavelength grating patterned on top of a Bragg reflector. We demonstrate dynamic control of the phase and amplitude of a plane wave reflected from such metagrating due to resonant coupling with the Tamm plasmon polariton. The tunability of the phase and amplitude of the reflected wave arises from modulation of the refractive index of a transparent conductive oxide layer by applying the bias voltage. The electrical switching of diffracted beams of the ±1st order is shown. The possibility of doubling the angular resolution of beam steering by using asymmetric reflected phase distribution with integer and half-integer periods of the metagrating is demonstrated.

The influence of the volume fraction of plasmonic nanoparticles on the efficiency of the Tamm-plasmon-polariton-based organic solar cell is investigated in the framework of temporal coupled mode theory and confirmed by the transfer matrix method. It is shown that, unlike a conventional plasmonic solar cell, in which the efficiency is directly proportional to the volume fraction of nanoparticles in the photosensitive layer, the efficiency of the proposed solar cell reaches the highest value at low volume fractions. This effect is explained by the fact that at these volume fractions, the critical coupling condition of the incident field with the Tamm plasmon polariton is fulfilled. Thus, for the incoming radiation range of 350 to 500 nm, a maximal cell efficiency of 28% is achieved with a volume fraction of nanoparticles equal to 10%. Additionally, the optical properties of the photosensitive layer are compared for the cases of determining its complex refractive index by effective medium theory and the S-parameter retrieval method. A good agreement between the results is demonstrated, which encourages the use of the effective medium theory for preliminary calculations.

The aim of this paper is to characterize the main properties and level of pollution of sealed soils in different land use zones of the Eastern administrative district (EAD) of Moscow. In 2016-2017 overall, 47 samples were taken from 35 soil pits. The list of soil properties analyzed included actual acidity, organic carbon content, particle-size distribution, and degree of salinity. Pollution of sealed soils with petroleum products (PPs), benzo[a]pyrene (BaP) and heavy metals and metalloids (HMMs) was evaluated. Sealed soils are characterized by the medium organic matter content (2.24%), alkaline reaction (pH 8.0), sandy loamy texture, and the absence of soluble salts in the upper part of the profile. The pronounced technogenic anomalies of hydrocarbons are mainly formed in the sealed soils of the industrial and traffic land use zones. The mean content of BaP in the sealed soils is 56 times higher than that in the background soils, it exceeds MPC by 9.5 times. The concentrations of most HMMs in the sealed soils exceed the background level by two-four times. The most intense accumulation of As, Ba, Cr, Cu, Ni, Pb, Sb, and Sn takes place in the industrial zone with the high degree of sealing. The hygienic standards for BaP and PPs contents approved in the Russian Federation in the sealed soils of EAO are exceeded by almost ten times. Maximum permissible concentrations are also exceeded for a large group of HMMs. The high contamination of the sealed soils can create dangerous ecological situation in the EAD if road covering will be removed and pollutants begin to migrate., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

In O-and C-band optical communications, Ge is a promising material for detecting optical signals that are encoded into electrical signals. Herein, we study 2D periodic Ge metasurfaces that support optically induced electric dipole and magnetic dipole lattice resonances. By overlapping Mie resonances and electric dipole lattice resonances, we realize the resonant lattice Kerker effect and achieve narrowband absorption. This effect was applied to the photodetector demonstrated in this study. The absorptance of the Ge nanoantenna arrays increased 6-fold compared to that of the unpatterned Ge films. In addition, the photocurrent in such Ge metasurface photodetectors increases by approximately 5 times compared with that in plane Ge film photodetectors by the interaction of these strong near-fields with semiconductors and the further transformation of the optical energy into electricity.

An electrode of a light-induced cell for water splitting based on a broadband Tamm plasmon polariton localized at the interface between a thin TiN layer and a chirped photonic crystal has been developed. To facilitate the injection of hot electrons from the metal layer by decreasing the Schottky barrier, a thin n-Si film is embedded between the metal layer and multilayer mirror. The chipping of a multilayer mirror provides a large band gap and, as a result, leads to an increase in the integral absorption from 52 to 60 percent in the wavelength range from 700 to 1400 nm. It was shown that the photoresponsivity of the device is 32.1 mA/W, and solar to hydrogen efficiency is 3.95%.

This numerical study demonstrates the possibility of exciting a chiral optical Tamm state localized at the interface between a cholesteric liquid crystal and a polarization-preserving anisotropic mirror conjugated to a metasurface. The difference of the proposed structure from a fully dielectric one is that the metasurface makes it possible to decrease the number of layers of a polarization-preserving anisotropic mirror by a factor of more than two at the retained Q -factor of the localized state. It is shown that the proposed structure can be used in a vertically emitting laser.

Chiral-selective Tamm plasmon polariton (TPP) has been investigated at the interface between a cholesteric liquid crystal and a metasurface. Different from conventional TPP that occurs with distributed Bragg reflectors and metals, the chiral-achiral TPP is successfully demonstrated. The design of the metasurface as a reflective half-wave plate provides phase and polarization matching. Accordingly, a strong localized electric field and sharp resonance are observed and proven to be widely tunable.

We report on a model of an organic solar cell in which a photosensitive layer doped with plasmon nanoparticles acts as not only an absorbing element but also a mirror involved in the formation of the Tamm plasmon polariton. It is shown that such solar cells can be fabricated without metal contacts, thus avoiding undesired losses in the system. Methods for an additional increase in the integral absorption by applying metal or dielectric mirrors to the lower boundary of the photonic crystal are proposed. It has been found that the integral absorption in the active layer can be increased by 15% compared to classical optimized planar solar cells.

Optical sensing is one of many promising applications for all-dielectric photonic materials. Herein, we present an analytical and numerical study on the strain-responsive spectral properties of a bioinspired sensor. The sensor structure contains a two-dimensional periodic array of dielectric nanodisks to mimic the optical behavior of grana lamellae inside chloroplasts. To accumulate a noticeable response, we exploit the collective optical mode in grana ensemble. In higher plants, such a mode appears as Wood's anomaly near the chlorophyll absorption line to control the photosynthesis rate. The resonance is shown persistent against moderate biological disorder and deformation. Under the stretching or compression of a symmetric structure, the mode splits into a couple of polarized modes. The frequency difference is accurately detected. It depends on the stretch coefficient almost linearly providing easy calibration of the strain-sensing device. The sensitivity of the considered structure remains at 5 nm/% in a wide range of strain. The influence of the stretching coefficient on the length of the reciprocal lattice vectors, as well as on the angle between them, is taken into account. This adaptive phenomenon is suggested for sensing applications in biomimetic optical nanomaterials.

We investigate optical Tamm states supported by a dielectric grating placed on top of a distributed Bragg reflector. It is found that under certain conditions the Tamm state may become a bound state in the continuum. The bound state, in its turn, induces the effect of critical coupling with the reflectance amplitude reaching an exact zero. We demonstrate that the critical coupling point is located in the core of a vortex of the reflection amplitude gradient in the space of the wavelength and angle of incidence. The emergence of the vortex is explained by the coupled mode theory.

The polarized components of transmission spectrum of a multilayered photonic structure containing a nematic liquid crystal under the magnetic-field-induced torsion deformation have been investigated. Since the planarly twisted director structure of the nematic is unrelated to a decrease in its optical anisotropy, the control of the polarization and spectral characteristics of the eigenmodes is based on the occurrence of a geometric phase, whose contribution gradually increases upon nematic deformation. Along with the previously observed blue shift of the cavity o modes, the anomalous shift of the cavity e modes to the long-wavelength region (red shift) of the transmission spectrum has been detected. It has been shown that the countershift of the modes narrows the intermode interval. Remarkably, the extremal approaching of e and o modes in magnetic field H&#95;{ex} occurs below the avoided crossing phenomenon observed in the stronger equalization field H&#95;{eq} (H&#95;{ex}

We consider light scattering by an anisotropic defect layer embedded into anisotropic photonic crystal in the spectral vicinity of an optical bound state in the continuum (BIC). Using a resonant state expansion method we derive an analytic solution for reflection and transmission amplitudes. The analytic solution is constructed via a perturbative approach with the BIC as the zeroth order approximation. The solution is found to describe the collapsing Fano feature in the spectral vicinity of the BIC. The findings are confirmed via comparison against direct numerical simulations with the Berreman transfer matrix method.

The resonant splitting of optical Tamm state numerically is demonstrated. The Tamm state is localized at the interface between a resonant chiral medium and a polarization-preserving anisotropic mirror. The chiral medium is considered as a cholesteric liquid crystal doped with resonant dye molecules. The article shows that the splitting occurs when dye resonance frequency coincides with the frequency of the Tamm state. In this case the reflectance, transmittance, and absorptance spectra show two distinct Tamm modes. For both modes, the field localization is at the interface between the media. The external field control of configurable optical and structural parameters paves the way for use in tunable chiral microlaser.

A concept of an easily tunable device based on hybrid Tamm modes is proposed. The device can be controlled using a high-sensitivity chiral liquid crystal serving as a mirror. The coupling of the chiral optical Tamm state with the Tamm plasmons is predicted. The Tamm plasmons are excited at different frequencies for the orthogonal linear polarizations, while the chiral Tamm state is excited at only one frequency. The properties of the proposed model are analytically and numerically calculated. The possibility of creating a two- and three-mode laser with tunable characteristics on the basis of the proposed model is discussed.

Electric-field-induced changes of the orientational structures of cholesteric liquid crystal layer with the tangential-conical boundary conditions have been investigated. The samples with the ratio of the cholesteric layer thickness d to the helix pitch p equalled to 0.57 have been considered. The perpendicularly applied electric field causes a decrease of the azimuthal director angle at the substrate with the conical surface anchoring. In the cells with d = 22 μm, the defect loops having the under-twisted and over-twisted areas are formed. At the defect loop the pair of point peculiarities is observed where the 180° jump of azimuthal angle of the director occurs. Under the action of electric field the loops shrink and disappear. In the cells with d = 13 μm, the over-twisted and under-twisted defect lines are formed. Applied voltage results in the shortening of lines or/and their transformation into a defect of the third type. The director field distribution near defect lines of three types has been investigated by the polarising microscopy techniques. It has been revealed that the length ratio between the over-twisted and third-type defect lines can be controlled by the electric field.

The polarized optical states in the transmission spectrum of a twisted-nematic Fabry-Pérot cavity with the distinctly broken Mauguin's waveguide regime have been theoretically and experimentally investigated. Specific features of the electric field-induced transformation of the polarization and spectral characteristics of eigenmodes of the neighboring series at the overlap resonant frequencies have been examined. It is demonstrated that the linear polarizations of eigenmodes at the cavity boundaries remain nearly orthogonal and their frequency trajectories reproduce the avoided crossing phenomenon. The experimental data are confirmed analytically and by the numerical simulation of light transmission through the investigated anisotropic multilayer with the use of a Berreman matrix method. The results obtained can be generalized to any materials with the helix response.

Coupling between the defect mode of a cholesteric liquid crystal and the localized mode of a cholesteric liquid crystal-phase plate-metal structure is theoretically demonstrated. It is shown that the transmittance spectrum can be tuned by changing the twist-defect angle and helix pitch, which are governed by external factors. The spectra for different circular polarizations of the incident light are different; specifically, at the nondiffracting polarization, there is no defect-mode transmittance peak.

We propose an elegant approach to produce photonic bandgap (PBG) structures with multiple photonic bandgaps by constructing quasiperiodic photonic crystals (QPPCs) composed of a superposition of photonic lattices with different periods. Generally, QPPC structures exhibit both aperiodicity and multiple PBGs due to their long-range order. They are described by a simple analytical expression, instead of quasiperiodic tiling approaches based on substitution rules. Here we describe the optical properties of QPPCs exhibiting two PBGs that can be tuned independently. PBG interband spacing and its depth can be varied by choosing appropriate reciprocal lattice vectors and their amplitudes. These effects are confirmed by the proof-of-concept measurements made for the porous silicon-based QPPC of the appropriate design.

The polarization exchange effect in a twisted-nematic Fabry-Pérot resonator is experimentally confirmed in the regimes of both uniform and electric-field-deformed twisted structures. The polarization of output light in the transmission peaks is shown to be linear rather than elliptical. The polarization deflection from the nematic director grows from 0^{∘} to 90^{∘} angle and exchanges the longitudinal and transverse directions. Untwisting of a nematic by a voltage leads to the rotation of the polarization plane of light passing through the resonator. The polarization exchange effect allows using the investigated resonator as a spectral-selective linear polarizer with the voltage-controlled rotation of the polarization plane.

The anthropogenic geochemical transformation of soil cover in large nonferrous mining centers of the Selenga River basin was assessed. The results of the geochemical survey of 2010-2012 revealed the spatial distribution patterns and abundances of 18 hazardous heavy metals and metalloids in the soils of Erdenet (Mongolia) and Zakamensk (Buryat republic, Russian Federation). In both cities, mining activities disturbed soil cover which accumulates Mo, Cu, As, Sb, W in Erdenet and Bi, W, Cd, Be, Pb, Mo, Sb in Zakamensk. Maximum accumulation of elements in Erdenet is restricted to the industrial zone. In Zakamensk, it has spread on ½ of the territory with the degree of multielemental pollution exceeding the extremely dangerous level by 16 times. The effect of mining centers on the state of the river system is local and does not spread to the Selenga River. Downstream from Erdenet, an artificial pool intercepts heavy metal and metalloid flows of the Erdenetii-Gol River. By contrast, downstream from the tailing dumps of the Dzhida tungsten-molybdenum plant the concentrations of ore elements W and Mo and their accessories Bi and Cd in the Modonkul River exceed background values by 146, 20, 57, and 21 times, respectively, decreasing by an order of magnitude 30 km downstream.

The present paper studies the generation mechanism of terahertz (THz) radiation from tightly focused femtosecond laser pulses in a gas medium. We measured the angular radiation pattern under different focusing conditions and observed that, with the deepening of focus, the angular radiation pattern changes and optical-to-THz conversion efficiency increases. The analysis of the observed phenomena led to the assumption that the dipole radiation prevails in most cases despite the existing conception regarding the dominating role of the quadrupole mechanism of radiation. Based on these assumptions, the transient photocurrent theory of the phenomenon presented in this paper was developed by us and used for the numerical fit of the experimental data.

We report on the spectral properties of an optically switchable tristable chiral-tilted homeotropic nematic liquid crystal (LC) incorporated as a tunable defect layer in one-dimensional photonic crystal. By varying the polarization angle of the incident light and modulating the light intensity ratio between UV and green light, various transmission characteristics of the composite were obtained. The hybrid structure realizes photo-tunability in transmission of defect-mode peaks within the photonic bandgap in addition to optical switchability among three distinct sets of defect modes via photoinduced tristable state transitions. Because the fabrication process is easier and less critical in terms of cell parameters or sample preparation conditions and the LC layer itself possesses an extra stable state compared with the previously reported bistable counterpart operating on the basis of biased-voltage dual-frequency switching, it has much superior potential for photonic applications such as a low-power-consumption multichannel filter and an optically controllable intensity modulator.

Anomalous spectral shift of transmission peaks is observed in a Fabry-Pérot cavity filled with a chiral anisotropic medium. The effective refractive index value resides out of the interval between the ordinary and the extraordinary refractive indices. The spectral shift is explained by contribution of a geometric phase. The problem is solved analytically using the approximate Jones matrix method, numerically using the accurate Berreman method, and geometrically using the generalized Mauguin-Poincaré rolling cone method. The o-mode blueshift is measured for a 4-methoxybenzylidene-4'-n-butylaniline twisted-nematic layer inside the Fabry-Pérot cavity. The twist is electrically induced due to the homeoplanar-twisted configuration transition in an ionic-surfactant-doped liquid crystal layer. Experimental evidence confirms the validity of the theoretical model.

We have studied spectral properties of a cholesteric liquid crystal with a combined defect consisting of a nanocomposite layer and a twist. The nanocomposite layer is made of metallic nanoballs dispersed in a transparent matrix and featuring effective resonant permittivity. A solution has been found for the transmission spectrum of circularly polarized waves in the structure. We have analyzed spectral splitting of the defect mode in the band gap of the cholesteric when its frequency coincides with the nanocomposite resonant frequency. Defect modes have characteristics strongly dependent on the magnitude and the sign of the phase difference of the cholesteric helix on both sides of the defect layer. It has been found that the band gap width and the position and localization degree of defect modes can be effectively controlled by external fields applied to the cholesteric.

A one-dimensional asymmetric photonic crystal with dual-frequency liquid crystal as a central defect layer was demonstrated. Such asymmetric structure was characterized by the dramatic increase in intensity of the electric field of light localized at the overlapped photonic bandgap edges, thereby enhancing the observed transmittance of the spectral windows originating from the defect layer. The defect layer was made of a dual-mode liquid crystal that exhibited not only electrical tunability and switchability but also optical bistability. Consequently, tunable and bistable defect modes can be realized in the photonic structure. This asymmetric photonic crystal structure is promising and should be further explored for photonic device applications.

The light transmission spectrum has been calculated for a "cholesteric liquid crystal-phase plate-metal" structure. It is shown that the system can have an isolated waveguide surface mode with characteristics efficiently controllable by external fields acting on the cholesteric. The degree of localization of surface modes and the transmission coefficients have been found to differ considerably for the light of different polarizations.

Defect modes are investigated in a band gap of an electrically tunable one-dimensional photonic crystal infiltrated with a twisted-nematic liquid crystal. Their frequency shift and interference under applied voltage are studied both experimentally and theoretically. We deal with the case where the defect layer thickness is much larger than the wavelength (i.e., the Mauguin condition). It is shown theoretically that the defect modes could have a complex structure with elliptic polarization. Two series of polarized modes are coupled with each other and exhibit an avoided crossing phenomenon in the case of opposite parity., (© 2012 American Physical Society)

We evaluated overall and relapse-free survival in patients with metastatic renal cell carcinoma (MRCC) with poor prognosis. The study involved 92 patients (median age 54.1 years, male 63%, female 29%), retrospectively; 48.9% had poor prognosis. They received oral sunitinib 59 mg/day in 6 cycles (4 weeks on, 2 weeks off). Median overall survival was 17.6 months, relapse-free--10.8 months. Risk of progression in the poor and good prognosis groups was identical (HR=09). Overall response was 29% in poor prognosis and 40%--in good one (p = 0.07). Drug tolerability was acceptable in both groups. Sunitinib was effective in both groups of MRCC patients.

Haplotype and allele frequencies of 17 Y-chromosomal short tandem repeat (Y-STR) markers in a population sample of 133 Yakut male volunteers from two regions: Central (n=41) and Western Yakutia (n=92) were determined using the AmpFlSTR Yfiler PCR Amplification Kit (Applied Biosystems). A total of 65 haplotypes were identified in the Yakut population, with 15 haplotypes in Central sample and 54 haplotypes in Western sample. Haplotype diversity values of 0.79 and 0.96, and average gene diversity values of 0.14 and 0.41 were calculated for Central and Western samples, respectively. The Fst distances between both our Yakut populations with other Russian, Siberian and Chinese populations were represented by MDS plot. The graphical view demonstrated close distances between most Yakut populations and differences with other Siberian populations., (Crown Copyright © 2010. Published by Elsevier Ireland Ltd. All rights reserved.)

The anti-HIV activity of new membranotropic compounds, i.e. of the polycarboxylate matrix and of its derivatives modified by adamantane and norbonene, was studied in respect of HIV-1 strains, whose tropicity to coreceptors CCR5 and CXCR4 was different, as well as in respect of HIV-1 variants resistant to azidothymidine (AZT) in a continuous culture of human lymphoid cells (MT-4) and in mononuclear cells of peripheral blood from healthy donors. Testing of complex compounds in a culture of infected MT-4 human lymphoid cells showed an effective inhibition of viral reproduction of LAV.04 (CXCR4-tropic variant) and of HIV11(EVK) as well as AZT-resistant variants. The studied pharmacophores-modified compounds displayed, in infection of the primary culture of human mononuclear cells of the HIV-1 R5 and X4 strains, a notable antiviral activity with their HIV efficiency significantly exceeding the one of the original matrix.

An open comparative randomized study of paroxetine (selective inhibitor of serotonin re-uptake) and tricyclic antidepressant amitriptiline has been conducted. These drugs were used for the treatment of 43 patients with recurrent depression (RD) with frequent relapses (ICD-10 F33.0-F33.2) during 12 months. There were 2 groups matched for demographic and clinical data, one included 21 patients treated by paroxetine and the other 22 patients switched to amitriptiline. Basing on clinical records and scores on a number of scales, i.e. HAM-D, CGI, quality of life, high efficacy of the drugs was confirmed, being estimated as 90,5% responders in the paroxetine group and 69,2% in the amitriptiline one, with the marked advantage of the former medication. The better tolerability, possibility of single intake and absence of severe side-effects argue for preferable use of paroxetine during long-term therapy in RD patients with frequent relapses.

The purpose was to develop an effective drug of local intravaginal membranetropic microbicide based on polycarboxylate and matrix modified by norbonene and/or peptide (simulator of CCR5 coreceptor). The drug was added to the composition of polyacrykic acid-polyvinylpyrrolidone (interpolymer complexes) in order to prevent the interplay of its non-specific groups with proteins. The antiviral effect and absence of toxicity of the finished microbicide form were demonstrated on the human lymphoid MT-4 culture.

Clinical and laboratory data on the treatment of 19 children with chronic toxoplasmosis were used for estimation of the efficacy of drug combination, such as spiramycin + lidase and lincomycin + lidase vs. the traditional therapy (co-trimoxazole, metronidazole). The combination designed by us, i.e. spiramycin + lidase, lincomycin + lidase used in consecutive courses proved to be more efficient.

Analysis of molecular mechanisms of HIV-infection and targets for therapeutic intervention allowed to offer strategy for design of new effective anti-HIV/AIDS agents on the basis of two key principles: 1) intervention to infectious process beginning from the earliest stages of the virus penetration into cells; 2) blockade of not only one but several molecular targets of the HIV life cycle. The paper presents the results of the in vitro investigation of the anti-HIV activity (against several HIV-1 strains, including AZT-resistant ones) of new generation complex substances synthesized with application of the molecular substrategy for bifunctional inhibitors on the basis of a combination of nonspecific antiviral active polymeric anions with selective virus sensitive membranotropic pharmacophores of the adamantane and norbornene lines. The HIV-1 inhibiting potential of polymeric carboxylic acids (PKA) of various nature: synthetic polymeric analogues of succinic acid and carboxymethylated dextran was evaluated. It was shown that the antiviral action of PKA is located at the initial stages of HIV-1 penetration into cells and is markedly defined by balance of electrostatic activity and conformational mobility of the macromolecules. This corresponds to the evidence of the negatively charged macromolecules ability to bind the positively charged V3 loop within the viral protein gp120, preventing the HIV-1 adsorption on the surface of permissive cells. Chemical conjugation of the PKA with derivatives of the adamantane (amantadine and rimantadine analogues) or norbornene (related to deitiforin and natural bicyclic therpenoids) via spacer groups provides synergistic elevation of the anti-HIV-1 activity, first of all for the flexible chain PKA. The obtained result experimentally confirmed the theoretically predicted expansion of the anti-HIV-1 action of the bifunctional kind antivirals due to cooperation of the electrostatic potential of PKA with the virus specific hydrophobic activity needed to block postadsorption events of the HIV-1 life cycle, including both the virus penetration into cells and the virus posterity release from the infected cells. Additional cooperation of PKA with some special vectors targeted towards "Raft" domains of cellular membranes, epicentres for natural location of initial and completed stages of the HIV-1 replication cycle was also shown promising. The structure-function optimized samples exhibit high indexes of anti-HIV-1 selectivity up to IS50 = 10000.

The capacity of a previously described plasmid vector pAZ to deliver bioactive proteins to targets in vivo has been studied. This vector molecule has a strong constitutive promoter, is extremely stable in cells of vaccinal S. choleraesuis strain, and encodes the synthesis of marker protein beta-galactosidase which helps monitor the vector's fate in the host. The gene encoding hepatitis B virus core antigen (HBcAg) has been inserted into pAZ under its constitutive promoter. The resultant recombinant plasmid p19-24 has been used to transform Enterobacteriaceae (E. coli and S. choleraesuis) cells. Transformed cells produce immunologically active HBcAg. p19-24 was stable in S. choleraesuis cells during their culturing and during this strain persistence in mice. Triple oral immunization of rabbits in a dose of 1 x 10(9) S. choleraesuis cells TC177 induced the production of virus-specific antibodies. Successful transformation of cells of another vaccinal strain S. abortus ovis by this plasmid extends the potentialities of the vector. The results demonstrate good prospects of using pAZ vector for the construction of live oral vaccines.

Evidence was obtained that the changed gravity, tension profiles of the magnetic fields inside the orbital station and other spaceflight factors (SFF) substantially influence the cell genome and synthesis of recombinant proteins. The authors proposed a technique of fixation of possible alterations in genes and expressed recombinant proteins in strains-producers of human alpha-interferon: HuIFN-alpha 2b, HuIFN-alpha 8a, HuIFN-alpha 10a, and HuIFN-alpha 14a. Spaceflight factors were simulated by way of gamma-irradiation at 10 Gy and 50 Gy by a cobalt unit, and centrifugation of samples at 10 g and 50 g. Cultivation of the strains-producers during the SFF simulation yielded HuIFN-alpha proteins with altered functional characteristics. Following exposure to simulated SFF, strains-producers expressed HuIFN-alpha that preserved a high titre of antiviral activity (AVA) but suppressed the antiproliferative activity (APA) inferring some structural/functional shifts in the HuIFN-alpha molecule due to, presumably, mutations in the active center responsible for APA. Determination of species specificity of the HuIFN-alpha recombinant proteins following exposure to SFF revealed dissociation of cross-AVA in homologous and heterologous cell cultures which can be also attributed to the structural/functional shifts in the HuIFN-alpha molecule. These changes can be localized in the receptor cluster of molecule or consequent to modification of the center defining HuIFN-alpha species specificity. The proposed simulation system allows fixation of shifts in the HuIFN-alpha structural/functional characteristics and investigations of the stability of eucaryotic genes in long-term space flights.

To solve the problems of biological safety of the cosmonaut on long-duration space mission and prediction of changes in macroorganism as a whole and constituting protein molecules under these conditions, it is important to study the influence of spaceflight factors (SFF) on microorganisms-carriers of modeled structures, protein molecules and pro- and eukaryotic genes in particular. Within the framework of scientific cooperation NAUKA-NASA, the authors proposed a model system of prokaryotic producers of pro- and eukaryotic proteins--staphylococcus alpha-toxin (SAT)--as a key protein in pathogenesis of staphylococcal infections, and human leukocytic interferon (HuIFN-alpha) as one of the homeostasis regulating proteins with well-studied structural and functional properties. Recombinant strains of E. coli with either a single or duplicated HuIFN-alpha 2b gene or other genes of the HuIFN-alpha family: HuIFN-alpha 8a, HuIFN-alpha 10a and HuIFN-alpha 14a were selected as producers of SAT and HuIFN-alpha. This biotechnologic system allows imitation and assessment of the SFF mutagenic effect both at the levels of genome of strain-carrier and gene-insertion and expressed CAT and HuIFN-alpha molecules including transcription, translation, assembly and post-translatory modifications of the target-protein. The developed methodology allows determination of highly mutable and conservative regions in the primary structure of a hypothetical protein associated with its functional activity, prediction of specific amino acid substitutes in these regions, and comparison of test calculations with a pool of natural mutations in the family of proteins under study. The structural/functional analysis of proteins and HuIFN-alpha genes made it possible to isolate and systematize functionally significant areas in the structure of hypothetical protein HuUFN-alpha, on the basis of which the most probable amino acid substitutions were prognosticated. This will present a possibility to identify expectable mutation events in HuIFN-alpha proteins, which so far have not been found in natural genes of the human interferon. Comparison of results of SFF modeling and space experiments aboard the International Space Station with monitoring of HuIFN-alpha mutant forms will help estimation of the extent of influence of the spaceflight factors on evolution of protein molecules.